Anat Guz-Mark

Objectives: Potential celiac disease (PCD) is defined by positive celiac serology without villous atrophy. We aimed to study the outcome of children with PCD consuming a gluten‐containing diet (GCD) over time. Methods: Children diagnosed with PCD between December 2018 and January 2022, in three pediatric gastroenterology centers, were longitudinally followed. Data were collected until October 2024, with a minimum follow‐up of 12 months, unless celiac disease (CeD) was diagnosed earlier. Baseline data included demographics, celiac serology, and histological findings. Follow‐up data included serology and biopsy results when performed. Results: The cohort included 88 patients with PCD, with a mean follow‐up of 39 (range 12– 69) months. During this period, 17 (19.5%) patients progressed to CeD. Normalization of anti‐tissue transglutaminase antibodies (tTG), while continuing a GCD, occurred in 33/88 (37.5%) while the rest remained with PCD. Specifically, among 16 patients with tTG levels >×10 upper limit of normal (ULN) at PCD diagnosis, three (18.8%) progressed to CeD, six (37.5%) normalized tTG while continued GCD, and the rest remained unchanged. Asymptomatic patients had higher rates of tTG normalization (61.9% vs. 35.8%, p = 0.0011). Neither tTG levels, nor having Marsh 1 histology, had a significant effect on PCD outcomes. Conclusions: Among pediatric patients with PCD, during a mean follow‐up of 3.3 years, one‐fifth progressed to CeD. Baseline serology levels do not reliably predict future mucosal deterioration. Over a third of children with PCD may achieve serological normalization while maintaining a GCD. This heterogeneous pattern of PCD warrants periodic serological and histological follow‐up.

Objectives: Celiac disease (CeD) is a common autoimmune condition requiring lifelong adherence to a gluten‐free diet (GFD). Patients and caregivers increasingly seek information online, and large language models (LLMs) have emerged as potential educational tools. However, their reliability in CeD remains uncertain. This study aimed to evaluate the performance of three popular LLMs in answering frequently asked questions (FAQs) about CeD and GFD management. Methods: We conducted a cross‐sectional comparative evaluation in which 12 FAQs were submitted to three LLMs: ChatGPT‐4 (OpenAI), Gemini Flash 2.5 (Google), and Claude Sonnet 3.7 (Anthropic). Six pediatric gastroenterologists with expertise in CeD research and education, independently assessed and rated responses for accuracy, completeness, clarity, and overall quality using a 5‐point Likert scale. Results: The mean overall score across models was 4.3 ± 0.35 out of 5. Clarity received the highest ratings (4.56 ± 0.21), followed by accuracy (4.26 ± 0.52), completeness (4.17 ± 0.21), and overall quality (4.20 ± 0.36). Responses to management‐related questions scored significantly higher than those to diagnostic questions (4.4 vs. 4.2, p = 0.013). Inter‐rater reliability was good (intraclass correlation coefficient = 0.74). Overall, Gemini achieved the highest ratings ( p < 0.01). Conclusions: LLMs provide clear and generally accurate responses to CeD FAQs, particularly on management‐related topics. While they represent a promising tool for patient education, variability in accuracy highlights the need for clinician oversight when interpreting artificial intelligence‐generated medical information.

Current professional guidelines enable diagnosing pediatric Celiac Disease (CeD) without a biopsy, when tissue transglutaminase (TTG) IgA antibodies are > × 10 the upper limit of normal (ULN) and anti-endomysial antibodies (EMA) are positive in a second sample. We compared baseline characteristics and serology normalization in children diagnosed with or without biopsies. A retrospective study of pediatric patients diagnosed with CeD during 2020: group A, no biopsy and group B, biopsy-based diagnosis. Baseline characteristics included demographics, anthropometrics, symptoms, family history, and celiac serology. Follow-up at 6-month intervals, up to 18 months, included dietary compliance, symptoms, and serology. Of 145 children diagnosed with CeD, 42 (29%) and 103 (71%) were from group A and B respectively. Mean age was 7.8 years (range 2.4–17.9 y), 91 (62.8%) females. Baseline symptoms or signs were present in 93 (64.1%) children, without significant difference between the groups. Baseline TTG levels were > × 10 ULN in all patients in group A and 71 (68.9%) in group B. Among these patients, the rate of TTG decline during follow-up did not differ at any time point between patients diagnosed with and without biopsy, and between patients with and without symptoms. At the last follow-up visit, 24 (57%) children in group A and 46 (65%) in group B had TTG < × 3 ULN without significant difference between the groups. Conclusion: Rate of TTG decline did not differ between CeD patients diagnosed with and without biopsy, suggesting that, at least in short term, no biopsy approach may not change patients’ adherence and families’ attitude towards treatment. What is Known: • Based on current guidelines, there is a rise in the incidence of pediatric celiac disease (CeD) diagnosis without an intestinal biopsy. • There is insufficient data regarding patients’ adherence to treatment, including pattern of serology decline, based on the method of CeD diagnosis. What is New: • Children with CeD have similar baseline characteristics, including presence or absence of symptoms, whether diagnosed with or without biopsies. • During 18-month follow-up, the rate of celiac serology decline, and the reported adherence to treatment, do not differ between patients diagnosed based on biopsy or no biopsy approaches.

OBJECTIVES: This study described disease characteristics and long-term outcomes in patients diagnosed with very early onset inflammatory bowel disease (VEOIBD) (diagnosed before 6 years of age) and infantile-IBD (before 2 years). METHODS: Cases from 21 centers worldwide diagnosed with VEOIBD (2008–2018), with minimum 2 years of follow-up, were retrospectively reviewed. RESULTS: The cohort included 243 patients (52% males, median follow-up of 5.8 [range 2−18] years, including 69 [28%]) with infantile-IBD. IBD subtypes included Crohn’s disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU) in 30%, 59%, and 11%, respectively. Among patients with CD, 94% had colonic involvement, and among patients with UC/IBDU, 75% had pancolitis. Patients with infantile-IBD presented with higher rates of IBDU, lower hemoglobin and albumin levels, and higher C-reactive protein, and had lower response rates to first-induction therapy and corticosteroids therapy (P < .05 for all). Colectomy and diversion surgeries were performed in 11% and 4%, respectively, with no significant differences between age groups. Corticosteroid-free remission rates were 74% and 78% after 3 and 5 years, respectively, and 86% at end of follow-up. Genetic testing was performed in 96 (40%) patients. Among tested population, 15 (16%) were identified with monogenic disease. This group demonstrated lower response rates to induction therapies, higher rates of surgical intervention, and higher rates of major infections (P < .05 for all). CONCLUSIONS: Patients with VEOIBD, including infantile-IBD, exhibit low rate of complications and surgical interventions at the long term. Patients with monogenic IBD are at risk for more severe disease course.

Background and Objectives: Potential Celiac Disease (PCD) is defined by positive celiac serology without villous atrophy. We aimed to describe the short-term outcome of pediatric PCD while consuming a gluten-containing diet (GCD). Materials and Methods: Retrospective analysis of pediatric PCD patients continuing GCD, between December 2018–January 2022. Baseline demographics, celiac serology and duodenal biopsy results were reviewed. Follow-up data included repeated serology and biopsy results when performed. Minimum follow-up was 12 months unless celiac disease (CeD) was diagnosed earlier. Results: PCD was diagnosed in 90 children (71% females) with a mean age of 7.2 (range 1.8–16.5) years. Baseline anti-tissue transglutaminase (TTG) levels were above 10 times the upper limit of normal (ULN) in 17/90 (18.9%), 3–10 × ULN in 56/90 (62.2%) and 1–3 × ULN in 17/90 (18.9%). During follow-up, the mean time was 17.6 (range 5–35) months, TTG normalized in 34/90 (37.8%), was stable in 48/90 (53.3%), and increased or remained >10 × ULN in 8/90 (8.9%). In 20/90 (22.2%) patients, a repeat endoscopy was performed, leading to CeD diagnosis in 12/20 (60%). Thus, at the end of follow-up, CeD was diagnosed in 12/90 (13.3%). In patients with TTG >10 × ULN at diagnosis, TTG normalized in 5/17, decreased to 3–10 × ULN in 8/17, and remained above 10 × ULN in 4/17. Conclusions: During the short-term follow-up of pediatric PCD patients, less than 15% progressed to CeD. A third had normalized TTG levels, including children with TTG >10 × ULN, indicating the need for periodic serological and histological follow-up among PCD patients.

Objective: There is no gold standard to assess adherence to gluten‐free diet (GFD) among patients with celiac disease (CeD). Gluten immunogenic peptides (GIPs) in urine and stool were suggested as novel markers for evaluating adherence to GFD. Our aim was to assess the presence of GIP in pediatric patients with CeD, and to compare the results with alternative methods for evaluating GFD adherence.Methods: Pediatric patients diagnosed with CeD, who were on GFD for at least 1 year, were enrolled and followed prospectively between November 2018 and January 2021. Study visits included clinical assessment, a dietitian interview, Biagi score, food questionnaires, anthropometric and laboratory measurements, and urine and stool samples obtained for laboratory GIP analysis.Results: The study included 74 patients (63.5% females), with median (interquartile range, IQR) age of 9.9 (7.8–11.7) years, and median (IQR) duration on GFD of 2.5 (2–5.5) years. Good GFD adherence, assessed by Biagi score, was reported in 93.1% of cases. GIP was evaluated during 134 visits, with GIP detected in 27 of 134 (20.1%) of the visits (16.3% of stool samples and 5.3% of urine samples). Positive GIP results were significantly more common in males compared to females (30.6% vs 14.1%, respectively, P < 0.05). Detection of positive GIP was not associated with dietary assessment of GFD adherence, celiac serology results, or reported symptoms.Conclusions: Stool and urine GIP can be detected in children with CeD, even when dietary assessment indicate good adherence to GFD. The role of GIP testing in clinical practice should be further explored.

Objectives: The glucagon‐like peptide‐2 analog Teduglutide has been shown to enhance intestinal absorption and decrease parenteral nutrition (PN) requirements in short bowel syndrome (SBS). As data in children is limited, we evaluated nationwide real‐life experience and treatment outcome in children with SBS.Methods: Longitudinal data of children treated with Teduglutide for ≥3 months was collected. Data included demographic and medical background, anthropometrics, laboratory assessments and PN requirements. Treatment response was defined as >20% reduction in PN requirement.Results: The study included 13 patients [54% males, median (interquartile range {IQR}) age of 6 (4.7–7) years]. The most common SBS etiology was necrotizing enterocolitis (38%), and median (IQR) small bowel length was 20 (15–40) cm. Teduglutide treatment ranged between 3 and 51 months [median (IQR) of 18 (12–30) months], with 10 patients (77%) treated >1 year. Response to treatment was observed in 8 patients (62%), with a mean [±standard deviation (SD)] treatment duration of 5.9 (±3.2) months. Among responders, 2 patients were weaned off PN and additional 4 decreased PN needs by >40%. There was a median (IQR) reduction in PN volume/kg of 36% (15%–55%) and in PN energy/kg of 27% (6%–58%). Response was not associated with patients’ background, and no correlation was found with bowel length or PN dependency at baseline.Conclusions: Real‐life response to Teduglutide is highly variable among children with SBS. While most patients did reach 20% reduction in PN, less achieved further significant reduction or enteral autonomy. No predictive factors of response to treatment were identified, and large multicenter studies are needed to elucidate predictive factors and long‐term outcome.

Background: The European Society for Clinical Nutrition and Metabolism database for chronic intestinal failure (CIF) was analyzed to investigate factors associated with nutritional status and the intravenous supplementation (IVS) dependency in children. Methods: Data collected: demographics, CIF mechanism, home parenteral nutrition program, z-scores of weight-for-age (WFA), length or height-for-age (LFA/HFA), and body mass index-for-age (BMI-FA). IVS dependency was calculated as the ratio of daily total IVS energy over estimated resting energy expenditure (%IVSE/REE). Results: Five hundred and fifty-eight patients were included, 57.2% of whom were male. CIF mechanisms at age 1–4 and 14–18 years, respectively: SBS 63.3%, 37.9%; dysmotility or mucosal disease: 36.7%, 62.1%. One-third had WFA and/or LFA/HFA z-scores < −2. One-third had %IVSE/REE > 125%. Multivariate analysis showed that mechanism of CIF was associated with WFA and/or LFA/HFA z-scores (negatively with mucosal disease) and %IVSE/REE (higher for dysmotility and lower in SBS with colon in continuity), while z-scores were negatively associated with %IVSE/REE. Conclusions: The main mechanism of CIF at young age was short bowel syndrome (SBS), whereas most patients facing adulthood had intestinal dysmotility or mucosal disease. One-third were underweight or stunted and had high IVS dependency. Considering that IVS dependency was associated with both CIF mechanisms and nutritional status, IVS dependency is suggested as a potential marker for CIF severity in children.

Objective: Tissue‐transglutaminase antibodies (TGA) may be used to diagnose celiac disease (CD) without biopsy in selected cases. We aimed to investigate real‐life performance of a CD serology automated analyzer (Bioplex2200), and to explore the correlation between TGA levels and intestinal biopsies in children.Methods: A retrospective review was performed in 2 pediatric gastroenterological centers, between November 1, 2018 and April 1, 2020 and included patients with both TGA serology testing and duodenal biopsies. Retrieved data included patients’ demographics, medical background, TGA levels, and biopsy results.Results: Overall, 538 children were evaluated, 256 with positive TGA (68.4% girls, median age 6.4 years), and 282 with negative TGA (53.9% girls, median age 13.4 years). Among patients with positive TGA, intestinal biopsies confirmed CD in 219 (85.5%). Overall, positive serology with normal histology was found in 14.5% of the cohort, with 52%; 21.6%; 21.1%; and 4.2% in TGA ranges of 1 to 3 times upper limit of normal (ULN); 3 to 5 ULN; 5 to 10 ULN; and above 10 times ULN, respectively, P < 0.001. Area under the receiver‐operating characteristic curve (AUC) was 0.963 (95% CI 0.947–0.980). Among patients with positive TGA, 216 (84.4%) had positive anti‐endomysial antibodies. In this sub‐group, the overall diagnostic performance was inferior, with AUC of 0.737 (95% CI 0.834–0.839).Conclusions: The Multiplex TGA assay had a very high diagnostic accuracy in real‐life. Among patients with positive TGA, adding EMA did not improve the diagnostic performance of the test. False‐positive rates differed between different ranges of TGA and were low with TGA above 10 times ULN.