Search Results (669)

Frailty is a complex syndrome characterized by a gradual decline in physical ability and a higher sensitivity to external stress. While it has traditionally been linked to aging, frailty is increasingly seen as an important factor affecting the health of patients with inflammatory bowel disease (IBD). IBD mainly affects the gastrointestinal tract but is often associated with systemic manifestations, such as extra-intestinal symptoms/signs, malnutrition, muscle loss, and other health problems, all of which could contribute to frailty. There are various tools to assess frailty in IBD patients, even though it is often not recognized or evaluated well in standard clinical practice. Recent evidence indicates that frailty in IBD may be partly driven by ongoing inflammation and is an independent predictor of negative health outcomes (e.g., hospitalization rates, surgical complications, and mortality). Proper management of frailty in IBD needs a broad, team-based approach that focuses on controlling disease symptoms, improving nutrition, physical abilities, and managing other comorbidities. This review aims to give a clear overview of the causes, clinical evaluation, and treatment options for frailty in IBD, emphasizing the need for early detection and intervention. Full article

Objective: To evaluate parental attitudes towards vaccination in children with inflammatory bowel disease (IBD), assess the level of adherence to immunization schedules, and identify key barriers hindering vaccination. Materials and Methods: A comparative survey was conducted involving 215 respondents, divided into an IBD group (109 parents of children with IBD) and a control group (106 parents of healthy children). The majority of respondents were mothers (96%) with higher education (81% and 79%, respectively) residing in a major metropolitan area. We assessed demographic data, vaccination history of both children and parents, sources of medical information, and reasons for vaccine refusal. Results: Routine vaccination coverage in children under 6 years of age was high and comparable in both groups (>93%). The majority of parents in the IBD group (n = 68; 62%) expressed a positive attitude towards vaccination. However, following the onset of IBD, only 24 (22%) continued vaccination, while 85 (78%) reported a categorical refusal to continue immunization. It was found that parents tend to misinterpret normal post-vaccination reactions as vaccine complications. A significant factor contributing to refusal is the lack of information from attending physicians and reliance on the Internet as a primary information source. Additionally, low rates of adult revaccination were noted, with over 30% of parents in both groups not being vaccinated in adulthood. Conclusions: The low vaccination rate in children with IBD after disease onset is driven not by initial anti-vaccination sentiment, but by acquired fears and a lack of professional communication from primary care providers and specialists. Improving immunization coverage requires the active implementation of educational programs for parents regarding vaccine safety during immunosuppressive therapy, as well as the development of specific guidelines for attending physicians. Full article

IBD pathogenesis is underpinned by an imbalance between excess inflammation caused by effector T-cells and inadequate suppression by regulatory T-cells (Tregs). Interleukin-37 (IL-37) is a potent, anti-inflammatory cytokine that signals via its receptors IL-1R5 and IL-1R8. Hence, augmenting anti-inflammatory mechanisms that drive IL-37 expression is a strategy to control IBD-associated inflammation. However, the role of IL-37 and its receptors in T-cells remains incompletely understood. Here, we investigated T-cell expression profiles of IL-37 and its receptors to understand the drivers of dysregulated T-cell responses in IBD and develop novel, more effective therapies. T-cell subsets from healthy control (HC), Crohn’s disease (CD) and ulcerative colitis (UC) peripheral blood mononuclear cells (PBMC) and lamina propria mononuclear cells (LPMC) were assessed for expression of IL-37 and its receptors by flow cytometry. CD3+IL-1R8+ T-cell transcriptomes underwent RNA sequencing. The phenotype and suppressive capacity of Tregs supplemented with IL-37 was assessed in vitro. Our results indicate that IL-37 and its receptors were differentially expressed among PBMC and LPMC T-cell subsets in IBD patients compared to HC. Transcription signatures unique to IBD were revealed, particularly histone and mitochondrial pathways. Remarkably, culturing Tregs with IL-37 preserved FOXP3 expression and suppressiveness at a level comparable to treatment with the well-established Treg stabilizing agent rapamycin. Altogether, our study identified differences in T-cells expressing IL-37 and its receptors that are indicative of T-cell dysfunction in IBD. These findings highlight a novel and promising avenue for restoring immune homeostasis in IBD by targeting and boosting the IL-37 signalling pathway. Full article

Beta-glucans are immunomodulatory compounds known to act as adjuvants in the beneficial regulation of various allergic conditions, particularly atopic dermatitis, as well as in the modulation of dysbiosis in patients with chronic gastrointestinal disorders. However, certain underlying conditions, such as inflammatory bowel disease (IBD) and the associated loss of oral tolerance, may alter the expected outcomes of supplementation and lead to dysregulated immune responses. This study reports cases of cutaneous allergic reactions in dogs with IBD following the oral administration of yeast-derived beta-glucan. Two dogs with controlled IBD received 9.13 ± 1.14 mg/kg of beta-glucan in a double-blind study designed to investigate its effects on the intestinal microbiota in IBD. Both animals were withdrawn from the study due to adverse effects, including cutaneous allergic manifestations and intense pruritus. These findings suggest that patients with impaired oral tolerance may develop cutaneous reactions following the ingestion of yeast-derived prebiotics. Full article

Background: The efficacy of upadacitinib in patients with Crohn’s disease (CD) has been shown in pivotal randomized controlled trials. However, real-world data is needed to assess its effectiveness and safety in routine clinical care with biologic-experienced patients. This study aimed to evaluate the clinical and endoscopic efficacy, patient-reported outcomes (PROs), and safety of upadacitinib in biologic-experienced patients with CD in a real-world setting. Methods: This prospective bi-centric real-world study enrolled 28 anti-TNF-experienced patients with CD receiving upadacitinib 45 mg daily for 12 weeks (induction), followed by 30 mg daily maintenance through week 52. Primary endpoints included endoscopic response (≥50% SES-CD reduction or ≥2-point decrease from baseline for baseline SES-CD ≤ 4) and clinical remission (Harvey–Bradshaw Index [HBI] ≤ 4). Secondary endpoints included endoscopic remission, clinical response (HBI decrease ≥ 3 points), and quality of life (IBD-Disk). Statistical analysis used the Wilcoxon signed-rank test with 95% confidence intervals (CIs). Results: Median patient age was 37 years; 75% had ≥3 prior biologic failures. Clinical remission rates (HBI) were 59% (95% CI: 41–75%) at week 12, 44% (95% CI: 27–63%) at week 26, and 53% (95% CI: 29–76%) at week 52. Endoscopic response rates were 48% (95% CI: 44–52%) at week 26 and 46% (95% CI: 21–72%) at week 52. Endoscopic remission was achieved in 43% (95% CI: 40–48%) at week 26 and 27% (95% CI: 10–57%) at week 52. Clinical response (HBI) improved progressively from 65% at week 2 to 71% at week 52. Quality of life, as assessed by the IBD-Disk, showed significant improvement: Reduced Disease Burden (defined as a decrease of 70% or a CED-Disk Score of ≤15) was observed in 33% of patients at week 12 and 35% at week 52. Median SES-CD decreased from 9 points (IQR: 6–17) at baseline to 5 points (IQR: 1–12, p = 0.005) at week 52. Adverse events occurred in 11% of patients (4% lymphopenia, 7% skin disease), with no serious adverse events or deaths. Conclusions: Upadacitinib demonstrates significant clinical and endoscopic efficacy in biologic-experienced, anti-TNF-pretreated patients with CD, achieving remission rates comparable to or exceeding those of the pivotal trials despite a highly refractory population (75% with ≥3 prior biologic failures). The favorable safety profile supports upadacitinib as an important therapeutic option in sequential treatment of refractory CD. Full article

Background/Objectives: The incidence of inflammatory bowel disease (IBD) is rising worldwide, particularly in Asia, while the highest prevalence remains in North America and Europe. Evidence on the relationship between IBD and the development of autoimmune thyroiditis is limited. This study investigated the association between IBD and a subsequent autoimmune thyroiditis in a large German primary care cohort over a 10-year period. Methods: Patients with IBD were propensity score matched to non-IBD individuals in a 1:5 ratio based on age, sex, index year, and average annual number of physician visits during follow-up. A total of 20,084 IBD patients—including 8791 with Crohn’s disease and 11,293 with ulcerative colitis—and 100,420 matched controls were included. The primary outcome was the cumulative incidence of autoimmune thyroiditis, including Hashimoto’s thyroiditis and Graves’ disease. The association between IBD and autoimmune thyroiditis was evaluated using univariable conditional Cox regression analysis. Results: In the overall cohort, no significant association was found between IBD (Crohn’s disease or ulcerative colitis) and autoimmune thyroiditis (Hashimoto’s or Graves’ disease). However, among patients aged ≥ 65 years, IBD was associated with a significantly increased risk of Graves’ disease (HR 2.83; 95% CI 1.56–5.15), an effect observed in both Crohn’s disease (HR 3.23; 95% CI 1.20–8.69) and ulcerative colitis (HR 2.64; 95% CI 1.25–5.60). Conclusions: While IBD was not associated with autoimmune thyroiditis overall, a significant positive association with Graves’ disease was observed among patients aged ≥ 65 years, highlighting the importance of age-specific risk assessment. Full article

Background/Objectives: Tumor necrosis factor alpha (TNF-alpha) plays a key role in systemic inflammation in multiple disorders, including inflammatory bowel diseases (IBDs). Our purpose was to investigate the contribution of two promoter single-nucleotide polymorphisms (rs361525/–238G/A and rs1800629/–308G/A) to disease susceptibility, clinical features, and response to biologic therapy in a cohort of Romanian patients with IBDs. Methods: A total of 198 patients with IBDs, 106 with Crohn’s disease (CD) and 92 with ulcerative colitis (UC), as well as 160 healthy controls, all Caucasians of Romanian origin, were genotyped using TaqMan Allelic Discrimination Assays. Phenotypical and anti-TNF treatment characteristics of the patients with IBDs were recorded. Statistical analyses were performed using OpenEpi and PLINK v1.07 software. Results: We found a significantly higher frequency of the minor allele A of rs361525 in patients with CD than in the controls (6.6% vs. 2.2%, p = 0.01, OR = 3.16). Half of the patients with extraintestinal manifestations (EIMs) had at least one copy of the rs1800629 A allele compared with approximately 10% of patients without EIM (p = 1 × 10⁻⁴, OR 9.58 for UC and p = 9 × 10⁻⁴, OR 6.60 for CD). In the whole IBD group of patients, the carriers of the minor allele (AA+GA) for both SNPs studied (rs1800629 and rs361525) were significantly more likely to have EIM associated with IBDs (p = 3 × 10⁻⁷, OR 7.87; p = 0.03, OR 3.02, respectively). In patients with UC, the analysis according to disease extension revealed that the frequency of the minor allele of rs1800629 was significantly higher in the subgroup with the E2 phenotype compared to the E1 and E3 phenotypes (16.6% versus 5.6%, p = 0.02, OR 3.32). Conclusions: These findings highlight the role of genetic TNF-alpha variants in disease susceptibility, phenotype, and systemic involvement, supporting their potential relevance in understanding IBD heterogeneity. Full article

Inflammatory bowel disease (IBD) is associated with an increased risk of venous thromboembolic events (VTEs) and a moderate risk of arterial cardiovascular events. This varies with inflammatory activity and acute-care exposure, with pathophysiological data supporting a thromboinflammatory phenotype in which intestinal inflammation influences systemic vascular homeostasis through innate immune activation, coagulation–platelet crosstalk, endothelial dysfunction, impaired fibrinolysis, and immunothrombosis. Clinically, prevention and management should be integrated into routine care and anchored in sustained, steroid-sparing disease control, combined with guideline-based in-hospital thromboprophylaxis and standard cardiovascular prevention. Decisions regarding anticoagulant therapy after VTEs should follow established principles while recognizing that recurrence prevention depends not only on anticoagulant choice but also on minimizing repeated inflammatory and treatment-related risk exposures. Cardiovascular risk assessment and optimization of modifiable factors should be considered before therapy escalation or treatment switching. Future advances will likely come from more personalized risk assessment across dynamic high-risk windows and from adjunctive, mechanism-informed strategies targeting key nodes of the gut–vascular interface and immunothrombosis. Full article

Background/Objectives: Differential diagnosis between Crohn’s disease (CD) and ulcerative colitis (UC) can be sometimes difficult resulting in the diagnosis of unspecified inflammatory bowel diseases (IBD-U). Data suggest that IgG antibodies against integrin αvβ6 (V6 Ab) help to identify UC patients. Recent studies suggest that measuring V6 Ab serum levels may be valuable for differential diagnostic purposes. The primary objective of the study was to assess the sensitivity and specificity of V6 Ab serum-level measurement in our IBD population to differentiate between colonic/ileocolonic CD and UC with an established diagnosis. Furthermore, we assessed the correlation between disease characteristics, activity and V6 Ab serum levels in UC patients. Methods: Consecutive IBD patients with an established diagnosis undergoing control colonoscopy in a tertiary IBD center were included. Baseline demographic data, current treatment, disease extent, clinical, biomarker, endoscopic and histologic disease activity were collected. V6 Ab serum levels were measured with the Anti-Integrin αvβ6 ELISA Kit (RUO). Patients’ written informed consent was obtained. Results: A total of 40 IBD patients, including 10 CD and 30 UC patients (15 with clinical activity and 15 in clinical remission) were enrolled. V6 Ab serum levels were significantly higher in UC patients compared to CD (p = 0.039). ROC analysis found 1.33 U/mL to be the best cut-off level (p = 0.04; AUC: 0.71) with 100% sensitivity and 50% specificity and a positive predictive value of 85.7% and a negative predictive value of 100% to differentiate between UC and CD. No significant correlation was found between V6 Ab serum levels and CRP (p = 0.057), fecal calprotectin (p = 0.77), endoscopic activity (p = 0.624) or disease extent (p = 0.624) in UC patients. Conclusions: Our study supports the value of V6 Ab serum level measurement as a differential diagnostic tool in IBD patients; however, the optimal cut-off value is yet to be determined. Our data do not support its role in disease activity monitoring. Full article

Introduction: The proportion of elderly patients with IBD is steadily increasing due to the aging population and improved survival. Patients in this age group present specificities in diagnosis and treatment, particularly regarding the use of biological agents, where immunosenescence, multimorbidity, and polypharmacy affect the precise assessment of benefit and risk. Aim: This systematic review, which was conducted in accordance with the PRISMA 2020 statement, aims to synthesize available data on the epidemiology, clinical characteristics, and therapeutic management of IBD in the elderly, with emphasis on the most recent data and practical guidelines for the use of biological therapies. Methods: A systematic search of PubMed, Scopus, and Embase was conducted. A total of 40 studies were included, comprising 5 randomized controlled trials, 15 prospective cohort studies, and 20 retrospective observational studies. Eligible studies included randomized controlled trials, observational cohort studies, and population-based analyses. Given substantial clinical and methodological heterogeneity, findings were synthesized narratively. Data on demographics, disease phenotype, comorbidities, and treatment outcomes were extracted and analyzed. In addition, a narrative synthesis of major randomized trials of biologic therapies, recent guidelines, and data from prospective studies and patient registries was performed with a focus on safety and real-world outcomes in the elderly. Risk of bias was assessed using the Newcastle–Ottawa Scale (NOS) and the Cochrane Risk of Bias tool. Results: The majority of included studies (85%) were found to have a low to moderate risk of bias, providing a reliable basis for the synthesis. Data show an increasing incidence of IBD in the elderly, often with a milder clinical course and a higher ratio of UC to CD. Multimorbidity and polypharmacy are significant challenges that increase the risk of adverse events. Although classic therapies remain effective, in many cases, a lower threshold is required to initiate advanced therapies, such as biologic agents. Anti-tumor necrosis factor (anti-TNF) agents, as well as biologics with alternative mechanisms of action such as vedolizumab (α4β7 integrin antagonist) and ustekinumab (interleukin-12/23 inhibitor), represent key therapeutic options in elderly patients with IBD. These biologic factors have efficacy comparable to that in younger patients and are considered attractive options due to reduced systemic immunosuppression and favorable safety profiles. JAK inhibitors are a practical option but are associated with an increased thromboembolic risk and require careful patient selection. Older age is associated with higher absolute rates of serious infections, hospitalizations, and, in some series, mortality. Individualized decision-making, including frailty assessment, vaccination coverage, infection control, and dose adjustments based on renal and hepatic function, is essential for optimal care. Conclusions: IBD in the elderly is a distinct clinical entity with unique challenges in diagnosis and management. A multidisciplinary approach and individualized treatment strategies are essential to ensure the balance between disease control and minimizing the risks associated with comorbidity and polypharmacy. Further research, including specifically designed clinical trials, is needed to optimize treatment and outcomes in this unique patient group. Full article

Background: Pediatric inflammatory bowel disease (pIBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is characterized by chronic intestinal inflammation and fibrosis. Identifying molecular mediators involved in inflammation and tissue repair is critical for improving disease management. Objective: To examine the expression of periostin, TGF-β, and SLUG in pIBD and assess their potential roles in intestinal inflammation, fibrosis, and mucosal healing. Methods: Intestinal biopsies from 33 pediatric patients (11 CD, 22 UC) and 10 healthy controls were analyzed immunohistochemically. Quantitative PCR evaluated POSTN, TGF-β1, and SNAI2 expression in 22 patients and 6 controls. Correlations with fecal calprotectin, the Pediatric Crohn’s Disease Activity Index (PCDAI), and the Pediatric Ulcerative Colitis Activity Index (PUCAI) were determined. Results: Periostin, TGF-β, and SLUG expression were significantly increased in pIBD compared with controls. Periostin levels were higher in CD than in UC. All markers correlated positively at mRNA and protein levels. Notably, periostin showed an inverse correlation with fecal calprotectin and PCDAI scores. Conclusions: Periostin, TGF-β, and SLUG may represent biomarkers of pIBD activity. Periostin appears to mediate inflammation and promote mucosal fibrosis or repair, and its inverse association with disease activity suggests a potential therapeutic role in pIBD. Full article

Background: Vedolizumab and ustekinumab are increasingly used off-label in pediatric inflammatory bowel disease (IBD) unresponsive or refractory to anti–TNFα therapy. Despite their increasing use in clinical practice, evidence in the pediatric population remains limited, especially regarding therapeutic exposure thresholds and the clinical utility of therapeutic drug monitoring (TDM). Methods: We report a series of five pediatric cases with Crohn’s disease or ulcerative colitis treated with ustekinumab or vedolizumab after anti-TNFα failure. Trough drug concentrations, anti-drug antibodies (ADAs), clinical scores (PCDAI/PUCAI), biomarkers (fecal calprotectin, C-reactive protein), and endoscopic findings were assessed longitudinally. Results: In all cases, we observed recurrent discordance between clinical indices (PCDAI/PUCAI), biochemical markers, and endoscopic activity. Clinical improvement frequently correlated with trough concentrations above commonly cited adult-derived reference ranges (>15 µg/mL for vedolizumab; >3 µg/mL for ustekinumab), although this alignment was not uniform across patients. Notably, one patient developed high-titre ADAs with undetectable ustekinumab levels, yet remained clinically stable, suggesting substantial interindividual variability in pharmacokinetics, immunogenicity, and disease control. Conclusions: Ustekinumab and vedolizumab are promising off-label options for pediatric refractory IBD. In this case series, TDM contributed to the interpretation of pharmacokinetic variability and immunogenicity, offering contextual insights that may support dose adjustments and therapeutic decision-making. Integrating TDM with clinical, biochemical, and endoscopic monitoring may improve optimize individualized treatment in this complex and vulnerable patient group. Full article

Background: Female individuals with inflammatory bowel diseases (IBDs) are more likely to develop restrictive eating disorders (REDs), with both conditions appearing to share common pathophysiological pathways. We conducted a case–control study exploring eating symptomatology and interoceptive profiles in female adolescents with IBDs compared with adolescents diagnosed with REDs, in order to test the hypothesis that the two clinical populations exhibit similar interoceptive characteristics. Methods: We recruited 33 female adolescents with IBDs and 54 controls with REDs matched for age and gender. All participants completed a validated psychometric battery assessing eating disorder features (EDI-3) and interoceptive awareness (MAIA-2). Results: Twenty-seven percent of patients with IBD scored above the cut-off (>70th percentile) on the EDI-3 Eating Disorder Risk Composite (EDRC), showing an eating and interoceptive profile comparable to that of patients with REDs. The two sub-cohorts within the IBD sample differed in the ‘Not-Worrying’ and ‘Trusting’ MAIA-2 subscales, with the IBD cohort at risk of developing an ED reporting lower scores. Conclusions: Our findings indicate comparable interoceptive profiles between adolescents with IBDs who are at risk of developing EDs and patients with a confirmed diagnosis of REDs. This similarity underscores the need to further investigate the shared pathogenic mechanisms underlying these conditions, particularly the role of the gut–brain axis (GBA). Full article

Background: Liver X receptors (LXRs) are critical regulators of cholesterol homeostasis that modulate T cell function with anti-inflammatory effects. LXR downregulation has been implicated in the pathogenesis of inflammatory bowel disease (IBD), although its underlying mechanisms remain to be fully elucidated. Recent evidence has confirmed the link between T cell senescence and autoimmune diseases. Here, we sought to investigate whether and how LXRs regulate T cell senescence in controlling intestinal inflammation. Methods and Results: We found that LXRβ expression was decreased in the colons of mice with experimental colitis, and LXRβ deficiency (Lxrβ^−/−) significantly aggravated their colitis. Intriguingly, this finding was accompanied by enhanced CD4⁺ T cell senescence both in the colons and spleens of Lxrβ^−/− mice, evidenced by upregulation of SA-β-gal levels and the remarkable expansion of effector memory subclusters in CD4⁺ T cells. Moreover, senescent Lxrβ^−/− CD4⁺ T cells secreted elevated levels of proinflammatory cytokines, especially in effector memory populations, exhibiting a pronounced proinflammatory phenotype. RNA-sequencing further confirmed the role of LXRβ in restricting CD4⁺ T cell senescence. Mechanistically, the absence of LXRβ in CD4⁺ T cells directly enhanced senescence by promoting the cGAS/STING pathway. Blocking STING signaling with a targeted inhibitor significantly alleviated senescence in Lxrβ^−/− CD4⁺ T cells. Conclusions: Our findings demonstrate the role of LXRβ in regulating intestinal CD4⁺ T cell senescence to inhibit colitis development, identifying LXRβ as a potential therapeutic target for treating IBD. Full article

Inflammatory Bowel Diseases (IBD), most notably ulcerative colitis (UC) and Crohn’s disease (CD), are long-standing disorders driven by dysregulated immune responses within the gastrointestinal tract and characterized by several metabolic disturbances, which are believed to influence disease progression. We have recently shown that a systemic deficiency of taurine, a semi-essential amino acid with anti-inflammatory properties, marks IBD. To characterize the temporal dynamics and determinants of taurine deficiency in IBD, we conducted a prospective longitudinal study assessing serum taurine levels in a cohort of 47 patients with IBD compared with 33 healthy controls. Serum taurine concentrations were measured at baseline and after a median follow-up period of 45 months using ELISA. Patients were stratified by disease subtype (UC and CD), age group, and clinical activity status at baseline and follow-up. Serum taurine levels were significantly lower in IBD patients at both baseline and the end of follow-up (p < 0.05), and remained stable over time within the CD and UC cohorts. In healthy individuals, but not in IBD patients, taurine concentrations declined with age, suggesting that age-related metabolic regulation of taurine is altered in the context of chronic intestinal inflammation. Stratification by disease activity revealed that taurine deficiency was present in both active and inactive IBD, particularly among younger patients, and differences between active and inactive disease were minimal. These findings indicate that the persistent reduction in serum taurine in IBD is independent of age, disease subtype, or clinical activity, and remains relatively constant over time across most patient subgroups, suggesting an underlying alteration in taurine metabolism or homeostasis associated with IBD pathophysiology. Further investigation is needed to elucidate the mechanisms linking taurine dysregulation to IBD progression. Full article