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Background and Objectives: Current data on ustekinumab therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBDU) are limited. We aimed to evaluate the effectiveness and safety of ustekinumab in pediatric UC and IBDU. Methods: This multicenter retrospective study included 16 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. Children with UC or IBDU treated with ustekinumab were enrolled. Demographic, clinical, laboratory, endoscopic, and imaging data as well as adverse events were recorded. Analyses were all based on the intention-to-treat principle. Results: Fifty-eight children (39 UC and 19 IBDU, median age 14.5 [IQR 11.5–16.5] years) were included. All had failed biologic therapies, and 38 (66%) had failed two or more biologics. Corticosteroid-free clinical remission (CFR) was observed in 27 (47%), 33 (57%), and 37 (64%) children at 16, 26, and 52 weeks, respectively. Normalization of C-reactive protein and calprotectin < 150 μg/g were achieved in 60% and 52%, respectively, by 52 weeks. Endoscopic and radiologic remissions were reached in 8% and 23%, respectively. The main predictors of CFR were diagnosis of UC compared with IBDU (hazard ratio [HR] 2.2, 95% CI 1.03–4.85; p = 0.041) and no prior vedolizumab therapy (HR 2.1, 95% CI 1.11–4.27; p = 0.023). Ustekinumab serum levels were not associated with disease activity. Adverse events were recorded in six (10%) children, leading to discontinuation of the drug in three. Conclusion: Based on these findings, ustekinumab appears as an effective therapy for pediatric refractory UC and IBDU. The potential efficacy should be weighed against the risks of serious adverse events. [ABSTRACT FROM AUTHOR]

Dental caries, gingivitis, and excess weight are highly prevalent, interconnected chronic conditions. The association of oral health with the development of adiposity among children is sparsely addressed. We examined the association of oral health to the development of excess weight and central obesity in early adolescence during a 2-year follow-up period. This prospective study was conducted with 2702 children aged 9–12 years at baseline from the Finnish Health in Teens study. Their weight development was followed up for 2 years. Body mass index with age- and sex-specific cut-offs and the waist–height ratio indicated weight status and central obesity. Oral health data (caries experience and gingivitis/calculus) were collected from outpatient records of public dental services. Having both caries experience and gingivitis/calculus was considered burden of oral diseases. Of the sample, 74% were caries-free but 70% exhibited gingivitis and/or calculus, and 20% had both caries experience and gingivitis/calculus. During the follow-up period, 5.3% (n = 124) and 4.7% (n = 118) of the children became overweight/obese or centrally obese, respectively. Having both caries experience and gingivitis/calculus associated with the development of excess weight in a fully adjusted model (HR 1.75, 95% CI 1.03–2.97) but not of central obesity. Caries experience or gingivitis/calculus alone did not associate with adiposity development. Conclusion: Having burden of oral diseases without excess weight at early adolescence could imply future weight gain; thus, normal-weight individuals with both caries experience and gingivitis/calculus could be targeted with preventive measures. Our findings warrant further research to explore whether oral diseases and the development of obesity merely share risk factors or if their relationship is of causal nature. What is Known: • Association of excess weight with caries experience and gingivitis is known to exist both cross-sectionally and longitudinally in children and adolescents. What is New: • Burden of oral diseases, that is, having both caries experience and gingivitis/calculus, was associated with becoming overweight or obese 2 years later during early adolescence. • Normal-weight individuals with burden of oral diseases at early adolescence could be targeted with preventive measures against excess weight gain. [ABSTRACT FROM AUTHOR]

The purpose of this study is to describe the defecation pattern of healthy infants up to 17 weeks of age. We included 1052 healthy term infants from the prospective HELMi cohort (NCT03996304). Parents filled in recurring online questionnaires on feeding, gastrointestinal function, and crying weekly for the first 17 weeks of life. Defecation frequency was highest at the age of 3 weeks (a median of 4 times/day, interquartile range (IQR) 2.9–5). At each time point, the median defecation frequency of breastfed infants was higher than that of infants receiving formula (e.g., at week 17 a median of 2 times/day, IQR 0.9–3.6, and a median of 1.1, IQR 0.6–1.4, respectively). The dominant color of the stool was most often yellow or light brown. Nearly black stools were reported in the first week of life in 3.4%. Nearly half (47.4%) of the infants had green stool color dominating for at least 1 week, with comparable frequency among breastfed (47.7%) and formula-fed (45.2%) infants. Green stools were associated with a higher defecation frequency (linear mixed-effect model p < 0.0001). Occasional blood in stool was reported in 9.3% and recurrent blood in 5.2% of the infants with no difference in stool consistency. Hard stools were rare (≤ 1%). Conclusion: This study enlightens the spectrum of defecation patterns in healthy term infants during the first 17 weeks of life. A better understanding of bowel function helps healthcare professionals distinguish normal from abnormal when addressing defecation, the color of stools, and the type of feeding. What is Known: • Breastfed infants have more frequent and more yellow-colored stools than formula-fed infants. • Stools with green color are often suggested by the parents or even by medical professionals to indicate disease or discomfort in early life. What is New: • Nearly half of the healthy term infants had green stool dominating for at least one week during the first 17 weeks and occasional blood was reported in almost 10% of the infants during this period. • Data on normal variation in bowel function and stool may serve primary health care professionals when educating the families and caretakers of infants. [ABSTRACT FROM AUTHOR]

Ustekinumab is an effective therapy for adult Crohn's disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn's disease treated with ustekinumab. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn's Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7–17.2) with a median follow-up of 7.4 months (IQR 5.6–11.8). Ninety-nine percent had received prior anti-TNF, 63% ≥ 2 anti-TNFα therapies and 22% vedolizumab. Baseline median wPCDAI was 39 (IQR 25–57.5) (71 (70%) patients with moderate-severe activity). Weeks 12 and 52 CS- and EEN-free remission were both 40.5%. Clinical response at week 6, iv induction route and older age at onset of ustekinumab treatment were predictive factors associated with clinical remission at week 12. Seven minor adverse events probably related to ustekinumab were reported. One patient died from an unrelated cause. Conclusion: Our results suggest that ustekinumab is effective and safe in children with chronically active or refractory CD. What is Known: • Ustekinumab is an effective therapy for adult moderate to severe Crohn's disease (CD). • Off-label use of ustekinumab in children is increasing especially in anti-TNF refractory CD. What is New: • Is the largest cohort of real-world use of ustekinumab in paediatric CD to date. • Clinical response at week 6, iv induction and older age at onset of ustekinumab were predictive factors associated with clinical response at week 12. [ABSTRACT FROM AUTHOR]

Purpose: Inflammatory bowel disease (IBD) in childhood often presents with a more extensive and more aggressive disease course than adult-onset disease. We aimed to evaluate if biological treatment started in childhood decreases the need for intestinal surgery over time. Methods: This was a retrospective, single-center, cohort study. All pediatric patients with IBD initiated to biological therapy at the Children's Hospital, were included in the study and followed up to the first surgical procedure or re-operation in their adulthood or until 31.12.2021 when ≥ 18 of age. Data were collected from the pediatric registry of IBD patients with biologicals and medical charts. Results: A total of 207 pediatric IBD patients were identified [150 with Crohn´s disease (CD), 31 with ulcerative colitis (UC), 26 with IBD unclassified (IBDU)] of which 32.9% (n = 68; CD 49, UC 13, IBDU 6) underwent intestinal surgery. At the end of a median follow-up of 9.0 years (range 2.0-25.9), patients reached a median age of 21.4 years (range 18–36). Patients who had intestinal surgery in childhood were more likely to have IBD-related surgery also in early adulthood. The duration of the disease at induction of the first biological treatment emerged as the only risk factor, with a longer duration in the surgical group than in patients with no surgery. Conclusion: Despite initiation of biological treatment, the risk of intestinal surgery remains high in pediatric IBD patients and often the need for surgery emerges after the transition to adult IBD clinics. [ABSTRACT FROM AUTHOR]

Vedolizumab (VDZ) is used off-label in pediatric inflammatory bowel disease (PIBD). There are less data on drug levels to achieve and maintain remission in children. We aimed to study vedolizumab (VDZ) trough levels in a pediatric population in a real-life setting. We traced 50 patients with PIBD receiving VDZ treatment at our hospital, reviewed their treatment protocol, trough levels, and antidrug antibodies, and compared those to fecal calprotectin (FC) levels and achievement of corticosteroid-free maintenance therapy (CF). VDZ trough level was available from 198 samples during a median follow- up of 12.6 months. Proceeding to maintenance therapy was associated with a decline in FC but not with VDZ trough levels that were comparable between patients with FC < 100 μg/g (remission), 100–1000 μg/g, or > 1000 μg/g at 3 months (mean levels of 36.8, 28.6, and 27 μg/mL, respectively p = 0.188). At 3 months, patients achieving CF (41%) and those on corticosteroids had comparable VDZ trough levels (33 vs. 27.5 μg/mL, respectively). At 6 months, the trough level was similar in groups with FC < 100 μg/g or FC > 1000 μg/g (31.5 and 27.6 μg/mL, p = 0.859). Treatment intensification did not improve the achieved CF at 12 months. None developed drug antibodies nor discontinued the therapy for an adverse event. Conclusion: VDZ was a well-tolerated and safe biologic treatment. A positive response on gut inflammation after induction predicted proceeding to maintenance therapy whereas trough levels did not. A VDZ trough level associated with clinical remission or continuing with VDZ treatment could not be determined. What is Known: • In pediatric inflammatory bowel disease, vedolizumab is still in off-label use. • The results on the relationship between drug levels of vedolizumab and clinical remission in pediatric patients are contradictory. What is New: • This real-life setting in pediatric-onset inflammatory bowel disease showed no benefit of therapy enhancement during a median follow-up of one year. • Trough levels of vedolizumab were not associated with therapy outcomes. [ABSTRACT FROM AUTHOR]

The purpose is to study liver biochemistry in a well-defined cohort of term infants. The methods include healthy term infants (n = 619) provided blood samples at 3 and 6 months of age when participating to the DIABIMMUNE study. The infants were followed up at clinical study visits 3, 6, 12, 18, 24, and 36 months the participation rate being 88.6% at the end of follow-up, while none disclosed any signs of a liver disease. The serum levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin (BIL), and conjugated bilirubin (BIL-conj) were determined using Siemens Atellica CH 930 analyzers. The results are at 3 months of age, the upper 90% CI for ALT, AST, ALP, GGT, BIL, and BIL-conj were higher than the current upper reference limits in our accredited hospital laboratory. At 6 months, the upper 90% CIs for ALT had declined but was still higher than the cut-offs for a raised value. The upper 90% CI for AST remained as high as at 3 months, whereas ALP, BIL-conj, and GGT had decreased close to the current cut-offs. The type of feeding was associated with the levels of liver biochemistry. Exclusively or partially breastfed infants showed higher ALT, AST, BIL, and BIL-conj values at 3 months than formula-fed. Breastfed infants had higher AST, Bil, and Bil-conj values also at 6 months. Conclusion: We encourage setting appropriate reference ranges for liver biochemistry for the first year of life and to note the type of feeding. What is Known: • Healthy infants may show higher values of liver biochemistry during their first year of life than in later life. • It has been speculated that type of feeding may play a role in liver biochemistry levels among infants. What is New: • In a cohort of healthy infants, several analytes of liver biochemistry were higher than the currently used upper reference limits at 3 and 6 months of age, and exclusively or partially breastfed infants showed higher values than formula-fed. • The findings address the importance of setting appropriate reference ranges for liver biochemistry for the first year of life. [ABSTRACT FROM AUTHOR]

To induce remission in luminal paediatric Crohn's disease (CD), the ESPGHAN/ECCO guideline recommends treatment with exclusive enteral nutrition (EEN) or oral corticosteroids. In newly diagnosed moderate-to-severe paediatric CD patients, we determined the proportion of patients in which EEN or corticosteroids induced remission and maintained remission on azathioprine monotherapy. We included patients from the "TISKids" study assigned to the conventional treatment arm. Patients were aged 3–17 years and had new-onset, untreated luminal CD with weighted paediatric CD activity index (wPCDAI) > 40. Induction treatment consisted of EEN or oral corticosteroids; all received azathioprine maintenance treatment from start of treatment. The primary outcome of this study was endoscopic remission defined as a SES-CD score < 3 without treatment escalation at week 10. Secondary outcomes included proportion of patients without treatment escalation at week 52. In total, 27/47 patients received EEN and 20/47 corticosteroids. At baseline, patient demographics and several inflammation parameters were similar between the two treatment groups. At 10 weeks, clinical remission rates were 7/23 (30%) for EEN and 7/19 (37%) for corticosteroids (p = 0.661). Twenty-nine of 47 consented to endoscopy at 10 weeks, showing endoscopic remission rates without treatment escalation in 2/16 (13%) of EEN-treated patients and in 1/13 (8%) of corticosteroid-treated patients (p = 1.00). At week 52, 23/27 (85%) EEN-treated patients received treatment escalation (median 14 weeks) and 13/20 (65%) corticosteroid-treated patients (median 27 weeks), p = 0.070. Conclusion: In children with moderate-to-severe newly diagnosed CD, induction treatment with EEN or CS regularly is insufficient to achieve endoscopic remission without treatment escalation at week 10. Trial registration number: NCT02517684 What is Known: • Endoscopic remission is associated with a low risk of disease progression. • FL-IFX was superior to conventional treatment in achieving and maintaining remission in paediatric patients with moderate-to-severe CD the first year from diagnosis. What is New: • In children with newly diagnosed moderate-to-severe CD, clinical remission rates and endoscopic remission rates without treatment escalation at week 10 were 30% and 13% after EEN and 37% and 8% after corticosteroid induction treatment. • The current treatment target was often not achieved by either EEN or corticosteroid induction treatment after bridging to azathioprine. [ABSTRACT FROM AUTHOR]

Pediatric inflammatory bowel disease (PIBD) is a globally increasing chronic inflammatory disease associated with an imbalanced intestinal microbiota and treated with several treatment options, including anti-tumor necrosis factor alpha (TNF-α), such as infliximab (IFX). Up to half of the patients do not respond to the drug and there are no methods for response prediction. Our aim was to predict IFX response from the gut microbiota composition since this is largely unexplored in PIBD. The gut microbiota of 30 PIBD patients receiving IFX was studied by MiSeq sequencing targeting 16S and ITS region from fecal samples collected before IFX and two and six weeks after the start of treatment. The response to IFX induction was determined by fecal calprotectin value < 100 µg/g at week six. The bacterial microbiota differed significantly between response groups, with higher relative abundance of butyrate-producing bacteria in responders compared to non-responders at baseline, validated by high predictive power (area under curve = 0.892) for baseline Ruminococcus and calprotectin. Additionally, non-responders had higher abundance of Candida, while responders had higher abundance of Saccharomyces at the end of the study. The gut microbiota composition in PIBD patients could predict response to IFX treatment in the future. [ABSTRACT FROM AUTHOR]

Background: The pathophysiology of Henoch-Schönlein purpura (HSP) is still unclear, but several findings suggest that genetic factors may influence disease susceptibility. We aimed to perform a genome-wide association study (GWAS) in pediatric HSP patients with an emphasis on severe HSP nephritis. Methods: The study included 46 HSP patients, 42 of whom had undergone kidney biopsy. Forty-nine pediatric patients with an inflammatory bowel disease (IBD) served as an autoimmune disease control group while Finnish bone marrow and blood donors represented the general reference population (n = 18,757). GWAS was performed for HSP and IBD samples in a case-control manner against the reference population. The analysis also included imputation of human leukocyte antigen (HLA) alleles. Results: GWAS analysis in HSP revealed several polymorphisms from the HLA region that surpassed the genome-wide significance level. Three HLA class II alleles were also significantly more frequent in HSP than in the reference population: DQA1*01:01, DQB1*05:01, and DRB1*01:01. Haplotype DQA1*01:01/DQB1*05:01/DRB1*01:01 occurred in 43.5% of HSP patients, whereas its frequency was 8.2% in IBD patients and 15.0% in the reference population. HSP patients with this haplotype showed similar baseline clinical findings and outcome as HSP patients negative for the haplotype. In IBD patients, no polymorphism or HLA allele appeared significant at the genome-wide level. Conclusions: Our results suggest that haplotype DQA1*01:01/DQB1*05:01/DRB1*01:01 is associated with susceptibility to HSP, but not with the severity of the kidney involvement. These HLA associations did not occur in IBD patients, suggesting that they are specific to HSP and not related to susceptibility to autoimmune diseases in general. [ABSTRACT FROM AUTHOR]

Type 1 diabetes mellitus (DM), autoimmune thyroiditis (AIT), juvenile idiopathic arthritis (JIA), and inflammatory bowel diseases (IBD) are common pediatric autoimmune diseases with unknown risk factors. Using nationwide registers, we searched for their perinatal risk factors. Our study followed up 11,407 children (born 2000–2005) for a median of 16.6 years (from birth to 2018). Of them, 2.15% received primary diagnosis and 0.08% also secondary: 0.89% had DM, 0.60% had AIT, 0.48% had JIA, and 0.25% had IBD. The incidences per 100,000 children/year were 106.1 for DM, 46.0 for AIT, 55.0 for JIA, and 23.7 for IBD. There were more preterm births (< 37 weeks) among children with studied autoimmune diseases compared with the rest of the cohort (8.6% vs. 5.3%, p = 0.035). Among those born preterm, children with studied autoimmune diseases received more postnatal antibiotics compared with other preterm children in the cohort (47.6% vs. 27.7%, p = 0.046). Children with IBD were born to older mothers compared with those without studied diagnoses (33.0 vs 30.2, p = 0.004). Conclusion: Preterm birth was a shared risk factor for autoimmune diseases in our study, especially when combined with postnatal antibiotic treatments. High maternal age was associated with IBD. What is Known: • Type 1 diabetes (DM), autoimmune thyroiditis (AIT), juvenile idiopathic arthritis (JIA), and inflammatory bowel diseases (IBD) are common pediatric autoimmune diseases • It is unclear whether these diseases have shared risk factors, since there are no previous simultaneous epidemiological nor follow-up studies on them in one cohort What is New: • Preterm births were more common in children with DM, AIT, JIA, or IBD compared with other children in the cohort, and preterm children who developed these diseases recieved more postnatal antibiotics compared with other preterm children • High maternal age was associated with IBD [ABSTRACT FROM AUTHOR]

Infliximab (IFX) is administered intravenously using weight-based dosing (5 mg/kg) in inflammatory bowel disease (IBD) patients. Our hypothesis is that especially young children need a more intensive treatment regimen than the current weight-based dose administration. We aimed to assess IFX pharmacokinetics (PK), based on existing therapeutic drug monitoring (TDM) data in IBD patients < 10 years. TDM data were collected retrospectively in 14 centres. Children treated with IFX were included if IFX was started as IBD treatment at age < 10 years (young patients, YP) and PK data were available. Older IBD patients aged 10–18 years were used as controls (older patients, OP). Two hundred and fifteen paediatric inflammatory bowel disease (PIBD) patients were eligible for the study (110 < 10 year; 105 ≥ 10 years). Median age was 8.3 years (IQR 6.9–8.9) in YP compared with 14.3 years (IQR 12.8–15.6) in OP at the start of IFX. At the start of maintenance treatment, 72% of YP had trough levels below therapeutic range (< 5.4 μg/mL). After 1 year of scheduled IFX maintenance treatment, YP required a significantly higher dose per 8 weeks compared with OP (YP; 9.0 mg/kg (IQR 5.0–12.9) vs. OP; 5.5 mg/kg (IQR 5.0–9.3); p < 0.001). The chance to develop antibodies to infliximab was relatively lower in OP than YP (0.329 (95% CI − 1.2 to − 1.01); p < 0.001), while the overall duration of response to IFX was not significantly different (after 2 years 53% (n = 29) in YP vs. 58% (n = 45) in OP; p = 0.56). Conclusion: Intensification of the induction scheme is suggested for PIBD patients aged < 10 years. What is Known? •Infliximab trough levels of paediatric IBD patients are influenced by several factors as dosing scheme, antibodies and inflammatory markers. •In 4.5–30% of the paediatric IBD patients, infliximab treatment was stopped within the first year. What is New? •The majority of young PIBD (< 10 years) have inadequate IFX trough levels at the start of maintenance treatment. •Young PIBD patients (< 10 years) were in need of a more intensive treatment regimen compared with older paediatric patients during 1 year of IFX treatment. •The chance to develop antibodies to infliximab was relatively higher in young PIBD patients (< 10 years). [ABSTRACT FROM AUTHOR]

We addressed growth of biliary atresia (BA) patients living with native livers between ages 0-6 and effects of post-surgical corticosteroid treatment on growth. Growth charts of 28 BA patients born in Finland between 1987 and 2017 were retrospectively evaluated. Dosage and length of corticosteroid treatment and hydrocortisone substitution were reviewed. At birth, BA patients were shorter (median height - 0.6 (interquartile range (IQR) - 1.3 to - 0.1) SDS, n = 28, P < 0.001) than general population. Height remained stable during early childhood (median height - 0.6 (IQR - 1.4 to 0.1) SDS for girls and - 0.4 (IQR - 1.6 to 0.2) SDS for boys at 6 years of age). Patients were of normal height adjusted weight at 6 years with a median age and sex-adjusted body mass index (ISO-BMI) of 20.9 (IQR 19.3 to 25.0) for girls and 22.1 (IQR 20.7 to 25.6) for boys. Higher (≥ 50 mg/kg) cumulative post-portoenterostomy prednisolone dosage resulted in 0.18 SDS lower height per treatment week (β - 0.18, SE 0.04, P < 0.001) compared to lower dosage (< 50 mg/kg).Conclusion: BA patients grow normally during early childhood. As high postoperative corticosteroid dosage has a short-term negative effect on height, very high dosages should be avoided. What Is Known: • Growth of biliary atresia patients has mostly been shown to be within normal limits • Corticosteroids may decrease growth rate What Is New: • Biliary atresia patients surviving with their native livers are shorter than general population and their mid-parental target height at birth • A high (> 50 mg/kg) cumulative prednisolone dosage has a negative transitory impact on height gain after portoenterostomy. [ABSTRACT FROM AUTHOR]

Background: Fecal calprotectin is a reliable surrogate marker for inflammatory activity in inflammatory bowel disease (IBD).Aims: For the noninvasive monitoring of the activity of colonic inflammation, we validated a symptom index suitable for ulcerative colitis and colonic Crohn's disease. By combining the symptom index with a rapid semi-quantitative calprotectin test, we constructed a new activity index based on the highest AUCs, using histological remission as a reference. We also evaluated the correlation of the patient-reported influence of the IBD in the daily life, measured by a VAS, with the inflammation activity.Methods: The disease activity of 72 patients with IBD of the colon was determined by endoscopic activity scores (SES-CD/UCEIS). The patients provided stool samples for determination of calprotectin and filled in a questionnaire about their symptoms during the last week.Results: The results of the symptom index demonstrated a statistically significant correlation with the rapid calprotectin test, histological inflammation activity, and the VAS. No correlations were found between the VAS and calprotectin or the histological inflammation activity. The sensitivity of the combination index to detect active inflammation was slightly superior to fecal calprotectin alone.Conclusion: The new symptom index and the combination index are simple, noninvasive means for distinguishing remission from active inflammation in colonic IBD. With the VAS, we can pick up patients who need psychosocial support because of the disease burden, even if their IBD is in remission. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Inflammatory bowel disease (IBD) is considered to result from interplay between host and intestinal microbiota. While IBD in adults has shown to be associated with marked changes in the intestinal microbiota, there are only a few studies in children, and particularly studies focusing on therapeutic responses are lacking. Hence, this prospective study addressed the intestinal microbiota in pediatric IBD especially related to the level of inflammation.METHODS:In total, 68 pediatric patients with IBD and 26 controls provided stool and blood samples in a tertiary care hospital and 32 received anti-tumor necrosis factor-α (anti-TNF-α). Blood inflammatory markers and fecal calprotectin levels were determined. The intestinal microbiota was characterized by phylogenetic microarray and qPCR analysis.RESULTS:The microbiota varied along a gradient of increasing intestinal inflammation (indicated by calprotectin levels), which was associated with reduced microbial richness, abundance of butyrate producers, and relative abundance of Gram-positive bacteria (especially Clostridium clusters IV and XIVa). A significant association between microbiota composition and inflammation was indicated by a set of bacterial groups predicting the calprotectin levels (area under curve (AUC) of 0.85). During the induction of anti-TNF-α, the microbial diversity and similarity to the microbiota of controls increased in the responder group by week 6, but not in the non-responders (P<0.01; response related to calprotectin levels). The abundance of six groups of bacteria including those related to Eubacterium rectale and Bifidobacterium spp. predicted the response to anti-TNF-α medication.CONCLUSIONS:Intestinal microbiota represents a potential biomarker for correlating the level of inflammation and therapeutic responses to be further validated. [ABSTRACT FROM AUTHOR]

OBJECTIVES:The objective of this study was to perform a meta-analysis investigating antibiotic exposure as a risk factor for developing inflammatory bowel disease (IBD).METHODS:A literature search using Medline, Embase, and Cochrane databases was performed to identify studies providing data on the association between antibiotic use and newly diagnosed IBD. Included studies reported Crohn's disease (CD), ulcerative colitis (UC), or a composite of both (IBD) as the primary outcome and evaluated antibiotic exposure before being diagnosed with IBD. A random-effects meta-analysis was conducted to determine overall pooled estimates and 95% confidence intervals (CIs).RESULTS:A total of 11 observational studies (8 case-control and 3 cohort) including 7,208 patients diagnosed with IBD were analyzed. The pooled odds ratio (OR) for IBD among patients exposed to any antibiotic was 1.57 (95% CI 1.27-1.94). Antibiotic exposure was significantly associated with CD (OR 1.74, 95% CI 1.35-2.23) but was not significant for UC (OR 1.08, 95% CI 0.91-1.27). Exposure to antibiotics most markedly increased the risk of CD in children (OR 2.75, 95% CI 1.72-4.38). All antibiotics were associated with IBD, with the exception of penicillin. Exposure to metronidazole (OR 5.01, 95% CI 1.65-15.25) or fluoroquinolones (OR 1.79, 95% CI 1.03-3.12) was most strongly associated with new-onset IBD.CONCLUSIONS:Exposure to antibiotics appears to increase the odds of being newly diagnosed with CD but not UC. This risk is most marked in children diagnosed with CD. [ABSTRACT FROM AUTHOR]

Purpose: Fecal MMP-9 and human beta-defensin-2 (HBD-2) levels, potential markers of intestinal inflammation, are insufficiently explored in pediatric inflammatory bowel disease (IBD). The aim was to study fecal MMP-9 and HBD-2 in pediatric IBD to compare their performance to calprotectin and to study whether they would provide additional value in categorizing patients according to their disease subtype. Methods: Fecal calprotectin, MMP-9, and HBD-2 levels were measured with ELISA in 110 pediatric patients with IBD (Crohn's disease, n = 68; ulcerative colitis (UC), n = 27; unclassified, n = 15; median age, 14). To compare the performance of the fecal markers, the area under the receiver operating characteristics curve (±95 % CI) was used. In addition, the best cut-off values of each measure to differentiate IBD patients and controls ( n = 27 presenting with diarrhea, abdominal pain, and/or anemia) were derived by maximizing sensitivity and specificity. Results: Of the fecal markers studied, calprotectin performed best for separation of IBD and non-IBD patients with the area under curve (AUC) of 0.944 (95 % CI, 0.907 to 0.981). For MMP-9, AUC was 0.837 (95 % CI, 0.766 to 0.909), the levels being significantly higher in active IBD and in UC compared with Crohn's disease ( p = 0.0013), but categorization of these patient groups did not take place. HBD-2 did not categorize any of the studied groups. Conclusions: Calprotectin was the best fecal marker in pediatric IBD, but MMP-9 showed almost comparable performance in UC, suggesting applicability as a surrogate marker of inflammation. Fecal HBD-2 did not bring information to the disease characteristics of pediatric IBD patients. [ABSTRACT FROM AUTHOR]

Background and Aim: Proctocolectomy with straight or J-pouch ileoanal anastomosis is the standard surgical treatment (ST) for ulcerative colitis (UC) also in children. Pelvic dissection may damage structures essential for sexual functions (SF). We compared SF in adults with ST during childhood or adolescence with adults with medical treatment (MT).Materials and Methods: Sixty-three sexually active patients (ST 25, males 8; MT 38, males 19) median age of 27 years (range 17-41) (ST) and 29 years (20-40) (MT) (P = NS) were included. UC was diagnosed 15 years (5.1-26) (ST) and 7.5 years (2-20) (MT) (P < 0.05) before. Median ages at and follow-up after ST was 13 years (5.0-19) and 13 years (4.4-22), respectively. In ST and MT groups the daily stooling frequency and the incidence of soiling were 6 (2-17) and 2 (1-12), and 13/25 (52%) and 3/38 (8%), respectively (P < 0.05). SF were assessed with a structured form.Results: In ST and MT groups, 21/25 (84%) and 31/38 (82%) reported satisfactory SF and 17/25 (68%) and 28/38 (74%) enjoyable sex life (P = NS). Urinary and faecal incontinence disturbed SF in both ST and MT groups in 2/25 (8%) and 3/38 (8%) and 13/25 (52%) and 15/38 (39%) (P = NS in each). Faecal incontinence inversely correlated with sexual satisfaction in all patients (R range; 0.36-0.68, P < 0.05). No erectile problems occurred. One patient (MT) reported ejaculatory problems. In females, dysorgasmia and dyspareunia were reported by 1/17 (6%) and 6/17 (35%) (ST) and 1/19 (5%) and 11/19 (58%) (MT) (P = NS). With intention to conceive 2/5 females in ST and 2/3 in MT group became pregnant within 1 year (P = NS). Only 2/25 (8%) (ST) and 7/38 (18%) (MT) had received information of the effect of treatment on SF.Conclusion: Compared with adult CU patients with MT, SF in patients with ST for CU in childhood or adolescence were similar. ST at a young age does not seem to affect SF in adulthood. Faecal incontinency disturbed SF in MT and ST groups. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) constitute a family of enzymes capable of degrading various extracellular matrices (ECM) and basement membrane components playing a role in ECM turnover. They activate and degrade signaling molecules, such as cytokines and chemokines. MMPs are involved in inflammation and have been implicated in tissue degradation and repair occurring in inflammatory bowel disease. The aim of this study was to investigate the MMP profile of intestinal Crohn's disease (CD) patients before and after immunosuppressive treatment (anti-TNF-α agents or corticosteroids and conventional immunosuppressants azathioprine or methotrexate) to learn more about the therapeutic pathways for immunosuppressive agents. Expression of MMP-1, MMP-7, MMP-9, MMP-10, and MMP-26 and tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-3 was studied by immunohistochemistry in pretreatment and post-treatment tissue samples. Semiquantitative immunohistochemical scores were tested for correlations with fecal and serum inflammation markers as well as endoscopic and clinical disease activity scores. Neutrophil MMP-9 ( p = 0.039) and MMP-26 ( p = 0.030) and stromal TIMP-1 ( p = 0.041) and TIMP-3 ( p = 0.029) decreased along with treatment. However, expression of TIMP-3 by enterocytes tended to increase. Total histological score demonstrated positive correlation with neutrophil MMP-9 ( p = 0.000), MMP-26 ( p = 0.014), and macrophage TIMP-1 ( p = 0.001). Calprotectin followed a similar pattern with stromal MMP-26 ( p = 0.011), TIMP-1 ( p = 0.000), and TIMP-3 ( p = 0.001). Crohn's disease endoscopic index of severity (CDEIS) value correlated positively with macrophage TIMP-1 ( p = 0.007) and stromal TIMP-3 ( p = 0.005). Epithelial TIMP-3 presented with negative correlations with CDEIS ( p = 0.006) and C-reactive protein values ( p = 0.004). Our results suggest that immunosuppressive drugs modulate disease activity in CD by downregulation of MMP-9 and MMP-26 positive neutrophils and stromal TIMP-1 and TIMP-3. [ABSTRACT FROM AUTHOR]