Combination biologic therapy in pediatric inflammatory bowel disease: Safety and efficacy over a minimum 12-month follow-up period.

OBJECTIVES: The severe course of inflammatory bowel diseases (IBDs) refractory to advanced therapies in children results in the search for new therapeutic methods. The aim of this study was to evaluate the efficacy and safety of dual therapy with biologics in a cohort of children with IBD. METHODS: Retrospective analysis of data from 29 children with a diagnosis of IBD, 19 with ulcerative colitis (66%), 10 with Crohn's disease (CD) (34%) qualified for dual biological therapy (DBT). The median age of patients was five (interquartile range [IQR], 1-15) years at diagnosis of IBD and 14 (IQR, 3-17) years at eligibility for dual therapy. Thirteen (45%) patients were treated with vedolizumab/adalimumab (VDZ + ADA), 13 (45%) with ustekinumab/adalimumab (UST + ADA), three (10%) with infliximab/vedolizumab (IFX + VDZ). RESULTS: Clinical remission was achieved in 13 (45%; seven UC and six CD) and 12 (41%; seven UC and five CD) Pediatric Weighted Crohn's Disease Activity Index (wPCDAI)/Pediatric Ulcerative Colitis Activity Index (PUCAI) patients after 4 and 12 months at the initiation of dual therapy. Clinical response based on wPCDAI/PUCAI was reported in 16 (55%; nine UC and seven CD) and 12 (41% seven UC and five CD) children after 4 and 12 months of follow-up, respectively. The median fecal calprotectin decreased significantly from 1240 µg/g (53-10,100) to 160 µg/g (5-2500; p = 0.004) between baseline and Month 4 and from 749 at baseline (57-10,100) to 17 (5-3110; p = 0.12) over 12 months. Moreover, 34% (six UC and four CD) of patients achieved endoscopic remission. CONCLUSIONS: DBT seems to be an effective alternative therapeutic option for patients with moderate and severe IBD.

Effect of the Crohn's Disease Exclusion Diet (CDED) on the Fecal Calprotectin Level in Children with Active Crohn's Disease.

(1) Background: The CDED + PEN (partial enteral nutrition) is a promising method of nutritional treatment in active Crohn's disease (CD). An increase in fecal calprotectin (FCP) level­a marker of mucosal inflammation­happens to be the first evidence of Crohn's disease exacerbation that appears ahead of clinical symptoms and usually co-exists with them. In this study, we present our own experience with using the CDED + PEN in the treatment of children with CD and an increased FCP level. (2) Methods: In total, 48 children (male/female: 27/21) aged 4−17 years (median value = 13.43; IQR = 4.00) were treated with CDED + PEN between June 2019 and July 2021. The main inclusion criteria for the study was active CD defined as an FCP level ≥ 250.00 µg/g. Patients with severe clinical manifestation of CD (PCDAI >40.00), as well as ones who started any new concomitant CD treatment later than at least 4 weeks before the start of dietary intervention, were excluded from the analysis. The PCDAI and fecal calprotectin level were assessed at weeks 0 and 12. The primary endpoint was ITT normalization of FCP level, i.e., a result < 250.00 µg/g at week 12. The Wilcoxon Matched Pairs Test was used for statistical analysis. (3) Results: The normalization of the FCP level was obtained in 17 children (35.42%) and an FCP level decrease of at least 50% occurred in 26 patients (54.17%). The reduction in fecal calprotectin level between week 0 and week 12 was statistically significant with a median value of 1045.00 µg/g; IQR = 1188.00, and 363.00 µg/g; IQR = 665.00, respectively (p < 0.05). Among 29 patients who were not in clinical remission at baseline, 16 (55.17%) achieved clinical remission (PCDAI < 10.00) at week 12 and 20 (68.97%) obtained a clinical response defined as at least a 12.50 point drop in PCDAI or remission. In this group, the reduction in PCDAI between baseline and week 12 was statistically significant (median value = 20.00 points; IQR = 7.50 and 5.00 points; IQR = 5.00, respectively (p < 0.05)). All patients with a normal FCP level at week 12 were in clinical remission and 16 (94.13%) of them had a normal CRP (C-reactive protein) value. In 10 children (20.83%) the full course of 12 weeks with CDED + PEN was not completed or the concomitant therapy had been started before week 12 due to the lack of efficacy/intolerance of nutritional treatment. (4) Conclusions: The 12-week course of treatment with the CDED + PEN has a beneficial effect on the fecal calprotectin level in children with active CD. The dietary intervention led to a significant decrease in the FCP level in the studied group and to the normalization of this parameter in every third patient.

Nutritional Therapy in Pediatric Crohn's Disease-Are We Going to Change the Guidelines?

In recent years, there has been a significant increase in the incidence of Crohn's disease. Despite significant medical progress, the treatment options available today do not meet the needs of all patients. Recent reports indicate that external environmental factors, including diet, are key in the pathomechanism of the disease. It was proven that the so-called Western dietary pattern is associated with an increased risk of disease. In the pediatric population, exclusive enteral nutrition is the only nutritional therapy option recommended today with proven high efficacy in inducing remission. Recent publications that indicate at least comparable efficacy and significantly better tolerability of a specialised elimination diet, the Crohn's Disease Exclusion Diet (CDED), provide the basis for a change in recommendations. This article discusses the mechanism of action, principles of use, and scientific evidence evaluating the efficacy of CDED in the treatment of children with Crohn's disease.

Analysis of frequency and risk factors for complications of enteral nutrition in children in Poland after percutaneous endoscopic gastrostomy placement.

OBJECTIVES: The aim of the study was to assess the complication rate and identify whether age, nutritional status, and history of respiratory aspiration prior to percutaneous endoscopic gastrostomy (PEG) are risk factors for post-PEG placement complications in Polish children. In addition, the safety of two enteral feeding methods (3 h vs. 8 h) after PEG insertion in children was compared. METHODS: Children with clinical indications for PEG placement were recruited from six medical centers in Poland to participate in the study. The patients were centrally randomized to receive the first bolus feed via a feeding tube at 3 h (group 1) or 8 h (group 2) after PEG placement. The preprocedural preparation, postoperative care, and resumption of feeding were performed on all of patients in accordance with the study protocol. Patients were followed for 12 mo. RESULTS: Of the 97 randomized patients, 49 were assigned to group 1 and 48 to group 2. Full feed after PEG placement was achieved within 24 to 48 h in most cases (74% vs. 82%). There were no differences between the groups regarding the number of early mild (31.3% vs. 31.3%) and serious (2.1% vs 8.3%) complications or the duration of hospitalization after PEG placement (P > 0.05). The most common serious complication after PEG placement was accidental displacement of PEG. Most reported late complications were mild. The results of the regression analysis indicate no statistically significant effect of age, body mass index standard deviation score, white blood cell count, serum albumin level, and respiratory aspiration in the medical history on the occurrence of mild and severe complications. CONCLUSIONS: The early initiation of post-PEG feeding was not associated with an increase in the number of complications. Most complications after the PEG procedure were mild. Age, serum albumin level, white blood cells, body mass index standard deviation score, and a history of aspiration to the respiratory tract were not confirmed as a risk factor for post-PEG complications in children.

Dietary management of infants and young children with feeding difficulties and unsatisfactory weight gain using a nutritionally complete hypercaloric infant formula. practical considerations from clinical cases.

INTRODUCTION: A decrease in weight velocity and feeding difficulties in infants may be caused by an inadequate caloric intake and underlying medical conditions. CASE DESCRIPTION: By focusing on four clinical cases, this article illustrates the temporary use of a special infant formula in orally-fed and enterally-fed infants with unsatisfactory weight gain and special medical conditions such as gastrointestinal and neurological disorders. The formula was a nutritionally complete hypercaloric infant formula containing partially hydrolyzed whey protein. It was used after full consideration of all feeding options including breastfeeding. CONCLUSION: Implementing appropriate feeding behaviors, adapted to age and potential comorbidities, is an essential prerequisite for therapeutic management. The use of a nutritionally complete hypercaloric infant formula can be helpful to manage unsatisfactory weight gain and feeding difficulties in infants.

Oral exclusive enteral nutrition for induction of clinical remission, mucosal healing, and improvement of nutritional status and growth velocity in children with active Crohn's disease - a prospective multicentre trial.

INTRODUCTION: Undernutrition and growth failure are common problems in paediatric patients with active Crohn's disease (CD). AIM: The aim of exclusive enteral nutrition (EEN) commencement is not only to induce clinical remission and promote mucosal healing but also to initiate weight and growth gain, especially in patients with poor nutritional status. We assessed the effectiveness of treatment with EEN and its impact on nutritional status in children with active CD. MATERIAL AND METHODS: Twenty children (male/female: 14/6) in median age of 14 years with active CD had EEN with polymeric industrial diet (Modulen IBD) applied for 6 weeks. The daily caloric intake was established according to the age and nutritional status. In patients with undernutrition, it was increased to 120-150% relative to recommendations for the healthy peers. The Paediatric CD activity index (PCDAI) - a marker of clinical remission, faecal calprotectin (FCP) - a marker of mucosal healing (MH), and nutritional status were assessed at baseline and 4 weeks following the end of the therapy (week 10). RESULTS: In the studied group the mean decrease in PCDAI score was statistically significant (from 25.6 ±12 to 5.4 ±10, p < 0.05). Full remission (defined as PCDAI < 10) was achieved in 65% of patients, and clinical response in another 30% of them. Only 5% of children did not respond to the treatment. Mean decline in FCP level was statistically significant as well (from 3380 ±7746 to 1046.6 ±1219, p < 0.05). All patients, apart from one who was fed with a nasogastric tube, accepted oral intake of industrial formula. EEN was generally well tolerated. Initially, in 20% of patients the symptoms of intolerance to the industrial diet were observed, but they receded within the first days of the therapy. The recommended daily intake of the formula was achieved in 95% of children. Only one child was unable to intake the prescribed amount of the diet due to intolerance. At baseline, undernutrition was observed in 30% of patients, which was established by a body mass index (BMI) score below the third percentile according to the recommended charts for the Polish paediatric population. In all patients, improvement in BMI status was reported at the end of the treatment. The mean increase in BMI score was 0.91, and it was greater in the malnourished group compared to patients with normal nutritional status (1.19 vs. 0.62). After the treatment two-thirds of children with malnutrition achieved a BMI score within the normal range. In 25% of patients, growth deficit was observed (defined as growth below the third percentile according to the Polish charts) before the EEN introduction. An increase in body height was obtained generally in 55% of children and in 80% of those with initial growth failure. The mean increase in growth was 1 cm, and it was greater in the group with initial growth deficit relative to patients with baseline normal height (1.5 cm vs. 0.8 cm, respectively). CONCLUSIONS: A 6-week course of oral EEN was an effective and well-tolerated method of treatment in children with active CD. Nutritional therapy not only induced full clinical remission and led to decline in FCP level (as a marker of MH) in the majority of patients, but also contributed to the improvement in their nutritional status and growth velocity. These are very important observations because proper development is crucial for paediatric CD patients.

The level of faecal calprotectin as a noninvasive biomarker of mucosal healing in children with ulcerative colitis.

INTRODUCTION: Recently, faecal calprotectin (FC) has been used as a marker of inflammatory processes in the gastrointestinal tract, such as inflammatory bowel disease (IBD), and has served to assess and monitor disease activity, mucosal healing (MH), and disease recurrence. AIM: To assess the correlation between FC and endoscopic activity of inflammation. MATERIAL AND METHODS: This retrospective study included 81 patients with ulcerative colitis (UC), with a median age of 15 years (range: 3-18 years), who were treated in the Children's Memorial Health Institute (CMHI) between 2013 and 2015. Within the study group there were two sub-groups created: patients with Baron score = 0 (n = 34, 42%) and ≥ 1 (n = 47, 58%). RESUTS: Statistical analysis was performed using Statistica 10 software (StatSoft, USA), and the value of p ≤ 0.05 was established as a significance level. In patients with Baron score ≥ 1, significantly higher FC values and PUCAI scores were found in comparison to children with Baron score = 0. The level of FC had greater accuracy than the PUCAI score in differentiation between patients with Baron score = 0 and ≥ 1 (Z = -1.73, p = 0.082). There was a significant correlation between PUCAI score and FC (R = 0.55, p < 0.001). CONCLUSIONS: Faecal calprotectin may be a good, noninvasive biomarker of mucosal healing in paediatric patients with UC.

Inflammatory bowel disease - one entity with many molecular faces.

Inflammatory bowel disease (IBD) is a heterogenous group of chronic inflammations in the gastrointestinal tract, which traditionally consists of two types: Crohn's disease and ulcerative colitis. They differ when it comes to clinical, endoscopic, and histopathological changes. The exact aetiology of IBD has not been fully comprehended, but what is known so far is that the aetiopathogenesis of the disease is compound. Many articles have been written on the cellular/molecular background of IBD. Based on various molecular pathways, new forms of the disease have been discovered, including very early-onset IBD (VEO-IBD) or IBD coexisting with primary sclerosing cholangitis. The aim of this article is to present the molecular mechanisms leading to IBD, focusing on new forms of this disorder.

Tolerability and safety of early enteral nutrition in children after percutaneous endoscopic gastrostomy placement: A multicentre randomised controlled trial.

BACKGROUND & AIMS: We assessed the tolerability and safety of implementing early enteral nutrition in children at 3 h after percutaneous endoscopic gastrostomy (PEG) placement to establish an optimum feeding mode in paediatric patients that reduced the fasting period, the inadequate nutritional support interval, and the hospitalisation time. METHODS: Children with clinical indications for PEG placement were recruited from six medical centres in Poland to participate in the study. The patients were centrally randomised to receive the first bolus feed, which comprised a polymeric diet (1 kcal/mL), via a feeding tube at 3 h (group 1) or 8 h (group 2) after PEG placement. The pre-procedural preparation, the post-operative care, and the resumption of feeding were performed on all of the patients in accordance with the study's protocol. The primary endpoint was the number of patients who consumed a full feed, which contained their total fluid and caloric requirements, within 48 h of the first bolus feed. The secondary endpoints were the number of complications and the duration of hospitalisation after PEG placement. RESULTS: Of the 97 randomised patients, 49 were assigned to group 1 and 48 were assigned to group 2. There were no differences between the groups regarding feeding tolerability (81.6% vs. 91.6%), the number of complications (25.5% vs. 37.5%), or the duration of hospitalisation after PEG placement (p > 0.05). Full feed post PEG placement was achieved within 24-48 h in most cases (74% vs. 82%). Most of the complications were mild. Two patients in group 2 due to dislocation of the PEG were qualified for laparotomy (at 6 days post-PEG placement in one case and at 14 days post-PEG placement in the other case). One patient in group 2 died at 7 days post-PEG placement; the death was unrelated to the investigation. CONCLUSIONS: Introducing feeding at 3 h post-PEG placement in children appears to be well tolerated. The early initiation of post-PEG feeding was not associated with an increase in the number of complications and it had no impact on the duration of hospitalisation. CLINICAL TRIAL REGISTRY: www.clinicaltrials.gov (NCT02777541; registration date: 18/05/2016).

The protocol for a randomised-controlled trial of the evaluation of the tolerance and safety of early enteral nutrition in children after percutaneous endoscopic gastrostomy placement. (protocol version 09.01.2015).

BACKGROUND: The appropriate time to initiate enteral nutrition after the placement of a percutaneous endoscopic gastrostomy (PEG) tube has been an area of limited research. There are no sufficient randomised prospective controlled trials in the paediatric population comparing the safety and tolerance of early feeding (3 h) after PEG placement. In order to reduce the period of fasting, inadequate nutritional support, and hospitalisation time, we decided to devise this study. METHODS/DESIGN: This study is a multicentre, randomised, open-label trial designed to evaluate the tolerance and safety of early enteral nutrition after PEG placement in children. Patients are randomised to receive the first feeding bolus with a polymeric diet (1 kcal/ml) via a feeding tube 3 h after the PEG placement (group I - early enteral feeding) or 8 h after the procedure (group II - late enteral feeding). The key objective of the study is to compare the tolerance and safety of the early- and late-feeding modes after PEG placement in children. The primary endpoint is the number of patients who will achieve full feed (total fluid and caloric requirements) within 48 h of the first feeding bolus. The secondary endpoints are: the number of early and late complications, the duration of hospitalisation after PEG placement, gastric residuals (ml) total in the period up to 48 h since the first feeding bolus. DISCUSSION: To our knowledge this is the first study in paediatric patients to evaluate the tolerance and safety of early enteral nutrition after PEG placement. The goal is to establish an optimum standard procedure in the group of paediatric patients qualified for the PEG insertion procedure in Poland. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02777541 , registration date 05/18/2016.