Search Results (2,340)

Introduction: Chronic inflammation in Crohn’s disease (CD) is associated with systemic alterations, including the loss of skeletal muscle mass. While nutritional deficits are known to impact clinical trajectories, the specific prognostic value of muscle wasting remains underutilised. The primary objective of this study is to construct a composite score integrating sarcopenia with paraclinical parameters to predict an unfavourable disease outcome (UO) more accurately. Materials and Methods: We conducted a retrospective study of patients with CD who were hospitalized at our institution between January 2020 and June 2024 and were treated with biologics or small molecules. Using previous CT scans, we measured skeletal muscle area (SMA) and skeletal muscle index (SMI) to assess their association with disease outcomes. Univariate and multivariate analyses were performed to identify significant predictors of UO, and Area Under the Curve (AUC) values were calculated to assess the predictive performance and to construct a composite prognostic score. Results: Multivariate analysis in the study group (52 patients) identified sarcopenia (low SMI), faecal calprotectin levels >129 μg/g, and complicated disease behaviour (Montreal B2/B3) as independent predictors of UO. Integrating these parameters into a composite risk score resulted in a promising predictive model with an Area Under the Curve (AUROC) of 0.864, significantly outperforming individual biomarkers. Conclusions: We performed a hypothesis-generating study suggesting that nutritional assessment in CD could provide an important benefit in stratifying patients for whom additional nutritional interventions may enhance the long-term outcomes. Full article

Background/Objectives: Although the exact etiology of Inflammatory Bowel Diseases (IBD) is not yet fully understood, recent evidence suggests that both genetic and dietary factors are involved in their pathogenesis. The aim of the present exploratory study was to investigate how first-degree relatives (FDRs) of individuals with IBD perceive familial risk and the role of diet in IBD onset and prevention. Methods: A mixed methods approach was followed. A total of 103 unaffected FDRs of individuals living with IBD in Greece participated in an online questionnaire examining demographic characteristics, disease-related knowledge, risk perception, and beliefs about the role of diet in IBD. In parallel, 16 semi-structured interviews explored participants’ beliefs, self-reported dietary practices, and the factors shaping them using a framework analysis guided by the Health Belief Model. Results: Exploratory quantitative findings indicated that belief in the role of diet was associated with higher odds of self-reported family dietary changes, while belief in genetic risk was associated with lower odds of self-reported family dietary changes. The findings did not characterize the nature, maintenance, or motivation of these changes. Qualitative findings provided a deeper understanding of participants’ beliefs, highlighting that diet was mainly viewed as relevant to IBD management rather than prevention. Fear of disease onset and healthcare professional guidance were perceived as key facilitators of dietary changes. Conclusions: Our findings highlight heterogeneous beliefs regarding familial IBD risk and self-reported family diet changes, and support future research addressing balanced familial-risk communication for unaffected FDRs. Full article

Background/Objectives: The C-reactive protein-to-albumin ratio (CAR) is an emerging biomarker of disease activity in adult inflammatory bowel disease; pediatric data remain limited. We evaluated CAR in pediatric Crohn’s disease (CD) versus ulcerative colitis (UC). Methods: We retrospectively reviewed 97 consecutive pediatric patients (79 CD, 18 UC) diagnosed at a single center between 2012 and 2023. Results: CAR was higher in CD (median 10.06) than UC (0.49; p < 0.001). In CD, CAR correlated with erythrocyte sedimentation rate, fecal calprotectin, and clinical and endoscopic disease activity (all p < 0.05), differed across severity categories (p = 0.001 clinical, p = 0.003 endoscopic), and was higher without perianal disease (p = 0.005); the corresponding analyses in UC (n = 18) were underpowered and did not reach significance. Receiver operating characteristic analysis yielded an area under the curve (AUC) of 0.840 (cut-off 1.62; sensitivity 86.1%, specificity 72.2%), not exceeding that of CRP alone (AUC 0.851; DeLong p = 0.090). CAR decreased significantly from diagnosis to one-year follow-up in both remission and relapse groups (both p < 0.001). Conclusions: CAR reflects disease severity in pediatric CD and responds to treatment, but did not outperform CRP alone for distinguishing CD from UC. Its plausible value lies in activity assessment and serial monitoring rather than in diagnostic discrimination, a hypothesis that the present design cannot test. Full article

Background: Patients with inflammatory bowel disease (IBD) often follow restrictive diets. Data on dietary habits and beliefs in pediatric IBD are scarce. Our aim was to assess dietary habits, beliefs, and knowledge regarding nutrition and IBD among children with IBD. Method: In this single-center, cross-sectional study, pediatric patients aged 12–18 years with IBD completed a non-scoring, 25-item questionnaire assessing general dietary habits, beliefs about diet’s role in IBD pathogenesis and treatment, food avoidance, and food-related experiences since diagnosis. Results: We included 72 IBD patients (mean age [SD]: 15.2 [2.3] years; 41 (57%) were male, 32 (45%) had Crohn’s disease (CD)). Almost half of the participants did not believe that eating habits contributed to the pathogenesis of IBD. One-third of patients considered diet to be more important than medication. Approximately two-thirds changed their eating habits after diagnosis, regardless of disease type (χ²: 0.70, p = 0.40), or induction therapy (nutritional vs. non-nutritional, χ²: 0.02, p = 0.88). At least one food was avoided by 65% of the participants. Conclusions: Most children have changed their dietary habits and avoided one or more food groups. The type of induction therapy did not relate to the knowledge and dietary beliefs after induction. Our findings suggest that repeated education and dietary counseling should be an integral part of the management of pediatric IBD. Full article

Background and aim: Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract resulting from a complex interplay among genetic susceptibility, immune dysregulation, environmental factors, and alterations in the gut microbiota. Among these, diet has emerged as a key modifiable factor influencing intestinal inflammation, barrier integrity, and disease progression. This review aims to critically evaluate the role of dietary patterns and food additives in the pathogenesis and management of Crohn’s disease, with particular emphasis on their effects on intestinal inflammation, epithelial barrier function, and host–microbiota interactions. Methods: A comprehensive literature search was conducted using the PubMed, Scopus, and Web of Science databases up to March 2026. Clinical trials, observational studies, and mechanistic research were included based on their relevance to dietary factors, food additives, and intestinal inflammation in CD. Evidence was synthesized narratively to integrate clinical and experimental findings. Results: Dietary interventions such as the Crohn’s disease exclusion diet (CDED), specific carbohydrate diet (SCD), low-FODMAP diet, and Mediterranean diet (MD) demonstrate varying degrees of efficacy in improving clinical symptoms and, in some cases, inflammatory markers. In contrast, high consumption of ultra-processed foods is consistently associated with increased disease risk and activity. Emerging evidence highlights the role of food additives—particularly emulsifiers and artificial sweeteners—in disrupting gut barrier integrity, promoting dysbiosis, and enhancing inflammatory responses. Recent human studies further suggest that exposure to these compounds may correlate with disease activity, supporting their potential role in CD pathophysiology. Conclusions: Diet plays a significant adjunctive role in the management of Crohn’s disease. Reducing exposure to ultra-processed foods and potentially harmful food additives, while promoting balanced dietary patterns, may improve clinical outcomes. Further research is needed to clarify long-term effects and to develop personalized, evidence-based nutritional strategies for patients with CD. Full article

Background/Objectives: Micronutrient deficiencies are common in inflammatory bowel disease (IBD) and contribute to anemia, impaired wound healing, neurologic injury, and adverse disease outcomes. Major societies, including ESPEN, ACG, and ECCO, recommend nutritional and micronutrient assessment in patients with IBD, yet few studies describe how comprehensively these recommendations are applied during hospitalization. This study aimed to characterize inpatient testing practices for vitamins B1, B6, B12, and zinc in hospitalized IBD patients, quantify deficiency frequency among those tested, and identify gaps between guideline-recommended and actual micronutrient assessment. Methods: A retrospective chart review was performed on adults with Crohn’s disease (CD) or ulcerative colitis (UC) hospitalized for an IBD flare at a tertiary care center. Demographics, comorbidities, and deficiency-associated clinical features were recorded. Yield was defined as the proportion of tested patients meeting institutional deficiency thresholds. Yield for each non-B12 micronutrient was compared with B12 as an internal benchmark. Results: Among 356 patients (285 CD, 71 UC), inpatient micronutrient testing was markedly imbalanced: B12 was tested in 97.2%, whereas B6, B1, and zinc were tested in only 34.8%, 30.6%, and 18.8%, respectively. Among those tested, deficiencies were common: B6 40.3%, zinc 32.8%, B1 22.9%, and B12 9.0%. Each non-B12 micronutrient yielded deficiency significantly more often per test than B12 (all p < 0.001), a testing-yield mismatch interpreted cautiously given selective testing of non-B12 nutrients. Deficiency frequencies did not differ significantly between CD and UC. Clinical contexts included tachycardia and edema (B1); elevated inflammatory markers and thromboembolism history (B6); anemia and neuropathy (B12); and diarrhea and hypoalbuminemia (zinc). Conclusions: Inpatient micronutrient assessment in IBD is heavily skewed toward B12, with B1, B6, and zinc under-tested despite a substantially higher yield of identified deficiency per test. This testing-yield mismatch represents a measurable implementation gap between guideline-recommended comprehensive assessment and actual inpatient practice; whether systematic panel-based assessment improves clinical outcomes warrants prospective evaluation. Full article

Background/Objectives: Intestinal diseases are a major global health problem due to their high prevalence, chronic course, and significant impact on quality of life. Increasing attention has been given to the extra-skeletal effects of vitamin D, particularly its role in immune regulation, maintenance of intestinal barrier integrity, and modulation of the gut microbiota. The aim of this review was to evaluate current evidence regarding the role of vitamin D in immune regulation, intestinal barrier function, and the pathogenic mechanisms of intestinal diseases, including inflammatory and functional gastrointestinal disorders. Methods: A structured narrative review was conducted using the PubMed, Scopus, and Web of Science databases to identify publications addressing the role of vitamin D in intestinal diseases. The literature search was updated in May 2026 and included studies published between 2004 and 2026. The aim of this review was to summarize current evidence on the effects of vitamin D on immune regulation, intestinal barrier integrity, gut microbiota, and their clinical relevance in intestinal diseases. Results: The included studies demonstrated that vitamin D plays an important role in maintaining intestinal homeostasis through regulation of innate and adaptive immune responses, preservation of epithelial barrier integrity, and modulation of gut microbiota composition. Vitamin D deficiency was associated with impaired VDR-dependent signalling, increased intestinal permeability, dysbiosis, and enhanced pro-inflammatory immune responses, which may contribute to the development and progression of inflammatory bowel disease, Crohn’s disease, ulcerative colitis, irritable bowel syndrome, and celiac disease. Conclusions: Current evidence supports the important role of vitamin D in immune regulation, intestinal barrier protection, and maintenance of gut microbial balance. Further clinical studies are required to better understand its therapeutic potential in intestinal diseases. Full article

Differentiating active ulcerative colitis (UC) from Crohn’s disease (CD) is one of the unmet needs addressed by biomarkers in inflammatory bowel disease (IBD). The immune landscapes of UC and CD differ, justifying the search for discriminatory markers and novel therapy targets among their mediators. Herein, 27 systemic cytokines were measured using flow cytometry-based methodology in 138 IBD patients, with an additional 21 being determined in 67 of the patients. Their discriminatory power was assessed individually and as exploratory multivariable signatures generated using logistic regression, hierarchical clustering, and principal component analysis. Eotaxin-1, macrophage inflammatory protein (MIP)-1β, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) showed fair discriminatory potential, while multivariable models performed better. Interleukin (IL)-1β, IL-4, and MIP-1α were strongly associated with CD, whereas IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), MIP-1β, and TRAIL were associated with UC. Active UC was characterized by mediators linked to eosinophil-, mastocyte-, and neutrophil-driven inflammation and tissue repair (eotaxin-1, IL-5, growth-regulated oncogene (GRO), MIP-1β, stem cell factor (SCF), GM-CSF, IL-1 receptor antagonist, TRAIL, stem cell growth factor (SCGF)-β, and cutaneous T cell-attracting chemokine (CTACK)), whereas active CD was associated with Th1/Th17 immunity, myeloid activation, fibrosis, angiogenesis, and neuroimmune remodeling (IL-1β, IL-12p70, IL-15, ‘regulated on activation, normal T-cell expressed and secreted’ (RANTES), MIP-1α, stromal cell-derived factor (SDF)-1α, nerve growth factor β (β-NGF), and leukemia inhibitory factor (LIF)). In conclusion, integrated circulating immune signatures identify several understudied cytokines as potential contributors to disease-specific pathways and show potential in distinguishing active UC from CD warranting further mechanistic studies and independent validation in larger cohorts. Full article

GNR-068 is a proposed biosimilar to the ustekinumab reference product (RP), which works through the antagonism of interleukin 12 and interleukin 23. Ustekinumab RP is used for the treatment of chronic inflammatory conditions, including certain forms of plaque psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis. Objectives: The purpose of the study is to study the safety, pharmacokinetics, and immunogenicity of the ustekinumab biosimilar GNR-068 and the reference drug Stelara^® after a single subcutaneous administration in healthy male volunteers. Methods: This was an open-label, randomized, comparative, parallel-group clinical trial of the safety, pharmacokinetics (PK), and immunogenicity of GNR-068 (JSC GENERIUM) and Stelara^® (Manufacturer: Silag AG, Switzerland; RU Holder: JOHNSON & JOHNSON) after a single subcutaneous administration of 45 mg in healthy volunteers. During the trial, 146 volunteers were screened, and 122 were randomized. Results: The results showed that PK similarity was established based on 90% confidence intervals (CIs) for the ratios of geometric means of the primary endpoints of area under the concentration-time curve from time 0 extrapolated to infinity (AUC_0–∞) and maximum observed serum concentration (Cmax) being contained within the pre-specified margin of 80.00–125.00%. The incidence of total ADA was lower in the GNR-068 group compared with the reference product group. Adverse events were similar between treatment groups and consistent with the safety profile of the ustekinumab RP. Conclusions: These results indicate that GNR-068 and the ustekinumab RP share similar PK and safety profiles. Full article

We conducted an online cross-sectional study to assess malnutrition risk, food and nutrition insecurity, and perceived barriers and facilitators to dietary management among adults (18–64 years old) with a self-reported clinical diagnosis of inflammatory bowel disease (IBD) in outpatient and community settings. We assessed malnutrition risk using the Saskatchewan IBD-Nutrition Risk screening tool, food security risk using the two-item Hunger Vital Signs questionnaire, and nutrition security risk using a validated four-item tool. Open-ended questions elucidated barriers and facilitators to dietary management of IBD. Among 57 participants who self-reported a clinical diagnosis of IBD, 52.6% (n = 30/57) had ulcerative colitis, and 47.4% (n = 27/57) had Crohn’s disease. Nutrition insecurity was higher among those at high risk of malnutrition than among those at low-to-medium risk (p = 0.018), and there were no differences in food security status (p = 0.081). Using univariate logistic regression, the odds of being classified as having a high risk of malnutrition were associated with being male, following a special diet or nutrition plan, experiencing IBD-related flare-ups, and nutrition insecurity. Furthermore, healthcare professionals and social support, as well as digital resources/nutrition-related apps, were identified as facilitators to dietary management, while barriers included food access and expense, limited nutrition knowledge and resources, and fear of IBD-related symptom flare-ups. Although self-reported malnutrition risk and food and nutrition insecurity are common, larger prospective studies incorporating validated disease-activity measures and comprehensive nutritional assessment are needed to clarify these relationships and evaluate integrated dietetic and social-support interventions. Full article

Background/Objectives. Crohn’s disease (CD) is a chronic immune-mediated inflammatory disease that affects the gastrointestinal tract. The management of CD is complex, and treatment requires numerous therapies. One of the best gut-selective biologic drugs with proven efficacy in induction and maintenance therapy in patients with CD is vedolizumab (VDZ). Nevertheless, not all patients with CD respond to VDZ treatment, possibly due to their individual pharmacogenomic profiles. In this study, the association of variants in genes encoding molecules involved in biological pathways targeted by VDZ, ITGA4, ITGB7, and MADCAM1, with VDZ response was analyzed. In addition, Human Leukocyte Antigen (HLA) alleles were investigated. Methods. Whole exome sequencing was performed on 63 CD patients treated with VDZ as first-line biologic therapy. Genetic variants were associated with response to VDZ treatment, estimated as follows: (1) good clinical response (patients assigned to standard maintenance protocol after 14-week induction) or partial (patients assigned to optimized maintenance protocol after 14-week induction); (2) good biochemical response (CRP ≤ 10 mg/L at week 14) or poor (CRP > 10 mg/L at week 14). Results. Two MADCAM1 variants were associated with VDZ response, as defined by CRP values in week 14 of VDZ therapy. The genetic variant MADCAM1 rs758941486 was associated with poor CRP reduction in response to VDZ induction therapy, while MADCAM1 rs1555716175 was associated with optimal CRP reduction. Anti-drug antibody-related HLA-DRB1, DQB1, and DQA1 alleles were not associated with VDZ response. Conclusions. This is a pioneering pharmacogenomics study on the VDZ direct therapeutic targets in bio-naïve CD patients, which opens the door for future research. Full article

Background: Artificial intelligence (AI) and machine-learning (ML) prognostic models are increasingly developed for inflammatory bowel disease (IBD), yet their reported performance and clinical readiness remain inadequately appraised. Methods: Following PRISMA 2020 and a registered protocol, we searched PubMed, Web of Science, IEEE Xplore, and arXiv (January 2012–January 2026) for studies developing or validating prognostic models in Crohn’s disease or ulcerative colitis. Two reviewers independently screened the studies, extracted data, and assessed risk of bias using PROBAST + AI; discrimination was summarized by area under the curve (AUC) and stratified by validation type. Results: Of the 3050 records, 111 studies were included. Treatment response was the most common target; laboratory data and electronic health records were the most frequent modalities. Across 83 studies, the median AUC was 0.850; externally validated models reached 0.870 versus 0.845 for internal-only and 0.790 for cross-validation-only. External validation was reported in 29.7%, calibration in 14.4% and analysis code in 3.6%; the analysis domain was the leading source of bias. Conclusions: The evidence base maps reported discrimination rather than demonstrated clinical readiness. Until calibration, decision-curve utility, and transportability are reported alongside external validation, clinical deployment remains premature. Full article

Background: Inflammatory bowel disease (IBD) involves chronic immune activation, yet alterations in the cortisol awakening response (CAR) remain poorly defined. We compared cortisol dynamics in patients with IBD and healthy controls and explored associations with phenotype, endoscopic activity, and inflammation. Methods: This single-centre, cross-sectional case–control study enrolled 100 patients with IBD (51 with ulcerative colitis [UC] and 49 with Crohn’s disease [CD]) and 78 frequency-matched controls. Salivary cortisol was measured at awakening (C0), 30–45 min later (C1), and bedtime (C2); 97 patients and 78 controls met timing criteria. The absolute post-awakening increment (ΔCAR) and area under the curve with respect to increase (AUCi) were calculated. Analyses included non-parametric tests, adjusted regression, mixed models, and multiplicity-corrected within-IBD comparisons and correlations. Results: Patients with IBD had lower C0 (median 0.478 vs. 1.067 µg/dL) and C1 (0.850 vs. 1.950 µg/dL; both p < 0.001), whereas C2 was comparable (p = 0.819). ΔCAR (0.130 vs. 0.461 µg/dL) and AUCi (2.080 vs. 7.770 min·µg/dL) were lower in IBD (both p < 0.001); adjusted analyses confirmed this pattern. Cortisol metrics did not differ consistently by IBD subtype or endoscopic activity. Higher high-sensitivity C-reactive protein (hs-CRP) correlated positively with C0 (ρ = 0.325; q = 0.041) and inversely with ΔCAR (ρ = −0.402; q = 0.002), AUCi (ρ = −0.408; q = 0.002), and relative CAR (ρ = −0.517; q < 0.001). Conclusions: IBD was associated with attenuated CAR and lower morning cortisol output, with preserved bedtime concentrations. These cross-sectional findings support a relationship between systemic inflammation and altered early-morning HPA-axis dynamics but do not establish causality. Full article

Introduction: Crohn’s disease (CD) remains associated with long-term morbidity despite biologic therapies. Surgery, historically considered a last-resort option, is increasingly integrated into disease management earlier. This review examines the evolving role of surgery in the biologic era. Methods: A focused narrative review of randomized controlled trials, meta-analyses, observational studies, and international guidelines addressing contemporary surgical strategies in CD was performed. Results: The LIR!C trial demonstrated that early ileocecal resection provides durable remission and improves long-term outcomes compared with biologic therapy in selected patients. The PISA II trial supported an early combined surgical and medical approach for perianal fistulizing disease. Preoperative optimization, including nutritional support and adjustment of immunosuppressive therapy, has become a cornerstone of perioperative management. Laparoscopic surgery remains the preferred approach whenever feasible, while robotic surgery is emerging as a promising platform that is expected to play an increasingly important role in the surgical management of CD. Postoperative recurrence remains a major challenge, prompting the development of innovative surgical strategies. Although the Kono-S anastomosis initially showed promising reductions in recurrence, recent prospective studies failed to confirm superiority over conventional techniques. Similarly, extended mesenteric excision did not demonstrate improved outcomes despite increasing evidence implicating the mesentery in CD pathogenesis. Strictureplasty remains an effective option for selected fibrotic small-bowel strictures. Conclusions: Surgery remains central to multidisciplinary CD management and offers the potential to modify disease when performed early in selected patients. The impact of innovative surgical strategies on postoperative recurrence remains uncertain, and ongoing trials are expected to further help with surgical decision-making. Full article

Background/Objectives: The safety profile of adalimumab in inflammatory bowel disease (IBD) has been established in clinical trials, but post-marketing surveillance remains important for detecting rare and late-onset adverse events (AEs). This study aimed to evaluate long-term safety and temporal dynamics of AEs in an IBD cohort treated with adalimumab, and to identify potential safety signals using the FDA Adverse Event Reporting System (FAERS). Methods: This retrospective single-center study included patients with IBD treated with adalimumab. Demographic, clinical, and treatment-related data, including AEs and newly identified extraintestinal manifestations (EIMs), were collected. Time-to-event (TTE) analyses were used to assess AEs temporal patterns and covariates associated with onset. FAERS disproportionality analysis was performed for cohort-identified AEs and EIMs. Results: A total of 217 patients with 591.29 patient-years (PYs) of exposure (up to 9.62 years) were included. AE incidence was 106.6/100 PY. Time to first AE was described using the Kaplan–Meier method, and additionally the Weibull distribution, with an estimated median time of 11.4 months (95% CI: 9.7–13.5). The most frequent AEs were infections (32.30/100 PY), hepatic events (9.98/100 PY), and cutaneous manifestations (8.46/100 PY), characterized by TTE analysis. Serious outcomes, including malignancies and demyelinating events, were rare. Several unlisted MedDRA preferred terms, including infectious, cutaneous, vascular, proliferative, and musculoskeletal events, emerged as FAERS signals. Conclusions: This study provides long-term real-world evidence supporting the established safety profile of adalimumab in IBD. First AEs occurred throughout treatment exposure with lower hazard over time. Isolated FAERS signals, including vascular occlusive events, may warrant further investigation and continued pharmacovigilance. Full article