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Background: The approval of ustekinumab (UST) has opened new options for the treatment of Crohn's disease (CD), but potential markers predicting the efficacy of this interleukin-12/23 inhibitor are lacking. Contrast-enhanced ultrasound (CEUS) is non-invasive alternative to endoscopy, demonstrating early transmural changes after treatment induction. Objectives: We conducted a prospective monocentric study aiming to explore the value of multimodal intestinal ultrasound (IUS) in predicting the response to UST in patients with active CD who have been previously exposed to anti-tumour necrosis factor α (TNFα). Design and methods: Consecutive patients with moderate-to-severe CD involving the terminal ileum who were scheduled to begin UST therapy were enrolled between January 2020 and October 2021 in the inflammatory bowel diseases outpatient centre. A complete IUS evaluation, including B-mode, Doppler, dynamic CEUS and elastography, was performed at the time of induction (T0) and after 8 (T1), 16 (T2), 24 (T3) and 48 (T4) weeks of therapy. Each IUS parameter and their variations from baseline were correlated with endoscopic response and mucosal healing after 1 year. Results: A total of 52 patients were included, 29 (55.8%) of which reached endoscopic response at T4. The univariate analysis revealed that, between T3 and T0, the percentage changes of bowel wall thickness, Limberg score, mean signal intensity, rise time, wash-in rate, C reactive protein and Harvey–Bradshaw Index were associated with long-term therapeutic outcome. Based on the above parameters, we developed an IUS score that showed a good performance in predicting 1 year-endoscopic response (area under the curve: 0.91). Conclusion: Multimodal ultrasound could be helpful to predict long-term therapeutic outcome in patients with CD treated with UST. Registration: NCT05987501. Plain language summary: Using ultrasound to predict how well ustekinumab works in Crohn's disease patients Background: The introduction of Ustekinumab (UST) as a treatment for Crohn's disease (CD) has provided new options, but there's a need for reliable markers predicting how well this interleukin-12/23 inhibitor will work. Contrast-enhanced ultrasound (CEUS) is a non-invasive alternative to endoscopy, showing early transmural changes post-treatment. Objectives: In a prospective monocentric study, researchers aimed to explore the value of multimodal intestinal ultrasound (IUS) in predicting UST response in patients with active CD who had previous exposure to anti-tumor necrosis factor α (TNFα). The study involved patients with moderate to severe CD in the terminal ileum, scheduled for UST therapy. Design and methods: Consecutive patients were enrolled between January 2020 and October 2021. Complete IUS evaluations, including B mode, Doppler, dynamic CEUS, and elastography, were conducted at induction (T0) and after 8 (T1), 16 (T2), 24 (T3), and 48 (T4) weeks of therapy. Various IUS parameters and their changes from baseline were correlated with endoscopic response and mucosal healing after 1 year. Results: Of the 52 patients, 29 (55.8%) achieved endoscopic response at T4. The analysis showed that changes in bowel wall thickness, Limberg score, mean signal intensity, rise time, wash-in rate, C-reactive protein, and Harvey-Bradshaw Index between T3 and T0 were associated with long-term therapeutic outcomes. An IUS score developed from these parameters demonstrated good performance in predicting 1-year endoscopic response (area under the curve: 0.91). Conclusion: The study suggests that multimodal ultrasound could be a valuable tool in predicting the long-term therapeutic outcome for patients with CD treated with UST. This non-invasive approach offers insights into treatment response, potentially aiding in personalized treatment strategies for individuals with Crohn's disease. [ABSTRACT FROM AUTHOR]

AbstractBackgroundObjectiveMethodsResultsConclusionGuidelines generally recommend a combination of immunological assays and chest X-ray imaging (CXR) when screening for latent tuberculosis infection (LTBI) prior to biologic treatment in inflammatory bowel disease (IBD).To investigate whether CXR identify patients with suspected LTBI/TB who were not identified with QuantiFERON tests (QFT) when screening for LTBI/TB before starting biologic treatment in IBD patients.Single-center, retrospective cohort study of patients with inflammatory bowel disease who had a QFT and a CXR prior to initiation of biologic treatment in a 5-year period (October 1st, 2017 to September 30th, 2022).520 patients (56% female, mean age 40.1 years) were included. The majority had none or few risk factors for TB (as reflected by the demographic characteristics) but some risk factors for having false negative QFT results (concurrent glucocorticoid treatment and inflammatory activity). QFT results were positive in 8 patients (1.5%), inconclusive in 18 (3.5%) and negative in 494 (95.0%). Only 1 patient (0.19%) had CXR findings suspicious of LTBI. This patient also had a positive QFT and was subsequently diagnosed with active TB. All patients with negative or inconclusive QFT had CXR without any findings suggesting LTBI/TB. One patient developed active TB after having initiated biologic treatment in spite of having negative QFT and a normal CXR at screening.In a population with low risk of TB, the benefits of supplementing the QFT with a CXR are limited and are unlikely to outweigh the cost in both patient test-burden, radioactive exposure, and economic resources. [ABSTRACT FROM AUTHOR]

\nBackground: The Lewis (Le) blood group system, unlike most other blood groups, is not defined by antigens produced internally to the erythrocytes and their precursors but rather by glycan antigens adsorbed on to the erythrocyte membrane from the plasma. These oligosaccharides are synthesized by the two fucosyltransferases FUT2 and FUT3 mainly in epithelial cells of the digestive tract and transferred to the plasma. At their place of synthesis, some Lewis blood group carbohydrate antigen variants also seem to be involved in various gastrointestinal malignancies. However, relatively little is known about the transcriptional regulation of FUT2 and FUT3. Summary: To address this question, we screened existing literature and additionally used in silico prediction tools to identify novel candidate regulators for FUT2 and FUT3 and combine these findings with already known data on their regulation. With this approach, we were able to describe a variety of transcription factors, RNA binding proteins and microRNAs, which increase FUT2 and FUT3 transcription and translation upon interaction. Key Messages: Understanding the regulation of FUT2 and FUT3 is crucial to fully understand the blood group system Lewis (ISBT 007 LE) phenotypes, to shed light on the role of the different Lewis antigens in various pathologies, and to identify potential new diagnostic targets for these diseases. The Lewis (Le) blood group system, in contrast to the majority of blood groups, is not able to synthesize its antigens itself. It depends on the attachment of different oligosaccharides to the erythrocyte membrane, which are adsorbed from the plasma. These glycans are modified by the fucosyltransferases 2 and 3 enzymes (FUT2/3). Beside their role in defining the Lewis blood group, FUT2 and FUT3 are also known to be involved in the susceptibility and progression of various gastrointestinal pathologies, like inflammatory bowel diseases (IBD) or colorectal cancer (CRC). Even though different expression levels of FUT2 and FUT3 have been described in these malignancies, relatively little is known about the mechanisms behind their transcriptional regulation. In this review, we aim to shed light on transcription factors (TFs) responsible for FUT2 and FUT3 expression as well as on post-transcriptional regulators by the means of RNA binding proteins (RBPs) and microRNAs (miRNAs). To achieve our goal, we combined previous knowledge on FUT2 and FUT3 expression regulation with a computational analysis to predict additional novel regulators. On this way, we are able to broaden our knowledge on FUT2 and FUT3 expression regulation and consequently might be able to transfer our findings into diagnostics or therapeutics in the future. [ABSTRACT FROM AUTHOR]

Exosome therapy has garnered significant attention due to its natural delivery capabilities, low toxicity, high biocompatibility, and potential for personalized treatment through engineering modifications. Recent studies have highlighted the ability of tumor cell-derived exosomes (TDEs) to interact with immune cells or modify the immune microenvironment to suppress host immune responses, as well as their unique homing ability to parental cells. The core question of this study is whether this immunomodulatory property of TDEs can be utilized for the immunotherapy of inflammatory diseases. In our experiments, we prepared exosomes derived from murine colon cancer cells CT26 (CT26 exo) using ultracentrifugation, characterized them, and conducted proteomic analysis. The therapeutic potential of CT26 exo was evaluated in our dextran sulfate sodium salt (DSS)-induced inflammatory bowel disease (IBD) mouse model. Compared to the control and 293T exo treatment groups, mice treated with CT26 exo showed a reduction in the disease activity index (DAI) and colon shortening rate, with no noticeable weight loss. Hematoxylin and eosin (H&E) staining of colon paraffin sections revealed reduced inflammatory infiltration and increased epithelial goblet cells in the colons of CT26 exo-treated group. Furthermore, we conducted preliminary mechanistic explorations by examining the phenotyping and function of CD4+ T cells and dendritic cells (DCs) in the colonic lamina propria of mice. The results indicated that the ameliorative effect of CT26 exosomes might be due to their inhibition of pro-inflammatory cytokine secretion by colonic DCs and selective suppression of Th17 cell differentiation in the colon. Additionally, CT26 exo exhibited good biosafety. Our findings propose a novel exosome-based therapeutic approach for IBD and suggest the potential application of TDEs in the treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD), a chronic inflammatory condition, is caused by several factors involving aberrant immune responses. Genetic factors are crucial in IBD occurrence. Mendelian randomization (MR) can offer a new perspective in understanding IBD's genetic background. Methods: Single nucleotide polymorphisms (SNPs) were considered instrumental variables (IVs). We analyzed the relationship between 731 immunophenotypes, 1,400 metabolite phenotypes, and IBD. The total effect was decomposed into indirect and direct effects, and the ratio of the indirect effect to the total effect was calculated. Results: We identified the causal effects of HLA-DR-expressing CD14 + monocytes on IBD through MR analysis. The phenotype "HLA-DR expression on CD14 + monocytes" showed the strongest association among the selected 48 immune phenotypes. Chiro-inositol metabolites mediated the effect of CD14 + monocytes expressing HLA-DR on IBD. An increase in Chiro-inositol metabolites was associated with a reduced risk of IBD occurrence, accounting for 4.97%. Conclusion: Our findings revealed a new pathway by which HLA-DR-expressing CD14 + monocytes indirectly reduced the risk of IBD occurrence by increasing the levels of Chiro-inositol metabolites. The results provided a new perspective on the immunoregulatory mechanisms underlying IBD, laying a theoretical foundation for developing new therapeutic targets in the future. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a significant inflammatory bowel disease caused by an abnormal immune response to gut microbes. However, there are still gaps in our understanding of how immune and metabolic changes specifically contribute to this disease. Our research aims to address this gap by examining mouse colons after inducing ulcerative colitis-like symptoms. Employing single-cell RNA-seq and 16 s rRNA amplicon sequencing to analyze distinct cell clusters and microbiomes in the mouse colon at different time points after induction with dextran sodium sulfate. We observe a significant reduction in epithelial populations during acute colitis, indicating tissue damage, with a partial recovery observed in chronic inflammation. Analyses of cell-cell interactions demonstrate shifts in networking patterns among different cell types during disease progression. Notably, macrophage phenotypes exhibit diversity, with a pronounced polarization towards the pro-inflammatory M1 phenotype in chronic conditions, suggesting the role of macrophage heterogeneity in disease severity. Increased expression of Nampt and NOX2 complex subunits in chronic UC macrophages contributes to the inflammatory processes. The chronic UC microbiome exhibits reduced taxonomic diversity compared to healthy conditions and acute UC. The study also highlights the role of T cell differentiation in the context of dysbiosis and its implications in colitis progression, emphasizing the need for targeted interventions to modulate the inflammatory response and immune balance in colitis. Chronic ulcerative colitis in mice is characterized by pro-inflammatory M1 macrophage phenotype and higher Nampt and NOX2 transcription, as well as a reduced taxonomic diversity in the mice gut microbiome. [ABSTRACT FROM AUTHOR]

The dysbiosis of microbiota has been reported to be associated with numerous human pathophysiological processes, including inflammatory bowel disease (IBD). With advancements in high-throughput sequencing, various methods have been developed to study the alteration of microbiota in the development and progression of diseases. However, a suitable approach to assess the global stability of the microbiota in disease states through time-series microbiome data is yet to be established. In this study, we have introduced a novel Energy Landscape construction method, which incorporates the Latent Dirichlet Allocation (LDA) model and the pairwise Maximum Entropy (MaxEnt) model for their complementary advantages, and demonstrate its utility by applying it to an IBD time-series dataset. Through this approach, we obtained the microbial assemblages' energy profile of the whole microbiota under the IBD condition and uncovered the hidden stable stages of microbiota structure during the disease development with time-series microbiome data. The Bacteroides-dominated assemblages presenting in multiple stable states suggest the potential contribution of Bacteroides and interactions with other microbial genera, like Alistipes, and Faecalibacterium, to the development of IBD. Our proposed method provides a novel and insightful tool for understanding the alteration and stability of the microbiota under disease states and offers a more holistic view of the complex dynamics at play in microbiota-mediated diseases. [ABSTRACT FROM AUTHOR]

Mesalazine is an established and recommended first-line treatment for mild-tomoderate ulcerative colitis (UC). For patients with moderately active UC, the choice to use mesalazine or to initiate treatment with an oral corticosteroid or anti-tumor necrosis factor (TNF) agent is not clearly informed from current guidelines. The use of mesalazine is supported by robust clinical evidence supporting its efficacy at inducing remission in patients with moderately active disease. A key advantage of mesalazine is its tolerability profile being similar to that of placebo, which contrasts with that of the corticosteroids and advanced therapies, where there is the potential for significant toxicities. Mesalazine also has cost advantages over anti-TNFs and other advanced therapies. Evidence supports the consideration of all patients with moderately active UC for first-line mesalazine therapy at an optimized dose of ≥4g/d (± 1g/d rectal). Patients responding to treatment within 2 weeks should continue at ≥4g/d for at least 6 months before a dose reduction is considered, since this then alters the pattern of disease. [ABSTRACT FROM AUTHOR]

Aim Method Results Conclusion Crohn's disease has debilitating effects on patients' quality of life. Currently, there are limited data on the effect of anastomotic configuration on health‐related quality of life after ileocaecal resection for Crohn's disease. This study aimed to assess the impact of Kono‐S anastomosis on quality of life after ileocolic resection, compared to the conventional side‐to‐side anastomosis.Patients with primary or recurrent Crohn's disease participating in the ongoing SuPREMe‐CD trial were interviewed about quality of life using the Inflammatory Bowel Disease Questionnaire (IBDQ). The primary endpoint was disease‐specific quality of life, assessed with IBDQ. Secondary outcomes were quality of life related to bowel symptoms, systemic symptoms, social function and emotional function.Of the 94 patients included, 51 (54%) received the conventional side‐to‐side anastomosis and 43 (46%) the Kono‐S anastomosis. Demographics were comparable between the two groups. The IBDQ was assessed at a mean follow‐up of 54.0 ± 18.7 months from surgical intervention. The mean total IBDQ score was 155.1 ± 28.07 in the conventional group and 163.8 ± 25.23 in the Kono‐S group (P = 0.11). When considering bowel symptoms and social function, mean scores were 50.7 and 23.5 in the conventional group, and 56.3 and 26.5 in the Kono‐S group (P = 0.002 and P = 0.02, respectively). Kono‐S anastomosis was independently associated with improved quality of life regarding bowel symptoms (P = 0.006) and social function (P = 0.03) after correcting for other confounding factors on linear regression analysis.Compared to conventional side‐to‐side anastomosis, patients with Kono‐S anastomosis presented significantly better bowel symptoms and social function scores at 54 months after surgery. [ABSTRACT FROM AUTHOR]

Summary: Background: The value of lower gastrointestinal endoscopy (LGIE; colonoscopy or sigmoidoscopy) relates to its ability to detect clinically relevant findings, predominantly cancers, preneoplastic polyps or inflammatory bowel disease. There are concerns that many LGIEs are performed on low‐risk patients with limited benefit. Aims: To determine the diagnostic outcomes of LGIE for common symptoms. Methods: We performed a cross‐sectional study of diagnostic LGIE between March 2019 and February 2020 using the UK National Endoscopy Database. We used mixed‐effects logistic regression models, incorporating random (endoscopist) and fixed (symptoms, patient age, and sex) effects upon two dependent variables (large polyp [≥10 mm] and cancer diagnosis). Adjusted positive predictive values (aPPVs) were calculated. Results: We analysed 384,510 LGIEs; 33.2% were performed on patients aged under 50 and 53.6% on women. Regarding colonoscopies, the unadjusted PPV for cancer was 1.5% (95% CI: 1.4–1.5); higher for men than women (1.9% vs. 1.1%, p < 0.01). The PPV for large polyps was 3.2% (95% CI: 3.1–3.2). The highest colonoscopy cancer aPPVs were in the over 50s (1.9%) and in those with rectal bleeding (2.5%) or anaemia (2.1%). Cancer aPPVs for other symptoms were <1% despite representing 54.3% of activity. In patients under 50, aPPVs were 0.4% for cancer and 1.6% for large polyps. Results were similar for sigmoidoscopy. Conclusions: Most colonoscopies were performed on patients with low‐risk symptoms, where cancer risk was similar to the general population. Cancer and large polyp yield was highest in elderly patients with rectal bleeding or anaemia, although still fell short of FIT‐based screening yields. [ABSTRACT FROM AUTHOR]

Summary: Background: Persistent gastrointestinal symptoms are prevalent in adult patients with inflammatory bowel disease (IBD), even when endoscopic remission is reached. These symptoms can have profound negative effects on the quality of life of affected patients and can be difficult to treat. They may be caused by IBD‐related complications or comorbid disorders, but they can also be explained by irritable bowel syndrome (IBS)‐like symptoms. Aims: To provide a practical step‐by‐step guide to diagnose and treat persistent gastrointestinal symptoms in patients with IBD in remission via a personalised approach. Methods: We scrutinised relevant literature on causes, diagnostics and treatment of persistent gastrointestinal symptoms (abdominal pain or discomfort, bloating, abdominal distension, diarrhoea, constipation and faecal incontinence) in patients with IBD in remission. Results: A graphical practical guide for several steps in diagnosing, identifying potential triggers and adequate treatment of persistent gastrointestinal symptoms in IBD in remission is provided based on supporting literature. The first part of this review focuses on the diagnostic and treatment approaches for potential IBD‐related complications and comorbidities. The second part describes the approach to IBS‐like symptoms in IBD in remission. Conclusions: Persistent gastrointestinal symptoms in IBD in remission can be traced back to potential pathophysiological mechanisms in individual patients and can be treated adequately. For both IBD‐related complications and comorbidities and IBS‐like symptoms in IBD in remission, pharmacological, dietary, lifestyle or psychological treatments can be effective. A systematic and personalised approach is required to reduce the burden for patients, healthcare systems, and society. [ABSTRACT FROM AUTHOR]

Summary: Background/Aim: We aimed to validate clinical decision support tools (CDSTs) to predict real‐life effectiveness of vedolizumab (VDZ) in patients with inflammatory bowel disease. Methods: We retrospectively enrolled patients with Crohn's disease (CD) or ulcerative colitis (UC) treated with VDZ at 10 tertiary referral centres in Korea between January 2017 and November 2021. We assessed clinical remission (CREM) and response (CRES), corticosteroid‐free clinical remission (CSF‐CREM) and response (CSF‐CRES), biochemical response based on C‐reactive protein (BioRES[CRP]) and faecal calprotectin (BioRES[FC]), endoscopic healing (EH), and the need to optimise or switch drugs based on CDST‐defined response groups. Additionally, the area under the receiver operating characteristics curve (AUC) for the CDSTs was calculated. Results: We included 143 patients with CD and 219 with UC. We observed incremental trends on CSF‐CRES at week 14 (W14) (ptrend = 0.004) and decreasing trends for the need to optimise or switch drugs (ptrend = 0.016) in CD from the low to high probability groups. Except for CSF‐CREM at W54, we noticed incremental trends for all clinical responses at W14, W26 and W54 (ptrend <0.001) in UC. W26 and W54 BioRES[CRP] and W14 EH also showed increasing trends (ptrend <0.05) in UC. With increasing probabilities of response, drug optimisation or switching was less frequently required in UC (ptrend = 0.013). With 26 points cut‐off, CDSTs effectively identified W14 CSF‐CRES, W26 BioRES[CRP], BioRES[FC] and W54 BioRES[CRP] in UC, all with AUCs >0.600, whereas CDSTs showed poor accuracy in CD. Conclusions: CDSTs for VDZ had acceptable accuracy in predicting effectiveness outcomes including clinical and biochemical outcomes in UC. However, their utility in CD was limited. [ABSTRACT FROM AUTHOR]

Fibrosis is an important complication in inflammatory bowel diseases. Previous studies suggest an important role of matrix Gla protein (MGP) and thrombospondin 2 (THBS2) in fibrosis in various organs. Our aim was to analyse their expression together with regulatory miRNAs in submucosal and subserosal fibroblasts in ulcerative colitis (UC) and Crohn's disease (CD) using immunohistochemistry and qPCR. Digital pathology was used to compare collagen fibre characteristics of submucosal and subserosal fibrosis. Immunohistochemistry showed expression of MGP, but not THBS2 in submucosa in UC and CD. In the subserosa, there was strong staining for both proteins in CD but not in UC. qPCR showed significant upregulation of THBS2 and MGP genes in CD subserosa compared to the submucosa. Digital pathology analysis revealed higher proportion of larger and thicker fibres that were more tortuous and reticulated in subserosal fibrosis compared to submucosal fibrosis. These results suggest distinct fibroblast populations in fibrostenosing CD, and are further supported by image analysis showing significant differences in the morphology and architecture of collagen fibres in submucosal fibrosis in comparison to subserosal fibrosis. Our study is the first to describe differences in submucosal and subserosal fibroblast populations, contributing to understanding of the pathogenesis of fibrostenosis in CD. [ABSTRACT FROM AUTHOR]

This observational study evaluated the impact of a sponsor company-provided Patient Support Program (PSP) on discontinuation of adalimumab in adult Australian patients eligible for Pharmaceutical Benefit Scheme (PBS)-reimbursed adalimumab for Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS), Psoriatic Arthritis (PsA), Crohn's Disease (CD), Ulcerative Colitis (UC), or Hidradenitis Suppurativa (HS). Patients initiating adalimumab between May 2018 and September 2019 were enrolled into two prospective cohorts based on their decision to opt for or decline the PSP (PSP or non-PSP cohorts). In addition, a historical, retrospective Non-PSP cohort was established from the Services Australia 10% PBS dataset by extracting data of patients initiating adalimumab prior to the introduction of adalimumab PSPs and based on adalimumab PBS listing dates (AS: April 2007 to March 2009; PsA/RA: January 2007 to December 2008; CD: January 2009 to December 2010; HS and UC indications not included). Follow-up for all cohorts was 12 months. The primary endpoint was the time to discontinuation, compared between the prospective PSP cohort and the prospective or retrospective Non-PSP cohort. Inverse probability of treatment weighting was used to balance the cohorts. A Cox proportional hazards model indicated no difference in time to discontinuation between the prospective PSP (n = 162) and non-PSP (n = 65) cohorts (HR [95% CI] = 1.256 [0.616–2.563], p = 0.5304). The 12-month adalimumab persistence rates (95% CI) were 78% (69%, 84%) and 82% (67%, 90%), respectively. In contrast, discontinuation was less likely in the prospective PSP (n = 151) compared with the retrospective non-PSP (n = 297) cohort (HR [95% CI] = 0.44 [0.28–0.68], p<0.001). The 12-month persistence rates (95% CI) were 81% (76%, 90%) and 61% (56%, 67%), respectively. Overall, this study suggests that optimal adalimumab persistence can be achieved with either a structured PSP or healthcare support from other sources, but this was not the case more than a decade ago. [ABSTRACT FROM AUTHOR]

Aims Design Methods Results Conclusion Implications for the Profession and Patient Care Impact Reporting Method Patient or Public Contribution To explore the psychosocial experiences during dietary management among Chinese adults with inflammatory bowel disease.Qualitative phenomenological design.Eighteen adults diagnosed with inflammatory bowel disease for more than 6 months were recruited using purposive sampling from June to December 2023. Two trained researchers used van Manen's approach to analyse the data.The three themes with multiple subthemes emerged: facing the unknown: at a loss and aggrieved, trying to cope: uncertain and distressed, and growing in adaptation: relieved and transcendent. The first theme included unknown relapses, overlooking diet management and the absence of dietary rules. The second theme showed different coping situations, like complex dietary information and ever‐closing worlds. The third theme explores how participants adapted to disease and their eating patterns.The psychosocial experiences during dietary management are complex. The accumulation of diet‐related experience, acceptance of illness and social support facilitate patients in overcoming negative emotions and adhering to dietary management.Nurses should provide tailored dietary guidance and appropriate psychological interventions to promote healthy eating in patients.This study may enhance healthcare professionals' understanding, particularly those in China, of the diet‐related experiences among patients.The Consolidated Criteria for Reporting Qualitative Research checklist.Participants contributed by sharing their first hand experiences. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to conduct a bibliometric analysis of research articles on the relationship between inflammatory bowel disease (IBD) and colorectal cancer (CRC) using CiteSpace to summarize the current research status, hotspots, and trends in this field and present the results visually. Method: Research articles on the relationship between IBD and CRC published from 2000 to 2023 and in English were selected from the Web of Science Core Collection (Woscc) database. The articles were downloaded as "full record and references". CiteSpace was used to conduct cooperative, cluster, co-citation, and burst analyses. Results: The literature search revealed 4244 articles; of which, 5 duplicates were removed, resulting in the inclusion of 4239 articles in this study. The United States of America had the highest number of publications, with Mayo Clinic and Harvard University being the most active institutions, and Bas Oldenburg being the most active author. Collaboration among core authors was inadequate. JA Eaden was the most cited author, and CRC was the most common keyword. Burst analysis indicated that Sun Yat-sen University might be one of the institutions with a large contribution to this research field in the future. Cluster analysis showed that earlier research focused more on microsatellite instability, whereas "gut microbiota" and "oxidative stress" are considered current research hotspots and trends. Conclusion: At present, the primary focus areas of research are "gut microbiota" and "oxidative stress". With the improvement of healthcare policies and standards, regular endoscopic monitoring of patients with IBD has become an indispensable diagnostic and therapeutic practice. More drugs will be developed to reduce the risk of progression from IBD to CRC. The findings of this study provide valuable insights into the relationship between IBD and CRC for researchers in the same field. [ABSTRACT FROM AUTHOR]

Background: Association between glucose and inflammatory bowel disease (IBD) was found in previous observational studies and in cohort studies. However, it is not clear whether these associations reflect causality. Thus, this study investigated whether there is such a causal relation between elevated glucose and IBD, Crohn's disease (CD) and ulcerative colitis (UC). Methods: We performed a two-sample Mendelian Randomization (MR) with the independent genetic instruments identified from the largest available genome-wide association study (GWAS) for IBD (5,673 cases; 213,119 controls) and its main subtypes, CD and UC. Summarized data for glucose which included 200,622 cases and glycemic traits including HbA1c and type 2 diabetes(T2DM) were obtained from different GWAS studies. Primary and secondary analyses were conducted by preferentially using the radial inverse-variance weighted (IVW) approach. A number of other meta-analysis approach and sensitivity analyses were carried out to assess the robustness of the results. Results: We did not find a causal effect of genetically predicted glucose on IBD as a whole (OR 0.858; 95% CI 0.649–1.135; P = 0.286). In subtype analyses glucose was also suggestively not associated with Crohn's disease (OR 0.22; 95% CI 0.04-1.00; P = 0.05) and ulcerative colitis (OR 0.940; 95% CI 0.628–1.407; P = 0.762). In the other direction, IBD and its subtypes were not related to glucose and glycemic traits. Conclusions: This MR study is not providing any evidence for a causal relationship between genetically predicted elevated glucose and IBD as well as it's subtypes UC and CD. Regarding the other direction, no causal associations could be found. Future studies with robust genetic instruments are needed to confirm this conclusion. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to investigate the potential causal relationship between autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and Type 1 diabetes, and age-related macular degeneration (AMD). By utilizing the two-sample Mendelian Randomization (MR) approach, we endeavor to address this complex medical issue. Methods: Genome-wide association study (GWAS) data for autoimmune diseases and AMD were obtained from the IEU Open GWAS database and the FinnGen consortium. A series of stringent SNP filtering steps was applied to ensure the reliability of the genetic instruments. MR analyses were conducted using the TwoSampleMR and MR-PRESSO packages in R. The inverse-variance weighted (IVW) method served as the primary analysis, complemented by multiple supplementary analyses and sensitivity tests. Results: Within the discovery sample, only a statistically significant inverse causal relationship between multiple sclerosis (MS) and AMD was observed (OR = 0.92, 95% CI: 0.88–0.97, P = 0.003). This finding was confirmed in the replication sample (OR = 0.85, 95% CI: 0.80–0.89, P = 3.32×10−12). No statistically significant associations were detected between systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, and Type 1 diabetes and AMD. Conclusion: Strong evidence is provided by this study to support the existence of an inverse causal relationship between multiple sclerosis and age-related macular degeneration. However, no causal evidence was found linking other autoimmune diseases with AMD. These findings not only offer novel insights into the potential etiological mechanisms underlying AMD but also suggest possible directions for future clinical interventions. [ABSTRACT FROM AUTHOR]

Objective: An improved understanding of the causes and experience of diagnostic delay in Inflammatory Bowel Disease (IBD). Methods: Framework analysis of semi-structured interviews with 20 adults with IBD. Results: Participants' prior knowledge of normal bowel function/IBD was limited. Symptoms were sometimes misattributed to mild/transient conditions or normalised until intolerable. Family pressures, work, education, mistrust of doctors, fear and embarrassment could exacerbate delays. Poor availability of face-to-face appointments deterred people from seeing a GP. Patients feared that by the time they got to see their GP, their symptoms would have resolved. Patients instead self-managed symptoms, but often regretted not seeking help earlier. Limited time in consultations, language barriers, embarrassment, and delays in test results subsequently delayed specialist referrals. GPs misattributed symptoms to other conditions due to atypical or non-specific presentations, leading to reduced trust in health systems. Patients complained of poor communication, delays in accessing test results, appointments, and onward referrals–all associated with clinical deterioration. GPs were sometimes unable to 'fast-track' patients into specialist care. Consultations and endoscopies were often difficult experiences for patients, especially for non-English speakers who are also less likely to receive information on mental health support and the practicalities of living with IBD. Conclusions: The framework analysis demonstrates delay in the diagnosis of IBD at each stage of the patient journey. Recommendations: Greater awareness of IBD amongst the general population would facilitate presentation to healthcare services through symptom recognition by individuals and community advice. Greater awareness in primary care would help ensure IBD is included in differential diagnosis. In secondary care, greater attention to the wider needs of patients is needed–beyond diagnosis and treatment. All clinicians should consider atypical presentations and the fluctuating nature of IBD. Diagnostic overshadowing is a significant risk–where other diagnoses are already in play the risk of delay is considerable. [ABSTRACT FROM AUTHOR]

Overconsumption of dietary sugar can lead to many negative health effects including the development of Type 2 diabetes, metabolic syndrome, cardiovascular disease, and neurodegenerative disorders. Recently, the human intestinal microbiota, strongly associated with our overall health, has also been known to be affected by diet. However, mechanistic insight into the importance of the human intestinal microbiota and the effects of chronic sugar ingestion has not been possible largely due to the complexity of the human microbiome which contains hundreds of types of organisms. Here, we use an interspecies C. elegans/E. coli system, where E. coli are subjected to high sugar, then consumed by the bacterivore host C. elegans to become the microbiota. This glucose-fed microbiota results in a significant lifespan reduction accompanied by reduced healthspan (locomotion), reduced stress resistance, and changes in behavior and feeding. Lifespan reduction is also accompanied by two potential major contributors: increased intestinal bacterial density and increased concentration of reactive oxygen species. The glucose-fed microbiota accelerated the age-related development of intestinal cell permeability, intestinal distention, and dysregulation of immune effectors. Ultimately, the changes in the intestinal epithelium due to aging with the glucose-fed microbiota results in increased susceptibility to multiple bacterial pathogens. Taken together, our data reveal that chronic ingestion of sugar, such as a Western diet, has profound health effects on the host due to changes in the microbiota and may contribute to the current increased incidence of ailments including inflammatory bowel diseases as well as multiple age-related diseases. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a prevalent neurodegenerative disorder with indistinct etiology and ill-defined pathophysiology. Intestinal inflammation involved in the pathogenesis of PD, but the underlying mechanism is not fully understood. Citrobacter rodentium (C.R) is a gram-negative bacterium that can be used to induce human inflammatory bowel disease in mice. Here, we investigated whether the proinflammatory effects caused by C.R infection initiate PD-like injury and/or exacerbate PD pathology and extensively studied the underlying mechanism. Mice were gavaged once with C.R and monitored for several pathological features at 9 days post infection. The results showed that C.R delivery in mice induced IBD-like symptoms, including significant weight loss, increased fecal water content, an impaired intestinal barrier, intestinal hyperpermeability and inflammation, and intestinal microbiota disturbances. Notably, C.R infection modified dopamine (DA) metabolism in the brains of both male and female mice. Subsequently, a single high dose of MPTP or normal saline was administered at 6 days post infection. At 3 days after MPTP administration, the feces were collected for 16 S rRNA analysis, and PD-like phenotypes and mechanisms were systemically analyzed. Compared with C.R or MPTP injection alone, the injection of C.R and MPTP combined worsened behavioral performance. Moreover, such combination triggered more severe dopaminergic degeneration and glial cell overactivation in the nigrostriatal pathway of mice. Mechanistically, the combination of C.R and MPTP increased the expression of TLR4 and NF-κB p65 in the colon and striatum and upregulated proinflammatory cytokine expression. Therefore, C.R infection-induced intestinal inflammation can impair dopamine metabolism and exacerbate PD pathological processes. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to use Mendelian randomization (MR) to investigate the potential causal association between inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH). Methods: Two-sample MR was performed to estimate the causal effect of IBD on AIH. The primary analysis employed the inverse variance weighted (IVW) method in univariable MR analysis, supplemented by additional methods including MR-Egger, weighted median, simple mode, and weighted mode. The p values were adjusted by FDR p-value adjustment. In the replication analysis, the primary IVW analysis was repeated and then pooled by meta-analysis. Sensitivity analyses were performed using Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out, and funnel plot analysis to evaluate the robustness of the MR findings. Additionally, multivariable MR (MVMR) was employed to estimate the direct causal effect of IBD on the risk of AIH. Results: In univariable MR analysis, a significant positive causal association was observed between IBD (both Crohn's disease (CD) or ulcerative colitis (UC)) and the risk of AIH (for CD and AIH, the IVW odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.00–1.16, P = 0.045, FDR P = 0.045; for UC and AIH, the IVW OR = 1.07, 95% CI = 1.00–1.13, P = 0.038, FDR P = 0.076). Furthermore, no significant positive correlation between IBD and the risk of AIH (OR = 1.13, 95% CI = 0.94–1.35, P = 0.194). Sensitivity analysis revealed no pleiotropic bias. MVMR analysis further confirmed the direct causal effect of CD or UC on the risk of AIH after adjusting for the common risk factors (cigarettes per day and osteoporosis). In the replication analysis, the positive causal association between UC and the risk of AIH remain significant (the IVW odds ratio (OR) = 1.32, 95% CI = 1.18–1.48, P = 2.90E-06). While no significant positive association was observed between CD or IBD and the risk of AIH in the replication analysis, a suggestive positive association between the identified risk factors (UC, CD, and IBD) and the risk of AIH was detected in the meta-analysis (OR = 1.09, 95% CI = 1.05–1.13, P<0.0001). Conclusion: This MR study revealed a positive impact of the identified risk factors (CD, UC and IBD) on the risk of AIH within the European population. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of unknown etiology and unpredictable course. The aim of the work was to assess the levels of adropin, fibroblast growth factor-1 (FGF-1), and Toll-like receptor-1 (TLR1) biomarkers in IBD patients compared to controls and evaluate the gene expression of TNF-α as a marker of disease severity. Methods: Adropin, fasting serum FGF-1 levels, TLR1, and TNF-α were measured in 60 IBD patients. They were also compared with 58 healthy controls matching age and gender. Moreover, the blood cells cDNA copy number of TNF-α were determined as a marker of severity. Results: Adropin and TLR1 levels were significantly lower in patients than controls. FGF-1 was reduced but not statistically significant. The expression of TNF-α gene in the IBD patients was significantly increased (42%) in comparison with control samples (P < 0.001). Conclusions: Adropin, IGF-I, and Toll-like receptor-1 biomarkers may have a role in the intricate pathophysiology of IBD and may possibly operate as predictors of disease activity. Thus, they may be therapeutic targets for IBD. Moreover, the expression of TNF-α gene can be used as a marker of severity. [ABSTRACT FROM AUTHOR]

Background: Bariatric surgery leads to sustained weight loss in a majority of recipients, and also reduces fasting insulin levels and markers of inflammation. We described the long-term associations between bariatric surgery and clinical outcomes including 30 morbidities. Methods: We did a retrospective population-based cohort study of 304,157 adults with severe obesity, living in Alberta, Canada; 6,212 of whom had bariatric surgery. We modelled adjusted time to mortality, hospitalization, surgery and the adjusted incidence/prevalence of 30 new or ongoing morbidities after 5 years of follow-up. Results: Over a median follow-up of 4.4 years (range 1 day-22.0 years), bariatric surgery was associated with increased risk of hospitalization (HR 1.46, 95% CI 1.41,1.51) and additional surgery (HR 1.42, 95% CI 1.32,1.52) but with a decreased risk of mortality (HR 0.76, 95% CI 0.64,0.91). After 5 years (median of 9.9 years), bariatric surgery was associated with a lower risk of severe chronic kidney disease (HR 0.45, 95% CI 0.27,0.75), coronary disease (HR 0.49, 95% CI 0.33,0.72), diabetes (HR 0.51, 95% CI 0.47,0.56), inflammatory bowel disease (HR 0.55, 95% CI 0.37,0.83), hypertension (HR 0.70, 95% CI 0.66,0.75), chronic pulmonary disease (HR 0.75, 95% CI 0.66,0.86), asthma (HR 0.79, 95% 0.65,0.96), cancer (HR 0.79, 95% CI 0.65,0.96), and chronic heart failure (HR 0.79, 95% CI 0.64,0.96). In contrast, after 5 years, bariatric surgery was associated with an increased risk of peptic ulcer (HR 1.99, 95% CI 1.32,3.01), alcohol misuse (HR 1.55, 95% CI 1.25,1.94), frailty (HR 1.28, 95% 1.11,1.46), severe constipation (HR 1.26, 95% CI 1.07,1.49), sleep disturbance (HR 1.21, 95% CI 1.08,1.35), depression (HR 1.18, 95% CI 1.10,1.27), and chronic pain (HR 1.12, 95% CI 1.04,1.20). Interpretation: Bariatric surgery was associated with lower risks of death and certain morbidities. However, bariatric surgery was also associated with increased risk of hospitalization and additional surgery, as well as certain other morbidities. Since values and preferences for these various benefits and harms may differ between individuals, this suggests that comprehensive counselling should be offered to patients considering bariatric surgery. [ABSTRACT FROM AUTHOR]

Background: Patients with inflammatory bowel disease (IBD) experience difficulties in daily life and demanding self-care needs. The goal of our support for patients is to ease their difficulties and improve their belief in their capacity to self-manage their disease (self-efficacy), by increasing their ability for self-care. The nurse's contribution is vital in empowering patients and supporting them to better manage their disease. There is evidence that higher nurse staffing levels are associated with better patient outcomes in acute care settings, but little is known about the outpatient setting. The objective of this study was to explore the impact of multidisciplinary team care with abundant nurse staffing levels on patient-reported outcome measures (PROMs) among patients with IBD, encompassing Crohn's disease (CD) and ulcerative colitis (UC), in clinical remission. Methods: Patients with IBD in clinical remission were included because disease activity influences the patient's subjective evaluation. A total of 499 valid responses from two different sources were analyzed: 318 from a specialized IBD clinic with abundant nurse staffing and a multidisciplinary care team (UC: 83, CD: 235) and 181 from an online survey panel (UC: 109, CD: 72). The IBD Self-Efficacy Scale (IBD-SES) and the difficulty of life scale (DLS) were used as disease-specific PROMs. Results: In two multiple regression models adjusted by background characteristics (age, sex, diagnosis [UC/CD], employment status, use of biologics, and disease duration) using the IBD-SES or DLS as a dependent variable, the responses from clinic patients showed a more favorable score (higher self-efficacy or lower difficulty) than the online responses. Conclusions: Multidisciplinary team care with abundant nurse staffing may improve self-efficacy and ease difficulties of life among patients with IBD in clinical remission. These results could help bring attention to nurse staffing in an outpatient setting, which has previously been overlooked, and be the first to provide evidence of its importance in encouraging enhanced staffing levels. [ABSTRACT FROM AUTHOR]

Mouth is the gateway to the total body wellness. Accordingly, oral microbiome influences overall health of an individual. Oral microbiome plays a key role in shaping up the host's health profile. Obvious differences have been reported between patients with gastrointestinal diseases and healthy controls. The oral and gut microbiome profiles are well-segregated due to the oral–gut barrier. However, the oral microbiota can translocate to the intestinal mucosa in conditions of the oral–gut barrier dysfunction. Oral bacteria can disseminate to the distal gut via enteral or hematogenous routes. The translocation of oral microbes to the gut may give rise to a variety of gastrointestinal diseases including Helicobacter-induced diseases, irritable bowel syndrome, inflammatory bowel disease, celiac disease, and colorectal cancer. Understanding the role of the oral-to-gut microbial translocation in the pathogenesis will contribute to precise diagnosis and effective treatment. In this review, we aim to highlight the role of oral microbiota dysfunction in various gastrointestinal disorders. [ABSTRACT FROM AUTHOR]

Background: Antibodies against tumor necrosis factor alpha (anti-TNF-α) are currently widely used in the treatment of inflammatory bowel diseases (IBD), despite a number of reported adverse effects. Diverse neurologic syndromes, including the Guillain-Barré syndrome (GBS), an immune-mediated disease characterized by evolving ascending limb weakness, sensory loss, and areflexia, have been described in association with anti-TNF-α therapy. Case Report: A 45-year-old White woman was in follow-up with fistulizing ileocolonic Crohn disease using combination therapy (infliximab plus azathioprine) as CD maintenance therapy. After 3 years of this immunosuppressive therapy, she presented with symmetrical and ascending paresis in the lower limbs, and later in the upper limbs, in addition to reduced reflexes in the knees, 1 day after an infliximab infusion. The patient was hospitalized and treatment for CD was suspended. Neurophysiology studies demonstrated a pattern compatible with acute inflammatory demyelinating polyradiculopathy, with predominantly motor involvement, consistent with Guillain-Barré syndrome (GBS). Clinical, laboratory, and imaging exams were unremarkable. She was treated with intravenous immunoglobulins, with a progressive and complete resolution of neurological symptoms. After 1-year follow-up, she presented with active Crohn disease, and we opted for treating her with vedolizumab, with which she achieved clinical and endoscopic remission. Conclusions: Patients receiving biological therapy with anti-TNF-α agents should be monitored for central or peripheral neurological signs and symptoms. The development of GBS can be secondary to anti-TNF-α treatment. The positive temporal relationship with TNF-α therapy and onset of neurological symptoms reinforces this possibility. [ABSTRACT FROM AUTHOR]

Background: In the management of inflammatory bowel disease, the emergence of drug resistance to monoclonal antibodies has come out as a significant impediment to achieving desired therapeutic outcomes. However, extensive evidence has substantiated that the induction of autophagy holds promise in counteracting the development of drug resistance. In this regard, the utilization of traditional Chinese medicine presents a potential avenue for alleviate drug resistance, specifically through Peilan and Fuling. Consequently, the objective of this study aims to investigate the regulatory effects of p -Cymene and pachymic acid on the autophagy signaling pathway, with the ultimate goal of reducing inflammatory response and alleviating drug resistance. Methods: The RAW 264.7 murine macrophage cell line was subjected to induction using varying concentration gradients of adalimumab in order to establish an adalimumab-resistant cell line. The cell growth curve and viability were assessed using the CCK-8 assay. The expression of cytokines was determined through the implementation of ELISA. The autophagy signaling pathway was evaluated using Western blot analysis. Results: p -Cymene and pachymic acid were found to exert an inhibitory effect on the proliferation of the adalimumab-resistant cell line. Additionally, treatment with p -Cymene and pachymic acid resulted in a decrease in the levels of proinflammatory cytokines, namely TNF-α, IL-1β, and IL-6, while concurrently increasing the level of IL-10. p -Cymene and pachymic acid demonstrated the capacity to suppress the expression of autophagy-related proteins and mRNA including PI3K, AKT, and mTOR. Conclusions: p -Cymene and pachymic acid exhibit the potential to alleviate adalimumab-resistance and ameliorate the inflammatory response, primarily through the activation of the PI3K/AKT/mTOR signaling pathway. These findings suggest that traditional Chinese medicine holds promise as a viable treatment option for mitigating monoclonal antibody resistance in inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Background: In the panorama of therapeutic strategies for inflammatory bowel diseases, oral upadacitinib stands out for its potential to improve short-term and long-term patient outcomes. Objective: This meta-analysis aspires to collate and assess the available evidence regarding the efficacy and safety of upadacitinib in managing moderate-to-severe Crohn's disease and ulcerative colitis. Methods: A meta-analysis was conducted using studies sourced from MEDLINE/PubMed, Cochrane Library, Scopus, and Embase, published from January 2010 to March 2024. Peer-reviewed articles that reported data on the effects of upadacitinib in adult patients with Crohn's disease and ulcerative colitis were included based on established inclusion and exclusion criteria. Results: Eight studies, encompassing a total of 2818 patients treated with upadacitinib, were included. In primary outcomes, for patients with Crohn's disease who were using upadacitinib, the weighted pooled clinical remission rate was found to be 45.8% (95% confidence interval [CI] 0.39–0.52), while for patients with ulcerative colitis who were using upadacitinib, the rate was 25.4% (95% CI 0.17–0.36). The pooled clinical response rate for Crohn's disease was 53.6% (95% CI 0.50–0.57), and for ulcerative colitis it was 72.6% (95% CI 0.69–0.76). The pooled serious adverse event rate was 6.0% (95% CI 0.07–0.09). Conclusions: Upadacitinib demonstrates significant efficacy in achieving clinical remission and response in patients with moderate-to-severe Crohn's disease and ulcerative colitis, as shown by clinical remission rates of 44.9% and 36.0%, respectively. The treatment also maintains a favorable safety profile with a serious adverse event rate of 7.8%, making it an effective option for those resistant or intolerant to traditional immunosuppressants or tumor necrosis factor antagonists. [ABSTRACT FROM AUTHOR]

Gut physiology is the epicenter of a web of internal communication systems (i.e., neural, immune, hormonal) mediated by cell-cell contacts, soluble factors, and external influences, such as the microbiome, diet, and the physical environment. Together these provide the signals that shape enteric homeostasis and, when they go awry, lead to disease. Faced with the seemingly paradoxical tasks of nutrient uptake (digestion) and retarding pathogen invasion (host defense), the gut integrates interactions between a variety of cells and signaling molecules to keep the host nourished and protected from pathogens. When the system fails, the outcome can be acute or chronic disease, often labeled as "idiopathic" in nature (e.g., irritable bowel syndrome, inflammatory bowel disease). Here we underscore the importance of a holistic approach to gut physiology, placing an emphasis on intercellular connectedness, using enteric neuroimmunophysiology as the paradigm. The goal of this opinion piece is to acknowledge the pace of change brought to our field via single-cell and -omic methodologies and other techniques such as cell lineage tracing, transgenic animal models, methods for culturing patient tissue, and advanced imaging. We identify gaps in the field and hope to inspire and challenge colleagues to take up the mantle and advance awareness of the subtleties, intricacies, and nuances of intestinal physiology in health and disease by defining communication pathways between gut resident cells, those recruited from the circulation, and "external" influences such as the central nervous system and the gut microbiota. [ABSTRACT FROM AUTHOR]

Psychosocial factors play an important role in the disease course and illness experience of patients with inflammatory bowel disease (IBD). Consultation with a health psychologist is an important component of care for many IBD patients and provides an opportunity to identify areas of psychosocial concern, recognize coping deficits and strengths, and facilitate treatment recommendations. Psychosocial assessment in IBD requires a nuanced approach that goes beyond general mental health screening and considers the disease-specific concerns that impact patients. In this paper, we outline strategies for an IBD-focused psychological evaluation, including specific guidance for assessing disease-specific concerns of anxiety, depression, post-traumatic stress, sleep, pain, body image disturbance, food-related quality of life, and psychological resilience. [ABSTRACT FROM AUTHOR]

The current study explored perspectives of those with inflammatory bowel disease (IBD) and comorbid anxiety and/or depression on a hybrid acceptance and committment therapy (ACT) intervention, compared to an active control. This qualitative study was nested within a randomized controlled trial (RCT) where an experimental group received an 8-week blended delivery ACTforIBD intervention (four sessions telehealth, four sessions pre-recorded self-directed), while an active control group received a psychoeducation program of similar intensity. Semi-structured interviews were conducted post-intervention and at a 3-month follow-up. Themes were interpreted using reflexive thematic analysis. Twenty individuals participated; ten in each condition. Seven themes were constructed, including three shared themes between groups: I Am Worth Advocating For, Present Moment Is My Biggest Ally, and Ambivalence About Self-Directed Modules. Two themes were identified for the ACTforIBD group: Symptoms Are Going to Happen and Moving Toward Values while two themes identified from the ActiveControl group were: Reset and Refresh and It's Ok to Say No. Acceptance and values modules from ACTforIBD were perceived as useful in reducing psychological distress for those with IBD, while the ActiveControl group felt their program affirmed existing effective coping strategies. Access to external resources for self-directed modules and networking may increase engagement with content long term. [ABSTRACT FROM AUTHOR]

This paper describes the implementation of inflammatory bowel disease (IBD)-specific cognitive behavioural therapy (CBT) for IBD patients with poor quality of life (QoL), anxiety and depression, in four hospitals in the Netherlands. Treatment outcomes were compared with those of a previously published randomized control trial (RCT) of 'IBD-specific CBT', following a benchmark strategy. Primary outcome was IBD-specific QoL (IBDQ) completed before and after CBT, secondary outcomes were anxiety and depressive symptoms (HADS, CES-D). Semi-structured interviews were conducted among a pilot of gastroenterologists, nurse specialists and psychologists to evaluate 'IBD-specific CBT'. 94 patients started treatment (280 screened). At follow-up, 63 participants (67% compared to 81% in the RCT benchmark) completed the IBDQ. Treatment effect sizes of the implementation study were comparable and slightly larger than those of RCT benchmark. Gastroenterologists, IBD nurses and psychologists found CBT necessary for IBD patients with poor QoL, depression and/or anxiety disorders. 'IBD-specific CBT' can be successfully implemented. Regular supervision of psychologists performing 'IBD-specific CBT' treatment is needed. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic resulted in increased feelings of emotional distress and disruptions in care across diverse patients subgroups, including those with chronic medical conditions such as inflammatory bowel diseases (IBD). We sought to understand the impact of the pandemic on the physical and emotional well-being of individuals with IBD and concurrent depression and/or anxiety symptoms. We conducted qualitative interviews after the beginning of the pandemic with 46 adults with IBD. Participants reported increased levels of emotional distress, feelings of social isolation, and uncertainty over whether IBD medications put them at increased risk. Young adults discussed feeling as if their lives had been disrupted. In addition, several individuals demonstrated resiliency and emphasized positives about the pandemic, including increased connectivity with family and friends, the convenience of being able to work from home despite their IBD symptoms, and lessened feelings of "missing out." Our findings highlight several opportunities to improve the health and well-being of individuals with IBD and beyond including increased support for combatting social isolation, enhanced counseling about medication risks and benefits, and the incorporation of resiliency skills building. [ABSTRACT FROM AUTHOR]

To identify the need for repeat stone surgery in patients with and without bowel disease. Few studies have compared risks between different types of bowel disease and whether their need for repeat stone surgery differs. From our IRB-approved study, we identified patients with and without bowel disease. We categorized patients' bowel disease into 4 categories: inflammatory bowel disease (IBD), bypass procedures, bowel resection, and bowel disease not otherwise specified (eg, irritable bowel syndrome, celiac disease). Differences between patient demographics, stone disease, and recurrent stone events for patients with and without bowel disease were compared using univariate and multivariate survival analyses (SPSS 25). Of all surgical stone patients (2011), 484 (24%) had some type of bowel disease. Compared to patients without bowel disease, patients with bowel disease presented with stones at an older age (62.2 ± 14.5 vs 58.4 ± 15.3 years; P <.001) and were more likely to be female (56 vs 46%; P <.001). Patients with bowel disease required more repeat stone surgery than those without bowel disease (31% vs 23%, P <.001). In multivariate analysis, patients with bypass and bowel resection were associated with more repeat surgery than patients without bowel disease (P <.001, P =.002, respectively). Patients with IBD and bowel disease not otherwise specified did not have higher risk for repeat surgery than patients without bowel disease. Surgical stone patients with bowel disease, specifically those with prior bowel resection and bypass, had a higher risk of repeat stone surgery over time than stone formers without bowel disease. The data sets generated and analyzed during the current study are available from the corresponding author on reasonable request. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Limited data exist evaluating antiobesity medications (AOM) in patients with inflammatory bowel disease (IBD). METHODS: We performed a case-control study evaluating the effectiveness and safety of AOM in patients with IBD with obesity, matched to non-IBD controls. RESULTS: After 12 months, the case (n = 36) and control (n = 36) groups achieved similar percent total body weight loss of -6.9 ± 8.3 and -8.1 ± 7.0 (P = 0.30), respectively. Side effect profiles were similar between groups. Seven patients experienced an IBD flare, all managed medically. DISCUSSION: AOM use in patients with IBD demonstrated similar effectiveness and safety when compared with that observed in the non-IBD population. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The purpose of this study was to investigate the relationship between ultra-processed food (UPF) consumption and (i) symptomatic disease and (ii) intestinal inflammation among adults with inflammatory bowel disease (IBD). METHODS: We identified participants (Crohn's disease [CD] and ulcerative colitis [UC]) from the Manitoba Living with IBD study. Active disease was defined using the IBD Symptom Inventory (score >14 for CD; >13 for UC); fecal calprotectin was measured for intestinal inflammation (>250 µg/g). Diet data were collected using the Harvard Food Frequency Questionnaire. UPF consumption was determined by the NOVA classification system. Percentage of energy consumption from UPFs was calculated and divided into 3 tertiles (T1 = low; T3 = high). Multiple linear regression analysis was used for active disease and inflammation predicted by UPF consumption. RESULTS: Among 135 participants (65% with CD), mean number of episodes of active disease (14.2 vs 6.21) and active inflammation (1.6 vs 0.6) was significantly higher among participants with UC in T3 compared with T1 of UPF consumption (P < 0.05). When adjusting for age, sex, disease type, and duration, number of episodes of active disease was lower in T1 compared with T3 (β = -7.11, P = 0.02); similarly, number of episodes of intestinal inflammation was lower in T1 (β = -0.95, P = 0.03). No significant differences were observed among participants with CD. DISCUSSION: UPF consumption may be a predictor of active symptomatic disease and inflammation among participants with UC. Reducing UPF consumption is a dietary strategy that can be suggested for minimizing symptoms and inflammation among people living with IBD. [ABSTRACT FROM AUTHOR]

Effective health communication is critical for understanding and acting on health information. This cross-sectional study explored participants' understanding of their health condition, their preferences for receiving health communications, and their interest in receiving clinical trial results across several therapeutic areas. The study recruited participants via social media, email newsletters, and advocacy organizations. An online screener captured demographic information (health conditions, age, race/ethnicity, gender, and education). Eligible participants were emailed an online survey assessing preferred sources and formats for receiving health information, interest in learning about topics related to the results of clinical trials, and health literacy levels. In total, 449 participants (median age, 35 years [range, 18–76]; White, 53%; higher education, 65%; mean (range) health literacy score, 1.9 [0.4–3.0]) from 45 US states completed the survey representing 12 disease indications (bipolar, blood and solid tumor cancers, irritable bowel syndrome, inflammatory bowel disease, major depressive disorder, migraine, Parkinson's, psoriasis/atopic dermatitis, retinal vein occlusion/macular degeneration, rheumatoid arthritis, and spasticity). Healthcare providers were the preferred source of health information (59%), followed by Internet searches (11%). Least preferred sources were social media (5%), friends/family (3%), and email newsletters (2%). Participants preferred multiple formats and ranked reading materials online as most preferred (33%), along with videos (28%) and infographics (27%). Printed materials (14%) and audio podcasts (9%) were the least preferred formats. A majority of the participants reported that the health information they found was hard to understand (57%) and confusing (62%). Most participants (85%) were somewhat/very interested in learning about clinical trial results, with the highest interest in short summaries of safety (78%) and efficacy (74%) results. Effective health communication may be achieved via multiple formats shared directly by healthcare providers. Researchers wanted to learn how people preferred to receive health-related communications, including information about the results of clinical trials. They surveyed 449 people from 45 US states with 12 different health conditions. The survey questions asked people about their preferred sources and ways of getting health information. It also asked about their interest in learning about clinical trials related to their health condition. The results showed that most people preferred to get health information from their healthcare providers (59%). The Internet was the second most popular choice (11%) for getting health information. People did not like getting health information from social media, friends or family, or email newsletters as much. When it came to how health information was shared, people liked reading materials online (33%), watching videos (28%), and looking at infographics (27%). They did not like printed materials and audio podcasts as much. Most people (85%) were interested in learning about the results of clinical trials in short summaries. They wanted to know about the safety (78%) and how well the treatments worked (74%) in the short summaries. In conclusion, people liked getting health information from healthcare providers like doctors, nurses, and others in different formats. Sharing information in different formats through healthcare providers may improve communication for patients with different health conditions. [ABSTRACT FROM AUTHOR]

The gut has been a focal point in the research of digestive system disorders. The internal microbiota generates metabolites that function as signaling molecules and substrates, interacting with the intestinal wall and influencing host physiology and pathology. Besides, the gut microbiota and metabolites owe highly diverse types and quantities, posing challenges for quantitative analysis, and monitoring frequent interactions between digestive tract metabolites and the intestinal wall remains a challenge. However, research targeting gut microbiota metabolites has elucidated their relevance to digestive diseases. By modulating metabolites such as short-chain fatty acids, bile acids, and lipopolysaccharides, it is possible to intervene in the progression of diseases such as inflammatory bowel disease and non-alcoholic fatty liver disease. Currently, research on gut microbiota is advancing, and more work is required to explore the interactions between host, microbes and underlying mechanisms. In this review, we have revisited the generation of gut microbiota-related metabolites, their impact on diseases, and modes of interaction, emphasizing the significant role of metabolites in digestive system disorders. It is believed that the linkage between gut microbiota and diseases in current research can be established through metabolites, providing a framework and foundation for research in the field of metabolomics and fundamental mechanisms. [ABSTRACT FROM AUTHOR]

Background: Therapeutic drug monitoring is effective for optimizing anti‐tumor necrosis factor therapies in inflammatory bowel disease, but for vedolizumab, a gut‐selective leucocyte migration inhibitor, data are scarce. Methods: Observational cohort study including 116 bio‐experienced inflammatory bowel disease patients treated with vedolizumab for active luminal disease. Biobanked trough blood samples (n = 676) covering 96% of patients were analyzed using a drug‐binding immunofluorometric assay. Steroid‐free treatment outcomes were classified by clinical disease activity indices and objective findings, primarily endoscopy. Results: Patients with clinical remission to vedolizumab induction therapy (37%) had significantly higher trough levels than those without at weeks 6 (mean 34.1 vs 28.0 μg/mL, P = 0.03) and 10 (34.8 vs 27.5 μg/mL, P = 0.01). Optimal thresholds for discrimination were 32.4 μg/mL (AUCROC 0.66, P = 0.04) and 23.5 (AUCROC 0.67, P = 0.01), respectively. This positive association persisted during maintenance phase with 11.9 μg/mL (AUCROC 0.69, P < 0.01) associated with clinical remission (37%) and 15.3 (AUCROC 0.74, P < 0.001) for objective remission (46%). Stratification by temporal evolution of treatment effects revealed higher induction and maintenance vedolizumab levels in persistent and slow responders as compared to secondary or persistent failures. Pharmacokinetics was influenced by rare formation of anti‐vedolizumab antibodies (2%), and to a lesser extent gender and albumin during induction, but not disease severity, concomitant steroids, or thiopurine metabolites. Switching to subcutaneous administrations resulted in 2.3‐fold increase in steady‐state trough levels. Conclusion: Our study supports maintaining adequate drug exposure being essential for sustained positive outcomes of vedolizumab and emphasizes individualized, therapeutic drug monitoring‐based treatment regimens. Controlled trials and pharmacokinetic modeling are, however, needed. [ABSTRACT FROM AUTHOR]

Background: Biologic drugs are highly effective for inflammatory bowel disease (IBD) management but are key drivers of costs of care especially when administered intravenously (i.v.). Availability of subcutaneous (SC) formulations has increased convenience for patients and improved access to care, but at the cost of revenue to health services. Aims: To evaluate the economic impact of transitioning a tertiary centre IBD cohort from i.v. to SC biologic administration and assess the implications for key stakeholders. Methods: A retrospective analysis of all patients who received i.v. infliximab or vedolizumab in the outpatient infusion centre of a tertiary IBD centre between July 2019 and June 2021 was undertaken. Data were collated from electronic medical records, pharmacy dispensing systems and the hospital business intelligence unit. An economic analysis and theoretical financial/capacity impact analysis of a transition to an SC model were estimated under two scenarios using a random 10% and 30% of the patient cohort. Results: Transitioning our IBD cohort from i.v. to SC administration would result in a loss to our health service of AU$2 732 123.75, composed of AU$1 463 003.75 in Weighted Inlier Equivalent Separation (WIES) and AU$1 269 120 in drug procurement revenue. However, it would ease capacity in the infusion centre by up to 5256 h. Conclusions: Transitioning patients to SC administration results in improved access to infusion centres and substantial savings to state governments; however, switching results in a loss of i.v. biologic‐generated WIES to health services. Alternative funding models are required to achieve sustainability in IBD care and reduce reliance on i.v. biologic‐generated income. [ABSTRACT FROM AUTHOR]

Crohn's disease (CD) is a chronic and debilitating inflammatory bowel disease that affects millions of individuals worldwide. Despite the availability of various treatment options, a significant number of patients do not achieve remission or experience adverse effects with conventional therapies. Vedolizumab, a novel therapeutic agent, has emerged as a promising approach in the management of CD. Despite improvements in treatment choices, there is still a demand for medicines that are efficient and well‐tolerated. Vedolizumab, a monoclonal antibody targeting α4β7 integrin, has emerged as a promising therapeutic approach for the treatment of CD. The review aims to provide a summary of vedolizumab, current treatment options, impact of vedolizumab on the patient's quality of life, mechanism of action, clinical effectiveness, safety and efficacy of vedolizumab, potential side effects or risks associated with vedolizumab therapy, and potential predictors. Furthermore, we investigate limitations and challenges associated with vedolizumab and possible future developments and medical implications. This review provides a comprehensive examination of the present data supporting vedolizumab as a possible treatment option for CD, highlighting its benefits and outlining prospective directions for future study and clinical practice improvement. [ABSTRACT FROM AUTHOR]

Vitamin D-binding protein (DBP), also known as Gc-globulin, is a protein that affects several physiological processes, including the transport and regulation of vitamin D metabolites. Genetic polymorphisms in the DBP gene have a significant impact on vitamin D levels and may have implications for disease risk. DBP polymorphisms are linked to differential immune responses, which could influence the onset of juvenile diseases. This narrative review examines the various roles of DBP, with a focus on bone health, immunological regulation, and lipid metabolism in children. Chronic disorders affected by DBP polymorphisms include bone abnormalities, autoimmune diseases, cardiovascular issues, childhood asthma, allergies, cystic fibrosis, acute liver failure, celiac disease, inflammatory bowel disease, and chronic kidney disease. Future research should focus on identifying the processes that underpin the many roles that DBP plays and developing customized therapeutics to improve health outcomes in the juvenile population. [ABSTRACT FROM AUTHOR]

Tuft cells are more than guardian chemosensory elements of the digestive tract. They produce a variety of immunological effector molecules in response to stimulation; moreover, they are essential for defense against protozoa and nematodes. Beyond the description of their characteristics, this review aims to elucidate the potential pathogenic and therapeutic roles of colonic tuft cells in inflammatory bowel disease and colorectal cancer, focusing on their primarily immunomodulatory action. Regarding inflammatory bowel disease, tuft cells are implicated in both maintaining the integrity of the intestinal epithelial barrier and in tissue repair and regeneration processes. In addition to maintaining intestinal homeostasis, they display complex immune-regulatory functions. During the development of colorectal cancer, tuft cells can promote the epithelial-to-mesenchymal transition, alter the gastrointestinal microenvironment, and modulate both the anti-tumor immune response and the tumor microenvironment. A wide variety of their biological functions can be targeted for anti-inflammatory or anti-tumor therapies; however, the adverse side effects of immunomodulatory actions must be strictly considered. [ABSTRACT FROM AUTHOR]

The immune system plays a crucial role in gastrointestinal (GI) diseases by protecting against infection, maintaining homeostasis, and regulating inflammation in the GI tract. GI diseases, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), diverticular disease (DD), and GI infections, pose significant challenges to global public health. Recent research has shown an increase in the global burden of IBD, particularly in developing regions, while IBS affects up to 15% of the global population. The imbalance in gut microbiota, called dysbiosis, has been linked to various GI pathologies. Understanding the interactions between the immune system and the GI tract is essential for developing new therapies and management strategies for these conditions. [Extracted from the article]

Vedolizumab (VDZ) is used for treating inflammatory bowel disease (IBD) patients. A study investigating colonic epithelial barrier function ex vivo following VDZ is lacking. This work aims to evaluate ex vivo the colonic epithelial barrier function in IBD patients at baseline and during VDZ treatment, and to investigate the relationships between barrier function and clinical parameters. Colonic specimens were obtained from 23 IBD patients before, and at 24 and 52 weeks after VDZ treatment, and from 26 healthy volunteers (HV). Transepithelial electrical resistance (TEER, permeability to ions) and paracellular permeability were measured in Ussing chambers. IBD patients showed increased epithelial permeability to ions (TEER, 13.80 ± 1.04 Ω × cm2 vs. HV 20.70 ± 1.52 Ω × cm2, p < 0.001) without changes in paracellular permeability of a 4 kDa probe. VDZ increased TEER (18.09 ± 1.44 Ω × cm2, p < 0.001) after 52 weeks. A clinical response was observed in 58% and 25% of patients at week 24, and in 62% and 50% at week 52, in ulcerative colitis and Crohn's disease, respectively. Clinical and endoscopic scores were strongly associated with TEER. TEER < 14.65 Ω × cm2 predicted response to VDZ (OR 11; CI 2–59). VDZ reduces the increased permeability to ions observed in the colonic epithelium of IBD patients before treatment, in parallel to a clinical, histological (inflammatory infiltrate), and endoscopic improvement. A low TEER predicts clinical response to VDZ therapy. [ABSTRACT FROM AUTHOR]