Search Results (248)

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 and Objectives: The management of localized ileocecal Crohn’s disease (CD) is undergoing a significant paradigm shift from traditional “step-up” medical escalation toward proactive early surgical intervention. With the evolution of surgical therapies as well as various minimally invasive procedures, as well as a better understanding of inflammatory bowel diseases, surgery is playing a more important role in the treatment of inflammatory bowel disease. One of the most common occurrences in Crohn’s disease, the ileocecal localization can present with a lot of dilemmas regarding the optimal treatment in both adult patients and pediatric patients alike. One of the biggest challenges remains the decision between early surgery and continuous biological treatment, which can prove a challenge from multiple standpoints ranging from cost-efficiency to recurrence rate. This review highlights the latest changes in surgical management in ileocecal Crohn’s disease, focusing primarily on the anastomotic type, comparison with biological therapy, early aggressive surgery and pediatric surgery. Materials andMethods: After respecting the review criteria, 16 articles were included in our study, which emphasize the importance and the recent trends in the surgical management of the ileocecal disease. Results: All 16 articles met criteria for good quality, suggesting a low risk of bias, focusing primarily on early surgery, the role of Kono-S anastomosis as well as pediatric considerations. Conclusions: While the choice of the Kono-S anastomosis remains debatable, significant progress has been made in terms of early surgery which improves the long-term outcomes in patients while minimizing the risk of morbidity and mortality. 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

Crohn’s disease (CD) in children with juvenile idiopathic arthritis (JIA) is frequently diagnosed late due to overlapping symptoms and non-specific biomarkers. We hypothesized that longitudinal cytokine profiling could identify a pre-symptomatic signature predictive of CD conversion in pediatric JIA patients. Ninety pediatric participants (JIA, CD, psoriatic arthritis, healthy controls) underwent serum cytokine profiling (IL-1α, IL-1β, IL-36α, IL-37, IL-6, IL-18, IL-27, IL-31) at baseline and 12 months. Statistical analysis used Mann–Whitney U tests for two-group comparisons, the Kruskal–Wallis test with Dunn’s post hoc for multi-group comparisons, Fisher’s Exact Test for categorical outcomes, and exploratory principal component analysis (PCA). Baseline screening identified a subgroup of JIA patients (N = 4) with significantly elevated IL-1α, IL-1β, and IL-36α. At 12 months, all four patients in this subgroup received a secondary CD diagnosis (4/4 converters vs. 0/21 non-converters; Fisher’s Exact Test: p < 0.0001). The longitudinal analysis at conversion revealed a broader pro-inflammatory shift, with marked increases in IL-18 and IL-31, alongside elevated IL-37, suggesting a compensatory regulatory response. PCA confirmed that converters clustered distinctly from both stable JIA and established CD. A baseline IL-1 family signature may represent a preliminary predictive signature for CD onset in pediatric JIA. Although constrained by the small converter subgroup (N = 4), these data support cytokine profiling for earlier diagnosis in high-risk populations. 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: Due to dysbiosis, intestinal barrier dysfunction, and immunosuppressive therapy, pediatric inflammatory bowel disease (PIBD) patients are more susceptible to infections. However, data on bacterial gastrointestinal (GI) infections in this population are scarce, and no guidelines explicitly address immunosuppressive therapy management during such infections. This single-center study aims to address these knowledge gaps. Methods: A retrospective study of bacterial GI infections was conducted in PIBD patients aged 0–18 years, treated between 2011 and 2021 at the Department of Pediatrics and Adolescent Medicine, Medical University of Graz. Data to assess the study endpoints were extracted from the hospital information system. Results: A total of 139 PIBD patients were screened for bacterial GI infections. The mean follow-up time was 49 months (standard deviation ±33) and the total follow-up time amounted to approximately 473 person-years. Fourteen patients developed infections, with three experiencing them twice, resulting in 17 cases of infection. Most infections were caused by opportunistic bacteria, and 10 infections were treated with antibiotics (11 antibiotic prescriptions in total). At infection onset, 12 patients were on (combined) immunosuppressive therapy, including corticosteroids (3 patients), immunomodulators (9 patients), and/or biologics (3 patients). Six infections required escalation of immunosuppressive therapy due to increased PIBD activity. Hospitalization was required in five cases, and one Clostridioides difficile infection progressed to sepsis, necessitating intensive care unit admission. This corresponds to an incidence of three infections (95% confidence interval 1.75–4.80) and 0.2 severe infections per 100 person-years (95% confidence interval 0.01–1.11). Conclusions: The incidence of bacterial GI infections was 3 per 100 person-years (95% confidence interval: 1.75–4.80), with most cases being clinically mild. Clostridioides difficile was the most common pathogen. Immunosuppressive therapy was generally continued or intensified, when necessary, while antibiotic therapy was administered as indicated. 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: Pediatric intussusception, a condition where part of the intestine telescopes into an adjacent segment, predominantly affects children aged 6–18 months. Prompt diagnosis and management are crucial to prevent serious complications such as ischemia or necrosis. This systematic review aims to comprehensively evaluate and synthesize existing research on predictive and prognostic biomarkers associated with pediatric intussusception that can aid in early diagnosis, severity assessment, outcome prediction, and treatment. Methods: A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science using specific MeSH and free-text terms related to intussusception, biomarkers, and the pediatric population. The review followed PRISMA guidelines, with independent screening, data extraction, and quality assessment using the Joanna Briggs Institute critical appraisal tools. A total of 47 studies, mostly retrospective cohorts from diverse countries, with over 20,000 patients, were included. Results: The studies identified numerous biomarkers associated with disease severity, including hematological markers and indices (e.g., WBC counts and neutrophil-to-lymphocyte ratio), inflammatory markers (CRP and cytokines), biochemical markers (serum lactate, D-dimer, and electrolytes), and novel molecular markers (I-FABP, MCP-1, and transfer RNA fragments). Elevated inflammatory markers and derived ratios consistently predicted bowel necrosis, ischemia, and need for surgery. Biochemical markers like serum lactate and D-dimer correlated with ischemic severity. Emerging molecular biomarkers show promise for early, non-invasive risk stratification. However, heterogeneity in study designs, assay methods, and cutoff values currently limits immediate clinical application. Conclusions: Biomarker research offers valuable tools for improving pediatric intussusception management, with the potential to enhance early diagnosis and outcome prediction. While traditional markers are useful, novel molecular and protein biomarkers hold promise for more specific and rapid assessment. Validation through multicenter, prospective studies and standardized protocols is essential before routine implementation. Integrating biomarkers with clinical and imaging data could refine decision-making, ultimately reducing morbidity and improving prognosis in affected children. Full article

Objectives: To evaluate the association between fecal calprotectin (FC) levels and routinely available blood-based inflammatory indices measured during the same clinical episode in pediatric patients, as well as to assess the diagnostic performance of a novel composite parameter, the Gastrointestinal Inflammation Index (GII). Methods: This retrospective cross-sectional study included pediatric patients who underwent simultaneous testing for FC, complete blood count, C-reactive protein, and albumin between 2022 and 2025. Hematological inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), red cell distribution width (RDW), platelet mass index (PMI), systemic immune-inflammation index (SII), and the newly developed GII, were calculated. Correlations between FC and inflammatory indices were analyzed. Receiver operating characteristic (ROC) curve analysis was performed to evaluate diagnostic performance, and multivariate logistic regression was used to identify independent predictors of FC positivity. Results: Elevated FC levels were significantly associated with higher C-reactive protein levels, lower albumin concentrations, and increased values of RDW, PMI, SII, and GII (all p < 0.001). GII scores increased progressively across FC categories. In ROC analysis, GII demonstrated the highest discriminatory ability for predicting FC positivity (AUC = 0.660), followed by SII and PMI. In multivariate logistic regression analysis, only NLR remained an independent predictor of FC positivity (OR = 0.65, 95% CI: 0.44–0.97; p = 0.033). Conclusions: Blood-based inflammatory indices show significant associations with fecal calprotectin levels in pediatric inflammatory bowel disease. The novel GII may reflect the integrated systemic inflammatory burden related to intestinal involvement, while NLR appears to be a robust and practical independent marker. These indices may serve as adjunctive, rapid, and cost-effective supportive tools in clinical decision-making, although their moderate diagnostic performance limits their use as standalone screening markers. 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