Familial Mediterranean fever in patients with inflammatory bowel diseases: A nationwide study from the epi-IIRN.

BACKGROUND AND AIMS: Inflammatory Bowel Diseases (IBD) and Familial Mediterranean Fever (FMF) are auto-inflammatory diseases with common clinical and biological features. We aimed to determine their association and characterize the natural history in patients with both diagnoses. METHODS: Utilizing data from the epi-IIRN cohort, which includes 98% of Israel's population, we calculated the adjusted prevalence of FMF among IBD patients vs non-IBD controls. Case ascertainment of IBD was determined according to validated algorithms and for FMF by ICD-9 codes and colchicine purchase. RESULTS: In total, 34 375 IBD patients (56% Crohn's disease [CD] and 44% ulcerative colitis [UC]) were compared with 93 602 matched controls. Among IBD patients, 157 (0.5%) had FMF compared with 160 (0.2%) of non-IBD controls (OR = 2.68 [95%CI 2.2-3.3]; p< 0.001). Pediatric-onset IBD had a higher prevalence of FMF compared with adult-onset IBD (30/5,243 [0.6%] vs 127/29 132 [0.4%]), without statistical significanse (OR = 1.31 [0.88-1.96]; p= 0.2). FMF was more prevalent in CD (114/19 264 [0.6%]) than UC (43/15 111 [0.3%]; OR = 2.1 [1.5-3.0]), p< 0.001). FMF diagnosis preceded that of IBD in 130/157 cases (83%). FMF was associated with a more severe disease activity in UC patients at diagnosis, but not in CD patients. Outcomes were comparable between patients with CD+FMF vs CD alone; however in patients with UC+FMF, time to biologic treatment was shorter. CONCLUSION: FMF is more prevalent in IBD patients than in the general population, particularly in CD. The diagnosis of FMF precedes the diagnosis of IBD in most cases, and may be associated with a more severe course in UC.

Severe Unexplained Iron Deficiency Anemia in Children: High Yield of Upper Gastrointestinal Endoscopy Regardless of Gastrointestinal Symptoms.

In this retrospective study spanning 2016 to 2022, we aimed to evaluate the diagnostic utility of upper gastrointestinal endoscopy (UGE) in children under 18 years presenting with severe unexplained iron deficiency anemia (IDA), defined as microcytic anemia of hemoglobin ≤7 g/dL with low ferritin levels. Of 106 children hospitalized for severe anemia, 29 had unexplained IDA (mean hemoglobin level of 6.2 [3.2 to 6.9] gr/dL), and 25 of them underwent UGE. The mean age was 10.7 ± 3.9 years, with 76% being female. Ten children (40%) had gastrointestinal (GI) symptoms at presentation. The cause of IDA was found in 18 (72%) of 25 children who underwent UGE, of whom 12 were without GI symptoms. Gastric nodularity, erosions, or polyps were observed in 68%, and gastritis was evident in 72% based on histopathology. Helicobacter pylori was found in 50% of those with gastritis. Follow-up showed normalized hemoglobin levels in 92% of cases, with only 2 children requiring repeat iron therapy. Our findings underscore the importance of incorporating UGE into the diagnostic investigation of severe unexplained IDA in children, irrespective of the presence of GI symptoms.

Helicobacter pylori infection found during upper endoscopy performed for the diagnosis of celiac, inflammatory bowel diseases, and eosinophilic esophagitis: A multicenter pediatric European study.

BACKGROUND: Helicobacter pylori may be found during upper gastrointestinal endoscopy (UGE) performed to diagnose celiac disease (CeD), inflammatory bowel disease (IBD), and eosinophilic esophagitis (EoE). We aimed to describe the frequency of H. pylori in children undergoing UGE for CeD, IBD, and EoE and the number of children receiving eradication treatment. MATERIALS AND METHODS: A retrospective multicenter study from 14 countries included pediatric patients diagnosed with CeD, IBD, and EoE between January 2019 and December 2021. DATA COLLECTED: age, gender, hematologic parameters, endoscopic, histologic, and H. pylori culture results, and information on eradication treatment. RESULTS: H. pylori was identified in 349/3890 (9%) children [167 (48%) male, median 12 years (interquartile range 8.1-14.6)]. H. pylori was present in 10% (173/1733) CeD, 8.5% (110/1292) IBD and 7.6% (66/865) EoE patients (p = NS). The prevalence differed significantly between Europe (Eastern 5.2% (28/536), Southern 3.8% (78/2032), Western 5.6% (28/513)) and the Middle East 26.6% (215/809) [odds ratio (OR) 7.96 95% confidence interval (CI) (6.31-10.1) p < 0.0001]. Eradication treatment was prescribed in 131/349 (37.5%) patients, 34.6% CeD, 35.8% IBD, and 56.1% EoE. Predictors for recommending treatment included erosions/ulcers [OR 6.45 95% CI 3.62-11.47, p < 0.0001] and nodular gastritis [OR 2.25 95% CI 1.33-3.81, p 0.003]. Treatment rates were higher in centers with a low H. pylori prevalence (<20%) [OR 3.36 95% CI 1.47-7.66 p 0.004]. CONCLUSIONS: Identifying H. pylori incidentally during UGE performed for the most common gastrointestinal diseases varies significantly among regions but not among diseases. The indications for recommending treatment are not well defined, and less than 40% of children received treatment.

Giardia lamblia Diagnosed During Upper Gastrointestinal Endoscopy: Clinical Manifestation, Histopathologic Findings and the Association With Celiac Disease.

BACKGROUND: Giardia lamblia may be found incidentally during upper gastrointestinal (GI) endoscopy, including when biopsies are taken for celiac disease (CeD) diagnosis. We aimed to study the clinical presentation and histopathology of G. lamblia and determine its association with CeD. METHODS: A retrospective case series of pediatric patients diagnosed with G. lamblia based on intestinal biopsies between January 1999 and January 2023. Baseline data; demographics, symptoms, celiac serology, stool testing, macroscopic and histopathologic findings. Follow-up data; treatment and repeated celiac serology. RESULTS: Of 38 patients with G. lamblia , 15 (39.5%) were female, mean age of 6.7 (±4.8 SD) years. Clinical symptoms; GI 19/38 (50%), growth retardation and/or iron deficiency anemia 8/38 (21.1%) or a combination 11/38 (28.9%). Celiac serology was positive in 13/38 (34.2%). Duodenal endoscopic findings; normal (n = 23, 60.5%), nodularity (n = 12, 32.4%), erosions in 2 (5.4%) and scalloping in 1 (2.7%). Histopathology; normal villi 24/38 (63.2%), villous shortening with increased intraepithelial lymphocytes (IEL) 5/38 (13.2%), isolated IEL 3/38 (7.9%) and duodenitis in 6/38 (15.8%). Children with positive CeD serology were younger (4 vs. 8.1 years, P = 0.019), had fewer GI symptoms (23.1% vs. 64%, P = 0.017) and a higher rate of villous shortening with increased IEL (38.5% vs. 0, P < 0.001) versus children with negative serology. On follow-up, metronidazole treatment was recommended to all but was documented to be given in 22/38 (57.9%). Among the 13 children with positive CeD serology, serology normalized in 10 (77%). CONCLUSIONS: G. lamblia is a rare histopathologic finding in children. It may be an incidental finding in CeD or may cause false positive celiac serology.

Characterization and Short-Term Outcome of Potential Celiac Disease in Children.

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.

Helicobacter pylori Found Incidentally During Upper Endoscopy Performed for Diagnosis of Common Pediatric Gastrointestinal Diseases.

BACKGROUND: Helicobacter pylori ( H. pylori ) gastritis may be an incidental finding during upper endoscopy performed to diagnose celiac disease (CeD), inflammatory bowel disease (IBD) and eosinophilic esophagitis (EoE). We aimed to describe the incidence of H. pylori in children undergoing endoscopy for CeD, IBD and EoE and determine the indications for treatment. METHODS: A retrospective, single-center study based on the review of endoscopy reports of pediatric patients, diagnosed with CeD, IBD and EoE, between January 2017 and December 2021. Data collected included; age, gender, hematologic parameters, endoscopic, histologic and H. pylori culture results, and information on eradication treatment. RESULTS: H. pylori gastritis was diagnosed in 120 of 558 (21.5%) children [72 (60%) female, mean age 10.6 years] during gastroscopy performed for the diagnosis of other GI diseases. H. pylori was present in 87 of 404 (21.5%) CeD, 27 of 113 (23.9%) IBD and 6 of 41 (14.6%) EOE patients ( P = 0.46). The main indication for treatment was the presence of ulcers, in 4 of 120 (3.3%), and erosions in 17 of 120 (14.2%). Eradication treatment was recommended in 22 of 120 (18.3%) patients, 8 of 87 (9.2%) CeD, 10 of 27 (37%) IBD and 4 of 6 (66.7%) EoE patients, P < 0.001. Four independent positive treatment predictors were identified; age above 10 years {odds ratio (OR) = 10.57 [95% confidence interval (CI) 1.88-59.36], P = 0.007} the presence of nodular gastritis (OR = 5.03 [95% CI 1.09-23.15], P = 0.38), erosions [OR = 49.21 (95% CI 8.19-295.83), P < 0.000] and ulcers [OR = 22.69 (95% CI 1.25-410.22), P = 0.035]. CeD was a strong negative predictor for treatment [OR = 0.23 (95% CI 0.002-0.241), P = 0.002]. CONCLUSIONS: H. pylori gastritis is a common incidental finding during endoscopy. The indications for treatment are not well defined and should be further investigated.

Clinical Features and Natural History of Paediatric Patients with Ulcerative Proctitis: A Multicentre Study from the Paediatric IBD Porto Group of ESPGHAN.

BACKGROUND AND AIMS: Ulcerative proctitis [UP] is an uncommon presentation in paediatric patients with ulcerative colitis. We aimed to characterize the clinical features and natural history of UP in children, and to identify predictors of poor outcomes. METHODS: This was a retrospective study involving 37 sites affiliated with the IBD Porto Group of ESPGHAN. Data were collected from patients aged <18 years diagnosed with UP between January 1, 2016 and December 31, 2020. RESULTS: We identified 196 patients with UP (median age at diagnosis 14.6 years [interquartile range, IQR 12.5-16.0]), with a median follow-up of 2.7 years [IQR 1.7-3.8]. The most common presenting symptoms were bloody stools [95%], abdominal pain [61%] and diarrhoea [47%]. At diagnosis, the median paediatric ulcerative colitis activity index [PUCAI] score was 25 [IQR 20-35], but most patients exhibited moderate-severe endoscopic inflammation. By the end of induction, 5-aminosalicylic acid administration orally, topically or both resulted in clinical remission rates of 48%, 48%, and 73%, respectively. The rates of treatment escalation to biologics at 1, 3, and 5 years were 10%, 22%, and 43%, respectively. In multivariate analysis, the PUCAI score at diagnosis was significantly associated with initiation of systemic steroids, or biologics, and subsequent acute severe colitis events and inflammatory bowel disease-associated admission, with a score ≥35 providing an increased risk for poor outcomes. By the end of follow-up, 3.1% of patients underwent colectomy. Patients with UP that experienced proximal disease progression during follow-up [48%] had significantly higher rates of a caecal patch at diagnosis and higher PUCAI score by the end of induction, compared to those without progression. CONCLUSION: Paediatric patients with UP exhibit high rates of treatment escalation and proximal disease extension.

The Association of Inflammatory Bowel Disease with Coeliac Disease and Coeliac Autoimmunity in Children and Adults: A Nationwide Study from the epi-IIRN.

BACKGROUND AND AIMS: Given the paucity of population-based data on the association between inflammatory bowel diseases [IBD], coeliac disease [CeD], and coeliac autoimmunity [CeA] we aimed to study the associations in a nationwide study. METHODS: Using health administrative data for all four health maintenance organisations in Israel, covering 98% of the population, we explored the prevalence of CeD in children and adults with IBD versus non-IBD matched controls. CeD was defined by three ICD-9 codes and CeA by positivity for tissue transglutaminase antibodies. RESULTS: In total, 34 375 IBD patients (56% Crohn's disease [CD] and 44% ulcerative colitis [UC]) were compared with 93 603 non-IBD controls. Among IBD patients, 319 [0.93%] had CeD versus 294 [0.31%] non-IBD controls (odds ratio [OR] = 2.97, 95% confidence interval [CI] 2.54-3.48; p <0.001). CeA was identified in 575 [1.67%] IBD patients vs 158 [0.17%] controls [OR = 10.06, 95% CI 8.43-12; p <0.001]. The prevalence of CeD was higher in paediatric-onset IBD (87/5243 [1.66%]) than adult-onset IBD (232/29 132 [0.79%]; p <0.001). CD patients had a higher prevalence of CeD (229/19 264 [1.19%]) than UC patients (90/15 111 [0.56%]; OR = 2.01, 95% CI 1.57-2.56; p <0.001). The diagnosis of CeD preceded the diagnosis of IBD in 241/319 cases [76%]. The time to treatment escalation was shorter in patients with both IBD and CeD than in patients with IBD without CeD [p = 0.017]. CONCLUSION: CeD and CeA are more prevalent in IBD patients, especially in paediatric-onset IBD and in CD. The diagnosis of CeD usually precedes that of IBD. Having CeD is associated with more intensified treatment for IBD.

Management of Helicobacter pylori infection in paediatric patients in Europe: results from the EuroPedHp Registry.

PURPOSE: The EuroPedHp-registry aims to monitor guideline-conform management, antibiotic resistance, and eradication success of 2-week triple therapy tailored to antibiotic susceptibility (TTT) in Helicobacter pylori-infected children. METHODS: From 2017 to 2020, 30 centres from 17 European countries reported anonymized demographic, clinical, antibiotic susceptibility, treatment, and follow-up data. Multivariable logistic regression identified factors associated with treatment failure. RESULTS: Of 1605 patients, 873 had follow-up data (53.2% female, median age 13.0 years, 7.5% with ulcer), thereof 741 (85%) treatment naïve (group A) and 132 (15%) after failed therapy (group B). Resistance to metronidazole was present in 21% (A: 17.7%, B: 40.2%), clarithromycin in 28.8% (A: 25%, B: 51.4%), and both in 7.1% (A: 3.8%, B: 26.5%). The majority received 2-week tailored triple therapy combining proton pump inhibitor (PPI), amoxicillin with clarithromycin (PAC) or metronidazole (PAM). Dosing was lower than recommended for PPI (A: 49%, B: 41%) and amoxicillin (A: 6%, B: 56%). In treatment naïve patients, eradication reached 90% (n = 503, 95% CI 87-93%) and 93% in compliant children (n = 447, 95% CI 90-95%). Tailored triple therapy cured 59% patients after failed therapy (n = 69, 95% CI 48-71%). Treatment failure was associated with PAM in single clarithromycin resistance (OR = 2.47, 95% CI 1.10-5.53), with PAC in single metronidazole resistance (OR = 3.44, 95% CI 1.47-8.08), and with low compliance (OR = 5.89, 95% CI 2.49-13.95). CONCLUSIONS: Guideline-conform 2-weeks therapy with PPI, amoxicillin, clarithromycin or metronidazole tailored to antibiotic susceptibility achieves primary eradication of ≥ 90%. Higher failure rates in single-resistant strains despite tailored treatment indicate missed resistance by sampling error.

Characterization of Eosinophilic Esophagitis From the European Pediatric Eosinophilic Esophagitis Registry (pEEr) of ESPGHAN.

OBJECTIVES: Few pediatric data on phenotypic aspects of eosinophilic esophagitis (EoE) are available. The pEEr registry was developed to prospectively characterize children with EoE from Europe and Israel. METHODS: pEEr is an ongoing prospective registry enrolling children with esophageal eosinophilia (≥15 eos/HPF). Anonymized data were collected from 19 pediatric centers. Data regarding demographics, clinical manifestations, endoscopy, histology, and therapies were collected. RESULTS: A total of 582 subjects (61% male) were analyzed. The median age at diagnosis was 10.5 years [interquartile range (IQR): 5.7-17.7], whereas the age at symptom onset was 9.2 years (IQR: 4.3-16.4), resulting in a median diagnostic delay of 1.2 years (IQR: 0.7-2.3). The diagnostic delay was longer below age <6 years. Shorter diagnostic delays were associated with the presence of food allergy or a family history for EoE. Symptoms varied by age with dysphagia and food impaction more common in adolescents, while vomiting and failure to thrive more common in younger children ( P < 0.001). Among endoscopic findings, esophageal rings were more common in adolescents, whereas exudates were more frequent in younger children( P < 0.001). Patients who responded to proton pump inhibitors (PPIs) were more likely to be older, males, and less often presented severe endoscopic findings. Patients unresponsive to PPIs received topical steroids (40%), elimination diet (41%), or a combined therapy (19%). CONCLUSIONS: EoE findings vary according to age in pediatric EoE. Young children are commonly characterized by non-specific symptoms, atopic dermatitis, food allergy, and inflammatory endoscopic lesions. Adolescents usually have dysphagia or food impaction, fibrostenotic lesions, and a better PPI response.

[CUFFING PRISONERS AND DETAINEES IN ISRAELI HOSPITALS - A MULTI-CENTER STUDY].

AIMS: To describe the extent of prisoner/detainee cuffing and characterize cuffing methods. BACKGROUND: Thousands of prisoners and detainees receive medical treatment in Israeli hospitals every year. According to the Israeli law, cuffing during hospital stay should be an exceptional measure, to be considered only in cases of real threat of violence or escape, based on individual assessment. There is no documentation of cuffing rates in hospitals. METHODS: A multi-center study in 12 hospitals was performed during 2020-2021. Data were collected prospectively or retrieved retrospectively from security records, when available. RESULTS: A total of 1857 prisoners/detainees were documented, of whom 1794 (96.6%) were cuffed. Of the 241 hospitalized patients, 230 (95.4%) were cuffed. Details regarding cuffing methods were available for 185 hospitalized patients, revealing that at least 63 patients (68% of patients for whom details regarding cuffing to bed were available) were cuffed to the bed with opposite arm and leg in a cross position. Cuffing rates of prisoners under custody of the Prisons Authority, police and the Israeli Defense Forces, were 98.5%, 96.6%, and 83%, respectively. Impaired mobility for medical reasons was documented in 64 cases, of whom 85.9% were cuffed regardless. CONCLUSIONS: Cuffing of prisoners/detainees in Israeli hospitals is performed non-selectively, in violation of the law. During hospitalization, cuffing is usually performed in a cross position, severely impairing mobility. Our findings highlight the need for routine documentation of cuffing due to its medical consequences and the responsibility of medical staff towards patients according to rules of ethics and regulations.

Mucus sialylation determines intestinal host-commensal homeostasis.

Intestinal mucus forms the first line of defense against bacterial invasion while providing nutrition to support microbial symbiosis. How the host controls mucus barrier integrity and commensalism is unclear. We show that terminal sialylation of glycans on intestinal mucus by ST6GALNAC1 (ST6), the dominant sialyltransferase specifically expressed in goblet cells and induced by microbial pathogen-associated molecular patterns, is essential for mucus integrity and protecting against excessive bacterial proteolytic degradation. Glycoproteomic profiling and biochemical analysis of ST6 mutations identified in patients show that decreased sialylation causes defective mucus proteins and congenital inflammatory bowel disease (IBD). Mice harboring a patient ST6 mutation have compromised mucus barriers, dysbiosis, and susceptibility to intestinal inflammation. Based on our understanding of the ST6 regulatory network, we show that treatment with sialylated mucin or a Foxo3 inhibitor can ameliorate IBD.

Real-life Performance of Multiplex Celiac Antibody Test in the Diagnosis of Pediatric Celiac Disease.

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.

Long-Term Follow-up and Predictors of Complicated Disease Behavior in Pediatric Crohn's Disease Patients.

OBJECTIVE: Identifying predictors of inflammatory bowel disease (IBD) outcome in order to optimize individual patient management in has become an important goal. We aimed to describe the long-term outcome of pediatric Crohn disease (CD) patients and identify risk factors for complicated behavior. METHODS: Pediatric CD patients diagnosed between 1998 and 2014, with long-term follow-up were included. Baseline data; age, gender, weight/height/BMI percentiles, and family history of IBD. Disease characteristics (Paris classification), laboratory testing, imaging and treatment were documented. Outcome data; evidence of stricturing or penetrating disease, hospitalizations, surgical intervention, malignancies, and mortality. RESULTS: Of 93 patients included, mean age at diagnosis 13.5 (±3.2), 51 (55%) male, median follow-up 10.3 years (±4 SD(. Disease location at diagnosis: 29 (31.2%) distal ileum, 17 (18.3%) colonic, 40 (43.0%) ileo-colonic. Seven (7.5%) had upper gastrointestinal and 36 (38.7%) perianal involvement. Behavior at diagnosis, 68 (73.1%) inflammatory (B1), and 25 (26.9%) complicated [(B2 (stricturing) and/or B3 (penetrating)]. Twenty (23.2%) of B1 evolved to B2 and/or B3, thus by the end of follow-up 45 (48.4%) had complicated behavior. Sixty-seven (72%) were hospitalized, 20 (21.5%) underwent surgery, two developed malignancy with no mortalities. In a logistic regression model, growth delay (hazard ratio [HR], 5.02 [1.10-22.85], P = 0.037) and low albumin levels (HR, 3.97 [1.32-11.97], P = 0.014) at diagnosis were predictors of complicated disease in adulthood. CONCLUSIONS: Over a quarter of pediatric Crohn disease patients present with complicated behavior. During follow-up another quarter progress to complicated disease behavior. Delayed growth and low albumin at diagnosis predict progression.

Systematic Review and Meta-analysis of Histological Gastric Biopsy Aspects According to the Updated Sydney System in Children.

OBJECTIVES: A descriptive and comparative study of gastric histological aspects according to the updated Sydney classification (USC), obtained from Helicobacter pylori-positive versus H pylori-negative children referred for upper gastrointestinal endoscopy. METHODS: The Prisma method was used to perform a systematic review and meta-analysis. Selection criteria were based on following key words USC, H pylori, children, endoscopy, or biopsy. Publication biases were assessed according to the Newcastle-Ottawa Scale, and a meta-regression analysis was done. The study was registered on the PROSPERO platform. RESULTS: Between 1994 and 2017, 1238 references were found; 97 studies were retained for the systematic review with a total number of 25,867 children; 75 studies were selected for the meta-analysis concerning 5990 H pylori-infected and 17,782 uninfected children.H pylori-positive versus H pylori-negative children, according to the USC, showed significantly higher relative risk for gastric antral and corpus chronic inflammation, presence of neutrophils, and of lymphoid follicles, and gastric mucosa atrophy, whereas, intestinal metaplasia showed a significantly higher RR only in antral biopsies. The meta-regression analysis showed that H pylori-positive versus H pylori-negative children had significantly higher risk only for corpus activity according to age, recurrent abdominal pain, and geographical area of low H pylori prevalence. CONCLUSIONS: H pylori infection in children was associated with higher relative risk for gastric antral and corpus chronic inflammation, presence of neutrophils, lymphoid follicles, and rare gastric mucosa atrophy, whereas, rare intestinal metaplasia was only significantly higher in the antral area.

Monitoring Enables Progress: A Nationwide Quality Improvement Program in Children With Crohn Disease.

OBJECTIVES: In this quality improvement program, named quality in pediatric inflammatory bowel disease, we constructed a nation-wide platform that prospectively recorded clinically important quality indicators in pediatric inflammatory bowel diseases (PIBD), aiming at improving clinical management across the country. METHODS: Representatives of all 21 PIBD facilities in Israel formed a Delphi group to select quality indicators (process and outcomes), recorded prospectively over 2 years in children with Crohn's disease 2-18 years of age seen in the outpatient clinics. Monthly anonymized reports were distributed to all centers, allowing comparison and improvement. Trends were analyzed using the Mann-Kendall test, reporting τ (tau) values. RESULTS: The indicators of 3254 visits from 1709 patients were recorded from September 2017 to September 2019 (mean age 14.7 ±â€Š3.1 years, median disease duration 1.8 years (interquartile range 0.69-4.02)). An increase in three of five process indicators was demonstrated: obtaining drug levels of anti-tumor necrosis factor (TNF) (τ = 0.4; P = 0.005), utilization of fecal calprotectin (τ = 0.38; P = 0.008) and bone density testing (τ = 0.45; P = 0.002). Among outcome indicators, three of nine improved as measured during the preceding year: calprotectin <300 µg/mg (τ = 0.35; P = 0.015), and "resolution of inflammation" defined as a composite of endoscopy, imaging and fecal calprotectin (τ = 0.39; P = 0.007). Endoscopic healing reached borderline significance (τ = 0.28; P = 0.055). An increase in the use of biologics throughout the study was observed (τ = 0.47; P = 0.001) with a concurrent decrease in the use of immunomodulators (τ = -0.47; P = 0.001). CONCLUSIONS: Quality improvement nationwide programs can be implemented with limited resources while facilitating standardization of care, and may be associated with improvements in measured indicators.

The Effect of Nutritional Therapy on Bone Mineral Density and Bone Metabolism in Pediatric Crohn Disease.

OBJECTIVES: Both the inflammatory burden of Crohn disease (CD) and corticosteroids have a negative effect on bone density. Exclusive enteral nutrition (EEN) avoids corticosteroids and promotes endoscopic healing. We aimed to explore the effect of nutritional therapy on bone health in pediatric CD. METHODS: This was a planned sub-study of a clinical trial enrolling children with new-onset mild-moderate CD. Children were randomized to either 6 weeks EEN followed by 6 weeks 25% partial enteral nutrition (PEN) or 6 weeks of 50% PEN with a CD exclusion diet followed by 6 weeks of 25% PEN with exclusion diet. Bone formation and resorption were measured at baseline, week 12 and week 24 by serum C-Propeptide of Type I Procollagen (CICP) and type I Collagen N-Telopeptide (NTX), respectively. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DXA) scan at baseline and week 24. RESULTS: Median CICP improved from 130 ng/mL (106-189) at baseline to 223 (143-258) at week 12 and 193 (143-252) at week 24 (P = 0.016 for both, n = 29 children). Median NTX remained unchanged (P = 0.45 and P = 0.45). Thirty-six children had DXA scans performed at diagnosis; 81% and 33% had z scores of <-1 and <-2, respectively. DXA z scores did not improve from baseline (adjusted total body less head [TBLH] BMD -1.62 ±â€Š0.87) to week 24 (-1.76 ±â€Š0.75; P = 0.30, n = 21 with both scans). CONCLUSIONS: Low bone density is common in new-onset mild-moderate pediatric CD. CICP, a sensitive marker of bone formation, improved following dietary intervention but this was not associated with improved BMD.

Adherence to gluten-free diet and follow-up of pediatric celiac disease patients, during childhood and after transition to adult care.

Long-term data on pediatric celiac disease (CD) patients after transition to adult care is scarce. We aimed to evaluate patients' adherence to a gluten-free diet (GFD), the normalization of celiac serology and the frequency of follow-up before age 18, and to study changes in adherence and follow-up frequency after transition to adult care. Presenting symptoms, serology and biopsy results, patients' reported GFD adherence, frequency of follow-up visits, and complications before and after 18 years were collected for CD patients diagnosed between 1998 and 2017. Of 441 CD patients diagnosed and followed in childhood, a quarter (108/441) were over 18 y (years) at data collection. Median age at diagnosis 7.1 y (9 months-18 y), at data collection 23 y (18-38 y), disease duration 11.3 y (2-36 y). Below the age of 18 y, most patients 386/436 (88.5%) reported adherence to GFD, and most 372/425 (85.7%) normalized serology. Of the 441 patients, only 3 failed to attend any follow-up visit, and 338/441 (76.6%) attended yearly visits. Over the age 18 y, serology testing was done in 78/108 (72.2%), every 1-3 y in 46/78 (59%). Serology normalized in 61/78 (78.2%). Most adult patients 77/108 (71.5%) never attended a gastroenterology clinic. CD-related complications were rare. Younger age at diagnosis, regular follow-up visits in childhood, resolution of symptoms, and normalization of serology before age 18 were identified as predictors of negative serology after the age of 18 y.Conclusions: Children who have regular follow-up and normalize serology before age 18 years are likely to maintain a GFD and have negative serology as adults. What is Known: • The rate of adherence to gluten-free diet (GFD) is higher among children compared to adults. • Data on long-term follow-up after transition to adult care is scarce. What is New: • Patients diagnosed with CD at a younger age (<12 y), who have yearly follow-up visits, resolution of symptoms, and negative serology in childhood are very likely to maintain GFD and have negative serology as adults. • Even though most patients do not attend GI clinics after transition to adulthood, most adhere to GFD, and complications are rare.

Dietary Therapies Induce Rapid Response and Remission in Pediatric Patients With Active Crohn's Disease.

BACKGROUND & AIMS: Dietary therapies based on exclusion of usual dietary elements induce remission in children with Crohn's disease (CD), whereas re-exposure induces rebound inflammation. We investigated whether a short trial of dietary therapy, to identify patients with and without a rapid response or remission on the diet (DiRe), can be used to predict success or failure of long-term dietary therapy. METHODS: We collected data from the multicenter randomized trial of the CD exclusion diet (CDED). We analyzed data from 73 children with mild to moderate CD (mean age, 14.2 ± 2.7 y) randomly assigned to groups given either exclusive enteral nutrition (EEN, n = 34) or the CDED with 50% (partial) enteral nutrition (n = 39). Patients were examined at baseline and at weeks 3 and 6 of the diet. Remission was defined as CD activity index scores below 10 and response was defined as a decrease in score of 12.5 points or clinical remission. Inflammation was assessed by measurement of C-reactive protein. RESULTS: At week 3 of the diet, 82% of patients in the CDED group and 85% of patients in the EEN group had a DiRe. Median serum levels of C-reactive protein had decreased from 24 mg/L at baseline to 5.0 mg/L at week 3 (P < .001). Among the 49 patients in remission at week 6, 46 patients (94%) had a DiRe and 81% were in clinical remission by week 3. In multivariable analysis, remission at week 3 increased odds of remission by week 6 (odds ratio, 6.37; 95% CI, 1.6-25; P = .008) whereas poor compliance reduced odds of remission at week 6 (odds ratio, 0.75; 95% CI, 0.012-0.46; P = .006). CONCLUSIONS: For pediatric patients with active CD, dietary therapies (CDED and EEN) induce a rapid clinical response (by week 3). Identification of patients with and without a rapid response to diet might help identify those who, with compliance, will be in clinical remission by week 6 of the diet. ClinicalTrials.gov no: NCT01728870.