Inflammatory Bowel Disease Patients Research Articles

Managing a 4000-participant cohort with a novel mobile app: data from the RisCoin study in Germany

Abstract Issue RisCoin, a prospective monocentric longitudinal observational study, aimed to identify risk factors for COVID-19 vaccine failure. Secondary aim is to monitor symptoms, SARS-CoV-2 infection, vaccination status of 3816 enrolled healthcare workers (HCW) and 180 patients with inflammatory bowel disease (IBD). Since the LMU University Hospital Munich served both as study sponsor and employer of the HCW, a secured approach was required. Description of the solution Participants accessed the study app (CentraXX, KAIROS GmbH, Germany) via pseudonymized Contact-ID with irreversible anonymization after 6 months. Key app features were the serological results report, bidirectional messaging, and weekly survey for self-reported data on vaccinations, infections, and symptoms. Active app use was defined as submitting >1 weekly survey during the study period 10.2021-12.2022. Results Over 15 months, our study team maintained 1964 two-way communications with 958 participants via the app. Of 3979 participants with app access, 3622 (91%) were active users, 2606 (65%) submitted 1 to 11 surveys, 1016 (26%) made ≥12 submissions (P75, “frequent users”). Frequent users were more likely to be IBD patients (p = 0.001), female (p < 0.001), aged 60 or older (p < 0.001). Staff in administration and nurses were more likely to be frequent users compared to physicians (p < 0.001). Main problems included the initial operational system disparities resulting in app crashes and continuous need for app reactivation. Both led to loss of active participants and required substantial staff resources to onboard and support participants during the study. Lessons The study app enabled secure, flexible, bidirectional communication with all participants. Despite technical issues, the majority actively used the app and provided valuable longitudinal data through weekly survey submissions. Key messages • A study-specific app provides a flexible and secure bidirectional anonymous communication for the study team and participants. • Adherence to app-based communication and data collection for pandemic monitoring was particularly high among patients, nurses and administrative staff.

Frequency, Types, and Risk Factors of Anemia in Pediatric Inflammatory Bowel Disease

Objective: Inflammatory bowel disease patients are prone to be anemic at diagnosis and follow-up. As it is a common extra-intestinal manifestation, its early identification and treatment are essential. We aimed to evaluate the frequency, types, and predictors of anemia and its treatment in pediatric inflammatory bowel disease patients. Methods: The electronic records of pediatric IBD patients who attended our outpatient clinics between 1 April 2018 and 01 May 2019 were retrospectively evaluated. Patients who had the results of hemoglobin, hematocrit, mean corpuscular volume, iron indices, vitamin B12 level, folic acid level, reticulocyte count, C-reactive protein, and erythrocyte sedimentation rate at least once on a single day were included in the study. Laboratory results associated with anemia and disease activity index scores at three- and six-months follow-ups were recorded. Anemia was diagnosed according to WHO criteria in childhood. Anemia, risk factors, and management of anemia were determined. Results: Forty patients were included in the study. At first evaluation, anemia was observed in 38.1% of Crohn’s disease patients and 57.9% of ulcerative colitis patients. Iron deficiency anemia was the main type of anemia in both groups. The rate of anemia decreased at follow-up. Out of 40 patients, 21 had treatment at the initial evaluation. Active disease was the only predictor of iron deficiency anemia. Conclusion: Anemia was common in pediatric inflammatory bowel disease patients, ranging between 25-47.5% during the 6-month follow-up in our study. Iron deficiency anemia was the main type of anemia. Having active disease was the only risk factor for anemia. The treatment of anemia and iron deficiency without anemia should be kept in mind in parallel with anti-inflammatory treatment.

The substantial role of sleep, stress and physical activity in persistent high levels of fatigue in patients with inflammatory bowel disease: A longitudinal trajectory study.

Fatigue is a common and burdensome problem for patients with inflammatory bowel disease (IBD). Previous studies lack insight into the individual variability in fatigue severity and course over time, and the characteristics of patients at risk of severe and persistent fatigue. This study aimed to identify distinct groups of IBD patients based on their level and course of fatigue over five years. Subsequently, we examined the relationship between these trajectories, patient characteristics and trajectories of perceived stress, sleep and physical activity. This longitudinal cohort study used prospectively collected data from the myIBDcoach telemedicine monitoring tool, including 320 IBD patients who completed three or more online consultations between 2016 and 2021. Latent class growth analyses were performed to identify distinct trajectories. We found five subgroups with distinct trajectories of fatigue, differing in level and course over time, with 33% of patients experiencing chronic stable and high levels of fatigue. Few differences in patient characteristics were found between trajectories, yet the chronic high fatigue subgroup was more likely to report persistent stable sleep problems, perceived stress, and little physical activity over time compared to the other groups. Distinct subgroups of IBD patients can be identified based on longitudinal fatigue trajectories. The relatively stable levels of fatigue, stress, sleep, and physical activity suggest that a one-time screening of patients on these topics may be sufficient to identify those at risk. Interventions aiming to reduce fatigue should target persistent stress, sleep problems, and low levels of physical activity.

Self-Efficacy, Patient Activation, and the Burden of Inflammatory Bowel Disease on Patients' Daily Lives.

The effective management of inflammatory bowel disease (IBD) requires complex self-management behaviors. Both patient activation (the degree to which patients are willing and able to engage in care) and self-efficacy (one's confidence in performing certain behaviors) are thought to play an important role in chronic disease self-management, but patient activation is a broad concept that can be more difficult to precisely target than self-efficacy. We aimed to describe the relationship between patient activation, self-efficacy, and the burden of IBD on patients' daily lives. Patients with IBD were recruited from a single center to complete a survey including the Patient Activation Measure (PAM-13®), the IBD Self-Efficacy Scale (IBD-SES), and an IBD-specific patient-reported outcome measure. Using multivariable linear regression, we examined the relationship between IBD burden, self-efficacy, and patient activation, adjusting a priori for age, gender, IBD type, IBD medications, active corticosteroid use, anxiety, and depression. We performed a post-hoc mediation analysis to examine self-efficacy as a potential mediator in the relationship between patient activation and the burden of IBD on patient's daily lives. A total of 132 patients with IBD completed the survey (59% Crohn's disease, 41% ulcerative colitis, 52% female). Higher levels of patient activation and higher levels of self-efficacy were each associated with lower IBD burden (patient activation: ß = -1.9, p < 0.001, self-efficacy: ß = -2.6, p < 0.001). Post hoc mediation analysis confirmed that the relationship between patient activation and daily IBD burden was mediated by self-efficacy (Average Causal Mediation Effect = -1.00, p < 0.001, proportion mediated = 0.62, p < 0.001). The relationship between patient activation and IBD burden is highly mediated by self-efficacy, suggesting that self-efficacy could be a more precise target for intervention. Future studies could focus on targeting self-efficacy to build individuals' confidence in IBD self-management and testing of IBD-tailored self-management programs to ultimately improve disease outcomes.

Medication Burden Before and After Prescription of Biologics in Patients with Inflammatory Bowel Disease.

Background: Biologics are a cornerstone in the treatment of severe cases of inflammatory bowel disease (IBD) and aim to control the disease and improve quality of life. This study investigated changes in nonbiologic medication prescriptions for IBD patients initiating biologic therapy in Germany. Methods: This study used data from anonymized pharmacy records in the German longitudinal prescription (LRx) database and included biologic-naive IBD patients who received their first biologic therapy prescription between 2016 and 2022. Changes in prescription rates and pill counts for nonbiologic medications (corticosteroids, 5-aminosalicylates (5-ASA), proton pump inhibitors, analgesics, immunosuppressants, Vitamin D, iron, and antibiotics) before and after the initiation of biologic therapy were assessed using descriptive statistics, McNemar's tests, and Poisson regression models, adjusting for age and sex. Results: A total of 29,559 biologic-naive IBD patients were included. Prior to index, 91.2% received at least one nonbiologic medication prescription, where corticosteroids and 5-ASA were the most common. Postindex, the overall prescription rate decreased to 87.7%, with significant reductions in prescriptions observed for corticosteroids, 5-ASA, and immunosuppressants (p-values < 0.001). The mean (SD) pill count dropped from 704 (1712) to 514 (1651), with the largest mean differences (95% CI) having been for corticosteroids (-77.9 [-80.3 to -75.5]), 5-ASA (-61.6 [-65.2 to -58.1]), and immunosuppressants (-55.0 [-57.5 to -52.6]). Older patients tended to have greater decreases in pill counts for corticosteroids and 5-ASA, while males showed statistically significant reductions in pill count for immunosuppressants compared with females. Conclusions: This study demonstrates that the prescription of nonbiologic medications significantly decreased after biologic therapy initiation. The use of biologics may therefore lead to improved disease management and potentially better patient outcomes.

Identification of spontaneous patient-reported complaints related to perianal fistula in patients with Crohn's disease.

To identify patient-reported complaints affecting quality of life in Crohn's disease patients with a perianal fistula, and to compare differences between subgroups. A questionnaire was distributed to 1667 patients from the Dutch Crohn's and Colitis Patients' organization, those patients with Crohn's disease and perianal fistula were included. Patients were asked to report (using free text) their most important fistula-related complaints affecting their quality of life. All responses were structurally analyzed and categorized. Data comparisons were made between subgroups: women versus men, patients with versus without current presence of a seton, and patients aged ≤40 versus >40 years. Of 743 respondents (44.6%), 123 patients with Crohn's disease and perianal fistula were included (92 women, median age 41 years [IQR 34-56] and 36 with seton). A total of 776 complaints were allocated to 36 categories, with 19 reported in >10% of patients. Perianal fistula-related complaints affected nearly all patients (95.9%). Impact on psychological status (71.7% vs. 29.0%; p < 0.0001) and on sexual activities (37.0% vs. 16.1%; p = 0.003) were more common in women than men. Younger patients more often reported insecurity (38.7% vs. 18.0%; p = 0.026), shame (29.0% vs. 11.5%; p = 0.024), and impact on sexual activities (40.3% vs. 23.0%; p = 0.048) than older patients. Patients with a seton more frequently reported self-experienced malodour (50.0% vs. 23.0%; p = 0.005), physical activity limitations (41.7% vs. 19.5%; p = 0.014), and work/study impact (22.2% vs. 5.7%; p = 0.019). We identified 19 perianal fistula-related complaints reported by >10% of patients. These complaints may guide improvement of current outcome measures.

The Bidirectional Effects of Periodontal Disease and Oral Dysbiosis on Gut Inflammation in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) flares can lead to excessive morbidity and mortality. This study aimed to determine whether oral dysbiosis/periodontal disease (PD) is common in IBD and is associated with disease activity in IBD. This single-center, prospective, cross-sectional, proof-of-concept, observational study assessed the frequency of periodontal inflammatory disease and interrogated oral and stool microbiota using 16S rRNA gene amplicon sequencing of active-IBD (aIBD), inactive-IBD (iIBD), and healthy controls (HC). Questionnaires assessed diet, alcohol usage, oral hygiene behavior, and disease activity. A subset of participants underwent comprehensive dental examinations to evaluate PD. PD was severer in aIBD subjects than in HC, as aIBD had poorer quality diets (lower Mediterranean diet scores) than iIBD and HC. Significant differences in microbial community structure were observed in unstimulated saliva, stimulated saliva, gingiva, and stool samples, primarily between aIBD and HC. Saliva from aIBD had higher relative abundances of putative oral pathobionts from the genera Streptococcus, Granulicatella, Rothia, and Actinomyces relative to HC, despite similar oral hygiene behaviors between groups. Our study suggests that patients with aIBD have severer periodontal disorders and higher relative abundances of putative "pro-inflammatory" microbiota in their oral cavity, despite normal oral hygiene behaviors. Our data are consistent with the potential presence of an oral-gut inflammatory-axis that could trigger IBD flare-ups in at-risk patients. Routine dental health assessments in all IBD patients should be encouraged as part of the health maintenance of IBD and as a potential strategy to decrease the risk of IBD flares.

Hexokinase 2 expression in apical enterocytes correlates with inflammation severity in patients with inflammatory bowel disease

BackgroundInflammation is characterized by a metabolic switch promoting glycolysis and lactate production. Hexokinases (HK) catalyze the first reaction of glycolysis and inhibition of epithelial HK2 protected from colitis in mice. HK2 expression has been described as elevated in patients with intestinal inflammation; however, there is conflicting data from few cohorts especially with severely inflamed individuals; thus, systematic studies linking disease activity with HK2 levels are needed.MethodsWe examined the relationship between HK2 expression and inflammation severity using bulk transcriptome data derived from the mucosa of thoroughly phenotyped inflammatory bowel disease (IBD) patients of two independent cohorts including both subtypes Crohn’s disease (CD) and ulcerative colitis (UC). Publicly available single-cell RNA sequencing data were analyzed, and immunofluorescence staining on colonic biopsies of unrelated patients with intestinal inflammation was performed to confirm the RNA-based findings on cellular and protein level.ResultsHK2 expression gradually increased from mild to intermediate inflammation, yet strongly declined at high inflammation scores. Expression of epithelial marker genes also declined at high inflammation scores, whereas that of candidate immune marker genes increased, indicating a cellular remodeling of the mucosa during inflammation with an infiltration of HK2-negative immune cells and a loss of terminal differentiated epithelial cells in the apical epithelium—the main site of HK2 expression. Normalizing for the enterocyte loss clearly identified epithelial HK2 expression as gradually increasing with disease activity and remaining elevated at high inflammation scores. HK2 protein expression was mostly restricted to brush border enterocytes, and these cells along with HK2 levels vanished with increasing disease severity.ConclusionsOur findings clearly define dysregulated epithelial HK2 expression as an indicator of disease activity in intestinal inflammation and suggest targeted HK2-inhibition as a potential therapeutic avenue.

Butyrate Inhibits the HDAC8/NF-κB Pathway to Enhance Slc26a3 Expression and Improve the Intestinal Epithelial Barrier to Relieve Colitis.

Dietary fiber is known to promote the production of short-chain fatty acids (SCFAs) by gut bacteria, which can enhance intestinal epithelial barrier function and ameliorate intestinal inflammation in patients with inflammatory bowel disease (IBD). Interestingly, some IBD patients show reduced expression of solute carrier family member 3 (Slc26a3) in intestinal epithelial cells. The objective of this research was to investigate the interaction between SCFAs and Slc26a3 during colitis and assess how this interaction affects intestinal epithelial barrier function. We showed that butyrate alleviated colonic inflammation in a dose-dependent manner in a dextran sulfate sodium salt (DSS)-induced colitis model. Consistent with this, butyrate increased Slc26a3 and tight junction protein levels. In addition, butyrate inhibited histone deacetylase (HDAC) levels and significantly increased the expression of Slc26a3 by the acetylation of histones in Caco-2BBe cells. The utilization of a pan-HDAC inhibitor or inhibitors specific to certain classes of HDACs revealed that butyrate primarily suppressed HDAC8 to blunt the NF-κB pathways and enhance the expression of Slc26a3. Notably, we demonstrated that HDAC8 activation counteracted the beneficial effect of butyrate in DSS-induced colitis. Therefore, we concluded that butyrate improves the expression of Slc26a3 via inhibition of the HDAC8/NF-κB pathway, leading to increased intestinal epithelial barrier function.

Exploring Dual-Targeted Therapy in the Management of Moderate to Severe Inflammatory Bowel Disease: A Retrospective Study

Abstract Background Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), often results in significant morbidity among patients with moderate to severe forms. While biologics and small molecules are effective in inducing remission, many patients experience refractory disease or extra-intestinal manifestations. This study assesses the safety and efficacy of dual-targeted therapy in IBD patients treated at the Inflammatory Bowel Disease Center. Methods This retrospective cohort study examined 79 patients with UC or CD who received dual-targeted therapy at the University from October 2018 to August 2023. Data collected included demographics, disease characteristics, previous treatments, and clinical outcomes. Primary outcomes were endoscopic, radiographic, and patient-reported clinical improvements, with secondary outcomes focusing on safety profiles. Results Among the 79 patients (42 UC, 37 CD), 97 dual-targeted therapy cases were analyzed, primarily involving a biologic combined with a JAK inhibitor (90.7%). The median therapy duration was 39.1 weeks. Endoscopic improvement occurred in 69% of matched samples, with significant differences between pre- and post-dual-targeted therapy Mayo scores for UC (p = 0.002) and SES-CD scores for CD (p = 0.018). The median pre- and post-dual-targeted therapy Mayo scores across matched samples were 3 (range 1-3) and 1 (range 0-3) respectively, and for SES-CD scores were 12 (range 0-36) and 4 (range 0-20) respectively. Clinical improvement was reported by 73.2% of patients, with notable reductions in ESR (median 19 [range 2-124] mm/hr to 9 [range 0-116] mm/hr, p = 0.006), CRP (median 8.0 [range 0.2-78.5] mg/L to 3.0 [range 0.2-68.2] mg/L, p &amp;lt;0.001) , and albumin levels (4.0 [range 2.2-4.9] mg/dL to 4.2 [range 3.4-5.2], p &amp;lt; 0.001). Non-obesity was associated with both more endoscopic improvement (p = 0.002) and clinical improvement (p = 0.007). Adverse events occurred in 37 cases, predominantly upper respiratory tract infections and dermatologic issues, with no thromboembolic events reported. Discussion Dual-targeted therapy demonstrated efficacy in improving clinical and endoscopic outcomes in patients with severe, refractory IBD, and exhibited an acceptable safety profile. Despite the promising results, further research is needed to confirm these findings and determine optimal therapy combinations.

Probiotic Potential in Irritable Bowel Syndrome and Inflammatory Bowel Disease: A Comprehensive Systematic Review.

Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) are prevalent gastrointestinal disorders with significant global prevalence. Conventional treatments often have adverse effects, prompting interest in probiotics as alternative therapies. This systematic review assesses the efficacy of probiotics in managing symptoms and improving outcomes in adult patients with IBS and IBD. A comprehensive search was conducted across databases such as PubMed, Cochrane Library, and Google Scholar and registers ClinicalTrials.gov and International Standard Randomized Controlled Trial Number (ISRCTN). Using targeted keywords, studies on probiotic efficacy in adult IBS and IBD patients were identified. Data screening, extraction, and quality assessment using theCochrane Risk of Bias 2 (RoB 2) tool for evaluating randomized controlled trials (RCTs) and Newcastle-Ottawa Scale (NOS) for cohort studies were rigorously performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. From the initial 22,037 references, 18 randomized control trials and two observational studies encompassing 2,675 adults, aged 18-76 years, were deemed eligible. The efficacy of probiotics for IBS and IBD is variable. While some IBS trials show symptom improvement, the results are inconsistent, likely due to the diversity of probiotic strains and patient populations studied. In contrast, probiotics demonstrate more consistent benefits for ulcerative colitis (UC) in IBD, particularly with specific formulations like the De Simone combination. However, probiotics' effects on Crohn's disease (CD) remain less clear, highlighting the need for further research to optimize probiotic regimens and understand their differential effects across the spectrum of IBS and IBD.

Relationship of Crohn’s disease and acute pancreatitis in pediatric practice: literature review

Inflammatory bowel diseases (IBD) are a certain group of pathologic conditions of the gastrointestinal tract (GIT), including Crohn’s disease (CD) and ulcerative colitis (UC). In the modern world, vigilance for these diseases is growing, because their characteristic feature is the involvement of other organs in the pathological inflammatory process, as well as the development of local and systemic complications. As a rule, in children CCD occurs mainly at the age of 12-16 years. Recently, the attention of the medical world has been drawn to the issue of extraintestinal manifestations of CD. Pathological manifestations associated with lesions of the skin and mucous membranes, eyes, bone and joint system, pancreas, negatively affect both physical and psychological health of the child. Such pathology associated with pancreatic malfunction, such as acute pancreatitis (AP) often occurs in patients with inflammatory bowel disease and is one of the main causes of hospitalization for diseases of the digestive system. According to statistics, the incidence ranges from 15 to 40 cases per 100,000 per year in European countries. According to the Gastroenterological Society, there are different variations in the course of acute pancreatitis, whether occurring in patients with IBS due to the disease itself or as a side effect of drug therapy. However, IBD patients are at increased risk of developing both acute and chronic pancreatitis. In this review, we consider the relationship and mutual influence of these two pathologies.

Comparative Analysis of Inflammatory Bowel Disease Management: Hospital-based Versus Community-based Care.

Inflammatory bowel disease (IBD) encompasses chronic gastrointestinal disorders characterized by recurrent inflammation. Achieving mucosal healing and preventing disease progression are primary treatment goals. This study aimed to compare disease characteristics, medication utilization, procedures performed, and hospitalizations between IBD patients treated in hospital and community settings using the Leumit Health Service database. A retrospective cohort study was conducted using data from the Leumit Health Service, comprising 3020 patients diagnosed with IBD from January 2010 to December 2019. Patients were divided based on primary care setting: hospital-based or community-based. Data included demographic characteristics, disease type, medication usage, procedures, and outcomes. Statistical analyses assessed differences between groups. Hospital-treated patients were significantly younger (49.4±18.4 vs. 40.4±18.7, P<0.001 ), had higher rates of Crohn's disease (45.9% vs. 71.4%, P<0.001), exhibited higher inflammatory markers (calprotectin 768±2182 vs. 1305±2526, P<0.001), lower albumin (4.23±0.27 vs. 4.12±0.32, P<0.001), hemoglobin levels (13.4±1.6 vs. 12.9±1.6, P<0.001), and lower BMI (26.2±5.3 vs. 24.6±5.6, P<0.001) compared with community-treated patients. Hospital-treated patients had more endoscopic procedures, higher medication utilization rates, shorter treatment durations, and increased hospitalization occurrence (12.1% vs. 23.6%, P<0.001), length (0.67±3.34 vs. 1.45±5.88, P<0.001), and colectomies (4.73% vs. 15.8%, P<0.001). Disparities exist in IBD management between hospital and community settings, influenced by disease severity and treatment approaches. Hospital-based care is associated with more aggressive disease and intensive interventions, while community-based care may reflect milder disease and conservative management. Integrating specialized care models and personalized approaches across settings can optimize patient outcomes and health care delivery for IBD management. Further research is needed to understand these disparities' underlying mechanisms and develop comprehensive care strategies.

GLP-1 Receptor Agonists Confer No Increased Rates of IBD Exacerbation Among Patients With IBD.

In patients with inflammatory bowel disease (IBD), multimorbidity with obesity and type 2 diabetes is common and increasing. Glucagon-like peptide 1 (GLP-1) receptor agonists are increasingly being prescribed for patients with IBD, yet their impact on patients with IBD is largely unknown. We aimed to assess the impact of GLP-1 receptor agonists on the course of IBD. We identified all IBD patients prescribed GLP-1 receptor agonists at a large academic healthcare network between 2009 and 2023. We analyzed demographics and IBD characteristics in the year pre- and post-GLP-1 receptor agonist prescription and matched them to non-IBD controls. Our primary outcome was IBD exacerbation in the year following GLP-1 receptor agonist initiation, measured as a composite of IBD-related hospitalization, corticosteroid prescription, medication escalation or changes, or IBD-related surgery. Secondary outcomes included change in metabolic risk factors. Overall, 224 patients met inclusion criteria. At GLP-1 receptor agonist initiation, the median age was 54 years, 63% were female, 77% were White, and median BMI was 33.2kg/m2. Compared to the 12-month period prior to GLP-1 receptor agonist initiation, in the 12 months post-GLP-1 receptor agonist initiation, there was no change in rates of IBD exacerbation, IBD-related hospitalization, steroids prescription, medication escalation or changes, or IBD-related surgery. There was a significant decrease in BMI in the year following GLP-1 receptor agonist initiation (median BMI 33.5 vs 31.6kg/m2, P < .01), with rates of decrease comparable to non-IBD matched controls. In patients with IBD, GLP-1 receptor agonists are effective for weight loss and associated with few episodes of disease exacerbation.

Post-Discharge Outcomes of Elderly Patients Hospitalized for Inflammatory Bowel Disease Flare Complicated by Clostridioides difficile Infection.

Elderly hospitalized patients with inflammatory bowel disease (IBD) flare and concurrent Clostridioides difficile infection (CDI) are considered at high risk of IBD-related complications. We aimed to evaluate the short, intermediate, and long-term post-discharge complications among these patients. A retrospective multicenter cohort study assessing outcomes of elderly individuals (≥60 years) hospitalized for an IBD flare who were tested for CDI (either positive or negative) and discharged. The primary outcome was the 3-months post-discharge IBD-related complication rates defined as: steroid dependency, re-admissions (emergency department or hospitalization), IBD-related surgery, or mortality. We assessed post-discharge IBD-related complications within 6-months and mortality at 12-months among secondary outcomes. Risk factors for complication were assessed by multivariable logistic regression. In a cohort of 654 patients hospitalized for IBD (age 68.9 [interquartile range {IQR}]:63.9-75.2) years, 60.9% ulcerative colitis), 23.4% were CDI-positive. Post-discharge complication rates at 3 and 6-months, and 12-months mortality, did not differ significantly between CDI-positive and CDI-negative patients (32% vs. 33.1%, p=0.8; 40.5% vs. 42.5%, p=0.66; and 4.6% vs. 8%, p=0.153, respectively). The Charlson comorbidity index was the only significant risk factor for complications within 3-months (aOR 1.1), whereas mesalamine (5-aminosalicylic acid [5-ASA]) use was protective (aOR 0.6). An ulcerative colitis diagnosis was the sole risk factor for complication at 6-months (aOR 1.5). CDI did not significantly impact outcomes or interact with IBD type. In elderly IBD patients hospitalized for IBD flare and subsequently discharged, a concurrent CDI infection was not associated with post-discharge IBD-related complications or mortality up to 1-year.

Incidence of thiopurine induced severe myelosuppression in a nationwide cohort of inflammatory bowel disease patients.

There is paucity of data on the incidence of severe thiopurine (TP)-induced myelosuppression (TIM) among inflammatory bowel disease (IBD) patients. Utilizing the Veterans Affairs Healthcare system we identified IBD patients with normal pre-treatment thiopurine S-methyltransferase(TPMT) levels who received TPs for 6 months and developed severe TIM. Among 73,392 IBD patients, 14,760 had received TPs, and 2823 had a normal TPMT level. The incidence rate of severe TIM was 1.25 per 1000 patient-years. The incidence of severe TIM was very low, calling into question the necessity of frequent long-term CBC monitoring among IBD patients on TPs.

Treatment outcomes of mild to moderate Clostridioides difficile infection in inflammatory bowel disease: an Australian experience.

The incidence of Clostridioides difficile infection (CDI) in inflammatory bowel disease (IBD) is rising and associated with adverse outcomes. Optimal treatment for CDI in IBD remains unknown, with various organisations suggesting vancomycin as first-line therapy. To compare treatment outcomes for metronidazole versus vancomycin in mild to moderate CDI in IBD. A retrospective analysis of IBD patients with CDI between January 2015 and December 2019 was conducted. Laboratory data and clinical outcomes were examined. Forty-seven discrete episodes of CDI in 34 patients occurred during the study period. Fifty-three per cent (18) had Crohn's disease, 44% (15) ulcerative colitis and 3% (1) IBD unclassified. Six per cent (3/47) of CDI cases were severe and excluded. In 68% (30/44) of mild to moderate CDI, metronidazole was prescribed, with treatment failure in 20% (6/30), CDI recurrence in 13% (4/30) and 20% (6/30) experiencing a further CDI episode. Comparatively, vancomycin was prescribed in 23% (10/44) without any treatment failures; however, 10% (1/10) had CDI recurrence and 40% (4/10) experienced another CDI episode. No statistically significant difference was noted between metronidazole and vancomycin therapy for treatment failure (P = 0.31), CDI recurrence (P = 1.0) or further CDI episodes (P = 0.23). Proton-pump inhibitor therapy was the only risk factor associated with a higher rate of the composite outcome and remained significant on multivariate logistic regression (odds ratio 12.99 (95% confidence interval = 1.21-139.97), P = 0.03). Metronidazole compared to vancomycin for treatment of mild to moderate CDI in IBD is effective however may be associated with higher rates of treatment failure.

Impact of SCN10A Polymorphism on Abdominal Pain Perception and Visceral Hypoalgesia in Crohn's Disease and Ulcerative Colitis.

Hypoalgesic inflammatory bowel disease (IBD) may provide critical insights into human abdominal pain. This condition was previously associated with homozygosity for a polymorphism (rs6795970,A1073V;1073val/val) related to Nav1.8, a voltage-gated sodium channel preferentially expressed on nociceptors. It was unclear whether this relationship existed for both Crohn's disease (CD) and ulcerative colitis (UC). This study evaluated a larger, carefully phenotyped IBD cohort to investigate this question. Allelic and genotypic frequencies of rs6795970 were compared among study cohorts characterized by concomitant assessment of intestinal inflammatory status and abdominal pain experience. Visceral sensory perception was performed in healthy individuals using rectal balloon distension(RBD). We analyzed 416 IBD patients (261CD:155UC) and 142 healthy controls. In the IBD cohort, 84 individuals (43CD:41UC) were determined to have hypoalgesic disease. The allelic frequency of rs6795970 was significantly higher in hypoalgesic IBD patients when compared to other IBD patients and healthy controls. Hypoalgesic IBD patients were also more likely to be homozygous for this polymorphism when compared to other IBD patients and healthy controls. Hypoalgesic CD (30%vs.12%,p=0.004) and hypoalgesic UC (32%vs.15%,p=0.036) were each significantly more likely to be associated with homozygosity for the rs6795970 polymorphism. In a cohort of healthy individuals(n=50), rs6795970 homozygotes(n=11) also demonstrated reduced abdominal discomfort to RBD. These findings indicate that Nav1.8 plays a key role in human visceral pain perception, and could serve as a novel diagnostic target in the management of hypoalgesic CD and UC, and potential therapeutic target for conditions associated with chronic abdominal pain.

Effectiveness of switching to subcutaneous infliximab in inflammatory bowel disease patients with inadequate biochemical response during intravenous administration

Infliximab (IFX) has transformed the management of inflammatory bowel diseases (IBD). While intravenous (IV) IFX has been effective, a subcutaneous (SC) formulation offers advantages in convenience and cost. However, there is lack of evidence regarding the transition from IV to SC-IFX, especially for patients with inadequate responses. This study investigates the effectiveness of switching from IV to SC-IFX in patients with inadequate responses during IV maintenance therapy. A retrospective study enrolled IBD patients who transitioned to SC-IFX after demonstrating inadequate responses during IV maintenance therapy. The study collected data of demographics of patients and dose and therapies administered prior to the IV-IFX. Primary outcomes included improvements in C-reactive protein (CRP) or fecal calprotectin (FC) levels. This study evaluated the trough levels and its differences between pre- and post-switching. Among 44 patients included, 10 exhibited CRP elevation before the switch, with 6 showing normalization post-switch. Similarly, 42 patients had elevated FC levels pre-switch, with 26 experiencing reductions post-switch. Trough levels increased after the switch. However, there were no significant differences between responders and non-responders. This study is the first study to investigate the transition therapy of IV to SC-IFX in patients with inadequate response. This suggests that SC-IFX could be a viable alternative in the management of IBD. However, further research is necessary to evaluate its efficacy in a larger population of patients who exhibit inadequate responses during IV-IFX maintenance therapy.

EQTL in diseased colon tissue identifies novel target genes associated with IBD.

Genome-wide association studies (GWAS) have identified over 300 loci associated with the inflammatory bowel diseases (IBD), but putative causal genes for most are unknown. We conducted the largest disease-focused expression quantitative trait loci (eQTL) analysis using colon tissue from 252 IBD patients to determine genetic effects on gene expression and potential contribution to IBD. Combined with two non-IBD colon eQTL studies, we identified 194 potential target genes for 108 GWAS loci. eQTL in IBD tissue were enriched for IBD GWAS loci colocalizations, provided novel evidence for IBD-associated genes such as ABO and TNFRSF14, and identified additional target genes compared to non-IBD tissue eQTL. IBD-associated eQTL unique to diseased tissue had distinct regulatory and functional characteristics with increased effect sizes. Together, these highlight the importance of eQTL studies in diseased tissue for understanding functional consequences of genetic variants, and elucidating molecular mechanisms and regulation of key genes involved in IBD.