Search

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. 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. 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). 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 [ABSTRACT FROM AUTHOR]

Objective We aimed to provide an evidence-supported update of the ECCO-ESPGHAN guideline on the medical management of paediatric Crohn's disease [CD]. Methods We formed 10 working groups and formulated 17 PICO-structured clinical questions [Patients, Intervention, Comparator, and Outcome]. A systematic literature search from January 1, 1991 to March 19, 2019 was conducted by a medical librarian using MEDLINE, EMBASE, and Cochrane Central databases. A shortlist of 30 provisional statements were further refined during a consensus meeting in Barcelona in October 2019 and subjected to a vote. In total 22 statements reached ≥ 80% agreement and were retained. Results We established that it was key to identify patients at high risk of a complicated disease course at the earliest opportunity, to reduce bowel damage. Patients with perianal disease, stricturing or penetrating behaviour, or severe growth retardation should be considered for up-front anti-tumour necrosis factor [TNF] agents in combination with an immunomodulator. Therapeutic drug monitoring to guide treatment changes is recommended over empirically escalating anti-TNF dose or switching therapies. Patients with low-risk luminal CD should be induced with exclusive enteral nutrition [EEN], or with corticosteroids when EEN is not an option, and require immunomodulator-based maintenance therapy. Favourable outcomes rely on close monitoring of treatment response, with timely adjustments in therapy when treatment targets are not met. Serial faecal calprotectin measurements or small bowel imaging [ultrasound or magnetic resonance enterography] are more reliable markers of treatment response than clinical scores alone. Conclusions We present state-of-the-art guidance on the medical treatment and long-term management of children and adolescents with CD. [ABSTRACT FROM AUTHOR]

Introduction The ability to predict risk for poor outcomes in Crohn's disease [CD] would enable early treatment intensification. We aimed to identify children with CD with complications at baseline and throughout the study period who are at risk for surgery 2 years from diagnosis. Methods Newly diagnosed children with CD were enrolled into a prospective, multicentre inception cohort. Disease characteristics and serological markers were obtained at baseline and week 12 thereafter. Outcome data including disease activity, therapies, complications and need for surgery were collected until the end of 104 weeks. A chi-square automatic interaction detection [CHAID] algorithm was used to develop a prediction model for early surgery. Results Of 285 children enrolled, 31 [10.9%] required surgery within 2 years. Multivariate analysis identified stricturing disease at baseline (odds ratio [OR] 5.26, 95% confidence interval [CI] 2.02–13.67 [ p = 0.001]), and Paediatric Crohn's Disease Activity Index [PCDAI] >10 at week 12 (OR 1.06, 95% CI 1.02–1.10 [ p = 0.005]) as key predictors for early surgery. CHAID demonstrated that absence of strictures at diagnosis [7.6%], corticosteroid-free remission at week 12 [4.1%] and early immunomodulator therapy [0.8%] were associated with the lowest risk of surgery, while stricturing disease at diagnosis [27.1%, p < 0.001] or elevated PCDAI at week 12 [16.7%, p = 0.014] had an increased risk of surgery at follow-up. Anti-OmpC status further stratified high-risk patients. Discussion A risk algorithm using clinical and serological variables at diagnosis and week 12 can categorize patients into high- and low-risk groups from diagnosis. [ABSTRACT FROM AUTHOR]

Background: Exclusive enteral nutrition [EEN] and corticosteroids [CS] induce similar rates of remission in mild to moderate paediatric Crohn's disease [CD], but differ with regard to mucosal healing. Our goal was to evaluate if EEN at diagnosis was superior to CS for improving long-term outcomes. Methods: We prospectively followed newly diagnosed children aged < 17 years, with mild to moderate CD at baseline, for 2 years in the GROWTH CD study. Patients were evaluated at baseline and at 8, 12, 78, and 104 weeks. Remission, relapses, complications [fibrostenotic disease, penetrating disease, and active perianal disease] and growth were recorded throughout the study. A propensity score analysis was performed. Results: A total of 147 children [mean age 12.9 ± 3.2 years], treated by EEN [n = 60] or CS [n = 87] were included. New complications developed in 13.7% of CS [12/87] versus 11.6% of EEN [7/60], = 0.29. Remission was achieved in 41/87 [47%] in CS and 38/60 [63%] EEN, p = 0.036. Median time to relapse did not differ [14.4 ± 1 months with CS, 16.05 ± 1.1 EEN, p = 0.28]. Mean height Z scores decreased from Week 0 to Week 78 with CS [-0.34 ± 1.1 to -0.51 ± 1.2, p = 0.01], but not with EEN [-0.32 ± 1.1 to -0.22 ± 0.9, p = 0.56]. In a propensity score analysis, EEN was superior to CS for inducing remission [p = 0.05] and trended to superiority for height Z score [p = 0.055]. Conclusions: Use of EEN was associated with higher remission rates and a trend toward better growth but with similar relapse and complication rates in new-onset mild to moderate paediatric CD. [ABSTRACT FROM AUTHOR]

Background: Loss of response [LoR] to biologics in Crohn's disease [CD] is a significant clinical problem. Dietary therapy as a treatment strategy in this setting has not been previously reported. We report the use of dietary strategies using enteral nutrition coupled with the Crohn's Disease Exclusion Diet [CDED] for LoR to infliximab or adalimumab as a single-centre experience. Methods: Patients with LoR to a biologic despite dose escalation or combination therapy were treated with partial enteral nutrition [PEN] by a polymeric formula and the CDED for 12 weeks. Paediatric patients with severe flares received 14 days of exclusive enteral nutrition followed by PEN + CDED as above. All patients were seen at weeks 6 and 12 for follow up. Current and prior treatment, Harvey Bradshaw Index [HBI], C-reactive protein [CRP] and albumin were recorded. Remission was defined as HBI <5 at week 6. Results: Twenty-one patients, mean age 22.1 ± 8.9 years [11 adults and ten children] met study criteria. Seventeen patients [81%] had used combination therapy, and 10/21 [47.6%] had failed a second biologic. Seven patients had a prior intestinal resection. Dose escalation had failed in 13/21 [62%] patients. Clinical remission by physician's global assessment and HBI after 6 weeks was obtained in 13/21 [61.9%]. Mean HBI decreased from 9.4 ± 4.2 to 2.6 ± 3.8 [p < 0.001], mean CRP decreased from 2.8 ± 3.4 to 0.7 ± 0.5 [p = 0.005] and mean albumin increased from 3.5 ± 0.6 to 3.8 ± 0.5 [p = 0.06]. Conclusion: Dietary treatment combining PEN with the CDED may be a useful salvage regimen for patients failing biological therapy despite dose escalation. [ABSTRACT FROM AUTHOR]

Background: Paediatric ulcerative colitis [UC] is more extensive than adult disease, and more often refractory to mesalamine. However, no prospective trials have evaluated mesalamine enemas for inducing remission in children. Our goal was to evaluate the ability of mesalamine enemas to induce remission in mild to moderate paediatric UC refractory to oral mesalamine. Methods: This was an open-label arm of a previously reported randomised controlled trial of once- daily mesalamine in active paediatric UC [MUPPIT trial]. Children aged 4-18 years, with a Paediatric Ulcerative Colitis Activity Index [PUCAI] score of 10-55, were enrolled after failing at least 3 weeks of full-dose oral mesalamine. Patients treated with steroids or enemas in the previous month and those with isolated proctitis were excluded. Children received Pentasa® enemas 25 mg/kg [up to 1g] daily for 3 weeks with the previous oral dose. The primary endpoint was clinical remission by Week 3. Results: A total of 38 children were enrolled (mean age 14.6 ± 2.3 years; 17/38 [45%] with extensive colitis). Clinical remission was obtained in 16 [42%] and response was obtained in 27 [71%] at Week 3. Eight children deteriorated and required steroids. There were no differences in baseline parameters between those who entered or failed to enter remission, including disease extent [43% in left-sided and 41% in extensive colitis] and disease activity [44% in mild and 41% in moderate activity]. Conclusion: Clinical remission can be markedly increased in children who are refractory to oral mesalamaine by adding mesalamine enemas for 3 weeks, before commencing steroids. [ABSTRACT FROM AUTHOR]

Background: Trials in adults suggested that, in ulcerative colitis [UC], once-daily [OD] dosing of 5-ASA [5-amino salicylic acid] may be as or more effective than twice-daily [BD] dosing. In this induction of remission, investigator-blinded, randomised controlled-trial, we aimed to compare effectiveness and safety of once- versus twice-daily mesalazine in paediatric UC. Methods: Children, aged 4–18 years with a PUCAI [Paediatric Ulcerative Colitis Activity Index] of 10–55 points at inclusion, were randomised in blocks of six with blinded allocation to OD or BD mesalazine, using a weight-based dosing table. The primary outcome was mean PUCAI score at Week 6. Results: A total of 83/86 randomised children were eligible and analysed: 43 in the OD group and 40 in the BD group (mean age 14 ± 2.7 years, 43 [52%] males, 51 [62%] extensive colitis). The groups did not differ with regard to disease activity or any other parameter at baseline. There was no difference in median PUCAI score between the OD group and BD group at Week 6: 15 ( interquartile range [IQR] 5–40) versus 10 [0–40]; p = 0.48]. Response was seen in 25 [60%] OD versus 25 [63%] BD dosing [p = 0.78]. Proportion of children in remission [PUCAI < 10] at Week 6 was 13 [30%] OD versus 16 [40%] BD; p = 0.35]. Most adverse events were related to disease aggravation; the rates of serious adverse events were similar [p > 0.2]. Conclusions: In this first randomised controlled trial in children, no differences were found between OD and BD dosing for any clinical outcome. Remission was achieved in 35% of children treated with mesalazine for active UC. [ABSTRACT FROM AUTHOR]

Abstract: Background: Crohn''s disease (CD) is characterized by an aberrant response to the gut microbiota. We aimed to assess whether azithromycin based therapy is effective in inducing remission in CD, due to its effect in inducing apoptosis and efficacy against biofilms and intracellular bacteria. Methods: Retrospective analysis of patients treated with an 8week course of combined azithromycin and metronidazole. Patients were included if they had active CD defined as pediatric CD activity index (PCDAI) ≥10, and were not receiving any other medication for inducing remission in active disease. PCDAI score and CRP were recorded at baseline and 8weeks thereafter. Results: Thirty two patients (mean age 13.1±3.9, mean duration of disease 0.65years) were included, of whom 21 (66%) entered clinical remission (PCDAI<10) after 8weeks of treatment. The mean age at treatment and duration of disease did not differ between patients entering remission and those unresponsive to therapy. CRP, normalized in 54% of patients with elevated CRP at baseline. Factors associated with lack of response were a more severe disease (reflected by higher PCDAI and CRP values at baseline), presence of arthritis and extensive disease (ileocolonic, or prominent upper intestinal disease). Conclusions: An 8week course of azithromycin and metronidazole therapy may be effective in inducing clinical remission in mild-moderate luminal CD in children and young adults. [Copyright &y& Elsevier]

Tube dependency is recognized as an unintended result of long-term tube feeding in infants and young children. The condition involves disturbing side effects such as vomiting, gagging, and active food refusal. It prevents infants from making the transition from tube to oral feeding and from starting to learn to eat in the absence of any medical indication for continuation of enteral feeding. Tube dependency can have a destructive impact on the child's development, even in cases when the nutritional influence might be beneficial. The authors set up recommendations for the prevention of tube dependency and suggest guidelines for weaning tube-dependent children based on the results of the Graz program and satellite programs using a similar model. A sample of 221 tube-dependent patients aged 4 months to 15 years of age provided the clinical study group on which this article is based. Begun in 1987, a comprehensive tube-weaning program was developed on the basis of clinical experience and encounters with more than 430 tube-dependent children in 20 years, resulting in a success rate of 78/81 (96% for 2007) and 79/84 (94% for 2008). Placement must be preceded by clear criteria and a decision as to the indicated nutritional goal and time of use. The placement of a temporary tube must generate a plan covering maintenance issues, including time, method, and team for weaning. Aspects of tube feeding that go beyond purely medical and nutritional issues need to be considered to minimize the frequency and severity of unintended tube dependency in early childhood. [ABSTRACT FROM PUBLISHER]

Aims: Post-infectious gastroparesis (PIGP) is a subgroup of idiopathic gastroparesis. The aim of this study was to identify post-viral gastroparesis and to characterize clinical and electrogastrographic aspects of the disease and their usefulness as a diagnostic tool. Methods: Patients diagnosed with gastroparesis were defined as PIGP if they had a clear history of an acute viral illness prior to the development of their symptoms. All patients underwent evaluation of gastric emptying and electrogastrography (EGG). Results: Seven patients met the criteria for diagnosis of PIGP. Patients' age ranged from 3 months to 47 years. A specific virus was identified in two patients (one cytomegalovirus [CMV] and one Epstein-Barr virus [EBV]). EGG was pathological in six out of seven patients. In four out of seven patients, symptoms resolved spontaneously within 4 weeks to 12 months, three patients had improved but were still symptomatic at the time of the writing of this work. Conclusion: We conclude that post-infectious gastroparesis is an uncommon and often over looked condition. It is self-limiting in most cases. EGG is pathological in most patients. [ABSTRACT FROM AUTHOR]

Background: As the microbiome plays an important role in instigating inflammation in ulcerative colitis (UC), strategies targeting the microbiome may offer an alternative therapeutic approach. The goal of the pilot trial was to evaluate the potential efficacy and feasibility of a novel UC exclusion diet (UCED) for clinical remission, as well as the potential of sequential antibiotics for diet-refractory patients to achieve remission without steroids. Methods: This was a prospective, single-arm, multicenter, open-label pilot study in patients aged 8–19, with pediatric UC activity index (PUCAI) scores >10 on stable maintenance therapy. Patients failing to enter remission (PUCAI < 10) on the diet could receive a 14-day course of amoxycillin, metronidazole and doxycycline (AMD), and were re-assessed on day 21. The primary endpoint was intention-to-treat (ITT) remission at week 6, with UCED as the only intervention. Results: Twenty-four UCED treatment courses were given to 23 eligible children (mean age: 15.3 ± 2.9 years). The median PUCAI decreased from 35 (30–40) at baseline to 12.5 (5–30) at week 6 (p = 0.001). Clinical remission with UCED alone was achieved in 9/24 (37.5%). The median fecal calprotectin declined from 818 (630.0–1880.0) μg/g at baseline to 592.0 (140.7–1555.0) μg/g at week 6 (p > 0.05). Eight patients received treatment with antibiotics after failing on the diet; 4/8 (50.0%) subsequently entered remission 3 weeks later. Conclusion: The UCED appears to be effective and feasible for the induction of remission in children with mild to moderate UC. The sequential use of UCED followed by antibiotic therapy needs to be evaluated as a microbiome-targeted, steroid-sparing strategy. [ABSTRACT FROM AUTHOR]