Ulcerative Colitis Group Research Articles

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.

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.

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.

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<0.05). On the biologics treated group and the anti-TNFa subgroup, there was statistically significant increase in IL-24 expression post treatment (P<0.01). In UC patients, the IL-24 expression was significantly increased after a successful treatment in relation with Mayo score ( P<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<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.

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.

P428 Nutritional, Muscular status and micronutrient deficiencies in patients with Inflammatory Bowel Disease

Abstract Background Malnutrition and micronutrient deficiencies are common in inflammatory bowel disease (IBD). Nutrient deficiencies increase the morbidity and complications of IBD. The aim of this study was to evaluate the nutritional and muscular status and identify micronutrient deficiencies of patients with IBD receiving treatment. Methods A total of 105 patients with IBD were enrolled prospectively in the department of gastroenterology and pediatrics from June 2019 to October 2021. To obtain objective data, iron, ferritin, phosphate, folate, Mg, 25-OH vitamin D, vitamin B12, and Zinc were measured in the patient's serum. In addition, body composition analysis was performed using bioelectrical impedance analysis to gain information regarding muscular status. Results There were 51 patients with ulcerative colitis (UC), 54 with Crohn's disease (CD), and the gender ratio (M:F) was 54:51. The average age was 37±18 years, which was significantly lower in patients with CD than UC (28.6±15.9 vs. 45.3±16.3, p<0.001). The mean body mass index (BMI) was 22.0 ± 3.7 kg/m2, lower in patients with CD than UC (21.2 ± 3.8 kg/m2, vs. 22.0 ± 3.3 kg/m2, p=0.030). The disease activity of the patients was 64.8% in remission, with 17.1% mild, 15.2% moderate, and 2.9% severe. In the UC and CD patient groups, skeletal muscle index(SMI) and adjusted skeletal muscle mass were lower in patients with CD compared to UC.(SMI : 35.8±5.5 vs. 32.8±4.7 %, p<0.004, adjusted skeletal muscle : 8.2±1.9 vs. 7.0±1.5 kg/m2, p<0.001) However, there was no difference of SMI and adjusted skeletal muscle according to disease activity in both UC and CD patients (Table 1). Iron was lower in patients with CD compared to UC (63.3 ± 42.5 vs. 82.8 ± 44.0 ug/dL, p=0.024). Ferritin, phosphorus, folic acid, vitamin B12, and zinc were also within normal limits. Magnesium was lower in patients with CD compared to UC (2.08 ± 0.15 vs. 2.15 ± 0.19, p=0.036 mg/dL). Vitamin D levels showed insufficient vitamin D in patients with UC and vitamin D deficiency (below 20 ng/mL) in patients with CD (20.1 ± 10.6 vs. 19.0 ± 9.9 ng/mL, p = 0.567) (Table 2). Conclusion Nutritional status of patients with IBD is favorable, and the lack of trace elements, specifically iron, magnesium, and vitamin D, and reduced skeletal muscle mass were observed to be prominent in patients with CD compared to UC.

Propolis alleviates ulcerative colitis injury by inhibiting the protein kinase C - transient receptor potential cation channel subfamily V member 1 - calcitonin gene-related peptide/substance P (PKC-TRPV1-CGRP/SP) signaling axis.

This study investigated the protective effect of water-soluble propolis (WSP) on colonic tissues in ulcerative colitis (UC) and the role of the protein kinase C - transient receptor potential cation channel subfamily V member 1 - calcitonin gene-related peptide/substance P (PKC-TRPV1-CGRP/SP) signaling pathway. Male SD rats were divided into a control group, a UC model group, various WSP groups (Low-WSP, Medium-WSP, and High-WSP) with UC, and a salazosulfapyridine (SASP) positive control group with UC. After UC was established, the WSP and SASP groups were treated with WSP or SASP, respectively, for 7 d. Each day, body weight measurements were obtained, and the disease activity index (DAI) was recorded by observing fecal characteristics and blood in the stool. After the experiment, hematoxylin and eosin (HE) colonic tissue staining was performed to observe pathological changes, western blotting and immunohistochemistry were performed to detect PKC, TRPV1, CGRP, and SP expression in colonic tissues, and laser confocal microscopy was performed to observe the fluorescence colocalization of PKC/TRPV1, TRPV1/CGRP, and TRPV1/SP. HE staining showed significant colonic tissue structure disruption and inflammatory infiltration in the UC group. Western blotting and immunohistochemistry showed that the expression of PKC, TRPV1, CGRP, and SP in the colonic tissues of the UC group increased significantly compared with that of the control group. Compared with the UC group, the expression of PKC, TRPV1, CGRP, and SP in colonic tissues was significantly reduced in the High-WSP, Medium-WSP, and SASP groups. Immunofluorescence showed the colocalized expression of PKC/TRPV1, TRPV1/CGRP, and TRPV1/SP proteins in the colon tissue of the UC group was significantly reduced after WSP and SASP interventions compared with that of the control group. The results suggest that the mechanism of UC alleviation by propolis may inhibit the PKC-TRPV1-CGRP/SP signaling pathway and the release of inflammatory mediators, thus alleviating inflammation.

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.

Can Serum Histone H4 Level Be a Biomarker in Ulcerative Colitis?

Histones are a part of neutrophil extracellular trap molecules which were reported to have diagnostic values in some inflammatory diseases. We aimed to evaluate whether serum histone H4 can be a diagnostic and prognostic marker for ulcerative colitis. This case-control study included 58 ulcerative colitis patients (34 males and 24 females) and 45 healthy controls (25 males and 20 females). The Mayo clinical scoring system was used for the clinical and endoscopic features. Truelove-Witt's method was applied to the histology activity index. The human histone H4 kit was used for the enzyme-linked immunosorbent assay of serum histone H4. Serum histone H4 was significantly lower in the ulcerative colitis group compared to the control groups [268 (14-1639) vs. 598 (310-2134) ng/L, P < .001, respectively]. Among the ulcerative colitis patients, there was no correlation between serum histone H4 and disease extent, Mayo clinical scoring, Mayo endoscopic activity subscoring, histology activity index, inflammatory markers, d-dimer, and leukocyte and neutrophil counts (r < 0.20, P > .05). Histone H4 levels were not statistically significant between the patients with no medication and those taking 5-aminosalicylate and/or other agents (P > .05). The receiver operating characteristic curve analysis revealed that serum histone H4 concentrations had a 0.782 (95%CI: 0.690-0.857, P < .001) diagnostic accuracy for ulcerative colitis. The specificity and sensitivity for the cutoff level of ≤364 ng/L were 88.9% and 72.4%, respectively. Decreased serum histone H4 values may be used as an auxiliary marker in the progression and diagnosis of ulcerative colitis. Further studies are needed to delineate this relationship between clinical and laboratory traits of ulcerative colitis and serum histone H4.

Methanogenic Archaea in the Pediatric Inflammatory Bowel Disease in Relation to Disease Type and Activity.

The inflammatory bowel disease (IBD) is associated with gut microbiota dysbiosis; however, studies on methanogens-especially those focused on children-are extremely limited. The aim of this study was to determine the abundance of total methanogenic archaea and their three subgroups: Methanobrevibacter (Mb.) smithii, Methanosphaera (Ms.) stadtmanae, and Methanomassiliicoccales, in the feces of children with both active and inactive Crohn's disease (CD) and ulcerative colitis (UC). The results of a quantitative real-time PCR were cross-referenced with the disease type (CD vs. UC) and activity assessed with the use of Pediatric Crohn's Disease Activity Index (PCDAI) and Pediatric Ulcerative Colitis Activity Index (PUCAI) indices, and fecal calprotectin (FCP) concentration, and compared with controls. There was a significant decrease in the number of total methanogens in CD and UC compared to controls. The prevalence of total methanogens was also lower in UC compared to controls. Furthermore, patients from the inactive UC group were colonized by a lower number of Mb. smithii, and demonstrated the most pronounced positive correlation between the number of Ms. stadtmanae and the FCP concentration. Our results demonstrate that gut methanogens are related to the type and activity of pediatric IBD.

Identification of cuproptosis-related molecular classification and characteristic genes in ulcerative colitis

Ulcerative colitis (UC) is a refractory inflammatory disease with imbalances in intestinal mucosal homeostasis. Cuproptosis serves as newly identified programmed cell death (PCD) form involved in UC. In the study, UC-related datasets were extracted from the Gene Expression Omnibus (GEO) database. A comparison of UC patients and healthy controls identified 11 differentially expressed cuproptosis-related genes (DE-CRGs), where FDX1, LIAS, and DLAT were differentially expressed in UC groups from the mouse models and clinical samples, with their expression correlating with disease severity. By comprehending weighted gene co-expression network analysis (WGCNA) and differential expression analysis, the key genes common to the module genes relevant to different cuproptosis-related clusters and differentially expressed genes (DEGs) both in different clusters and patients with and without UC were identified using several bioinformatic analysis. Furthermore, the mRNA levels of four characteristic genes with diagnostic potential demonstrated significant decrease in both mouse models and clinical UC samples. Our discoveries offer a theoretical foundation for cuproptosis effect in UC.

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.

Predictive Value of MHR and NLR for Ulcerative Colitis Disease Activity.

Numerous non-invasive serologic tests are available to diagnose and monitor ulcerative colitis (UC), but their accuracy levels are limited. Thus, there is a pressing need for a serologic biomarker with higher precision for clinical practice. This study aims to evaluate the predictive capacity of monocyte/HDL ratio (MHR) and neutrophil/lymphocyte ratio (NLR) for UC disease activity. We conducted a retrospective analysis of 81 UC patients and 77 age- and sex-matched healthy controls. UC patients were categorized into active and inactive groups based on the Mayo score. The Mayo endoscopic subscore classified them into mild-to-moderate and severe UC groups. The optimal cut-off values for diagnosing UC were 0.34 for MHR (85.7% sensitivity, 76.0% specificity, 88.9% positive predictive value, 70.4% negative predictive value) and 2.49 for NLR (66.1% sensitivity, 88.0% specificity, 92.5% positive predictive value, 53.7% negative predictive value). The optimal MHR and NLR cut-off values to differentiate between mild-to-moderate UC and severe UC were 0.38 (92.9% sensitivity, 56.6% specificity, 53.1% positive predictive value, 93.7% negative predictive value) and 3.46 (71.4% sensitivity, 88.7% specificity, 76.9% positive predictive value, 85.5% negative predictive value), respectively. NLR and MHR are simple yet effective biological predictors of disease activity in UC patients.

Ethyl acetate extract of Terminalia chebula alleviates DSS-induced ulcerative colitis in C57BL/6 mice.

Background: The Chinese pharmacopeia records Terminalia chebula as effective in treating prolonged diarrhea and dysentery, blood in the stool, and prolapse. Modern pharmacological research proves it has multiple pharmacological benefits, including antioxidant, anti-inflammatory, analgesic, hepatoprotective, neuroprotective, and other properties. Objectives: This study aims to clarify the role of Terminalia chebula's ethyl acetate extract (TCEA) on ulcerative colitis (UC) induced by dextran sodium sulfate (DSS) in mice, as well as explore the potential mechanism of action. Materials and methods: The variation of different extracts of T. chebula was detected using the HPLC technique, and the main components in TCEA were identified. DSS was used to establish a mouse model to mimic the physiological state of UC in humans; the alleviating effect of TCEA and positive control 5-ASA on UC mice were evaluated by gavage treatment. Disease progression was assessed by monitoring the mouse's weight change and disease activity index (DAI). The changes in colon tissue were estimated by measuring colon length, HE, and AB-PAS staining and detecting oxidative stress parameters. The results draw from Western blot and real-time PCR showed the TLR4/MyD88/NF-κB pathway may involve in the anti-inflammatory activity of TCEA. Furthermore, the gut flora sequencing technique was employed to monitor the differentiation of intestinal microbiota of mice induced by DSS and TCEA treatment. Results: TCEA significantly lowered DAI scores and inhibited the weight loss and colonic shortening induced by DSS. The colon histomorphology and oxidative stress levels were enhanced after TCEA treatment compared with DSS induced UC group. TCEA attenuated the inflammatory response by regulating TLR4/MyD88/NF-κB pathway activation. Intestinal flora sequencing showed that DSS and TCEA greatly impacted mice's composition and diversity of intestinal microorganisms. But TCEA increased the abundance of Bacteroidetes and decreased the abundance of Firmicutes and Proteobacteria compared with the DSS group, which contributed a lot to returning the intestinal flora to a balanced state. Conclusion: This study confirms the alleviating effect of TCEA on UC and provides new ideas for developing TCEA into a new drug to treat 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.

Gut microbial signatures in clinically stable ulcerative colitis according to the mucosal state and associated symptoms.

The gut microbiome of patients with clinically stable ulcerative colitis (UC) differs from that of healthy individuals depending on the state of the colonic mucosa, especially with or without advanced scarring; however, the underlying mechanism is unclear. Therefore, this study examined the gut microbiome compositional signatures in patients with significant mucosal scarring and UC-related symptoms. Stool samples for gut microbiome analysis were prospectively collected from 57 patients with clinically stable UC between January 1 and December 31, 2022. Data from 57 individuals without inflammatory bowel disease (non-IBD) paired by age and sex were selected from our previous study as the control group. The fecal samples were subjected to 16S rRNA gene sequencing. Associations between gut microbiome profiles and clinical or colonoscopic assessments were examined using diversity and differential abundance analyses. Gut microbiome compositions between the patients with clinically stable UC and non-IBD controls differed significantly. Furthermore, gut microbiome compositions varied between the preserved and altered mucosa groups identified based on mucosal changes in the UC group. Differential abundance test of patients with UC for symptomatic remission based on stool frequency from the two-item patient-reported outcome identified several overlapping taxa specified as gut microbiome signatures, including the Enterobacteriaceae unknown genera (Enterobacteriaceae_g), Klebsiella,and several Lachnospiraceae spp. both in mucosal and symptom change analyses. The gut microbiome can change with mucosal changes, even in clinically stable UC, and some gut microbial signatures may explain the symptom manifestations in patients with UC showing significant mucosal changes.

Association of ulcerative colitis and acute gastroenteritis with prostate specific antigen: results from National Health and Nutrition Examination Survey from (2009 to 2010) and Mendelian randomization analyses.

An increasing number of studies have demonstrated that gastrointestinal inflammation may increase prostate cancer risk and raise the prostate-specific antigen (PSA) level. However, the association between ulcerative colitis (UC) and acute gastroenteritis (AGE) with PSA remains unclear and complicated. Herein, we evaluated the relationship between UC and AGE with PSA concentration using the National Health and Nutrition Examination Survey (NHANES) database and Mendelian randomization (MR) analyses. A total of 1,234 participants fit into the study after conducting the screening based on the NHANES survey conducted from 2009 to 2010. UC and AGE were the independent variables, and PSA was the dependent variable. Weighted multiple linear regressions were utilized to estimate the association of UC and AGE with PSA concentration. To detect the causal relationship between UC and AGE with PSA, a two-sample Mendelian randomized analysis was conducted. After controlling for all covariates, PSA (log2 transform) concentrations in the UC group were increased by 0.64 (0.07, 1.21). AGE was not independently associated with PSA levels after adjusting potential confounders. In patients with coronary artery disease, AGE promotes elevated PSA (log2 transform) concentrations (β = 1.20, 95% CI: 0.21-2.20, p < 0.001). Moreover, an IVW MR analysis indicated that genetically predicted UC was associated with increased PSA, and that AGE was not associated with PSA. This study indicated that a positive causal association exists between UC and the PSA level. However, there is no evidence to support the relationship between AGE and the PSA level.

Increased synthesis and intestinal expression of IL-39 in patients with inflammatory bowel disease.

IL-39 (Interleukin-39) is a heterodimeric cytokine composed of IL-23p19 and EBI3 (Epstein-Barr virus-induced gene 3) subunits. Despite the evidence that correlates the role of IL-39 in regulating inflammation, its expression in the intestinal microenvironment of IBD (inflammatory bowel disease) patients is still unknown. Thus, this work was focused on characterizing relative mRNA (messenger RNA) IL-39 expression and intestinal synthesis in IBD patients. This study includes 37 patients diagnosed with ulcerative colitis (UC), 15 with Chron's disease (CD), and 22 controls. Gene expression of IL-39 subunits (IL-23p19/EBI3) was measured by RT-PCR (real time polymerase chain reaction). Intestinal synthesis was evaluated by immunohistochemistry and serum levels by ELISA. Statistical analysis was done using Prism GraphPad V6. Relative mRNA IL-39 expression was increased in patients with active UC and active CD compared to the remission UC, remission CD, and control group. High levels of relative mRNA expression of IL-39 (IL-23p19 subunit) were associated with histological activity. IHQ analysis showed increased IL-39 production in mucosa, submucosa, muscular, and serosa layer of patients with active disease. IL-39 serum production was increased in patients with UC. IL-39 gene's upregulation was found in patients with active IBD and was associated with severe histological activity in UC. This is the first report regarding the role of IL-39 in patients with IBD. The findings suggest that IL-39 might play a role as an inflammatory mediator in active IBD and could be considered a new alternative in treating this condition.

Evaluation of the diagnostic performance of estimated fecal calprotectin and serum intelectin-1 and C-reactive protein solo or in combination for differentiation between patients with query ulcerative colitis and irritable bowel syndrome

ObjectivesEvaluation of the ability of estimated levels of fecal calprotectin (FCP), serum intelectin-1 (ITLN1), and C-reactive protein (CRP) to differentiate between patients with ulcerative colitis (UC) and irritable bowel syndrome (IBS).PatientsThree-hundred forty-two patients were evaluated clinically for diagnostic criteria of UC and IBD and underwent colonoscopic examination and grading according to Mayo endoscopic scores (MES). Colorectal biopsies were taken for microscopic examination. Fecal and blood samples were obtained for ELISA estimation of levels of the studied variate. Patients were grouped according to microscopic examination of the obtained biopsies as UC and IBD groups. Study outcome is the ability of the laboratory variate for prediction of the microscopic diagnosis.ResultsIn UC patients, FCP and serum CRP levels were notably elevated compared to controls and IBS patients. Conversely, UC patients exhibited significantly reduced serum ITLN1 levels in comparison to controls and IBS patients with insignificantly lower levels in samples of IBS patients. Statistical analyses defined high FCP and low serum ITLN1 as the significant predictors for UC diagnosis with high specificity for FCP level > 150 µg/ml and high sensitivity for serum ITLN1 ≤ 30 and ≤ 18 ng/ml to predict colonoscopic and microscopic UC diagnosis, respectively.ConclusionThe combination of high FCP and low serum ITLN1 could accurately predict the colonoscopic and microscopic findings of UC and can differentiate UC from IBS and may spare the need for colonoscopy and biopsy especially for IBS patients.