Crohn's Disease Group Research Articles

Comparing clinical profiles in spondyloarthritis with Crohn's disease or ulcerative colitis: insights from the ASAS-PerSpA study.

Assuming SpA manifestations may vary among patients with different inflammatory bowel disease (IBD) subtypes, we explored the clinical characteristics associated with the presence of Crohn's disease (CD) or ulcerative colitis (UC) in patients with spondyloarthritis (SpA). We included 3152 patients of ASAS-PerSpA study diagnosed with either axial SpA or peripheral SpA, according to their treating rheumatologist. Of these, 146 (4.6%) had confirmed IBD by endoscopy and were categorized into CD or UC groups. Demographics, clinical characteristics, treatments and patient-reported outcomes were compared between the two subgroups. From 146 patients included in the current analysis, 87 (59.6%) had CD [75 (86.2%) axial SpA and 12 (13.8%) peripheral SpA], and 39 (26.7%) had UC [34 (87.2%) axial SpA and 5 (12.8%) peripheral SpA]. CD and UC groups had similar age with average of 44.9 (13.5) vs 44.0 (13.0) years, respectively, and a slight male predominance in CD (63.2%) compared with UC (51.3%). Diagnostic delay for SpA was 7.0 (6.9) years for CD and 8.8 (8.1) years for UC. Chronic back pain was the most reported symptom present in 95.4% of CD patients and 89.7% of UC patients. Both groups had similar musculoskeletal phenotyping, with higher frequency of psoriasis (15.4%) and uveitis 28.2% in UC; and higher tendency to be HLA-B27 positive in CD (51.9% in CD vs.s 39.4% in UC). In our analysis patients with SpA and concurrent CD or UC had mainly similar musculoskeletal phenotypes. However, they differ slightly in extra-musculoskeletal manifestations and HLA-B27 prevalence.

Increased CpG methylation at the CDH1 locus in inflamed ileal mucosa of patients with Crohn disease

BackgroundE-cadherin, a major actor of cell adhesion in the intestinal barrier, is encoded by the CDH1 gene associated with susceptibility to Crohn Disease (CD) and colorectal cancer. Since epigenetic mechanisms are suspected to contribute to the multifactorial pathogenesis of CD, we studied CpG methylation at the CDH1 locus. The methylation of the CpG island (CGI) and of the 1st enhancer, two critical regulatory positions, was quantified in surgical specimens of inflamed ileal mucosa and in peripheral blood mononuclear cells (PBMC) of 21 CD patients. Sixteen patients operated on for a non-inflammatory bowel disease, although not normal controls, provided a macroscopically normal ileal mucosa and PBMC for comparison.ResultsIn ileal mucosa, 19/21 (90%) CD patients vs 8/16 control patients (50%) (p < 0.01) had a methylated CDH1 promoter CGI. In PBMC, CD patients with methylated CGI were 11/21 (52%) vs 7/16 controls (44%), respectively. Methylation in the 1st enhancer of CDH1 was also higher in the CD group for each of the studied CpGs and for their average value (45 ± 17% in CD patients vs 36 ± 17% in controls; p < 0.001). Again, methylation was comparable in PBMC. Methylation of CGI and 1st enhancer were not correlated in mucosa or PBMC.ConclusionsMethylation of several CpGs at the CDH1 locus was increased in the inflamed ileal mucosa, not in the PBMC, of CD patients, suggesting the association of CDH1 methylation with ileal inflammation. Longitudinal studies will explore if this increased methylation is a risk marker for colorectal cancer.

P158 Expression of IL-19 and IL-24 in intestinal mucosa of inflammatory bowel disease: An immunohistochemical study

Abstract Background Interleukins are considered as targets for future inflammatory bowel disease ( IBD) treatments. IL-19 and IL-24 are members of IL-10 family and through the JAK-STAT pathway induce proinflammatory cytokine production. A retrospective single center study was performed to study the IL-19 and IL-24 expression in 121 patients with moderate to severe IBD, before and after treatment with biologics. Methods A retrospective study of 121 patients with moderate to severe IBD was performed using immunochemistry between 1999 and 2017. This study included 72 patients with Crohn's disease (CD), 49 with Ulcerative Colitis (UC) and 20 healthy controls. The age, gender, disease extent, severity and treatment choice were recorded. Endoscopy reports before and after 12 months of treatment were retrieved. Intestinal biopsy samples were retrieved from the Histopathology Lab before and 1 year after treatment with biologics. A signed consent was received from all the patients involved and the study was approved by the Bioethics Committee of Aristotle University of Thessaloniki. The histological specimen were stained for IL-19 and IL-24 before and one year after treatment with biologics. The results were analysed using SPSS for each of the IBD groups (CD, UC) and further to subgroups depending the biologic treatment they received, anti-Tumor Necrosis Factor alpha(anti-TNFa), Vedolizumab (VDZ), Ustekinumab (USK). Results A statistically significant increase was found in IL-19 and IL-24 patients in IBD patients versus healthy controls (P&amp;lt;0.05). On the biologics treated group and the anti-TNFa subgroup, there was statistically significant increase in IL-24 expression post treatment (P&amp;lt;0.01). In UC patients, the IL-24 expression was significantly increased after a successful treatment in relation with Mayo score ( P&amp;lt;0.01). On the CD group, a reverse statistically significant correlation was found between the pre-treatment IL-19 expression and the Harvey Bradshaw Index (H.B.I.) score reduction in the anti-TNFa and the VDZ subgroups (p&amp;lt;0.05). Conclusion A possibly proinflammatory role of IL-19 was found on the CD group. This can be used as a tool in the future to assess the disease activity and support the diagnosis as a diagnostic biomarker, as IL-19 was found normal in healthy controls. An anti-inflammatory role of IL-24 was found especially in the UC group and in relation with the activity index score post-treatment. This can be used potentially as a marker of response to treatment in active UC, assisting the clinical management. Further research is needed to delineate the exact role of these interleukins in intestinal inflammation.

P1241 Distinct gut microbiota in Crohn's Disease between inflammatory B1 and stricturing B2 phenotype

Abstract Background The gut microbiome represents a promising avenue to elucidate distinct underlying pathophysiology in Crohn's disease (CD).Our aim was to evaluate the composition of the microbiota in Inflammatory B1 and Stricturing B2 Phenotype. Methods We performed 16S ribosomal RNA sequencing on stool samples of 108 patients (64 B1 and 44 B2) included in the Chinese CD cohort and 58 health controls without any inflammatory disorder, in order to explore the structural composition of gut microbiota in different phenotype of CD. Results Comparison of gut microbiota between patients with CD and healthy controls, α diversity and β diversity were statistically different. At the genus level, compared with the normal group, the abundance of Blautia, Bifidobacterium, Faecalibacterium, Collinsella, Coprococcus, Gemmiger, Prevotella, Dialister, Roseburia and Clostridium were decreased significantly in the CD group. In contrast, the abundance of Bacteroides, Ruminococcus, Streptococcus, Enterococcus, Dorea, Escherichia, Phascolarctobacterium, Veillonella and Eubacterium increased significantly. Compared with B1 phenotype, Streptococcus, Collinsella, Veillonella, Coprococcus and Gemmiger were significant decreased in B2 phenotype group. However, Ruminococcus, Dorea, Lactobacillus and Dialister were significant increased. Conclusion Comparison of gut microbiota between patients with CD and healthy controls, α diversity and β diversity were statistically different. At the genus level, compared with the normal group, the abundance of Blautia, Bifidobacterium, Faecalibacterium, Collinsella, Coprococcus, Gemmiger, Prevotella, Dialister, Roseburia and Clostridium were decreased significantly in the CD group. In contrast, the abundance of Bacteroides, Ruminococcus, Streptococcus, Enterococcus, Dorea, Escherichia, Phascolarctobacterium, Veillonella and Eubacterium increased significantly. Compared with B1 phenotype, Streptococcus, Collinsella, Veillonella, Coprococcus and Gemmiger were significant decreased in B2 phenotype group. However, Ruminococcus, Dorea, Lactobacillus and Dialister were significant increased.

P662 Discontinuation of biologic therapy in Inflammatory Bowel Disease: longer term outcomes

Abstract Background The National Institute of Health and Care Excellence (NICE) in the UK recommends evaluation of all patients receiving biological therapy for IBD at 12 months, with a view to discontinuation of therapy for those with stable disease in remission. We recently evaluated the outcomes of discontinuation of biologics at our centre and the disease relapse rate at 12 months was 14.5%. Following this, longer-term outcomes were evaluated for patients who did not relapse at 12 months. Methods All patients on Biologics therapy who underwent biologics discontinuation were identified via our IBD registry. Retrospective data was collected between January 2015 and January 2022 and these included baseline demographics, disease type, type and duration of biological therapy, when therapy was discontinued and disease relapse initially at 12 months, and beyond. All patients had disease re-assessment prior to discontinuation. Disease relapse was defined as evidence of disease activity requiring steroid, biologic or surgical therapies. Patients with perianal Crohn’s disease were excluded. Results A total of 62 patients were included and divided in two groups. 37 (60%) patients had Crohn’s disease (CD) and 25 (40%) had Ulcerative Colitis (UC). Disease extent in the CD group included Ileal (32%), Colonic (53%) and Ileocolonic (15%). In the UC group disease extent included Proctitis (28%), Left sided (56%) and Extensive disease (32%). At 12 months, 14.5% (9) patients had disease reactivation, 13.5% with CD and 16% with UC. The duration of treatment prior to discontinuation ranged between 9 to 74 months (Median 47.5). Beyond 12 months of discontinuation, a total of 48 patients (CD 29 and 19 UC) had their data analysed, with 5 patients excluded due to being lost to follow up. 29% of these patients eventually had a relapse (CD 7, UC 7). The median follow up period was 53 months (range 21-84 months) in the CD group and 42 months (range 24-76 months) in the UC group. The rate of relapse post 12 months of de-escalation was 24% in the CD group and 36% in the UC group. Conclusion In this study, the rate of disease recurrence beyond 12 months of discontinuation of biological therapy was 29 % (median follow up in CD 53 months and UC 42 months) compared to 14.5% at 12 months. Despite careful selection of patients with up-to-date disease activity assessment prior to discontinuation, our data suggests that the overall disease recurrence rate was high at 40% (35% in CD and 48% in UC) and recurrence rates increase over time. We would therefore suggest that discontinuing treatment should only be considered after clear discussions with patients about the high risk of disease relapse and based on an individual basis.

P980 Dietary perceptions and practices in patients with Inflammatory Bowel Disease

Abstract Background Patients with Inflammatory bowel disease (IBD) have a strong interest in the role that diet can play in the disease.However, studies evaluating the perception of diet in Tunisian patients are lacking.The aim of this study was to investigate the dietary beliefs and behaviours of adult patients with IBD. Methods We conducted a longitudinal study using a self-administered questionnaire distributed online to the «Association Tunisienne des Maladies de Crohn et de RCH» group. Through 17 items, we collected data assessing the dietary behaviours and beliefs of patients with Crohn's disease (CD) or ulcerative colitis (UC). Results A total of 121 patients (CD: 59%,UC 41%)were enrolled, with a mean age of 38.1±11.4 years and a sex ratio of M/F= 0.73.Twenty-three patients were active smokers. At the time of the enrollment, 26.4% of patients had an active disease. Eighty-three patients believed that diet was a trigger for the disease, with a male predominance(80% versus 60.8%, p=0.02) but no difference between the UC and CD groups was found(p=0.61). Fourty-one patients felt that diet was more important than medical treatment for disease control, with equal importance for 47 patients and no impact for 6 patients. Ninety-two patients thought that diet could induce a relapse of the disease, with 86.8% resorting to an exclusion diet, and 76% thought that a change in diet could induce remission of the disease. The most frequently avoided were spices(33.1%),and gluten(17.4%). Spicy foods were considered to be the main responsible for IBD flares by 90.1% of patients,followed by fast foods(75.9%), citrus fruits(70.4%) and legumes(64.7%). Respectively 57% and 34.7% of the patients believed that milk and dairy products could induce or worsen disease symptoms. Around half of our patients thought that pasta had no impact on the disease course, while rice was considered to be the major aliment able to prevent relapse and improve symptoms by 47.7% of patients. On the other hand, 52.2% of patients considered high fiber vegetables to be potentially responsible for relapses. Fourty-two percent of the patients believed that fruits could have a negative impact on IBD while 20.4% thought they have a positive effect. Around half the patients thought that red meats and coffee had no impact on the course of the underlying disease. Fifty-five percent of the patients believed that fasting could prevent relapses, while 53 patients felt that it had no significant effect. Half of our patients had at least once consumed nutritional supplements, with a medical prescription noted in 65.6%. Conclusion Our study underlines the importance of a holistic approach to the treatment of IBD, taking into account both traditional medical treatments and appropriate dietary education.

P628 Vedolizumab in Indian patients with Inflammatory Bowel Disease: Interim results from a prospective, multicentre, open-label, phase 4 study

Abstract Background Although anti-tumour necrosis factor (TNF)-α agents have revolutionised the management of ulcerative colitis (UC) and Crohn’s disease (CD), they have demonstrated a therapeutic ceiling with numerous safety concerns. Vedolizumab (VDZ) has consistently demonstrated safety and efficacy in patients with UC and CD in pivotal clinical trials, but its efficacy and safety data are very limited in the developing world where infectious diseases predominate. Methods This prospective, multicentre, open-label, single-arm, phase 4 study (Clinicaltrial.gov: NCT04804540) included patients (aged 18-65 years [yrs]) with moderate-to-severe active UC and CD who were non-responsive to available conventional therapies and/or anti-TNF agents. Patients received VDZ 300 mg through intravenous infusion for induction (Week [W]0, W2, W6) and maintenance (W14, W22, W30, W38, and W46) treatment phase. This interim analysis included data collected till the last patient completed W14 visit. Safety endpoints including incidence of adverse events (AE), serious AEs (SAE), adverse drug reactions (ADR), and adverse events with special interest (AESI), and efficacy endpoints including clinical response and clinical remission were analysed. Results Of 215 patients screened, 150 were eligible (UC, 102 [68.0%], median age: 39 yrs; CD, 48 [32.0%], median age: 31 yrs). Median VDZ treatment duration was 155 days in UC and 143 days in CD groups. Overall, 71 (47.3%) patients (UC, 49 [48.0%]; CD, 22 [45.8%]) experienced ≥1 AE; of these, 40.7% patients had mild AEs (UC, 40.2%; CD, 41.7%). Forty-six (45.1%) patients with UC and 22 (45.8%) patients with CD had ≥1 treatment-emergent AE (TEAE); 5 (4.9%) patients with UC had treatment-related TEAEs. Seven (4.7%) patients (UC, 6 [5.9%]; CD, 1 [2.1%]) had ≥1 SAE (2 [1.3%] were treatment-related), 5 (3.3%) had ≥1 ADR, and 4 (2.7%) had ≥1 AESI. One patient (0.7%) each reported pulmonary tuberculosis and tuberculous pleural effusion as ADR/AESI. Anaemia and small intestinal obstruction were the frequently reported TEAE and SAE, respectively. Most of the AEs were resolved and no AE-related death was reported during study (Table 1). Overall, 90 (60.0%) patients (UC, 56 [54.9%]; CD, 34 [70.8%]) at W14, 37 (63.8%) patients (UC, 29 [61.7%]; CD, 8 [72.7%]) at W30, and 4 (57.1%) patients (UC, 4 [66.7%]) at W46 had the clinical response. Similarly, 62 (41.3%) patients (UC, 40 [39.2%]; CD, 22 [45.8%]) at W14, 23 (39.7%) patients (UC, 19 [40.4%]; CD, 4 [36.4%]) at W30, and 3 (42.9%) patients (UC, 3 [50.0%]) at W46 had the clinical remission (Figure 1). Conclusion Treatment with vedolizumab was safe and effective in Indian patients with moderate-to-severe active UC and CD as per this first multicentre prospective study on vedolizumab from India.

P290 Evaluation of response to chronic and acute stress in patients with Crohn’s disease

Abstract Background Impaired response to stress in patients with chronic inflammatory disease, such as rheumatoid arthritis, is associated with decreased cortisol secretion. The aim of this study was the evaluation of response to chronic and acute stress in patients with Crohn’s Disease (CD). Methods Data was collected from patients who underwent surgery due to complications of Crohn’s (n=26)(CD group) or due to other indications (n=31) (control group). Patients on corticosteroid treatment during last 3 months and other immunological comorbidities were excluded. Cortisol concentration of the hair (proximal 3cm to the sculp) was measured as an indicative marker of stress taking place the last 3 months (chronic stress). Cortisol concentration in the saliva was measured at day 2 post surgery in a daily fluctuation manner (6 measurements in 24h), as an indicative marker of response to acute stress. The chemiluminescence method was used for cortisol measurements. Cortisol concentrations were correlated with DASS 21 questionnaire (validated Greek version),consisting of 21 questions which correspond to separate measurment scales for stress, anxiety or depression. SPSS was used for statistical analysis. Results Hair samples were measured from 17 CD patients and 20 controls. CD patients had significant lower concentrations of hair cortisol (median = 6.375 pgF/mg, IQR = 4.821 - 9.949) compared to control group (median = 9.643 pgF/mg, IQR = 6.602-14.637) (Mann-Whitney U-test P = 0.034). Saliva samples were measured from 21 CD patients and 27 controls. In regards to the post surgical cortisol fluctuation (acute stress), there was no significant difference between the two groups. No significant difference was observed between cortisol concentrations, and questionnaires results. Conclusion In CD, as in other immunological diseases, hypothalamic-pituitary–adrenal axis appears to be affected, leading in decreased response to chronic stress. This observation may have important implications for the pathophysiology, prognosis and treatment of CD.

P180 Novel biomarkers associated with inflammatory bowel disease

Abstract Background Inflammatory bowel disease (IBD) is a chronic multi-factorial disease characterized by inflammation of the gastrointestinal tract. Currently, the mechanisms underlying the disease are far from being elucidated. Thus, the study of proteins involved in its pathogenesis would allow further insights into the molecular mechanisms underlying IBD. Methods The serum and intestinal mucosa (ileum and left colon) proteomic profiles of patients with Crohn´s disease (CD) and ulcerative colitis (UC) and healthy controls (HC) were analyzed using a label-free quantitative proteomics approach (Table 1). Data mining and pattern recognition techniques were performed to identify hidden relationships that are not detectable using classical linear classifiers, and thus identify potential markers able to discriminate between the different study groups. Six candidate biomarkers were selected for further validation using enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) in serum and intestinal tissue samples, respectively (Table 2). Results Comparison of serum proteins between UC patients and HC revealed statistically lower levels of protein 1 and 2 and higher levels of protein 3. The comparison of potential biomarkers between CD and HC group showed lower levels of protein 1 and higher levels of protein 3. In addition, protein 4 was differentially upregulated in CD patients compared to UC (Figure 1A). Regarding the intestinal biopsies, protein 5 showed higher intensity in the IHC staining of ileum from CD patients compared to HC, whereas protein 6 was significantly decreased in left colon and ileum from CD and UC patients compared to HC (Figure 1B). These proteins are involved in thyroxine transport, regulation of chemotactic chemokine activity, inflammatory processes, triglyceride homeostasis, oxidative stress and regulation of NF-kappa-B activation in the cytosol. Conclusion In this study, we have identified a panel of six potential biomarkers that could help to elucidate mechanisms involved in IBD pathogenesis. Their roles in the pathophysiology need to be clarified in further experiments.

P1029 Prevalance and risk factors of thromboembolism in Inflammatory Bowel Disease

Abstract Background Inflammatory bowel disease (IBD), as a chronic inflammatory condition, can affect atherosclerotic process, arterial events, and increase the formation of venous thromboembolism. The aim of this study was to determine the frequency of thromboembolism and the risk factors associated with acute thromboembolism in our IBD cohort. Methods A total of 3133 patients with 1414 Crohn's Disease (CD), 1667 Ulcerative Colitis (UC) and 52 Indeterminate Colitis who were admitted between 1999 and 2021 were retrospectively analyzed. Patients with acute arterial events and venous thromboembolism (n=39) during the follow-up period were compared with a control group (n=78) of the same gender and same diagnosis. Patients with Behçet's syndrome (n=126),systemic vasculitis (n=16) and hereditary thrombophilia (n=5) were excluded. Results Among 3133 IBD patients, number of patients with arterial events or venous thromboembolism at any time was 124, and the frequency was 3,95%. A total of 132 thromboembolic events, 86 arterial (65,2%) and 46 venous (34,8%) were recorded.Coronary artery disease was significantly higher in the UC group (2,3% vs. 1,2%; p=0.028). During follow-up, 40 acute thromboembolic events, 25 arterial and 15 venous, were seen in 39 patients (frequency 1,24%). There was no significant difference between the CD and UC groups in terms of acute thromboembolism (p=0.871). The presence of exacerbation, the presence of hospitalization, the number of priot hospitalizations and clinical activity at the last visit were associated with both arterial and venous thromboembolism; smoking history, age at diagnosis, body-mass index, non-mucosal CD (Montreal B2-B3) and higher basal CRP were associated with arterial thromboembolism only; higher CRP at the last visit, annual exacerbation frequency, presence of an additional inflammatory disease, presence of complications (surgery, abcess), longer total steroid traetment duration and also recent steroid therapy were associated only with venous thromboembolism. In regression analysis, recent steroid therapy and additional inflammatory disease were considered as independent risk factors for venous thromboembolism whereas age at diagnosis of IBD was considered as an independent risk factor for arterial events. Conclusion In addition to risk factors such as age, smoking and obesity, parameters indicating disease activity, inflammatory comorbidities and recent steroid therapy appear to be associated with acute thromboembolism in IBD patients.

P1219 Changes in gut microbiota of patients with inflammatory bowel disease receiving biologic therapy

Abstract Background Inflammatory bowel disease (IBD), comprising the predominant forms Crohn’s disease (CD) and ulcerative colitis (UC), is associated with compositional and metabolic changes in the intestinal dysbiosis. The aim of this study is to evaluate the composition in the microbiota of IBD patients who received biologic therapy Methods This is a prospective study recruited 14 patients with IBD received biologic therapy and 13 IBD controls who received conventional treatment . The taxonomic composition of the gut microbiota was determined by 16S ribosomal RNA gene sequencing of stool samples. The stool samples at baseline, weeks 6 and 48 after biologic therapy initiation were assessed. We also evaluated the level of inflammation and treatment response of biologics by BD activity score (CD patient by Crohn’s disease activity index [CDAI] and in UC patient by Mayo score). Results In CD group, we recruited 7 CD patients receiving biologic therapy (Anti-tumor Necrosis Factor for 4 and anti-integrin for 3) and 6 controls.In UC group, we recruited 7 UC patient receiving biological therapy (Anti-tumor Necrosis Factor for 2 and anti-integrin for 5) and 7 controls. Community α-diversity was lower in patients at baseline of biologics group compare to controls significantly but increase abundance and richness after achieving remission in trend at week 6 and week 48, respectively. In Top 10 taxon bacterial distribution, the Firmicutes were increase its abundances gradually ( relative abundance in biologics W0,W6,W48 and controls were 46.3%, 51.7%,62.0%, and 66.4%, respectively). Conversely, the Bacteroidetes were decrease its abundances ( relative abundance in biologics W0,W6,W48 and controls were18.3%, 18.8%, 10.2% and 6.4%, respectively). Increased F/B ratio significantly after biologics therapy also found in our study. (F/B ratio were 9.4, 12.5,64.0,and 84.3,respectively). Patients in control group had higher abundance of Firmicutes of the phylum.By contrast, Enterobacteriaceae and Bacteroidaceae were significantly more abundant in patients of biologics group at W0 . Conclusion Treatment with biologic therapy induced improvement of community diversity and increased F/B ratio in IBD patients which seemed correlate the level of clinical inflammation. The dysbiosis-representative bacteria, such as Enterobacteriaceae, could induce colonic inflammation,were more abundant in patients who had higher activity of IBD. Further larger prospective studies are needed to determine whether the biologic therapy could induce long-term changes of intestinal microbiome.

P439 Mild Crohn’s disease is characterized by a unique serum metabolomic signature

Abstract Background Approximately 20-30% of patients with Crohn's disease (CD) experience a mild disease course following initial diagnosis. Balancing the effectiveness and safety of medical treatments is crucial in the management of mild CD. However, the main clinical challenge currently lies in identifying patients likely to maintain this mild disease course, underscoring the urgent need for biomarkers of mild CD. In this study, we therefore aimed to identify potential circulating biomarkers for patients with mild CD leveraging a metabolomics approach. Methods Patients with mild CD were retrospectively identified from participants of the Mount Sinai Crohn's and Colitis Registry (MSSCR). Baseline screenings in MSSCR included assessments of the use of biologicals and immunomodulators, history of IBD-related surgeries, and the presence of disease complications (including stricturing, penetrating, and perianal CD). Mild CD was defined as the absence of all these variables at baseline as well as after a 5-year follow-up period. Untargeted serum metabolomic profiling was performed to measure the circulating metabolome of these patients. Multivariable logistic regression analyses, adjusting for age, sex, measurement batch, and smoking behavior, were conducted to identify metabolites associated with mild CD. Results In total, 114 patients with CD were characterized in which 1,456 different metabolites were profiled, with 32 patients (28.1%) meeting the criteria for mild CD. The remaining 82 patients (71.9%) partially met criteria for mild CD; these were all biologic-naïve and did not undergo IBD-related surgeries. Multivariable logistic regression revealed 45 distinct metabolites that were significantly associated with the mild CD group (nominal P&amp;lt;0.05). Sphingomyelin compounds and ceramides exhibited the most prominent associations with mild CD (odds ratios [OR] all &amp;gt;2.0), while tryptophan, pantothenate, and salicylate metabolites were also linked to mild CD. Conversely, primary and secondary bile acid metabolites and amino acid derivatives from lysine-, tyrosine-, and proline metabolism were all inversely associated with mild CD. Conclusion Mild CD is associated with distinct alterations in metabolic pathways compared to patients with moderate-to-severe CD. Future research should focus on longitudinal assessments of these metabolites for disease monitoring and determining optimal therapeutic strategies for this clinical subgroup.

CT energy spectral parameters of creeping fat in Crohn's disease and correlation with inflammatory activity.

Creeping fat is a kind of unique abnormal mesenteric tissue at the sites of diseased bowel of Crohn's disease. By using dual-energy CT enterography, this study aimed to evaluate the feasibility of spectral parameters in the quantitative analysis of mesenteric adipose tissue or creeping fat. In this study, patients with known or suspected Crohn's disease who underwent dual-energy CT enterography from March 1, 2019, to March 31, 2021, were enrolled. Among them, 40 patients with surgery and pathology-proven creeping fat were selected as the creeping fat Crohn's disease group, and 40 normal patients were selected as the control group. The quantitative spectral parameters including the slope of the Hounsfield unit curve, normalised fat-water concentration, normalised fat-iodine concentration, and normalised fat volume fraction at the enteric phases were obtained. Mann-Whitney U test, Kruskal-Wallis H test, and receiver operating characteristic curve analysis were applied to compare quantitative parameters among various groups. A significant difference was observed in the slope of the Hounsfield unit curve, normalised fat-water concentration, normalised fat-iodine concentration, and normalised fat volume fraction between mesenteric adipose tissue and creeping fat with Crohn's disease at the enteric phase (all p < 0.001). The slope of the Hounsfield unit curve of creeping fat at the enteric phase had a better capability to distinguish inactive and active Crohn's disease (AUC = 0.93, p < 0.001). Dual-energy CT enterography with quantitative spectral parameters is a potentially novel noninvasive tool for evaluating creeping fat in Crohn's disease. Energy spectral parameters of creeping fat in Crohn's disease are significantly different from normal mesenteric adipose tissues and are correlated with inflammatory activity. • Dual-energy CT enterography allows quantitatively assessing creeping fat with spectral parameters. • The creeping fat has distinct spectral parameters to normal mesenteric adipose. • The spectral parameters accurately differentiate active and inactive Crohn's disease.

Circulating miR-199a and long noncoding-RNA ANRIL as Promising Diagnostic Biomarkers for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), involving both Crohn's disease (CD) and ulcerative colitis (UC), represents a chronic, immune-mediated inflammatory disease due to an uncontrolled, ongoing inflammatory response to intestinal bacteria in those with genetic susceptibility. MicroRNA (miRNA) extrusion from relevant remote organs or tissues is reflected in the expression of miRNAs in serum and plasma. Both UC and CD patients had higher blood levels of expressed miR-199a. Long noncoding RNA (lncRNA) ANRIL is a proinflammatory gene that mediates nuclear factor κB to play a role in inflammatory diseases, such as IBD. The aim of the current study is to investigate the potential role of both miR-199a and ANRIL in diagnosing IBD in adult patients. Sixty-seven IBD patients diagnosed clinically, radiologically, endoscopically, and histologically were included in this prospective cohort study. Participants were classified into 3 groups: the UC group (n = 35), the CD group (n = 32), and the control group (n = 30). Demographics, history taking, laboratory characteristics, and treatments were recorded. Tumor necrosis factor α, miR-199a, and ANRIL were measured. The findings suggested that miR-199a and ANRIL might be associated with the occurrence or progression of IBD because both genes were substantially expressed in the peripheral blood of patients with this condition. Receiver-operating characteristic curve analysis indicated that the detection of miR-199a and ANRIL had a predictive sensitivity of 62.9% and 88.6% and a specificity of 70.7% and 96.7% for the occurrence of UC cases, respectively, and a predictive sensitivity of 72.4% and 46.9% and a specificity of 96.7% and 34.7% for the occurrence of CD cases, respectively. Both miR-199a and ANRIL are abundant in the sera of IBD adult Egyptian patients (UC and CD). Both can represent a noninvasive marker for early disease diagnosis.

Evaluation of Voice in Inflammatory Bowel Diseases

Introduction: Inflammatory bowel diseases, which are among the most common chronic gastrointestinal diseases, can also affect the voice for different reasons. The aim of this study was to investigate acoustic, perceptual, and subjective voice evaluation parameters in inflammatory bowel diseases (IBD). Methods: This prospective case-control study included a total of 80 participants: 28 patients with ulcerative colitis (UC), 22 patients with Crohn’s disease (CD), and 30 healthy controls. Following the endoscopic examination, the fundamental frequency (F0), shimmer (dB), jitter (%), and harmonic/noise ratio (HNR) were measured. GRBAS (grade, roughness, breathiness, asthenia, strain) scale was used for perceptual evaluation, and Voice Handicap Index-10 (VHI-10) Turkish version was used for subjective assessment. Results: The F0 value was within normal limits in both disease groups in male and female participants and in the control group. Jitter and shimmer values were statistically higher in the UC and CD groups than in the control group. HNR did not differ between CD and control; however, it was statistically lower in the UC group when compared to both the control and CD groups. The total GRBAS score did not differ between the UC and CD groups; however, it was greater in IBD patients compared to the control group. However, these differences were within normative parameters. Although total VHI-10 score did not differ between UC and CD groups, both had a higher voice handicap than the control group. Conclusion: IBD might have an effect on the voice and voice quality. This disease group was discovered to have perceptual and subjective voice problems additionally.

Outcomes of treatment cessation after switching to subcutaneous vedolizumab treatment in inflammatory bowel diseases.

The usability of subcutaneous vedolizumab (s.c. VDZ) treatment in inflammatory bowel diseases (IBD; ulcerative colitis (UC), Crohn's disease (CD)) has been proven via clinical trials while real-world data collection is ongoing. Our study evaluates the effectiveness, safety, patients' preferences, and psychological factors associated with s.c. VDZ treatment, after switching from intravenous (i.v.) formulation. Prospective, multicenter cohort study including IBD patients switching from i.v. VDZ to s.c. treatment and were evaluated over 52 weeks. Serum VDZ levels and C-reactive protein (CRP) were measured at the baseline and w52. At w12, a questionnaire on the patient's satisfaction and psychological characteristics was administered. The primary outcome was the drug persistence rate (cessation was due to loss of response (LOR), adverse events, patient request, and other causes) at w52, while the secondary outcomes were the changes in the clinical corticosteroid-free remission (CSFR) and biochemical remission (BR; CRP ⩽ 5 mg/L) rates, safety issues, serum drug levels, patients' preferences, and psychological features. In total, 70 IBD patients were evaluated (32 CD patients, 38 UC patients; male/female ratio: 41.4%; median age: 43.2 years). In the CD group, 81.3% were in CSFR and 65.6% were in BR, while in the UC group, 71.7% were in CSFR and 69.4% were in BR. Overall, 17.1% of the patients ceased s.c. VDZ treatment after a median of 26.2 (interquartile range 20-47) weeks. LOR was registered in 3/12 ceased patients. In addition, CSFR and BR rates were stable, while serum VDZ levels increased by w52 (p < 0.001). The transition from i.v. to s.c. VDZ treatment was effective, the overall persistence rate was associated with high serum drug levels, and no novel safety issues were reported. Although s.c. administration after induction can save resources, some patients still insisted on i.v. VDZ treatment, due to its proven formulation.

Calprotectin Is Associated with HETE and HODE Acids in Inflammatory Bowel Diseases.

Intestinal diseases are identified as autoimmune phenomena attributed to a specific virus that binds to the mucosal epithelium. The importance of precise diagnostic processes and identification is emphasized, but the multifaceted and complex etiological factors pose challenges for effective treatment. A recent supplementary study suggested a linkage between the secretion of calprotectin, a protein associated with inflammatory processes, and increased levels of hydroxyeicosatrienoic acids (HETE) and hydroxyoctadecadienoic (HODE) compounds. Sixty-two patients (average age: 14.06 ± 2.93 years) suffering from inflammatory bowel diseases were included in this study. Comparative analyses were performed to assess the concentrations of calprotectin against the levels of arachidonic acid derivatives. The calprotectin concentration was determined using the enzyme-linked immunosorbent assay (ELISA) method. The derivatives of HETE and HODE were identified through liquid chromatography. Patients with Crohn's disease (CD) displayed higher average concentrations of fatty acid metabolites; however, no correlation with calprotectin was observed. A dependency of 12S HETE concentration relative to age was noted in the CD group, and a similar trend was also identified in ulcerative colitis (UC), with the significant metabolites being 15 HETE and 5 oxoETE. In UC patients, a positive correlation was established between the calprotectin concentration and the acids 5-HETE and 12-HETE. These findings may be instrumental for monitoring the inflammatory states of patients and indicating a pathway for intervention. The metabolite 16RS HETE is associated with UC activity, and 15-HETE is related to the disease's duration. A relatively more significant role of HETE acids in the progression of the disease was observed in UC.

Risk Factors of Low Bone Mineral Density in Newly Diagnosed Pediatric Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract with an increasing worldwide incidence. IBD is frequently diagnosed during childhood in the adolescent period of ongoing growth and development, and it can affect patients' linear growth, puberty, nutrition, and bone health. Therefore, its treatment and monitoring are critical to prevent secondary outcomes. However, few studies have highlighted the association between pediatric IBD and skeletal outcomes in Asian populations. We aimed to identify the prevalence and risk factors for low bone mineral density (BMD) in Korean children and adolescents with newly diagnosed IBD. Patients aged 10-18 years diagnosed with either Crohn's disease (CD) or ulcerative colitis (UC) who underwent lumbar spine bone mineral density (LSBMD) and femoral bone mineral density (FBMD) analyses via dual-energy X-ray absorptiometry at the time of IBD diagnosis were included. Low BMD was considered when the age- and sex-matched BMD Z-score was <-1.0. The LSBMD and FBMD Z-scores were correlated with clinical parameters, including general characteristics, anthropometry, and IBD-associated laboratory markers. Regression analyses were performed to identify the risk factors for low BMD. Although the general characteristics between CD (n = 42) and UC (n = 9) groups did not differ, the mean Z-scores of LSBMD and FBMD of the 51 subjects were -0.11 ± 1.24 and -0.58 ± 1.38, respectively. Furthermore, 7.8% and 18% of the study subjects had LSBMD and FBMD Z-scores < -2.0, whereas more than 50% had scores of 0--1.0. Among the clinical factors, body mass index (BMI) Z-score, duration of clinical manifestations, and serum alanine aminotransferase and selenium levels were associated with LSBMD Z-scores in the final multivariate regression analyses. Odds ratios of BMI < -2.0 standard deviation for low LSBMD and FBMD Z-scores were 31.97 and 41.45, respectively. A BMI Z-score < -0.93 was determined as the best cut-off for predicting low BMD. In newly diagnosed pediatric IBD, a substantial number of children are likely to have low BMD in prior to initial treatment while lower BMI, longer duration of clinical manifestation, and higher selenium concentration could affect initial BMD status. Routine bone health surveillance from initial IBD diagnosis throughout the treatment's completion is recommended for preventing the early development of secondary osteoporosis.

The Role of Crohn Disease on Breast Cancer Incidence: A Clinical Analysis.

Crohn disease is a chronic inflammatory disease that can affect the entire gastrointestinal tract. The pathophysiology of this disease characteristically involves transmural inflammation, which predisposes patients to various gastrointestinal cancers such as colon cancer. Although the increased risk of gastrointestinal cancers in Crohn disease has been well established, the risk of extra-gastrointestinal cancers remains unknown. We sought to study the risk of breast cancer in patients with Crohn disease. The data for this retrospective study were compiled using the International Classification of Disease Ninth Revision (ICD-9) and ICD 10th Revision (ICD-10) codes from the national Health Insurance Portability and Accountability Act (HIPAA)-compliant PearlDiver database from 2010 to 2019. Patients were matched for age, sex, and Charlson Comorbidity Index (CCI). Statistical analyses were implemented to assess Chi-squared, logistic regression, and odds ratio. The database query resulted in 70,027 patients in both the control and Crohn disease groups. The incidence of breast cancer was 4,087 in the control group compared to 654 in the Crohn disease group. The P value was < 2.2 × 10-16 and the odds ratio was 0.15 (95% confidence interval (CI)). Patients without Crohn disease had an increased prevalence of breast cancer throughout all age ranges compared to patients with Crohn disease. Additionally, patients without Crohn disease had higher rates of breast cancer throughout the four major regions of the United States. In terms of healthcare costs, patients with breast cancer and a history of Crohn disease paid $23.87 more per hospital visit compared to patients with breast cancer and no history of Crohn disease. The results of this study indicate a statistically significant correlation between Crohn disease and a reduced incidence of breast cancer. This finding is true across all age groups and across the United States. Further study is required to investigate a possible mechanism between the pathophysiology of Crohn disease ultimately leading to reduced tumorigenesis in the breast.

The mechanism by which hsa_circRNA_103124 highly expressed in peripheral blood of patients with active Crohn's disease regulates macrophage differentiation, pyroptosis and inflammation

Objective: To investigate the role and related mechanism of the highly expressed circular RNA molecule 103124 (hsa_circRNA_103124) in macrophage differentiation, pyroptosis and inflammation in peripheral blood mononuclear cells (PBMC) of patients with active Crohn's disease (CD). Methods: Patients with active CD (CD group) admitted to the Affiliated Suzhou Hospital of Nanjing Medical University from April to September 2018 and healthy people (control group) from the physical examination center of the hospital from July to October 2018 were retrospectively selected. The levels of hsa_circRNA_103124 and Toll-like receptor 4 (TLR4) in PBMC of the two groups were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Tohoku hospital pediatrics-1 (THP1) cell line was used as a model for the study of hsa_circRNA_103124 regulating macrophage differentiation. Lentivirus infection was used to construct hsa_circRNA_103124 overexpressed or down-regulated THP1 cells to induce macrophage-like differentiation. According to the expression level of hsa_circRNA_103124, THP1 cell lines were divided into the following four groups: pLC5-ciR was overexpression control group; hsa_circRNA_103124 OE was the overexpression group; ShRNActrl was down-regulated expression control group; hsa_circRNA_103124 ShRNA was the down-regulated expression group. Flow cytometry was used to detect levels cluster of differentiation (CD) 68, CD80, interleukin (IL)-6, tumor necrosis factor α (TNF-α) and reactive oxygen species (ROS). The expression levels of IL-6, TNF-α, IL-1β, TLR4 and myeloid differentiation factor 88 (MyD88) were detected by RT-qPCR. The levels of gasdermin D (GSDMD), IL-18 and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) were determined by immunofluorescence and RT-qPCR. Pearson correlation analysis was used to analyze the correlation between the abundance of hsa_circRNA_103124 and TLR4 expression level or Crohn's disease activity index (CDAI). Results: A total of 50 patients were included in the CD group, including 36 males and 14 females, aged (35±10) (19-64) years. A total of 30 subjects were included in the control group, including 22 males and 8 females, aged (38±9) (24-64) years. hsa_circRNA_103124 [(0.009±0.016) vs (0.003±0.002), P=0.042] and TLR4 [(0.005±0.003) vs (0.001±0.001), P<0.001] were all upregulated in the PBMC of patients in the CD group, compared with the control group. And hsa_circRNA_103124 was positively correlated with TLR4 (r=0.40, P=0.004). hsa_circRNA_103124 level was positively correlated with CDAI (r=0.32, P=0.024). The expression of CD68 (P=0.002) and CD80 (P<0.001) were enhanced. hsa_circRNA_103124 promoted production of ROS and the expression of IL-6, TNF-α, IL-1β, TLR4, MyD88, GSDMD, IL-18 and NLRP3 in macrophage-like M1 differentiated THP1 cells (all P<0.05). Conclusion: High expresion of hsa_circRNA_103124 in PBMC of patients with active CD may promote macrophage M1 differentiation, pyroptosis and inflammation through enhancing the expression of TLR4, MyD88, NLRP3 and GSDMD.