Infantile and Very Early Onset Inflammatory Bowel Disease: A Multicenter Study.

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.

Antibiotic-Impregnated Ventriculoperitoneal Shunts Decrease Bacterial Shunt Infection: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Antibiotic-impregnated shunts seem to be beneficial in preventing bacterial infections and decreasing mortality by effectively inhibiting microbial growth in the shunt system and reducing the risk of shunt-associated infections. This study aimed to evaluate the efficacy of antibiotic-impregnated shunt catheters (AISC) in reducing the incidence of bacterial shunt infection in patients with hydrocephalus. METHODS: The protocol was registered on PROSPERO. A meta-analysis was conducted by searching 3 databases (PubMed, Scopus, CENTRAL) for relevant randomized controlled trials and observational studies. We included all studies published until November 2022 in any language. The primary outcome was the rate of bacterial infections, whereas the rate of shunt failure was our secondary endpoint. Odds ratios (OR) with 95% CI were calculated using a random-effects model. RESULTS: A total of 27 articles with 27 266 shunt operations were included in this study. The results indicated that using AISC is significantly associated with reduction in infections (OR = 0.42; 95% CI: 0.33-0.54). Regarding shunt failure, there was a tendency in favor of AISC use (OR = 0.73; 95% CI: 0.51-1.06). CONCLUSION: Our study provided evidence that AISC is significantly associated with the reduction in the rate of bacterial ventriculoperitoneal-shunt infection. In addition, there was a tendency toward AISC to decrease shunt failure compared with the standard shunt.

Health related quality of life is associated with gastroesophageal reflux symptoms in overweight children.

OBJECTIVES: The association between obesity and gastroesophageal reflux disease (GERD) is well-established in adults; however, data in pediatric population is scarce. Our study aimed to assess the association between GERD and health-related quality of life (HRQoL) in overweight children. METHODS: From April to August of 2020, we included children aged 7-18 years who attended the Endocrinological Outpatient Clinic at the Paediatric Institute, University of Debrecen, Hungary. The participants completed two questionnaires: the Pediatric Gastroesophageal Reflux Disease Symptom Questionnaire (PGSQ) and the HRQoL questionnaire (PedsQL). Based on the criteria of the World Health Organization (WHO), the patients were categorized into two groups: an overweight or obese group and a group with normal weight. RESULTS: A total of 107 children (51 % female, mean age 13.2 years, 46 % overweight or obese) completed the questionnaires. The median PGSQ score was similar in both groups (4.0 (IQR: 1.0-7.8) vs. 3.0 (IQR: 1.0-7.0), p=0.6). However, the total PedsQL score was significantly lower in the children with overweight or obesity compared to those with normal weight (80.1 (71.1-91.0) vs. 88.0 (76.1-94.6), p=0.031). The PedsQL score was lower among overweight patients with GERD symptoms than that of normal-weight patients without GERD symptoms. CONCLUSIONS: Our findings highlight the importance of raising awareness about GERD to enhance the HRQoL and prevent long-term complications in obese children.

Immunization of children with inflammatory bowel disease against SARS-CoV-19 infection: A prospective single centre cohort study.

Background: Real-world data of children with inflammatory bowel disease (IBD) after SARS-CoV-2 vaccination are needed. Method: This prospective, observational study evaluate antibody kinetics of children with IBD 6 months after immunization with COVID-19 mRNA vaccine. Results: 24 children with IBD were included, 22 received immunosuppressive treatment. After five weeks the spike protein antibody level was positive in 95% of the cases. After six months all participants had seropositivity results, though the titre was decreasing. Conclusion: These data show the effectiveness of SARS-CoV2 immunization and the antibody decay over time, that highlight the importance of booster vaccines.

Long-Term Efficacy of T3 Analogue Triac in Children and Adults With MCT8 Deficiency: A Real-Life Retrospective Cohort Study.

CONTEXT: Patients with mutations in thyroid hormone transporter MCT8 have developmental delay and chronic thyrotoxicosis associated with being underweight and having cardiovascular dysfunction. OBJECTIVE: Our previous trial showed improvement of key clinical and biochemical features during 1-year treatment with the T3 analogue Triac, but long-term follow-up data are needed. METHODS: In this real-life retrospective cohort study, we investigated the efficacy of Triac in MCT8-deficient patients in 33 sites. The primary endpoint was change in serum T3 concentrations from baseline to last available measurement. Secondary endpoints were changes in other thyroid parameters, anthropometric parameters, heart rate, and biochemical markers of thyroid hormone action. RESULTS: From October 15, 2014 to January 1, 2021, 67 patients (median baseline age 4.6 years; range, 0.5-66) were treated up to 6 years (median 2.2 years; range, 0.2-6.2). Mean T3 concentrations decreased from 4.58 (SD 1.11) to 1.66 (0.69) nmol/L (mean decrease 2.92 nmol/L; 95% CI, 2.61-3.23; P < 0.0001; target 1.4-2.5 nmol/L). Body-weight-for-age exceeded that of untreated historical controls (mean difference 0.72 SD; 95% CI, 0.36-1.09; P = 0.0002). Heart-rate-for-age decreased (mean difference 0.64 SD; 95% CI, 0.29-0.98; P = 0.0005). SHBG concentrations decreased from 245 (99) to 209 (92) nmol/L (mean decrease 36 nmol/L; 95% CI, 16-57; P = 0.0008). Mean creatinine concentrations increased from 32 (11) to 39 (13) µmol/L (mean increase 7 µmol/L; 95% CI, 6-9; P < 0.0001). Mean creatine kinase concentrations did not significantly change. No drug-related severe adverse events were reported. CONCLUSIONS: Key features were sustainably alleviated in patients with MCT8 deficiency across all ages, highlighting the real-life potential of Triac for MCT8 deficiency.

Adherence to the Porto Criteria Based on the Hungarian Nationwide Pediatric Inflammatory Bowel Disease Registry (HUPIR).

Objectives: According to the Porto criteria, upper endoscopy and ileocolonoscopy with histology for patients with pediatric inflammatory bowel disease (pIBD) are recommended with small bowel imaging (SBI). We aimed to evaluate the adherence to the Porto criteria and biopsy sampling practice and to evaluate the diagnostic yield of magnetic resonance enterography (MRE) first time in a nationwide pIBD inception cohort. Methods: Newly diagnosed pIBD cases (ages 0-18 years) are registered in the prospective, nationwide Hungarian Paediatric IBD Registry (HUPIR). We analyzed the diagnostic workup of patients recorded between the 1st of January 2007 and the 31st of December 2016. Results: Data for diagnostic workup was available in 1,523 cases. Forty percent of the cases had complied with the Porto criteria. Adherence to the Porto criteria increased significantly from 20 to 57% (p < 0.0001) between 2007 and 2016. The most frequent reason for the incomplete diagnostic work-up was the lack of small bowel imaging (59%). In 2007, 8% of cases had a biopsy from all segments, and this rate reached 51% by 2016 (p < 0.0001). We analyzed the diagnostic yield of MRE in 113 patients (10.1%), who did not have any characteristic lesion for Crohn's disease. The MRE was positive for the small bowel in 44 cases (39%). Conclusions: Adherence to the Porto criteria increased significantly during the 10-year period. This is the first study that reports multiple biopsy sampling as the less accepted recommendation. The diagnostic yield of MRE in patients without characteristic lesion for Crohn's disease is 39%.

Role of microRNA-223 in the regulation of poly(ADP-ribose) polymerase in pediatric patients with Crohn's disease.

OBJECTIVES: Crohn's disease (CD) is a multifactorial disease, characterized by oxidant-induced tissue injury with a possible activation of poly(ADP-ribose) polymerase (PARP)-1. MicroRNAs (miRs) can offer a potential link between the genetic susceptibility, environmental and immunologic factors in the pathogenesis of CD. Previously, PARP-1 was identified as a direct target gene of miR-223 in an epithelial cell line. Our aim was to examine PARP activation and miR-223 expression in colonic biopsies of pediatric CD. To support our in vivo findings, the effect of lipopolysaccharide (LPS) on same parameters was examined in HT-29 colonic epithelial cell line. METHODS: Colonic biopsies were taken from patients with macroscopically inflamed and intact mucosa with CD and controls. LPS treated HT-29 cells served as our in vitro model. To analyze the PARP-1 expression real-time PCR, Western blot and immunohistochemical analyses were used. PARP-1 enzymatic activity was assessed on the basis of poly(ADP-ribosyl)ated proteins. Expression of miR-223 was examined by real-time PCR. RESULTS: PARP-1 mRNA and miR-223 expression was significantly elevated, however, the amount of PARP-1 protein and poly(ADP-ribose) was reduced in pediatric CD compared to controls. LPS incubation did not affect the expression of PARP-1 mRNA, however, decreased miR-223 expression, and enhanced PARP-1 activity. CONCLUSIONS: In our study, we showed that the expression of miR-223 is up-regulated and poly(ADP-ribosyl)ation is reduced in pediatric patients with CD. Moreover, we confirmed their opposite change in LPS treated epithelial cells, too. These data suggest that the hypofunctionality of PARP-1 may play a potential role in the pathomechanism of CD.

Role of Altered Expression of miR-146a, miR-155, and miR-122 in Pediatric Patients with Inflammatory Bowel Disease.

BACKGROUND: Evidence suggests the central role of tumor necrosis factor (TNF)-α in the pathomechanism of inflammatory bowel disease (IBD); however, its effect on epigenetic factors, including small non-coding microRNAs (miRs), is less known. Our present aim was the comparative investigation of the expression of TNF-α and immune response-related miRs in children with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Fresh-frozen (FF) and formalin-fixed, paraffin-embedded (FFPE) biopsies were used to analyze the expression of miR-146a, -155, -122, and TNF-α by real-time reverse transcription polymerase chain reaction in macroscopically inflamed (CD: 12 FFPE and 24 FF; UC: 10 FF) and intact (CD: 12 FFPE; 14 FF) colonic biopsies of children with IBD and controls (16 FFPE; 23 FF). The expression of miR-146a, -155, and -122 was also determined in TNF-α-treated HT-29 colonic epithelial cells. RESULTS: Increased expression of TNF-α was observed in the colonic mucosa of children with CD and UC in comparison with controls. Expression of miR-146a and -155 was higher in the inflamed mucosa of children with CD and UC than in the intact mucosa. Expression of miR-122 elevated in the macroscopically intact colonic regions of CD compared with controls and patients with UC. In HT-29 cells, TNF-α treatment increased the expression of miR-146a and -155, but not that of miR-122. CONCLUSIONS: Our results showed altered expression of miR-146a, -155, and -122 in the colonic mucosa of children with IBD and in TNF-α-treated colonic epithelial cells. Our data suggest the TNF-α-related involvement of these miRs in the pathogenesis of IBD.

Baseline Characteristics and Disease Phenotype in Inflammatory Bowel Disease.

OBJECTIVES: Predicting short-term relapses and long-term prognosis is of utmost importance in paediatric inflammatory bowel disease (IBD). Our aim was to investigate the short-term disease outcome and medication during the first year in a paediatric incident cohort from Hungary. In addition, association laboratory markers and disease activity indices with short-term disease outcome and medication were analysed. METHODS: From January 1, 2008 to December 31, 2010, demographic data and clinical characteristics of newly diagnosed paediatric patients with IBD < 18 years of age were prospectively recorded. RESULTS: A total of 420 patients were identified (Crohn disease [CD] 266 and ulcerative colitis [UC] 124). Initially, 48% (124/256) of the patients with CD had moderate-to-severe disease (Pediatric Crohn's Disease Activity Index [PCDAI] > 31), and this rate decreased to 2.1% at 1-year follow-up. Proportion of patients with UC with moderate-to-severe disease (Pediatric Ulcerative Colitis Activity Index > 35) at diagnosis declined from 57.5% (69/120) to 6.8% at 1-year follow-up. Terminal ileal involvement correlated with higher initial C-reactive protein (CRP) (P = 0.021) and initial PCDAI (P = 0.026). In UC, elevated CRP (P = 0.002) was associated with disease extension. CRP and PCDAI at diagnosis were associated with the need for immunomodulators at 1 year in children with CD. Initial CRP was also associated with the need for immunomodulators in patients with UC at 1-year follow-up. CONCLUSIONS: At diagnosis, half of the patients with IBD had moderate-to-severe disease, and this rate decreased to <10% after 1 year. Initial CRP and PCDAI were related to the need for aggressive therapy in CD.

Incidence rates and disease course of paediatric inflammatory bowel diseases in Western Hungary between 1977 and 2011.

BACKGROUND: Limited data are available on paediatric inflammatory bowel diseases in Eastern Europe. Our aim was to analyse disease characteristics in the population-based Veszprem province database between 1977 and 2011. METHODS: 187 (10.5%, ulcerative colitis/Crohn's disease/undetermined colitis: 88/95/4) out of 1565 incident patients were diagnosed with a paediatric onset in this population-based prospective inception cohort. RESULTS: The incidence of Crohn's disease and ulcerative colitis increased from 0 and 0.7 in 1977-1981 to 7.2 and 5.2 in 2007-2011 per 100,000 person years. Ileocolonic location (45%) and inflammatory disease behaviour (61%) were most frequent in Crohn's disease, while azathioprine use was frequent (66%) and surgical resection rates were high (33% at 5 years) in cases with paediatric onset. In ulcerative colitis, 34% of patients were diagnosed with extensive disease, with high rates of disease extension (26% and 41% at 5 and 10 years), fulminant episodes (19.3%) and systemic steroid use (52.3%). The cumulative rate of colectomy was low (6.9%). CONCLUSIONS: The incidence of paediatric inflammatory bowel diseases has rapidly increased in the last three decades in Western Hungary. Ileocolonic disease and a need for azathioprine were characteristic in paediatric Crohn's disease, while paediatric onset ulcerative colitis was characterised by extensive disease and disease extension, while the need for colectomy was low.

Foreign body impaction in the sigmoid colon: a twenty euro bet.

Foreign body ingestion is a common clinical problem in early childhood. However, it may occur even in adults, unknowingly. Most ingested foreign bodies entering the stomach pass through the gastrointestinal tract uneventfully. Here we report on a 13-year-old boy who presented with chronic abdominal pain, weight loss and occult gastrointestinal bleeding for 6 mo. Colonoscopy was negative; however, a ballpoint pen was impacted in the sigmoid region. Subsequently, the child admitted swallowing a pen as a 20-euro bet 6 mo previously. Crohn's disease is a chronic relapsing inflammatory gastrointestinal disease. It is often difficult to diagnose due to the fact that there is no single pathognomonic sign or symptom. This case is a description of an adolescent with chronic gastrointestinal symptoms due to a foreign body. Therefore, an ingested foreign body should be included in the differential diagnostic procedure related to gastrointestinal symptoms.

Incidence, Paris classification, and follow-up in a nationwide incident cohort of pediatric patients with inflammatory bowel disease.

OBJECTIVES: The aim of the study was to evaluate the incidence, baseline disease characteristics, and disease location based on the Paris classification in pediatric inflammatory bowel disease (IBD) in the Hungarian nationwide inception cohort. In addition, 1-year follow-up with therapy was analyzed. METHODS: From January 1, 2007 to December 31, 2009, newly diagnosed pediatric patients with IBD were prospectively registered. Twenty-seven pediatric gastroenterology centers participated in the data collection ensuring the data from the whole country. Newly diagnosed patients with IBD younger than 18 years were reported. Disease location was classified according to the Paris classification. RESULTS: A total of 420 patients were identified. The incidence rate of pediatric IBD was 7.48/105 (95% confidence interval [CI] 6.34/105-8.83/105). The incidence for Crohn disease (CD) was 4.72/105 (95% CI 3.82-5.79), for ulcerative colitis (UC) 2.32/105 (95% CI 1.71-3.09), and for IBD-unclassified 0.45/105 (95% CI 0.22-0.84). Most common location in CD was L3 (58.7%); typical upper gastrointestinal abnormalities (ulcer, erosion and aphthous lesion) were observed in 29.9%. Extensive colitis in patients with UC (E4, proximal to hepatic flexure) was the most common disease phenotype (57%), whereas only 5% of children had proctitis. A total of 18.6% of patients had ever severe disease (S1). Frequency of azathioprine administration at diagnosis was 29.5% in patients with CD, and this rate increased to 54.6% (130/238) at 1-year follow-up. In UC, only 3.3% received azathioprine initially, and this rate elevated to 22.5% (25/111). Use of corticosteroid decreased from 50% to 15.3% in patients with UC. Rate of bowel resection in patients with CD during the first year of follow-up was 5%. CONCLUSIONS: The incidence of pediatric IBD in Hungary was among the higher range reported. This is the first large, nationwide incident cohort analyzed according to the Paris classification, which is a useful tool to determine the characteristic pediatric CD phenotype.