Search Results (181)

Fecal microbiota transplantation (FMT) has emerged as a microbiota-directed therapeutic strategy with established efficacy in recurrent Clostridioides difficile infection (rCDI) and expanding investigational applications in pediatric medicine. Given the central role of the gut microbiota in immune maturation, metabolic homeostasis, and colonization resistance—particularly during early life—restoring microbial diversity represents a biologically plausible intervention for disorders characterized by dysbiosis. This narrative review critically examines current evidence regarding the indications, efficacy, safety, and practical considerations of FMT in pediatric populations. A structured literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Library from inception through December 2025. Eligible studies included randomized controlled trials, observational studies, systematic reviews, meta-analyses, and guideline statements addressing pediatric FMT. RCDI remains the primary and best-supported indication, with reported success rates exceeding 80% after a single FMT and approaching 90% with repeat procedures. Evidence for other indications—including inflammatory bowel disease (IBD), malignancy-associated CDI, transplant recipients, multidrug-resistant organism (MDRO) decolonization, neurodevelopmental disorders, allergic colitis, and functional gastrointestinal disorders—remains limited and heterogeneous. While short-term remission rates in pediatric ulcerative colitis appear promising, data derive largely from small, non-standardized studies, and long-term efficacy and safety remain insufficiently defined. FMT usage in immunocompromised children, particularly oncology and transplant populations, is controversial due to limited pediatric-specific evidence and theoretical risks. Substantial variability in donor screening, preparation methods, dosing, and administration routes further limits standardization. Currently, FMT should be considered established therapy for pediatric rCDI, whereas other applications require well-designed, multicenter trials with long-term follow-up to clarify safety and clinical benefit. Full article

Inflammatory bowel disease (IBD) with an onset in childhood is characterized by a more extensive phenotype, a more aggressive clinical course, and a higher risk of long-term complications, including growth retardation, compared to adult-onset disease. While tumor necrosis factor-alpha (TNF-α) inhibitors are the cornerstone of therapy, achieving sustained remission in children is often hindered by unique pharmacokinetic challenges, such as accelerated drug clearance and a higher propensity for immunogenicity. This review explores the evolving role of therapeutic drug monitoring (TDM), specifically the paradigm shift from reactive to proactive strategies. While proactive TDM remains a subject of debate in adult IBD, emerging pediatric data strongly support its routine use to optimize treatment durability and prevent secondary loss of response. Evidence-based target trough concentrations for pediatric patients are critical for achieving mucosal healing: 8–13 µg/mL at week 6 and >5–7 µg/mL during maintenance for infliximab, and >13–14 µg/mL post-induction for adalimumab. Beyond clinical outcomes, this review emphasizes the economic viability of proactive TDM, which has been shown to reduce total healthcare expenditures by 18–30% by minimizing hospitalizations and avoiding premature treatment switches. By integrating pharmacological data with clinical pathways, proactive TDM serves as an essential tool for personalized medicine, ensuring safer and more cost-effective management of pediatric IBD. Full article

Objectives: We aimed to assess fractional exhaled nitric oxide (FeNO) and spirometry in pediatric patients with inflammatory bowel disease (IBD) and relate these parameters to disease activity, duration, and current treatment. Methods: This prospective case–control study included 161 subjects: children with newly diagnosed, active IBD (N = 55), children in clinical remission (N = 53), and healthy controls (N = 53). FeNO was measured using a chemiluminescent analyzer, and pulmonary function was assessed by spirometry. Results: FeNO was higher in patients with IBD than in controls (p = 0.025) and positively correlated with CRP (ρ = 0.22; p = 0.027). Respiratory function measured by spirometry in children with IBD was preserved. No association was found between respiratory parameters, disease activity, and duration. The correlation between FeNO and aminosalicylate treatment was of borderline significance (ρ = 0.28; p = 0.052). Conclusions: Children with IBD, although having normal pulmonary function measured by spirometry, do have increased FeNO, which is positively correlated with CRP. FeNO reflects systemic inflammation, but its role as a clinical marker of disease activity or relapse remains uncertain. Full article

Background: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), represents a chronic immune-mediated disorder frequently associated with extraintestinal manifestations. While musculoskeletal, dermatologic, and ocular complications are well recognized, ear, nose, and throat (ENT) involvement remains underrecognized despite its potential morbidity. Objective: To systematically evaluate the spectrum of ENT manifestations in IBD, focusing on clinical presentation, diagnostic approaches, and outcomes. Methods: A systematic literature search was conducted in PubMed and Scopus in accordance with PRISMA 2020 guidelines. Eligible studies included English-language human studies (2015–2026) reporting ENT manifestations in UC or CD. Following screening, 23 studies were included in the qualitative synthesis. Extracted data comprised study design, IBD subtype, patient demographics, ENT manifestations, diagnostic methods, and clinical outcomes. Results: The majority of studies consisted of case reports and small observational series. Sensorineural hearing loss (SNHL) was the most frequently reported manifestation in both adult and pediatric populations, with evidence suggesting immune-mediated mechanisms and variable responsiveness to corticosteroids. Nasal involvement included pyoderma gangrenosum, pyoderma vegetans, and aseptic nasal septal abscess, occasionally resulting in severe structural complications such as saddle-nose deformity. Laryngeal and airway involvement included dysphonia, tracheitis, and rare but potentially life-threatening inflammatory airway disease. Additional findings included associations with chronic rhinosinusitis. Diagnosis relied on audiometry, imaging, endoscopy, and histopathology. Systemic corticosteroids were frequently effective; however, delayed recognition may lead to irreversible sequelae. Conclusions: ENT manifestations in IBD constitute a clinically heterogeneous but important group of extraintestinal complications. Increased awareness of ENT manifestations may support earlier diagnosis and multidisciplinary management of IBD, potentially reducing irreversible complications. Full article

Background/Objectives: Very early onset inflammatory bowel disease (VEO-IBD), frequently associated with monogenic defects, is increasingly recognized worldwide but remains poorly characterized in Vietnam. This study aimed to characterize the clinical phenotypes and genetic spectrum of Vietnamese children with VEO-IBD. Methods: We conducted a retrospective cohort study at a tertiary pediatric referral center in Vietnam from July 2016 to January 2026. Clinical, laboratory, endoscopic, histopathological, genetic, and treatment data were systematically collected and analyzed. Monogenic variants were identified using next-generation sequencing and classified according to ACMG criteria. Results: Thirty-six children were included, with a median age at onset of 7.5 months, and 72.2% presenting before 24 months. Crohn’s disease predominated (72.2%). Disease burden was high, with growth impairment in 75.0% and anemia in 91.7%. Extraintestinal manifestations were frequent, particularly recurrent infections (72.2%), dermatitis (44.4%), and oral ulcers (44.4%). Perianal disease occurred in 58.3%, with early complications including perianal ulcer (44.4%), perianal abscess (30.6%) and fistulas (33.3%). Inflammatory markers were markedly elevated, and disease activity indices indicated moderate-to-severe disease at diagnosis. Genetic testing was performed in 91.7% of patients, identifying monogenic etiologies in 30.3%. Identified variants involved genes related to immune regulation (IL10RA/IL10RB, FOXP3, XIAP), autoinflammation (TNFAIP3), host defense (CYBB), and epithelial function (MYO5B). Conclusions: Monogenic etiologies account for a substantial proportion of VEO-IBD and are associated with distinct clinical phenotypes and therapeutic implications. Early integration of genomic testing with clinical phenotyping is essential to improve diagnostic precision and enable pathway-based treatment, supporting precision medicine in pediatric IBD. Full article

Background/Objectives: Adolescents and young adults (AYAs) with inflammatory bowel disease (IBD) experience persistent physical symptoms and psychosocial challenges that can impair functioning and quality of life. Health mindset, beliefs about whether health is fixed versus malleable and responsive to effort, is linked to positive health outcomes but has not been examined in AYAs with IBD. This study evaluated the internal reliability of a health mindset measure in AYAs with IBD and examined associations between health mindset and depressive symptoms, peer relationships, global health, pain interference, fatigue, and disease activity. Methods: Participants were 101 AYAs with IBD (M = 18.4 years; 54.4% ulcerative colitis; 63.4% female) recruited from an outpatient pediatric IBD clinic and a national IBD network. Participants completed a one-time online survey consisting of the Health Mindset Scale, Patient-Reported Outcomes Measurement Information System (PROMIS) measures for physical, psychosocial, and global health outcomes, and IBD disease activity indices. Results: The Health Mindset Scale demonstrated good internal reliability in this sample. Additionally, a growth health mindset was significantly associated with lower pain interference, lower Crohn’s disease activity, and better global health. No significant associations were observed between health mindset and depressive symptoms, peer relationship quality, fatigue, or ulcerative colitis disease activity. Conclusions: This novel study provides initial evidence that health mindset is associated with clinically meaningful outcomes in AYAs with IBD. These findings highlight that health mindset may be an important psychological construct in chronic illness adjustment and management, extending mindset theory and research to a young clinical population with IBD. Full article

Background: Patients with inflammatory bowel disease (IBD) exhibit a hypercoagulable state with increased thrombotic risk. Previous studies demonstrated elevated thrombin generation in pediatric IBD, paradoxically accompanied by prolonged lag time during active disease. We hypothesized that elevated tissue factor pathway inhibitor (TFPI) levels during active inflammation contribute to this paradox. Methods: We prospectively enrolled 25 pediatric patients (10 Crohn’s disease [CD], 15 ulcerative colitis [UC]) aged 7–18 years with newly diagnosed IBD. Blood samples were collected at diagnosis and in remission. Thrombin generation was assessed using calibrated automated thrombography. Plasma levels of TFPI, tissue factor activity (TFA), vascular endothelial growth factor (VEGF), and interleukin-6 (IL-6) were measured. Results: TFPI levels correlated positively with thrombin generation lag time (r = 0.43, $p_{\mathrm{adj}}$ < 0.05) and disease activity scores (r = 0.54, $p_{\mathrm{adj}}$ < 0.05) in patients with active disease (PCDAI/PUCAI > 0). Longitudinal analysis of 16 patients achieving remission revealed elevated TFPI and prolonged lag time during active disease compared to quiescence (both $p_{\mathrm{adj}}$ < 0.05), while TFA did not change significantly. VEGF decreased significantly upon remission ($p_{\mathrm{adj}}$ < 0.05), whereas IL-6 showed no significant change. Conclusions: Elevated TFPI levels during active IBD likely contribute to the paradoxical prolongation of thrombin generation lag time. TFPI normalization upon remission reflects vascular inflammation resolution, suggesting TFPI as a potential biomarker and therapeutic target. Full article

Background/Objectives: An imbalance in oxidative stress (OS) has been implicated in the pathogenesis of Inflammatory Bowel Disease (IBD). We compared OS status in IBD children and adults versus healthy controls by exploring variables impacting the OS disruption in IBD. Methods: Total antioxidant capacity (ferric-reducing ability of plasma (FRAP)), reactive species (ROS), oxidative products (advanced oxidation protein products (AOPPs) and thiobarbituric acid reactive substances (TBARSs)), and antioxidant defenses (glutathione, GSH and intracellular activity of the main antioxidant enzymes) were evaluated. Correlations between OS markers, clinical features, disease characteristics, and inflammatory indices were explored. Results: Eighty-two IBD patients (67.5% in clinical remission) and 73 healthy subjects were enrolled. IBD children showed significant FRAP reduction compared to controls and IBD adults (p < 0.0001), increased AOPPs and reduced GSH compared to controls (p < 0.0001 and p = 0.0011, respectively), higher total GSH (p = 0.020), and lower TBARSs (p = 0.023) compared to IBD adults. In the pediatric group, FRAP was significantly reduced in those with IBD and increased in older subjects and males, while AOPP levels were positively affected by increasing age. In the total IBD cohort, higher FRAP was associated with male gender, increasing age, overweight, and mesalazine therapy. The diagnosis of Ulcerative Colitis was associated with lower FRAP and AOPP levels compared to Crohn’s disease. Increased fecal calprotectin significantly decreased the total antioxidant capacity. Conclusions: The antioxidant system shows significant differences in IBD compared to controls, particularly in the pediatric group. The observed pediatric–adult pattern may suggest age-related differences in oxidative balance, but these findings should be interpreted with caution, given the modest sample size. Clinical Trial Registration Number: NCT04513015. Full article

Background/Objectives: Inflammatory bowel disease (IBD) management has evolved from conventional therapies to advanced biologics and targeted small molecules; however, clinical practice often relies on empirical treatment sequencing rather than individualized approaches. The heterogeneity of IBD phenotypes, variable treatment responses, and expanding therapeutic options necessitate a shift toward precision medicine. This review aims to synthesize current evidence on personalizing IBD therapy and provide an implementation framework for clinical practice. Methods: A narrative review was conducted encompassing peer-reviewed literature, recent network meta-analyses, and clinical guidelines. Evidence was gathered on treat-to-target strategies, therapeutic drug monitoring (TDM), clinical decision support systems, artificial intelligence applications, multi-omics platforms (genomics, transcriptomics, microbiome, metabolomics), advanced imaging modalities, and special populations including pediatric patients and pregnant women. Results: Treat-to-target strategies incorporating endoscopic and biochemical endpoints improve long-term outcomes when individualized to patient-disease factors. TDM-guided optimization enhances biologic efficacy and reduces immunogenicity. Emerging AI tools and multi-omics platforms show promise in predicting treatment response and patient stratification. Network meta-analyses provide comparative effectiveness estimates guiding advanced therapy selection in both Crohn’s disease and ulcerative colitis. Implementation of precision medicine frameworks remains constrained by regulatory, economic, and technical barriers. Conclusions: Personalizing IBD therapy through integration of precision medicine tools, patient-specific factors, and comparative effectiveness data represents the future of IBD management. Overcoming implementation barriers through standardized frameworks and multidisciplinary collaboration is essential to translate these advances into routine clinical practice. Full article

Objectives: This study aimed to evaluate the knowledge, attitudes, and perceptions of Italian general dentists, pediatric dentistry residents and pediatric residents regarding IBD-related oral manifestations, in order to identify educational gaps and promote a multidisciplinary approach. Methods: A cross-sectional survey using a validated questionnaire was conducted among pediatric residents, pediatric dentistry residents and general dentists. The tool included sociodemographic questions, 30 true/false items on knowledge and 20 Likert-scale items on attitude and perception. Data were collected online and on paper and analyzed using descriptive statistics, chi-square tests, and ANOVA. Results: Out of 228 respondents, general knowledge of IBD was high, while specific knowledge about oral manifestations was limited. Pediatric dentistry residents and pediatric residents performed significantly better than general dentists on targeted items (p = 0.01). Attitudinal responses revealed low clinical confidence, with only a minority feeling prepared to recognize or manage oral lesions, though most were willing to pursue further education. Perception was overall positive, with strong support for multidisciplinary collaboration (96.5%), and 89.5% recognized the role of dentists in early IBD detection. General dentists more often reported the need for additional training (p = 0.02). No significant differences emerged by sex or age. Conclusions: Our study highlights significant knowledge gaps and limited clinical confidence but also reveals a strong willingness to improve and collaborate. While the number of children with IBD seen by general dentists and primary care pediatricians is limited, considering the increasing incidence of pediatric IBD, our results support the need for targeted educational interventions. Full article

Background: Gut microbiota alterations are increasingly recognized as key contributors to the development and clinical course of inflammatory bowel disease (IBD), particularly in pediatric patients, in whom microbial maturation and immune regulation are still evolving. Objective: This study aimed to assess intestinal microbiota composition and dysbiosis severity in pediatric IBD, with comparative analyses according to disease phenotype (Crohn’s disease versus ulcerative colitis) and therapeutic strategy (biologic versus non-biologic treatment). Methods: A prospective cohort of 60 pediatric patients diagnosed with IBD based on Porto criteria was evaluated. Fecal samples were obtained at baseline and after three months of combined standard IBD treatment and adjunct microbiota-targeted therapy, and were analyzed using an AI-assisted microbiota profiling platform. A semi-quantitative dysbiosis score was calculated based on the relative abundance of proinflammatory taxa and depletion of short-chain fatty acid (SCFA)-producing bacteria. Microbial parameters were correlated with clinical and therapeutic variables, including the Organism of Interest metric and the Gut Microbiota Index (GMI). Results: Dysbiosis severity was significantly higher in patients with Crohn’s disease compared with ulcerative colitis (9.65 ± 1.44 vs. 8.42 ± 1.88, p = 0.037). Patients receiving biologic therapy showed a trend toward lower dysbiosis scores and improved microbial indices, although statistical significance was not reached. Severe dysbiosis was identified in 46.7% of the cohort. Strong positive correlations were observed between the dysbiosis score, Organism of Interest metric and GMI (r = 0.68–0.72, p < 0.01). Conclusions: Pediatric IBD is associated with a reproducible dysbiotic profile, more pronounced in Crohn’s disease and partially modulated by biologic therapy. The observed correlations between microbiota-derived indices support their potential utility as complementary markers of intestinal microbial imbalance and disease activity. Full article

Background: Pediatric inflammatory bowel disease (IBD) is characterized by a heterogeneous and often aggressive disease course, requiring complex multimodal assessment and long-term monitoring. Artificial intelligence (AI) has emerged as a promising tool to support clinical decision-making by enabling an objective analysis of large, multidimensional datasets. Objectives: This narrative review aims to critically synthesize current evidence on the application of AI across the diagnosis, monitoring, and treatment of pediatric IBD. Methods: A narrative literature review was conducted using the PubMed (MEDLINE) and Cochrane Library databases, including publications available up to December 2025. Pediatric-focused studies were prioritized. However, due to the limited availability of pediatric-specific AI research, a considerable proportion of the evidence reviewed derives from adult or mixed cohorts, which were included when methodological frameworks or clinically relevant endpoints were applicable to pediatric IBD. Eligible publications included narrative and systematic reviews, observational studies, and clinical trials focusing on AI applications in endoscopy, histology, imaging, disease monitoring, and therapeutic response prediction. Results: AI-based models, particularly those using machine learning and deep learning, demonstrated promising performance in the automated analysis of endoscopic, histological, and imaging data, reducing interobserver variability and improving workflow efficiency. Multimodal approaches integrating imaging, clinical, and biomarker data consistently outperformed unimodal models. Emerging applications in patient-centered monitoring, digital biomarkers, and telemedicine enabled continuous disease assessment and early detection of flares, with particular relevance in pediatric settings where repeated, non-invasive monitoring is essential. AI-driven models also showed promising accuracy in predicting therapeutic response, supporting treatment stratification and precision medicine strategies. Conclusions: AI shows promising potential to complement clinical expertise in pediatric IBD by supporting diagnostic assessment, disease monitoring, and therapeutic optimization. However, translation into routine clinical practice remains constrained by methodological heterogeneity, limited pediatric-specific validation, and unresolved ethical and regulatory challenges. Future research should prioritize prospective multicenter pediatric studies, the development of transparent and explainable models, and the integration of AI-based tools into clinically meaningful and patient-centered care pathways. 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

This detailed narrative review focuses on the current understanding of unique alterations in GM colonization and subsequent complications following surgery for significant childhood conditions, such as necrotizing enterocolitis (NEC), Hirschsprung’s disease (HD), inflammatory bowel disease (IBD), and short bowel syndrome (SBS). Surgical interventions can alter the diversity and structure of the GM and potentially cause post-surgical complications. Although the data are well-established in adults, there is a lack of pediatric-specific data on post-surgical GM dysbiosis and its complications, including surgical infections, intestinal obstructions (IO), and anastomotic leak (AL). This gap constitutes both a clinical risk and an important therapeutic opportunity. Therefore, research on how to modulate the GM perioperatively in children is needed. Current research provides an initial understanding of the possible post-surgical implications for outcomes of these intestinal disorders. Future studies could clarify GM alterations associated with various pediatric intestinal surgical procedures and their complications, which may influence the evaluation of GM-targeted treatments. 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