To assess the impact of the biological era on colectomy rates in ulcerative colitis (UC) patients and identify factors associated with the necessity for colectomy in a large cohort from Eastern Europe.

A retrospective cohort study was conducted on UC patients followed at a tertiary care center covering 1999 to 2021. Patients who underwent colectomy due to disease activity were compared to those who did not. Factors related to colectomy and the influence of the biological era were analyzed.

Among 1197 patients with a median follow-up of 3.3 years, 18% received biological agents and 5.3% underwent colectomy due to disease activity. The colectomy rate was lower in the biological era compared to the pre-biological era (2% vs. 12%; p < 0.001). Independent predictors of colectomy included steroid dependency, steroid resistance, lack of mucosal remission, and elevated CRP levels. Patients who achieved and maintained mucosal remission and had CRP levels below 3 mg/L had a significantly lower risk of colectomy.

The biological era has significantly reduced colectomy rates in UC patients. Achieving mucosal remission and maintaining low CRP levels are essential for preventing colectomy and improving long-term outcomes.

Background: Individuals with inflammatory bowel diseases (IBDs) have an increased risk of developing psychiatric co-morbidities, including restrictive eating disorders (REDs), with which they share common pathogenic mechanisms, including gut-brain axis dysregulation. We conducted a case-control study systematically exploring the psychopathological profiles and alexithymia in adolescents with IBDs compared with a clinical group of adolescents diagnosed with REDs in order to test the hypothesis of common psychological characteristics between the two patient populations. Methods: We recruited 76 patients with IBDs and 76 age-matched controls with REDs (64 adolescents with anorexia nervosa and 12 adolescents with avoidant/restrictive food intake disorder). All participants completed a validated psychometric battery assessing psychological symptoms (SCL-90-R), ED features (EDI-3), and alexithymia (TAS-20). Comprehensive socio-demographic and clinical data were extracted from the medical records. Results: A total of 12 patients with IBDs (15.8%) scored higher than the cut-off (>70th percentile) on the EDI-3 scale for Eating Disorder Risk (EDI-EDRC), with a psychological profile comparable to RED patients. Female gender (OR = 0.133, p = 0.020) and longer disease duration (OR = 1.055, p = 0.036) were identified as significant risk factors for the development of EDs. Conclusions: Our findings suggest common psychological traits between patients with REDs and patients with IBDs at risk of developing EDs during adolescence, highlighting the need for early screening for EDs in patients with IBDs who present with specific socio-demographic and disease characteristics.

This study aimed to evaluate the effect of overweight and obesity at the start of anti-TNF therapy on treatment response and relapse rate in children with inflammatory bowel disease (IBD).

This multicenter, retrospective cohort study included 22 IBD centers in 14 countries. Children diagnosed with IBD in whom antitumor necrosis factor (anti-TNF) was introduced were included; those who were overweight/obese were compared with children who were well/undernourished.

Six hundred thirty-seven children (370 [58%] males; mean age 11.5 ± 3.5 years) were included; 140 (22%) were in the overweight/obese group (OG) and 497 (78%) had BMI ≤1 SD (CG). The mean follow-up time was 141 ± 78 weeks (median 117 weeks). There was no difference in the loss of response (LOR) to anti-TNF between groups throughout the follow-up. However, children in OG had more dose escalations than controls. Male sex and lack of concomitant immunomodulators at the start of anti-TNF were risk factors associated with the LOR. There was no difference in the relapse rate in the first year after anti-TNF introduction; however, at the end of the follow-up, the relapse rate was significantly higher in the OG compared with CG (89 [64%] vs 218 [44%], respectively, P < .001). Univariate and multivariate analysis revealed that being overweight/obese, having UC, or being of male sex were factors associated with a higher risk for relapse.

Overweight/obese children with IBD were not at a higher risk of LOR to anti-TNF. Relapse in the first year after anti-TNF was introduced, but risk for relapse was increased at the end of follow-up.

Background: Pediatric-onset familial inflammatory bowel disease (IBD) may differ from sporadic pediatric-onset IBD in its genetic and environmental background and may have distinct clinical and therapeutic implications. Objective: To evaluate the influence of a positive family history of IBD on the use of medical therapies and surgical interventions in adult patients with pediatric-onset IBD. Methods: Retrospective case-control study using the Spanish ENEIDA registry, including adults diagnosed with pediatric-onset IBD since 2006. Familial forms (FFs) (defined by a first-degree relative with IBD) and sporadic forms (SF) (with no relatives of any grade with IBD) were matched 1:4 by type of IBD, sex, age at IBD diagnosis, disease location, disease pattern, development of perianal disease and smoking status at diagnosis. The study outcomes were the use of immunomodulators, biological therapies, intestinal surgery, and perianal surgery during follow-up. Results: Six-hundred and fifty-five Crohn's disease (CD) (131 FF) and 440 ulcerative colitis (UC) (88 FF) patients were included. Immunomodulators, biological therapy, and intestinal surgery were used evenly among FF and SF patients for both UC and CD. However, a higher requirement for perianal surgery among FF-CD patients (18.3% vs. 10.5%, p = 0.014), together with a shorter time to perianal surgery (11 vs. 20 months, log-rank p = 0.004), was observed. Conclusions: Patients with FF of pediatric-onset IBD do not exhibit an increased use of immunomodulators, biological agents, or intestinal surgery, but do exhibit a higher need for perianal surgery, as compared to patients with SF pediatric-onset IBD.

Stride-II recommends monitoring early biomarker targets to achieve treat-to-target (T2T) endoscopic remission (ER) in ulcerative colitis (UC). Predictive capabilities of intestinal ultrasound (IUS) for ER remain unknown. We evaluated IUS response to predict ER in children with UC.

Prospective longitudinal cohort study of children with UC (Mayo endoscopic score [MES ≥2) starting advanced therapy undergoing IUS (including Milan Ultrasound Criteria [MUC], Civitelli Ulcerative Colitis Index, and International Bowel Ultrasound Group Segmental Activity Score), fecal calprotectin (FC), C-reactive protein (CRP), and Pediatric Ulcerative Colitis Activity Index at baseline, week 8, and T2T. Primary outcome was accuracy to predict T2T ER (MES = 0) for change in bowel wall thickness (BWT) from baseline to week 8, and absolute BWT at week 8. Logistic regression with forward selection determined an optimal prediction model for endoscopic outcomes.

Of 42 children, 21 (50%) achieved ER. Week 8 BWT ≤ 2.7 mm (OR 6.4 [95% CI, 1.8-27.0], P = .007), MUC < 6.0 (OR 5.7 [95% CI, 1.5-25.3], P = .015), and FC ≤ 177 (OR 4.5 [95% CI, 1.1-23.6], P = .049) were associated with ER.

Combining noninvasive biomarkers of BWT and the MUC on IUS, and FC, is a feasible tight control monitoring strategy in children with UC that is predictive of endoscopic outcomes. Larger, multicenter validation studies are needed to understand how an IUS and FC monitoring strategy may improve outcomes in children with UC.

Data on upadacitinib therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBD-U) are scarce. We aimed to evaluate the effectiveness and safety of upadacitinib as an induction therapy in pediatric UC or IBD-U.

In this multicenter retrospective study, children treated with upadacitinib for induction of remission of active UC or IBD-U from 30 centers worldwide were enrolled. Demographic, clinical, and laboratory data, as well as adverse events (AEs), were recorded at Week 8 post-induction.

One hundred children were included (90 UC and 10 IBD-U, median age 15.6 [interquartile range 13.3-17.1] years). Ninety-eight were previously treated with biologic therapies, and 76 were treated with ≥2 biologics. At the end of the 8-week induction period, clinical response, clinical remission, and corticosteroid-free clinical remission (CFR) were observed in 84%, 62%, and 56% of the children, respectively. Normal C-reactive protein and fecal calprotectin (FC) <150 mcg/g were achieved in 75% and 50%, respectively. Combined CFR and FC remission was observed in 18/46 (39%) children with available data at 8 weeks. Adverse events were recorded in 37 children, including 1 serious AE of an appendiceal neuroendocrine tumor. The most frequent AEs were hyperlipidemia (n = 13), acne (n = 12), and infections (n = 10, 5 of whom with herpes viruses).

Upadacitinib is an effective induction therapy for refractory pediatric UC and IBD-U. Efficacy should be weighed against the potential risks of AEs.

Presence of deep ulcerations (DU) at diagnosis seems to be predictive of a more severe phenotype in adult Crohn's disease (CD). The aim of our study was to investigate if the presence of DU at diagnosis was associated with a more severe disease course over time in children.

In this monocentric retrospective study, we analysed data from paediatric patients with a new diagnosis of CD from 2009 to 2017. Clinical, laboratory data, treatments and complications were recorded for each patient at diagnosis and at 1, 3 and 5 years of follow-up. Patients were compared according to the presence or absence of DU on colonoscopy.

Among the 116 patients included in the study, 52 patients had DU at diagnosis. Comparison showed an increased risk for patients with DU to develop abdominal abscesses (p = 0.045) and to experience more relapses (p = 0.013) at 1 year. At 3 and 5 years, there was no longer any difference between groups. The time from diagnosis to first anti-TNF alpha was shorter in DU patients.

The presence of DU at diagnosis is associated with more complications during the first year of follow-up but not after, due to a more active therapeutic management.

This study aimed to characterize pain intensity (average, worst) and disease severity in youth with inflammatory bowel disease in the 12-month postdiagnosis, and to examine the relation between pain and risk (disease severity) and resilience (optimism, pain self-efficacy) factors over time.

Data collection ran from February 2019 to March 2022. Newly diagnosed youth aged 8 to 17 with IBD completed numerical rating scales for average and worst pain intensity, Youth Life Orientation Test for optimism, and Pain Self-Efficacy Scale for pain self-efficacy through REDCap; weighted Pediatric Crohn's Disease Activity Index and the Pediatric Ulcerative Colitis Activity Index were used as indicators of disease severity. Descriptive statistics characterized pain and disease severity. Multilevel modeling explored relations between variables over time, including moderation effects of optimism and pain self-efficacy.

At baseline, 83 youth ( Mage =13.9, SD=2.6; 60.2% Crohn's disease; 39.8% female) were included. Attrition rates at 4 and 12 months were 6.0% and 9.6%, respectively. Across time, at least 52% of participants reported pain. Participants in disease remission increased from 4% to 70% over 12 months. Higher disease severity predicted higher worst pain, regardless of the time since diagnosis. Higher pain self-efficacy (1) predicted lower average and worst pain, especially at later time points and (2) attenuated the association between disease severity and worst pain when included as a moderator. Higher optimism predicted lower worst pain.

Pain is prevalent in pediatric inflammatory bowel disease and impacted by disease severity, pain self-efficacy, and optimism. Findings highlight modifiable intervention targets.

Functional constipation (FC) is a common problem in childhood and the first-line therapy is macrogol. The role of FC in the onset of inflammatory bowel disease (IBD) is poorly understood. Our main aim was to investigate the prevalence of FC in children before the diagnosis of IBD.

This is a cross-sectional observational study in pediatric IBD-patients. We collected data on demographics, clinical and endoscopic characteristics at IBD diagnosis, and on the presence of FC and its treatment before IBD diagnosis.

A total of 238 children with IBD, 104 (44%) with Crohn disease (CD), 130 (56%) with ulcerative colitis (UC) and 4 (0.016%) with IBD Unclassified (IBD-U) were enrolled. The mean age was 174 ± 47 months, 56% were male. Forty-seven out of 238 (19.7%) had a FC history before the IBD diagnosis and 31 out of these 47 patients (65%) received macrogol therapy. In the FC group, we found a delay in the diagnosis of IBD compared to the group with no FC [median (interquartile range [IQR]): 5 months (2.5-9.5) and 2 months (0-4), respectively, p ≤ 0.001]. The difference in terms of endoscopic localization was statistically significant in UC patients presenting FC (p = 0.026) with a prevalence of proctitis and left side colitis (30% and 15%, respectively).

In conclusion our study highlighted a prevalence of constipation in pediatric IBD patients at diagnosis of 19.7%, which must be taken into account to avoid diagnostic delay and which is associated with limited extent of disease in UC pediatric patients.

Exclusive enteral nutrition (EEN) is highly effective in achieving remission and improving nutritional status in pediatric Crohn's disease (CD), commonly associated with altered body mass composition (BC). Bioimpedance analysis (BIA) with phase angle (PA) assessment is a noninvasive, reliable tool in screening for BC alterations. In the present study we aimed to assess the PA's usefulness in the detection of malnutrition in newly diagnosed pediatric CD, ongoing EEN treatment, and during 1-year follow-up. Patients and study design: Fourty-three patients with CD, qualified for EEN, were enrolled in the study. Additionally, 22 healthy children, being in the same age category, served as controls. Fat-free mass (FFM), fat-free mass index (FFMI), and BIA-derived PA were assessed at diagnosis, after EEN completion, and at week 52. The same parameters were obtained in the control group once. The majority of patients presented with normal body mass index at diagnosis. PA values were lower than 5 degrees in 65% of the study group. FFMI deficiencies were observed in 74% of patients. After EEN completion, an increase in FFM (P < .001) was observed. The highest mean of FFM (P < .001) and PA (P < .001) were observed at week 52. A strong correlation between PA and FFM at CD diagnosis (Spearman's rho = 0.671, r = 0.702, P < .001), after EEN completion (Spearman's rho = 0.781, P < .00) and at week 52 (Spearman's rho = 0.657, P < .001) was present. PA has been observed as positively associated with albumin concentrations both at diagnosis and after EEN. Our study provides some support that PA may be a reliable tool for screening alteration in BC, especially FFM and lean tissue mass (LTM). Moreover, PA has been observed as positively associated with albumin levels at CD diagnosis, which provides some evidence that it may be considered as a risk indicator of malnutrition and protein deficiency in newly diagnosed CD pediatric patients.

Human leukocyte antigen (HLA) DQA1*05 has been associated with the development of anti-drug antibodies (ADA) to tumor necrosis factor antagonists (anti-TNFα) and treatment failure among adults with Crohn's disease (CD). However, findings from other studies have been inconsistent with limited pediatric data.

We analyzed banked serum from patients with CD aged <21 years enrolled in clinical outcomes of Methotrexate Binary Therapy in practice, a multicenter, prospective randomized trial of anti-TNFα monotherapy vs combination with methotrexate. The primary outcome was a composite of factors indicative of treatment failure. The secondary outcome was ADA development.

A trend toward increased treatment failure among HLA DQA1*05-positive participants was not significant (hazard ratio 1.58, 95% confidence interval [CI] 0.95-2.62; P = 0.08). After stratification by HLA DQA1*05 and by methotrexate vs placebo, patients who were HLA DQA1*05 negative and assigned to methotrexate experienced less treatment failures than HLA DQA1*05-positive patients on placebo (hazard ratio 0.31, 95% CI 0.13-0.70; P = 0.005). A trend toward increased ADA development among HLA DQA1*05-positive participants was not significant (odds ratio 1.96, 95% CI 0.90-4.31, P = 0.09). After further stratification, HLA DQA1*05-negative participants assigned to methotrexate were less likely to develop ADA relative to HLA DQA1*05-positive patients on placebo (odds ratio 0.12, 95% CI 0.03-0.55; P = 0.008).

In a randomized trial of children with CD initiating anti-TNFα, 40% were HLA DQ-A1*05 positive, which was associated with a trend toward increased risk of both treatment failure and ADA. These risks were mitigated, but not eliminated, by adding oral methotrexate. HLA DQ-A1*05 is an important biomarker for prognosis and risk stratification.

The long-term efficacy and safety of infliximab (IFX) in Japanese children with inflammatory bowel disease (IBD) remain unclear. This study aimed to examine the long-term outcomes of IFX treatment in Japanese children with IBD.

We retrospectively recruited patients aged <16 years who were diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) at Kurume University Hospital in Japan between 2011 and 2022 and examined the effectiveness and safety of IFX. We characterized the responses to IFX as primary response, primary nonresponse (PNR), secondary loss of response (sLOR), or still receiving IFX.

Among the 77 enrolled patients with UC (median age, 10 years) and 48 with CD (median age, 12 years), 55 (27 with UC and 28 with CD) received IFX treatment. IFX treatment was significantly more common in patients with CD (58.3%) than in those with UC (35.1%; p=0.016). The PNR was significantly greater in patients with UC (18.5%) than in those with CD (0.0%; p=0.023), as was the sLOR (UC, 51.9%; CD, 21.4%; p=0.026). The likelihood of continuing IFX treatment during follow-up (median, 38 months) was significantly higher in patients with CD (71.4%) than in those with UC (29.6%; p=0.003). Adverse events resulting in the discontinuation of IFX occurred in 3.6% of the patients; one patient with CD developed leukemia, and the other had a serious infusion reaction.

The long-term durability of IFX in Japanese pediatric patients with IBD was inadequate in UC compared with CD. Serious adverse events in 3.6% of patients required discontinuation.

Crohn's Colitis Care, a structured, disease-specific electronic medical record, is proven to promote more complete data capture in adult Inflammatory Bowel Disease care. This study aimed to determine whether similar effectiveness was seen in pediatrics.

Matched patient records from a hospital's standard electronic medical record (pre-Crohn's Colitis Care) and those in Crohn's Colitis Care were retrospectively reviewed (12 months each). The presence of disease-specific data items per platform were compared (21 core, 5 age-specific). Data are presented as percentage recorded (recorded items/total eligible for age). Descriptive and statistical analytics were used.

Paired records were reviewed for 114 children, of whom 78 (68%) had Crohn's disease and 69 (61%) were male. Median age at diagnosis was 13.5 years (IQR12.0-15.5), with mean disease duration 3.6 years (±2.4). Crohn's Colitis Care was more likely to capture 9 items: general wellbeing, stool urgency and frequency, disease duration, comorbidities, pubertal stage, sexual activity, alcohol and drug usage (each p < 0.05). The standard platform was more likely to capture 4 items: liquid stools, phenotype, disease indices, and vaccinations (each p < 0.05). Crohn's Colitis Care achieved more eligible data items recorded per patient (75.3% ±11.5 vs. 67.7% ± 8.9; p < 0.001). Item completion rate in both platforms inversely correlated with patient age (p < 0.05).

Consistent with findings in adult care, Crohn's Colitis Care achieved more complete disease-data capture in pediatrics compared to a standard platform. Given that not all items were better recorded in the structured platform, work to understand and address barriers is needed to optimize complete data capture for care and research.

Sarcopenia has a negative impact on clinical outcome in adult patients with Crohn's Disease (CD), but data on children are scarce. The aim of this study is to evaluate the prevalence of sarcopenia in children with CD using magnetic resonance enterography (MRE) and describe its relationship with baseline values and clinical outcome.

We included children with a new diagnosis of CD from 2 tertiary referral pediatric Inflammatory Bowel Disease (IBD) centres, who underwent MRE at diagnosis between 2013 and 2023. Muscle mass was assessed by measuring the total area of the total psoas muscle (tPMA) at the level of the fourth and fifth lumbar vertebrae (L4/L5). Data were compared with pediatric reference values of tPMA, and sarcopenia was defined as a tPMA below the 3rd percentile. Demographic and anthropometric data, laboratory results, clinical disease activity and endoscopic index were collected at diagnosis and during follow-up. Clinical outcomes included relapse frequency, treatment changes, surgery, and IBD-related complications.

A total of 74 children (25 females, mean age 13.2 years) with CD were enrolled in the study. Sarcopenia was present in 34/74 patients (46 %) at diagnosis. Patients with sarcopenia had a lower Body Mass Index z-score and hemoglobin levels. Clinical disease activity (assessed using the Pediatric CD Activity Index) and endoscopic activity (assessed using the Simple Endoscopic Score for CD) were significantly higher in sarcopenic compared to non-sarcopenic children (median and quartiles scores: 25 [20, 40] vs. 21 [13, 35] and 10 [5, 13] vs. 6 [3, 13], respectively). During the follow-up period (median: 35 months; range: 1-99 months), no significant differences were observed between the sarcopenic and non-sarcopenic groups in terms of the composite outcome (defined as the occurrence of at least one unfavorable event). However, the rate of flares (number per person-year) was also higher in sarcopenic children compared to non-sarcopenic ones (27 % vs. 15 %; p = 0.0679).

Sarcopenia is highly prevalent among children with CD at diagnosis. MRE-based muscle mass measurement correlates with traditional anthropometric measurements and can be valuable for comprehensive nutritional screening in pediatric CD patients. Patients with sarcopenia presented with more severe clinical, laboratory, and endoscopic findings at diagnosis; although sarcopenic children experienced more clinical relapses we were not able to show a significant association between sarcopenia and outcomes. Larger series need to be studied.

Little is known about thepsychological correlates of inflammatory bowel diseases (IBDs) in the pediatric population. We, therefore, conducted a case-control study systematically exploring psychopathological profiles and alexithymia in adolescents with IBDs.

We recruited 52 patients with IBDs (of whom 43 in clinical remission) and 52 age- and gender-matched healthy controls. All participants completed a validated psychometric battery assessing psychological symptoms Symptom Checklist-90-Revised and alexithymia Toronto Alexithymia Scale-20.

Adolescents with IBDs reported significantly higher scores across all psychopathological domains compared to controls, with more pronounced differences in depression and obsessive-compulsive symptoms (both P < 0.001). However, there were no significant differences in alexithymia scores between the two groups.

These findings underscore the psychological distress experienced by adolescents with IBDs, emphasizing the importance of early identification and intervention to prevent the development of fully fledged psychiatric disorders. Further research is needed to better characterize the psychopathological profiles of different clinical phenotypes of IBDs and to explore possible correlations with the clinical course of these chronic conditions.

Intestinal ultrasound (IUS) is a noninvasive tool for detecting and monitoring disease activity in children with inflammatory bowel disease (IBD). Remission values for bowel wall thickness (BWT) are extrapolated from adult data. We aimed to define normal BWT in children with IBD in sustained deep remission.

Multicenter, retrospective pediatric IUS database including children with IBD, without a history of surgery or complications, who underwent IUS after achieving sustained deep remission, defined as the absence of ulcerations on ileocolonoscopy and/or transmural healing on magnetic resonance enterography and steroid-free clinical remission for ≥6 months. Univariate and multivariable analyses were performed using mixed-effect modeling.

Ninety-eight children (40 [41%] female; 64 [5%] Crohn's disease [CD]: 29 (30%) ulcerative colitis [UC]: 5 (5%) IBD-unspecified), median age 15.2 [13.8-16.8] years), and 484 bowel segments were included. Median BWT was 1.4 (1.1-1.6) mm, with no difference in BWT between bowel segments (p = 0.28). In multivariable analysis, a positive association remained between BWT and weight (univariate β = 0.004 [95% confidence interval, CI = 0.001-0.007], p = 0.016, multivariate β = 0.006 [95% CI = 0.001-0.011], p = 0.041). A negative association remained between BWT and disease duration (unadjusted β = -0.024 [95% CI = -0.047 to -0.001] p = 0.046, adjusted β = -0.028 [95% CI = -0.052 to -0.003], p = 0.039).

Previously inflamed BWT for children with IBD in sustained deep remission was less than 2.5 mm, which is less than 3 mm in adults, and unaffected by age, sex, and bowel segment in this population. BWT may be affected by weight and disease duration. These findings are crucial to the standardized assessment of transmural healing in children.

Pediatric gastroenterology is entering a pivotal phase marked by significant challenges and emerging opportunities in treating conditions like celiac disease (CeD), eosinophilic esophagitis (EoE), inflammatory bowel disease (IBD), and autoimmune hepatitis (AIH) pose significant clinical hurdles, but new therapeutic avenues are emerging. Advances in precision medicine, particularly proteomics, are reshaping care by tailoring treatments to individual patient characteristics. For CeD, therapies like gluten-degrading enzymes (latiglutenase, Kuma030) and zonulin inhibitors (larazotide acetate) show promise, though clinical outcomes are inconsistent. Immunotherapy and microbiota modulation, including probiotics and fecal microbiota transplantation (FMT), are also under exploration, with potential benefits in symptom management. Transglutaminase 2 inhibitors like ZED-1227 could help prevent gluten-induced damage. Monoclonal antibodies targeting immune pathways, such as AMG 714 and larazotide acetate, require further validation in pediatric populations. In EoE, biologics like dupilumab, cendakimab, dectrekumab (IL-13 inhibitors), and mepolizumab, reslizumab, and benralizumab (IL-5/IL-5R inhibitors) show varying efficacy, while thymic stromal lymphopoietin (TSLP) inhibitors like tezepelumab are also being investigated. These therapies require more pediatric-specific research to optimize their use. For IBD, biologics like vedolizumab, ustekinumab, and risankizumab, as well as small molecules like tofacitinib, etrasimod, and upadacitinib, are emerging treatments. New medications for individuals with refractory or steroid-dependent AIH have been explored. Personalized therapy, integrating precision medicine, therapeutic drug monitoring, and lifestyle changes, is increasingly guiding pediatric IBD management. This narrative review explores recent breakthroughs in treating CeD, EoE, IBD, and AIH, with a focus on pediatric studies when available, and discusses the growing role of proteomics in advancing personalized gastroenterological care.

The incidence of pediatric-onset inflammatory bowel disease (IBD) and the costs of caring for individuals with IBD are both increasing. We calculated the direct healthcare costs of pediatric IBD in the first year after diagnosis and developed a model to predict children who would have high costs (top 25th percentile).

Using data from the Canadian Children IBD Network inception cohort (≤16 years of age, diagnosed between 2013 and 2019) deterministically linked to health administrative data from Ontario, Canada, we estimated direct healthcare and medication costs accrued between 31 and 365 days after diagnosis. Candidate predictors included age at diagnosis, sex, rural/urban residence location, distance to pediatric center, neighborhood income quintile, IBD type, initial therapy, disease activity, diagnostic delay, health services utilization or surgery around diagnosis, regular primary care provider, and receipt of mental health care. Logistic regression with stepwise elimination was used for model building; 5-fold nested cross-validation optimized and improved model accuracy while limiting overfitting.

The mean cost among 487 children with IBD was CA$15 168 ± 15 305. Initial treatment (anti-tumor necrosis factor therapy, aminosalicylates, or systemic steroids), having a mental health care encounter, undergoing surgery, emergency department visit at diagnosis, sex, and age were predictors of increased costs, while having a regular primary care provider was a predictor of decreased costs. The C-statistic for our model was 0.71.

The cost of caring for children with IBD in the first year after diagnosis is immense and can be predicted based on characteristics at diagnosis. Efforts that mitigate rising costs without compromising quality of care are needed.

Assessment of small bowel involvement when diagnosing inflammatory bowel disease (IBD) delineates clinical subtype and disease extension. The gold standard for small bowel assessment is magnetic resonance enterography (MRE), but MRE is not always feasible for children. Standard, non-contrast enhanced abdominal ultrasound is an acceptable alternative. The study aimed to evaluate the utility of ultrasound in the diagnostic work-up of pediatric IBD to identify small bowel involvement.

A retrospective study was conducted among children (< 18 years) who had abdominal ultrasound during assessment for IBD (2019-2023) at Christchurch Hospital, New Zealand. Descriptive analysis compares small bowel ultrasound to MRE, endoscopy and histology.

The cohort comprised 47 children, mean age 9.9 years (± 4.1), 23 (49%) males and 42 (89%) with Crohn's disease. All had endoscopy and histology data available for comparison, and 26 had MRE. Fourteen (30%) had no small bowel disease on ultrasound, MRE, endoscopy, or histology. Ultrasound confirmed small bowel disease diagnosed by other modalities for 12 (26%). Ultrasound identified small bowel disease for 7 (15%) that had not been seen during the diagnostic process by MRE, endoscopy or histology, possibly due to the limitations of endoscopy and time-delays between diagnosis and MRE. Small bowel disease was not picked up on ultrasound for 14 (30%) children, disease locations being duodenum (n = 6), TI (n = 5), proximal ileum (n = 3), and jejunum (n = 2).

Abdominal ultrasound is a valuable resource for assessing disease extent in suspected pediatric IBD. This study highlights the clinical benefit and feasibility of a multi-modal diagnostic approach.

There are scarce data available on upadacitinib in children with Crohn's disease (CD).

To evaluate the effectiveness and safety of upadacitinib as an induction therapy in paediatric CD.

This was a multicentre retrospective study between 2022 and 2024 of children treated with upadacitinib for induction of remission of active CD conducted in 30 centres worldwide affiliated with the IBD Interest and Porto group of the ESPGHAN. We recorded demographic, clinical and laboratory data and adverse events (AEs) at week 8 post-induction. The analysis of the primary outcome was based upon the intention-to-treat (ITT) principle.

We included 100 children (median age 15.8 [interquartile range 14.3-17.2]). All were previously treated with biologic therapies including 89 with ≥ 2 biologics. At the end of the 8-week induction period, we observed clinical response, clinical remission and corticosteroid- and exclusive enteral nutrition-free clinical remission (CFR) in 75%, 56% and 52%, respectively. By the end of induction, 68% had achieved normalisation of C-reactive protein, and 58% had faecal calprotectin (FC) < 150 mcg/g. There was combined CFR and FC remission in 13/31 children with available data at 8 weeks (13% of the ITT population). AEs were recorded in 24 children; the most frequent was acne in 12. Two AEs (severe acne and hypertriglyceridemia) led to discontinuation of therapy.

Upadacitinib is an effective induction therapy for refractory paediatric CD. Efficacy should be weighed against the potential risks of AEs.

Inflammatory bowel disease (IBD) results from genetic susceptibility, gut microbiome, and environmental factors. Diet, one modifiable environmental factor, has been linked to the increased prevalence of IBD. This study aimed to evaluate a potential association between food deserts and disease severity at diagnosis.

This retrospective study included newly diagnosed IBD patients (ages of 2 and 21 years of age; diagnosed between January 1, 2019, and December 31, 2021). The United States Department of Agriculture (USDA's) Food Access Research Atlas was used to determine if patients resided in a food desert. The Modified Retail Food Environment Index (mRFEI) determined the ratio of healthy to unhealthy food options. The primary endpoint was disease severity at diagnosis based on endoscopy scores. Statistical analyses were applied as appropriate.

Ninety-eight patients were enrolled (75 [77%] Crohn' disease; 23 [23%] ulcerative colitis), 59 (60%) identified as Non-Hispanic White. Fifteen (15%) patients lived in a food desert. Food deserts consisted of more Black patients than White (67%; p = 0.05), more public insurance (12; 80%), and lower median vitamin D (17.6 [interquartile range (IQR): 10.8-24.]). In an adjusted (sex, age, insurance, race) multivariable model mRFEI was associated with reduced odds of a living in a food desert (0.91 [95% confidence interval (CI): 0.83-0.98]). There was no difference between the severity of disease and living in a food desert or food swamp.

Fifteen IBD patients lived in a food desert. Food deserts have less access to healthy food retailers and higher rates of unhealthy food retailers. Further work is needed to better understand spatial disparities related to food accessibility and IBD.

Many of the patients with inflammatory bowel disease (IBD) are children and adolescents, and the incidence of pediatric IBD is increasing. However, understanding epidemiological trends is crucial for effective prevention and treatment and reducing the local and global burden of IBD. Little data exist regarding the incidence of IBD in the child population in the Kujawsko-Pomorskie Voivodeship. The aims of this study were to evaluate the incidence of IBD in the period 2011 - 2022 and to compare the data regarding three types of IBD, namely ulcerative colitis (UC), Crohn's disease (CD), and unclassified inflammatory bowel disease (IBD-U), from the first half, i.e. 2011 - 2016, to the second half, i.e. 2017 - 2022.

This retrospective study analyzed the medical records of 118 IBD patients hospitalized at the Department of Pediatrics, Allergology and Gastroenterology from the central-northern part of Poland.

Of the 118 patients diagnosed with IBD, 48 (40.68%) had CD, 57 (48.31%) had UC, and 13 (11.01%) had IBD-U. Between 2011 and 2016, 48 new IBD patients were diagnosed, with a further 70 new cases added between 2017 and 2022, representing a significant increase over the period (P = 0.033). Also, a significant increase was seen for UC, i.e. rising from 19 new cases between 2011 and 2016, to 38 between 2017 and 2022 (P = 0.015). The increase in CD was not significant.

The incidence of pediatric IBD in the central-northern district of Poland is lower than other countries, it nonetheless appears to be increasing, particularly in children with UC. The number of IBD diagnoses in children has increased by nearly 50% over the last 6 years.

Quantitative magnetic resonance imaging (MRI) can evaluate bowel motility in children with Crohn's disease. As inflammation increases, motility decreases.

Our aim was to show that quantitative MRI correlates with magnetic resonance enterography (MRE). We hypothesize that the motility score will inversely correlate with the Endoscopic Biopsy Acute Histologic Inflammatory Score (eAIS), the Crohn's Disease Endoscopic Index of Severity (CDEIS) score, and the MR Index of Activity (MaRIA) score.

This was a retrospective study of 50 pediatric patients with ileal and/or cecal Crohn's disease who underwent endoscopy and MRE within 7 days of each other without exposure to therapy. Cine images were used from patients' previously obtained MREs to obtain a motility score using GIQuant (Motilent, London, UK). The relationships between the motility score and MaRIA, eAIS, and CDEIS were then calculated by Spearman's rank correlation coefficient (ρ).

The MaRIA and motility scores inversely correlated (ρ=-0.66, 95%CI (-0.79, -0.46), P<0.0001). MaRIA positively correlated with CDEIS (ρ=0.30, 95%CI (0.02, 0.53), P=0.03) and eAIS (ρ=0.26, 95%CI (0.02, 0.50), P=0.07). The motility score showed a non-significant negative correlation with CDEIS (ρ=-0.17, 95%CI (-0.43, -0.12), P=0.24) and eAIS (ρ=-0.23, 95%CI (-0.48, -0.05), P=0.11).

Quantitative MRI correlates with standard MRE in identifying inflammation of the bowel in Crohn's disease. The cine image used to produce a motility score is obtained faster than standard MRE and does not require the use of intravenous contrast, a spasmolytic agent, and breath-holding techniques.

Real-world data on ustekinumab for the treatment of pediatric Crohn's disease (CD) are limited. This study sought to evaluate the effectiveness, long-term durability, and safety of ustekinumab in the treatment of children with CD.

A retrospective longitudinal cohort study of children with CD treated with ustekinumab from two large centers between 2015 and 2020 was performed. The primary outcome was frequency of steroid-free clinical remission at 1 year. Secondary outcomes included time to steroid-free clinical remission, frequency of clinical and biochemical remission, drug escalation and discontinuation, serum level data, and adverse events. Standard descriptive and comparative statistics were performed. Logistic regression was used to identify factors associated with steroid-free remission at 1 year. Kaplan-Meier curves were used to visualize time-to-event relationships for outcomes.

A total of 101 patients were included. Median follow-up time on ustekinumab was 16.6 months (interquartile range [IQR]: 8.71-31.2) with drug failure in 28% at 1 year. Fifty-nine patients were in steroid-free clinical remission at 1 year. Higher baseline disease activity (odds ratio [OR]: 0.91 (95% confidence interval [CI]: 0.84-0.97), p = 0.01) and stricturing/penetrating disease phenotype (OR: 0.14 (95% CI: 0.03-0.65), p = 0.02) were associated with decreased likelihood of steroid-free clinical remission at 1-year. Ustekinumab drug escalation occurred in 70% of patients, and after escalation, 50 (70%) achieved clinical remission, and 49 (69%) achieved steroid-free remission at the last follow-up. Adverse events were rare and did not require therapy discontinuation.

Ustekinumab is effective and safe in the treatment of children with CD. Escalation of therapy occurs frequently but results in sustained durability.

CD4+ memory T cell (TM) reactivation drives chronicity in inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis. Defects driving loss of TM regulation likely differ between patients but remain undefined. In health, approximately 40 % of circulating gut-homing CD38+TM express co-inhibitory receptor T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT). TIGIT+CD38+TM have regulatory function while TIGITnegCD38+TM are enriched in IFN-γ-producing cells. We hypothesized TIGITnegCD38+TM are inflammatory and drive disease in a subgroup of IBD patients. We characterized TIGIT+CD38+TM in a uniquely large cohort of pediatric IBD patients from time of diagnosis into adulthood. Circulating TIGITnegCD38+TM frequencies were higher in a subgroup of therapy-naïve CD patients with high plasma IFN-γ and a more severe disease course. TIGITnegCD38+TM were highly enriched in HLA-DR+ and ex-Th17/Th1-like cells, high producers of IFN-γ. Cultures of healthy-adult-stimulated TM identified IL-12 as the only IBD-related inflammatory cytokine to drive the pathogenic ex-Th17-TIGITnegCD38+ phenotype. Moreover, IL12RB2 mRNA expression was higher in TIGITnegCD38+TM than TIGIT+CD38+TM, elevated in CD biopsies compared to controls, and correlated with severity of intestinal inflammation. Overall, we argue that in a subgroup of pediatric CD, increased IL-12 signaling drives reprogramming of Th17 to inflammatory Th1-like TIGITnegCD38+TM and causes more severe disease.

Neutrophil-to-lymphocyte ratio (NLR) is a novel biomarker studied in several autoimmune diseases including inflammatory bowel disease (IBD) in adults but poorly characterized in pediatric IBD (pIBD). We aimed to primarily investigate the relationship between NLR and pIBD endoscopic disease severity. We also examined whether NLR predicted hospitalization, surgery, and therapy response by 52 weeks.

We used the Canadian Children IBD Network prospective inception cohort including patients < 18 years old with baseline data from 2013 to 2022. We excluded patients with concurrent diseases affecting NLR. Both Mayo endoscopic score (MES) and simple endoscopic scale for Crohn's disease (SES-CD) were dichotomized as low activity (quiescent-mild) and high activity (moderate-severe). For therapy responses, we examined year-1 steroid- and biologic-free remission. We used logistic regression for binary outcomes.

A total of 580 patients with ulcerative colitis and 1,081 patients with CD were included. High NLR was associated with high-activity MES and SES-CD in both univariate and multivariable analyses (odds ratio = 1.45, 95% CI = 1.07-1.97, P value = 0.016; and odds ratio = 1.42, 95% CI = 1.04-1.94, P value = 0.026, respectively). We also calculated the best NLR cutoff point to predict MES (1.90, sensitivity = 68%, specificity = 67%, area under the curve [AUC] = 0.67, AUC 95% CI = 0.59-0.74) and SES-CD (2.50, sensitivity = 63%, specificity = 69%, AUC = 0.66, AUC 95% CI = 0.59-0.75) high activity. NLR did not predict therapy response in either ulcerative colitis or CD.

Patients with pIBD with high baseline NLR are more probable to have worse endoscopic disease at diagnosis. This highlights NLR potential as a reliable noninvasive biomarker of disease activity. The predictive power of NLR is based mostly on neutrophils and the balance between neutrophils and lymphocytes.

Mucosal healing (MH) is a key therapeutic target in Crohn's disease (CD) and is associated with improved outcomes. While adult studies indicate a positive correlation between serum anti-tumor necrosis factor (TNF) levels and MH, data in pediatric patients is limited. We aimed to define the association of serum anti-TNF levels with MH in pediatric patients with CD during maintenance therapy.

Retrospective data (2014-2023) was collected from pediatric CD patients treated with infliximab or adalimumab who performed an ileocolonoscopy at least 26 weeks after initiating therapy. Serum anti-TNF levels around endoscopic time were compared with endoscopic findings. MH was defined as complete absence of inflammatory or ulcerative lesions across all segments of the gastrointestinal tract. Univariable and multivariable logistic regression analysis was conducted to identify factors associated with MH.

Data were obtained from 107 patients (41 infliximab and 66 adalimumab), with a median age at diagnosis of 12.6 (9.9-14.0) years. Median time until ileocolonoscopy following anti-TNF initiation was 89.0 (56.3-152.3) weeks. MH was identified in 31 (29.0%) patients. Anti-TNF serum levels were comparable in the MH and non-MH groups (9.5 [4.9-13.9] vs. 9.3 [6.4-15.7] µg/mL; p = 0.73), without differences in patients treated with infliximab or adalimumab. In multivariable analysis, diagnosis weight Z-score (odds ratio [OR] = 2.860, 95% confidence interval [CI] = 1.005-8.138; p = 0.049), along with C-reactive protein (OR = 0.037, 95% CI = 0.002-0.687; p = 0.027) and fecal calprotectin (OR = 0.995, 95% CI = 0.990-1.000; p = 0.037) at time of ileocolonoscopy were significantly associated with MH.

In our cohort, anti-TNF levels during maintenance were not associated with MH in pediatric CD.

We determined the prevalence of anemia and its characteristics in children with newly diagnosed inflammatory bowel disease (IBD) and investigated its trend during follow-up.

An observational, multicenter cohort study of IBD children with anemia at the diagnosis enrolled in the Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition IBD registry. Data were collected at the diagnosis and at 1 year.

Five hundred eighty-nine (295 Crohn's disease [CD] [50%] and 294 ulcerative colitis [UC]/IBD unclassified [IBDU] [50%]) of 1634 patients with IBD presented with anemia (36%). Anemia rate was higher in CD than in UC (39% vs. 33%, p = 0.009), and most patients had moderate anemia (55%). Children with CD had higher rates of mild anemia than UC (38% vs. 33%, p < 0.0001), while severe anemia was more common in UC (13% vs. 6%, p = 0.001). In CD, lower age at the diagnosis and lower albumin level correlated with anemia severity (p = 0.0007 and <0.0001, respectively). In UC, severe disease was more common in patients with severe anemia compared to those with mild and moderate anemia (20.6% vs. 43.6%, p = 0.01; 17% vs. 43.6%, p = 0.001). At 1 year, 99 children (22.9%) were persistently anemic and were characterized by a more severe disease compared to those who had resolved their anemia.

More than one third of IBD children present with anemia, most commonly moderate. Severe anemia is more common in UC compared to CD. One in four patients is still anemic after 1 year from the diagnosis, suggesting inadequate attention to the issue and the need for dedicated therapeutic management and careful monitoring.

This study aims to evaluate and compare the perspectives of pediatric Crohn's disease (CD) patients and their parents/caregivers concerning global physical, emotional, and social health as well as health-related quality of life (HRQQL), using both the Patient-Reported Outcomes Measurement Information System (PROMIS) and the IMPACT III questionnaire.

In a cross-sectional study, 31 dyads of pediatric CD patients (aged 8-17 years) and their parents/caregivers were recruited from an outpatient Pediatric Gastroenterology Center. Participants completed PROMIS (Global Health, Depressive Symptoms, Anxiety, Meaning and Purpose Pain Interference Life Satisfaction, Peer Relationships, Physical Activity and Fatigue) and IMPACT III measures. Comparative analyses using t-tests and multivariate analyses assessed the impact of demographic factors on score differences. Cohen's Kappa analysis evaluated the alignment between parent and child perceptions of disease status.

The sample comprised 58% females with a mean age of 15.2 (± 2) years and a mean disease duration of 2.7 (± 2.7) years. Most patients were in disease remission (83.9%) and perceived their disease as better or unchanged in the past 6 months. Concerning PROMIS scores, parents reported significantly lower global health scores (p < 0.001) and higher meaning and purpose scores (p = 0.029) compared to their children. Parental education and professional status significantly influenced PROMIS score differences. Specifically, mothers with specialized professions showed smaller differences in PROMIS depression and pain interference, although greater differences in PROMIS meaning and purpose, as compared to their respective children's scores. Fathers with specialized professions demonstrated greater differences in PROMIS anxiety scores but smaller differences in PROMIS life satisfaction scores. A significant misalignment between parent and child subjective perceptions of disease status was observed (p = 0.004), suggesting that parents may overestimate symptom severity or underestimate improvements compared to their children's experiences.

This study highlights the importance of integrating patient and parental perspectives in the clinical management of pediatric CD. The observed discrepancies in disease-related perceptions, influenced by parental educational and professional background, underscore the need for comprehensive assessments to ensure accurate, patient-centered care. For broader generalization, further research should explore these dynamics in newly diagnosed and hospitalized patients.