Inflammatory Bowel Disease Patients Research Articles

Perforin Generated by CD8+ T Cells Exacerbates IBD-Induced Depression by Promoting CXCL9 Production in Intestinal Epithelial Cells.

Perforin Generated by CD8+ T Cells Exacerbates IBD-Induced Depression by Promoting CXCL9 Production in Intestinal Epithelial Cells.

Roles of fibroblasts in the pathogenesis of inflammatory bowel diseases (IBDs) and IBD-associated fibrosis.

Ulcerative colitis and Crohn's disease, the principal forms of inflammatory bowel disease (IBD), are chronic relapsing inflammatory disorders of the gastrointestinal tract. The incidence and prevalence of IBD have been increasing worldwide, but their etiology remains largely unknown. Although anti-TNF agents can be highly effective in IBD patients, 10%-40% of patients do not respond to primary anti-TNF therapy. Furthermore, anti-TNF therapy for IBD does not prevent the incidence and progression of fibrosis. A growing body of evidence suggests that IBD pathogenesis is associated with epithelial barrier dysfunction, inappropriate immune responses to luminal microorganisms, and environmental factors as well as host genetics. Recently, a variety of mesenchymal stromal cell populations, including fibroblasts and myofibroblasts, have been characterized in individual tissues under homeostatic and inflammatory conditions. The compositions of fibroblasts and myofibroblasts are altered in the intestinal mucosa of IBD patients, and diverse properties of these cells, such as production of pro-inflammatory cytokines and extracellular matrix components, are remodeled. Several studies have demonstrated that IBD-specific fibroblasts are involved in anti-TNF therapy refractoriness. Therefore, a better understanding of the interaction among fibroblasts, epithelial cells, immune cells, and microbes associated with the maintenance and perturbation of intestinal homeostasis may facilitate the identification of novel therapeutic targets for IBD. This review presents the key findings obtained to date regarding the pathological and homeostatic mechanisms by which functionally distinct fibroblasts and myofibroblasts regulate epithelial barrier integrity, immunity, and tissue regeneration in health and in gastrointestinal disorders.

Why and when are activity scores and advanced ultrasound techniques needed in inflammatory bowel disease (IBD)?

In addition to avoidance of radiation exposure, the main advantages of ultrasound diagnostics in inflammatory bowel disease (IBD) patients are its’ immediate availability, also as a component of the physical examination (extended point of care), its’ repeatability and its’ high patient comfort. The fact that the examination is carried out directly by the treating physician and is not delegated to the radiologist increases compliance and therapy adherence of the patients.In the current series of papers a synopsis of recommendations for ultrasound in IBD guidelines, ultrasound parameters in inflammatory bowel disease including activities scores, the value of contrast enhanced ultrasound (CEUS), small intestinal contrast ultrasound (SICUS) and elastography, perineal ultrasound (PNUS), endoscopic ultrasound (EUS) including endorectal ultrasound (ERUS), interventional ultrasound (INVUS), detection of disease complications (stenoses, fistula, abscess), extraintestinal manifestations, differential diagnosis, evaluation of treatment response and outlook are discussed and illustrated.

Reducing severity of inflammatory bowel disease through colonization of Lactiplantibacillus plantarum and its extracellular vesicles release

Inflammatory bowel disease (IBD) is characterized by compromised intestinal barrier function and a lack of effective treatments. Probiotics have shown promise in managing IBD due to their ability to modulate the gut microbiota, enhance intestinal barrier function, and exert anti-inflammatory effects. However, the specific mechanisms through which probiotics exert these therapeutic effects in IBD treatment remain poorly understood. Our research revealed a significant reduction of Lactiplantibacillus plantarum (L. plantarum) in the gut microbiota of IBD patients. L. plantarum is a well-known probiotic strain in the list of edible probiotics, recognized for its beneficial effects on gut health, including its ability to strengthen the intestinal barrier and reduce inflammation. We demonstrated that supplementation with L. plantarum could alleviate IBD symptoms in mice, primarily by inhibiting apoptosis in intestinal epithelial cells through L. plantarum’s bacterial extracellular vesicles (L. plant-EVs). This protective effect is dependent on the efficient uptake of L. plant-EVs by intestinal cells. Intriguingly, watermelon enhances L. plantarum colonization and L. plant-EVs release, further promoting intestinal barrier repair. Our findings contribute to the understanding of L. plant-EVs in the probiotic-based therapeutic approach for IBD, as they are promising candidates for nanoparticle-based therapeutic methods that are enhanced by natural diets such as watermelon. This study thereby offers a potential breakthrough in the management and treatment of IBD.Graphical

SOD mimics delivered to the gut using lactic acid bacteria mitigate the colitis symptoms in a mouse model of inflammatory bowel diseases

Inflammatory bowel diseases (IBD), which include Crohn's disease and ulcerative colitis, represent a global health issue as a prevalence of 1% is expected in the western world by the end of this decade. These diseases are associated with a high oxidative stress that induces inflammatory pathways and severely damages gut tissues. IBD patients suffer from antioxidant defenses weakening, through, for instance, an impaired activity of superoxide dismutases (SOD)—that catalyze the dismutation of superoxide—or other endogenous antioxidant enzymes including catalase and glutathione peroxidase. Manganese complexes mimicking SOD activity have shown beneficial effects on cells and murine models of IBD. However, efficient SOD mimics are often manganese complexes that can suffer from decoordination and thus inactivation in acidic stomachal pH. To improve their delivery in the gut after oral administration, two SOD mimics Mn1 and Mn1C were loaded into lactic acid bacteria that serve as delivery vectors. When orally administrated to mice suffering from a colitis, these chemically modified bacteria (CMB) showed protective effects on the global health status of mice. In addition, they have shown beneficial effects on lipocalin-2 content and intestinal permeability. Interestingly, mRNA SOD2 content in colon homogenates was significantly decreased upon mice feeding with CMB loaded with Mn1C, suggesting that the beneficial effects observed may be due to the release of the SOD mimic in the gut that complement for this enzyme. These CMB represent new efficient chemically modified antioxidant probiotics for IBD treatment.

Inflammatory bowel disease-associated serrated lesions with dysplasia are frequently associated with advanced neoplasia: supporting a unified classification approach.

Inflammatory bowel disease (IBD)-associated serrated lesions are categorized into three distinct subtypes: traditional serrated adenoma (TSA)-like lesion, sessile serrated lesion (SSL)-like lesion, and serrated lesion, not otherwise specified (NOS). Although the risk of neoplastic progression of serrated lesions without dysplasia has not been shown to exceed that of sporadic cases, the clinicopathologic features of the three serrated subtypes with dysplasia remain poorly understood in the context of IBD. We analysed 87 serrated lesions with dysplasia (collectively referred to as serrated dysplasia) identified endoscopically in 58 IBD patients, including 51 (59%) TSA-like dysplasia, 24 (28%) SSL-like dysplasia, and 12 (14%) serrated dysplasia NOS. Inclusion criteria required all three serrated subtypes to show morphologic evidence of dysplasia and to be located within areas of colitis. We also compared the clinicopathologic features of serrated dysplasia with those of 239 conventional (adenomatous) dysplastic lesions from 149 IBD patients. The cohort included 39 (67%) men and 19 (33%) women, with a mean age of 54 years and a mean IBD duration of 20 years. Most patients had ulcerative colitis (n = 41; 71%) and pancolitis (n = 48; 83%). The majority of serrated lesions with dysplasia had a polypoid or visible endoscopic appearance (n = 73; 84%), with a mean size of 1.4 cm, and were found in the left colon (n = 66; 76%). Most lesions (n = 73; 84%) demonstrated low-grade dysplasia at the time of biopsy diagnosis, whereas high-grade dysplasia (HGD) was identified in the remaining 14 (16%) lesions. SSL-like dysplasia was more frequently associated with ulcerative colitis (94%) compared to TSA-like dysplasia (67%) and serrated dysplasia NOS (56%) (P = 0.042). Although only seven (12%) patients had a concurrent history of primary sclerosing cholangitis, it was exclusively identified in the TSA-like dysplasia group (19% versus 0% in both the SSL-like dysplasia group and the serrated dysplasia NOS group; P = 0.017). Serrated dysplasia NOS more commonly demonstrated HGD at the time of biopsy diagnosis (42%) compared to TSA-like dysplasia (12%) and SSL-like dysplasia (13%) (P = 0.022). Serrated dysplasia NOS was also more frequently associated with synchronous and/or metachronous nonconventional dysplasia (60%) compared to TSA-like dysplasia (16%) and SSL-like dysplasia (9%) (P = 0.037). Serrated dysplasia, regardless of subtype, was associated with high rates of advanced neoplasia (HGD or colorectal cancer) at the previous biopsy site or in the same colonic segment during follow-up. Within a mean follow-up time of 13 months, advanced neoplasia was detected in 50% of the TSA-like dysplasia group, 67% of the SSL-like dysplasia group, and 100% of the serrated dysplasia NOS group (P = 0.622). Moreover, at least one-third of patients in each group (58% in the TSA-like dysplasia group, 44% in the SSL-like dysplasia group, and 33% in the serrated dysplasia NOS group; P = 0.332) developed synchronous/metachronous dysplasia, with at least 50% of these lesions progressing to advanced neoplasia within a mean follow-up time of 11 months (P = 1.000). The serrated dysplasia group showed nearly six times the incidence of advanced neoplasia upon follow-up (59%) compared to the conventional dysplasia group (10%) (P < 0.001). TSA-like dysplasia, SSL-like dysplasia, and serrated dysplasia NOS show distinct clinicopathologic features. However, all three serrated subtypes were associated with high rates of advanced neoplasia (50%-100%) during follow-up, suggesting that these lesions could potentially be combined into one diagnostic category, such as serrated dysplasia.

Serum extracellular RNAs as a non-invasive approach to differentiate IBD subtypes: a proof-of-concept study.

Extracellular RNAs (exRNAs) including in serum, show potential as non-invasive biomarkers. However, their (patho)physiological role is still not fully understood. In this study, we characterized serum exRNAs in patients with inflammatory bowel diseases (IBD), and evaluated their ability to differentiate ulcerative colitis (UC) from Crohn's disease (CD). We profiled serum exRNAs from 26 IBD patients (15 UC, 11 CD) with active endoscopic disease. Using Small Input Liquid Volume Extracellular RNA-sequencing, we investigated co-expression networks followed by randomized generalized linear modelling. An independent cohort (n=109 UC, n=150 CD) was studied to assess the exRNA reflection within the inflamed colonic and ileal mucosa. We detected 41,910 exRNAs, capturing 80.9% of genes expressed in intestinal tissue. Network analysis identified 69 clusters, of which one correlated with the distinction between CD and UC (r=-0.70, adjusted p=0.006), featuring GNA12 as a hub gene. Serum GNA12 showed no association with faecal calprotectin, disease duration, age or sex; but did correlate with UC-specific encoding genes (p<0.05). Modelling within this upregulated UC-cluster prioritized a signature of 8 exRNAs including GNA12, distinguishing UC from CD with an accuracy [95% CI] of 95.8% [86.7-100.0%]. This elevated 8-marker signature was mirrored in the inflamed UC colon, when compared to the inflamed CD colon and ileum, also when evaluated along the disease location spectrum (p<0.05). Liquid biopsies may represent a novel, non-invasive approach in IBD biomarker development. Although larger in-depth studies are needed, this proof-of-concept study bridges non-invasive measurements with established IBD mechanisms, offering a promising tool for accurately distinguishing CD from UC.

Development and validation of a risk prediction tool for the diagnosis of inflammatory bowel disease in patients presenting in primary care with abdominal symptoms.

Patients with Inflammatory Bowel Disease (IBD) may experience delays in their diagnosis. This study aimed to develop and validate a risk prediction tool for IBD. A retrospective cohort study was conducted using primary care data from 2010 to 2019, including symptomatic patients aged ≥18. UK-based primary care databases linked to hospital records, were utilized for model development and validation. Cox proportional hazards models were used to derive risk equations for IBD, ulcerative colitis (UC), and Crohn's disease (CD) in men and women. Candidate predictors included demographics, comorbidities, symptoms, extraintestinal manifestations, and laboratory results. Model performance was evaluated using measures of fit, discrimination, and calibration at 1, 2, 3, and 5 years after symptom onset. 2,054,530 patients were included in the derivation cohort and 673,320 in the validation cohort. In the derivation cohort, 0.7% were diagnosed with IBD (66.3% UC and 33.7% CD). Predictors in the final IBD model included age, smoking, body mass index, gastrointestinal symptoms, extraintestinal manifestations, comorbidities, family history of IBD and laboratory investigations. The model demonstrated good discrimination and calibration; C-statistic 0.78 (95%CI 0.77-0.79) in men and 0.78 (95%CI 0.77-0.79) in women. In the validation cohort the model tended to slightly overestimate IBD risk at higher risk thresholds. A risk model using patient demographics, symptoms, and laboratory results accurately predicted IBD, UC, and CD at 1, 2, 3, and 5 years after symptom onset, potentially aiding in prioritizing patients for referral or faecal calprotectin (FC) testing in primary care.

Low incidence of Varicella in Pediatric Patients with Inflammatory Bowel Disease.

Immune-modifying therapies in pediatric inflammatory bowel disease (IBD) increase infection risks, including varicella. Using Optum's de-identified Clinformatics® Data Mart Database,a nationwide U.S. commercial insurance claims database (2007-2022), we conducted a retrospective study of 5,368 IBD patients aged ≤21 years matched to a non-IBD cohort. The primary outcome was incidence of varicella. Varicella incidence was low in both groups (IBD: 0.570 vs non-IBD: 0.297 per 1,000 person-years, p=0.23). At year 4, cumulative varicella incidence was 0.27% for IBD and 0.18% for non-IBD (p=0.24). No hospitalizations or deaths occurred. Despite immune-modifying therapy, pediatric IBD patients demonstrate low varicella incidence.

Impact of Clostridioides difficile Infection on Clinical Outcomes in Hospitalized IBD Patients and the Role of Fecal Microbiota Transplantation: A Retrospective Cohort Study.

Clostridioides difficile infection (CDI) worsens the prognosis of patients with inflammatory bowel disease (IBD). This retrospective cohort study aimed to evaluate the risk factors, clinical manifestations, and outcomes of CDI in hospitalized patients with IBD, including those with toxin A/B results between April 2007 and April 2021. Patients were classified into the CDI and control groups. Patients with IBD and recurrent or refractory CDI underwent fecal microbiota transplantation (FMT). A total of 144 inpatients with IBD-45 in the CDI group and 99 in the control group-were analyzed. The incidence of CDI in inpatients with IBD was 31%. The Risk factors for CDI included longer IBD duration, biological therapy failure, and biological use. More patients in the CDI group presented with abdominal pain (77.8% vs. 55.6%, p = 0.011). In the antibiotic treatment-only group, the symptom improvement rate was 60.7% (17/28), the microbiological cure rate was 89.3% (25/28), and the overall success rate was 71.4% (20/28). After antibiotic treatment and FMT, 71.4% (10/14) of the patients tested negative for CDI, and 64.3% (9/14) had improved clinical symptoms. CDI led to more hospitalizations (median two times [range 0-12] vs. median one time [range 0-19], p = 0.008), a lower steroid-free remission rate (46.7% vs. 67.7%, p = 0.017), and higher Mayo scores (median 5 points [range 2-12] vs. median 3 points [range 0-12]). Patients who received FMT had fewer hospitalizations and fewer IBD-related complications during follow-up than those who received antibiotics alone. FMT should be considered in patients with IBD with refractory or recurrent CDI to improve clinical outcomes.

Racial Disparities In Utilization Of Medications And Disease Outcomes In Inflammatory Bowel Disease Patients

Abstract Background Although traditionally associated with White European ancestry, inflammatory bowel disease (IBD) has increased among different races and ethnicities. Large studies conducted in the United States (US) and Canada have identified more complex disease phenotypes among Black patients. Our study aimed to investigate disparities in IBD treatments and outcomes between Black and White patients in the US. Methods Using TriNetX database, adult IBD patients were divided into two groups based on race: Black and White patients with IBD, Crohn’s disease (CD) or ulcerative colitis (UC). Medical therapy and disease outcomes were evaluated in both groups with 1:1 propensity-score matching. Methodologic limitations include the potential for missing data, lack of information on socioeconomic strata, and patient-level medication coverage plans. Results In comparison to White patients, Black patients with CD were less likely to receive advanced therapies; Adalimumab (adjusted odds ratio- aOR 0.89), Certolizumab (0.81), Vedolizumab (0.66), Ustekinumab (0.82), or Tofacitinib (0.58). Black patients with UC were less likely to receive advanced therapies; Adalimumab (0.83), Golimumab (0.62), Vedolizumab (0.69), Ustekinumab (0.73) or Tofacitinib (0.55). Black patients with IBD were at higher odds of utilizing corticosteroids (CD 1.18 and UC 1.20) and opioids (CD 1.26 and UC 1.09). Black patients with CD had higher rates of hospitalization (1.35) and perianal abscess (1.56), perianal fistula (1.28) and intestinal fistula (1.38). Black patients with UC had higher rates of hospitalization (1.29), Clostridioides difficile infection (1.11), and toxic megacolon (1.34). Conclusions There were racial disparities in IBD medical therapy and disease outcomes. Black IBD patients had lower treatment with advanced therapies, higher opioid and corticosteroid use, and higher IBD-related complications.

Non-invasive monitoring of inflammatory bowel disease using intestinal ultrasound.

Intestinal ultrasound (IUS) is a safe and effective way for the diagnosis and surveillance of patients with inflammatory bowel disease (IBD). It allows a noninvasive and reproducible follow-up for patients with IBD. To compare the outcomes of colonoscopy and IUS in diagnosing and monitoring patients with IBD. A prospective study was conducted over a three-year period (January 2021 to April 2024) comparing endoscopic and IUS findings. A total of 101 patients were included in the study (68 with Crohn's disease and 33 with ulcerative colitis). All patients underwent both IUS and colonoscopy within a 10-day period. The study found a strong correlation between bowel thickening on IUS and inflammatory activity (P = 0.004), IUS remission and endoscopic remission (P = 0.03), IUS and endoscopic location (P = 0.04), as well as IUS and computed tomography scan findings for collection diagnosis (P < 0.01). The study's findings demonstrated excellent results for using IUS in the diagnosis and follow-up of IBD patients.

T cell branched glycosylation as a mediator of colitis-associated colorectal cancer progression: a potential new risk biomarker in Inflammatory Bowel Disease.

Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, established as a risk factor for Colorectal Cancer (CRC) development. Long-standing inflammation appears to play a central role in Colitis-associated Colorectal Cancer (CAC). However, the molecular mechanism underlying CAC progression is still elusive. Previous evidence showed that levels of branched glycosylation regulate T cell-mediated immune response associated with IBD severity. Here, we revealed that colonic T cells from IBD patients are dynamically regulated by branched N-glycosylation and associated with the risk of CAC development. The combined analysis of human IBD and CAC clinical samples, together with glycoengineered mouse model susceptible to CAC, revealed a gradual and dynamic increase of branched N-glycans in T cells from colitis to dysplasia and cancer. This glycosylation switch was shown to impose inhibitory properties in T cells, precluding an effective anti-tumor immune response. Mechanistically, we demonstrated that the deletion of branched N-glycans in Mgat5 KO mice led to CAC suppression due to increased infiltration of CD8+ and γδ T cells, contributing to an effective anti-tumor immune response. From the clinical standpoint, we demonstrated that branched N-glycosylation levels detected in inflamed lesions from IBD patients predicted CAC progression with a sensitivity of 83.3% and specificity of 67.9%, when assessed together with age at diagnosis. Overall, we here disclosed a new mechanism underlying CAC development, identifying a potential clinical biomarker plausible to improve the efficacy of cancer surveillance programs through the early identification of high risk IBD patients, for preventive clinical and therapeutic strategies.

Mycophenolate Mofetil for the Treatment of Resistant Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

Background: This systematic review evaluates the efficacy and safety of Mycophenolate Mofetil (MMF) for managing treatment‐resistant Inflammatory Bowel Disease (IBD), emphasizing remission rates and adverse effects. Methods: Observational and controlled trials assessing MMF’s impact on IBD were included, excluding non-English and pediatric studies. Comprehensive searches were conducted in Embase, Medline/PubMed, Scopus, and Web of Science through October 2023. The risk of bias was evaluated using the NIH quality assessment tool, and results were synthesized using a random-effects meta-analysis model. Results: Twelve studies comprising 446 participants (333 with Crohn’s disease and 113 with ulcerative colitis) were analyzed. The meta-analysis revealed remission rates of 62.2% at 8 weeks and 52.8% at 6 months. Adverse effects occurred in 26.1% of patients, with nausea and vomiting being most common. Treatment discontinuation due to failure and intolerance was observed in 29.7% and 20% of cases, respectively. Discussion: The findings suggest that MMF effectively induces remission in IBD patients unresponsive to conventional therapies, although a notable proportion experienced adverse events or treatment failure. Careful patient selection and monitoring are essential. Conclusion: MMF presents a promising alternative for managing resistant IBD, but its adverse effect profile warrants cautious application. Further research is needed to optimize dosing strategies and assess long-term outcomes in this challenging patient population. These results underscore the potential of MMF as an effective therapeutic option, while emphasizing the importance of individualized treatment plans and rigorous clinical monitoring. Future studies should focus on long-term safety, dosing. Additional robust research is required.

Dietary risk factors in Crohn's disease and ulcerative colitis: a cohort study with paired healthy relatives as controls.

Conflicting results have been reported on dietary factors in inflammatory bowel diseases (IBDs). Here, we compared the dietary intakes of IBD patients with those of paired healthy relatives (HRs), aiming to minimize the impact of genetic and environmental confounders. Patients with Crohn's disease (CD, N = 45) and ulcerative colitis (UC, N = 20), their paired HRs (NCD-HR = 45, NUC-HR = 20) and healthy non-relative (HNR, NCD-HNR = 25, NUC-HNR = 55) controls were recruited. Participants have kept dietary habits since the onset of IBDs and report no other recent digestive diseases or surgeries. Pre-illness dietary factors were assessed through 24-hour recall interviews. Statistical analyses included Analysis of Variance, Fisher's exact tests, Wilcoxon rank sum tests, logistic regressions, Area Under the Receiver-Operator Curve (AUROC) analysis, and Least Absolute Shrinkage and Selection Operator (LASSO) regression. Dietary features identified in IBD patients using the HR controls differed from those identified using the HNR controls. For CD, lower intakes of vitamin C, dietary fiber, calcium, vegetables, decanoic acid (10:0), milk, dairy foods, and β-carotene were identified as risk factors when compared to HRs. LASSO regression highlighted milk, vegetables, and vitamin C as the most significant risk factors for CD. In UC patients, lower intakes of phosphorus, docosapentaenoic acid (DPA, 22:5, n-3), vitamins B-2 and B-12, and choline, along with a higher intake of α-carotene, were identified as risk factors compared to HRs. LASSO regression emphasized DPA, vitamins B-2 and B-12, and α-carotene as the most significant risk factors for UC. Monitoring dietary intake patterns is crucial for the prevention and personalized treatment of CD and UC.

Bile acid 7α-dehydroxylating bacteria accelerate injury-induced mucosal healing in the colon.

Host-microbiome communication is frequently perturbed in gut pathologies due to microbiome dysbiosis, leading to altered production of bacterial metabolites. Among these, 7α-dehydroxylated bile acids are notably diminished in inflammatory bowel disease patients. Herein, we investigated whether restoration of 7α-dehydroxylated bile acids levels by Clostridium scindens, a human-derived 7α-dehydroxylating bacterium, can reestablish intestinal epithelium homeostasis following colon injury. Gnotobiotic and conventional mice were subjected to chemically-induced experimental colitis following administration of Clostridium scindens. Colonization enhanced the production of 7α-dehydroxylated bile acids and conferred prophylactic and therapeutic protection against colon injury through epithelial regeneration and specification. Computational analysis of human datasets confirmed defects in intestinal cell renewal and differentiation in ulcerative colitis patients while expression of genes involved in those pathways showed a robust positive correlation with 7α-dehydroxylated bile acid levels. Clostridium scindens administration could therefore be a promising biotherapeutic strategy to foster mucosal healing following colon injury by restoring bile acid homeostasis.

Is IBD Disk a Reliable Tool to Detect Depression in IBD Patients? A Comparison with Becks’ Depression Inventory

Background: Disability and poor quality of life are frequently reported by patients with inflammatory bowel diseases (IBDs). There is an increased interest in the use and development of self-administered questionnaires of patient-reported outcomes including depression symptoms, potentially allowing easier and even remote monitoring of health status and permitting treatment adjustments. Aim: We noticed a significant overlap in some of the parameters evaluated by Beck’s Depression Inventory and the IBD Disk, which led to the idea that the IBD Disk might be a useful and easy-to-use tool to assess the mental state and quality of life of patients with IBD. Our objective was to validate the IBD Disk in measuring depression symptoms, as well as the correlation between IBD Disk scores and patient background and disease activity. Methods: Patients included in this study were asked to complete Beck’s Depression Inventory (BDI) and the IBD Disk. The resulting scores of BDI and IBD Disk were compared and both questionnaires were corelated with the patients’ background and disease activity. Results: Eighty-two patients with IBD, age 43.11 +/− 13.07, 63.4% male, 61.0% with Crohn’s disease and 39.0% with Ulcerative Colitis, were included. The total scores of BDI and IBD Disk significantly correlated (rs(80) = 0.951, p &lt; 0.001), as well as the overlapping questions. Disease remission was associated with lower total scores in both questionnaires (BDI and IBD Disk) (rs(80) = 0.559, p &lt; 0.016; rs(80) = 0.951, p &lt; 0.005, respectively). Conclusions: Our findings suggest that IBD Disk is a useful and easy-to-use tool for screening for depression symptoms and establishing the quality of life of IBD patients. We encourage its routine use in patients during IBD care and follow-up.

Genetic Polymorphisms on TNFA, TNFRSF1A, and TNFRSF1B Genes Predict the Effectiveness of Anti-TNF-α Treatment in Inflammatory Bowel Disease Patients

Background/Objectives: Tumor necrosis factor alpha (TNF-α) is the key inflammatory cytokine involved in the pathogenesis of inflammatory bowel diseases (IBDs). Anti-TNF-α therapy has been successfully used for IBD treatment, although the therapeutic response differs among patients due to the genetic background. The aim of this study was to investigate whether the presence of single nucleotide polymorphisms (SNPs) on TNFA, TNFRSF1A, and TNFRSF1B genes could affect anti-TNF-α treatment effectiveness in IBD patients. Methods: In this prospective cohort study, 83 European IBD patients treated with infliximab or adalimumab (with or without steroid bridge therapy) as first-line therapy were enrolled. Genomic DNA was extracted from peripheral blood, and TNF-α (rs1800629, rs361525, rs1799724), TNFRSF1A (rs767455), and TNFRSF1B (rs1061622, rs1061624, rs3397, rs976881) SNPs were assessed. Steroid-free remission (SFR) (clinical remission together with steroid interruption) and anti-TNF-α therapy persistence after 12 months of follow-up were evaluated. Patients who stopped anti-TNF-α therapy before the end of follow-up, due to side effects or treatment failure, were defined as discontinuers. Results: A higher frequency of the G/G genotype in rs1800629 and the A/A genotype in rs1061624 was observed in the SFR group compared to non-SFR (97.7% vs. 82.8%; p = 0.025 and 32.6% vs. 10.3%; p = 0.029, respectively). Moreover, carriers of the A/A genotype in rs361525 and the C/C genotype in rs767455 had a lower probability of achieving SFR than wild-type patients (OR = 0.14; 95% CI= 0.03–0.69; p = 0.016 and OR = 0.10; 95% CI = 0.02–0.60; p = 0.012, respectively). Furthermore, an increased frequency of rs1800629 A allele was observed in patients who discontinued treatment compared to completers (27.3% vs. 6.9%; p = 0.033), as well as a high risk of interrupting therapy (HR = 6.47; 95% CI = 1.15–36.38). Conclusions: These results suggest that the evaluation of SNPs in TNF-α, TNFR1A, and TNFR1B genes could improve the management of IBD, leading to more effective, individualized treatment plans and a reduction in healthcare costs associated with ineffective therapies and disease complications.

Risk Factor Analysis and Prevalence of Infectious Agents in Inflammatory Bowel Disease Flares: A Retrospective Study

Background: Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a chronic relapsing-remitting disorder with a rising global incidence. Infectious agents, particularly Clostridium difficile, are frequently considered during IBD flares. However, the role of other infectious agents during these exacerbations remains unclear. Objectives: The objective of the current study was to assess the prevalence of infectious agents, including C. difficile, in stool samples of patients with IBD flares and to assess potential risk factors. Methods: A retrospective review was conducted on medical records of IBD patients admitted for flare-ups at Mount Sinai Hospital, Toronto, from October 2018 to August 2019. Stool testing, including cultures, ova, parasites, and C. difficile, was analyzed. Demographic and clinical data were collected, and chi-square tests were used for statistical analysis. Results: A total of 96 patients (51 CD, 43 UC, 2 IBD-U) were included. Nine patients (9%) tested positive for C. difficile. No other bacterial or parasitic infections were detected. Testing for Cytomegalovirus was performed in 33 patients, with no positive cases. Risk factors, including IBD phenotype, biologic or steroid therapy, and prior antibiotic use, showed no significant association with C. difficile infection. Conclusions: Clostridium difficile was the predominant infectious agent in IBD flares, while other bacterial and parasitic infections were rare. Routine stool testing, particularly for non-C. difficile pathogens, has a low diagnostic yield in this population. Further studies with larger, generalized cohorts are needed to explore these associations and identify risk factors for infectious colitis in IBD patients.

Strengths, weaknesses, opportunities, and threats analysis of combination therapy for inflammatory bowel disease

Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, manifests as a chronic, recurrent, and refractory intestinal inflammatory condition significantly impacting patients’ quality of life. Despite ongoing research, its etiology and pathogenesis remain incompletely understood. Recent advancements in medical research highlight the critical role of drug combination therapies in managing IBD. This paper employs the strengths, weaknesses, opportunities, and threats framework to evaluate the four strategic elements (strengths, weaknesses, opportunities, and threats) pertaining to combination therapies for IBD. Among the strengths, the paper underscores the efficacy of multi-targeted strategies, the advancement of personalized medicine, and the mitigation of drug resistance. Nonetheless, the analysis identifies significant weaknesses, including the prohibitive cost of treatment, issues with patient compliance, and the necessity for comprehensive long-term safety data. The paper also delineates opportunities to augment therapeutic success through the incorporation of biomarkers, the application of artificial intelligence, and extensive international collaborative efforts. In contrast, the paper does not shy away from addressing the threats, which include the potential for therapeutic resistance and the logistical challenges inherent in global therapy deployment. These initiatives aim to refine future therapeutic practices, fostering safer, more effective, and personalized treatment paradigms for IBD patients.