Very early and early nutrition in children with pancreatitis-A randomised trial.

OBJECTIVES: The aim of our study was to assess the impact of the very early introduction of refeeding on the course of acute pancreatitis (AP) in children. Additionally, we evaluated the effect of nutrition on inflammatory markers, including cytokines. METHODS: This prospective randomised study was conducted in three university hospitals in Poland. Patients, aged 1-18 years with AP, were randomised into two groups: A-refeeding within 24 h of hospital admission (very early), and B-refeeding at least 24 h after admission (early nutrition). The severity of AP was assessed after 48 h. The serum concentrations of four cytokines (tumour necrosis factor α [TNFα], interleukin-1ß [IL-1ß], interleukin-6 [IL-6] and interleukin-8 [IL-8]) and C-reactive protein, as well as the activity of amylase, lipase and aminotransferases, were measured during the first 3 days of hospitalisation. RESULTS: A total of 94 children were recruited to participate in the study. The statistical analysis included 75 patients with mild pancreatitis: 42-group A and 33-group B. The two groups did not differ in the length of hospitalisation (p = 0.22), AP symptoms or results of laboratory tests. Analysis of cytokine levels was conducted for 64 children: 38-group A and 26-group B. We did not find a difference in concentrations of the measured cytokines, except for IL-1ß on the third day of hospitalisation (p = 0.01). CONCLUSIONS: The time of initiation of oral nutrition within 24 h (very early) or after 24 h (early) from the beginning of hospitalisation had no impact on the length of hospitalisation, concentrations of TNF-α, IL-1ß, IL-6 and IL-8, activity of amylase and lipase or occurrence of symptoms in children with mild AP.

Pediatric endoscopy in times of pandemic: A nationwide retrospective analysis.

BACKGROUND: Gastrointestinal endoscopy is a procedure that carries an increased risk of transmission of SARS-CoV-2 infection to medical staff. In patients, COVID-19 is a risk factor for adverse events of medical procedures. This study analyzed the real-life risk of, and factors contributing to, infection transmission to endoscopic personnel, and possible adverse events of the endoscopy procedure and anesthesia in children with COVID-19. METHODS: Nationwide retrospective analysis of medical records of children with confirmed SARS-CoV-2 infection who underwent gastrointestinal endoscopy in Poland between February 2020 and February 2022. RESULTS: Fifty-eight patients were included in the analysis, 35% of whom had COVID-19 symptoms at the time of endoscopy. The dominant indications for endoscopy were foreign body or corrosive substance ingestion and gastrointestinal bleeding. Nine cases of virus transmission were registered among endoscopic personnel. In all of these cases, the endoscopy team was unaware of the patient's infection (p < 0.01), although symptoms were present in 78% of the children. Lack of use of personal protective equipment was the strongest predictor of SARS-CoV-2 transmission (p < 0.01). The risk of infection was not statistically significantly dependent on the method of anesthesia, intubation or the type of endoscopy. No statistically significant correlation was found between symptomatic infection and adverse events of endoscopy or anesthesia occurrence. There was one reported anesthesia-related adverse event involving extubation difficulties due to worsening respiratory infection symptoms. CONCLUSIONS: The risk of transmitting SARS-CoV-2 to endoscopic personnel during procedures in children is low and depends on compliance with infection prevention and control measures. Performing gastrointestinal endoscopy in children with COVID-19 does not appear to be associated with an increased risk of adverse events.

Pancreatic Involvement in the Course of Inflammatory Bowel Disease in Children-A Multi-Center Study.

The coexistence of inflammatory bowel disease (IBD) with pancreatic pathology is rare in children. A retrospective analysis of data from 1538 children diagnosed with IBD in 2014-2021 was conducted to determine the frequency and causes of pancreatitis and asymptomatic hyperlipasemia (HL) or hyperamylasemia (HA) in this group of patients. Among the 176 children (11.4%) with pancreatic involvement (PI), acute pancreatitis (AP) was diagnosed in 77 children (43.8%), and HA or HL was observed in 88 children (50.0%). Only a few patients were diagnosed with autoimmune or chronic pancreatitis (6.2%). PI was observed at the time of the IBD diagnosis in 26.1% of the cases. A total of 54.5% of the patients had moderate to severe IBD, and 96% had colonic involvement at the time of diagnosis of PI. Idiopathic PI was the most common (57%), followed by drug-induced PI (37%) and azathioprine (AZA). In patients with AZA-induced AP, the successful introduction of 6-mercaptopurine (6-MP) to therapy was noted in 62.5% of the children. Our results suggest that routine monitoring of pancreatic enzymes in patients with IBD should be performed, especially after the initiation of the AZA treatment. The presence of transient HA/HL in IBD does not necessarily indicate pancreatic pathology.

Characteristics of gastroesophageal reflux disease in children with interstitial lung disease.

BACKGROUND: Childhood interstitial lung disease (chILD) is a rare group of respiratory tract disorders. One of the factors suggested to be associated with its etiopathogenesis is microaspiration related to gastroesophageal reflux disease (GERD). The aim of the present study was to determine the frequency and characteristics of GERD in children with chILD, with a particular focus on proximal GER episodes. METHODS: This was a prospective cross-sectional study. Consecutive patients with chILD underwent 24-h multichannel intraluminal pH-impedance monitoring. Different types of gastroesophageal reflux episodes (GER) were recorded and compared with regard to the GERD diagnosis. RESULTS: Sixty-two children (median age of 1.22 years) were included. GERD was diagnosed in 20 (32.3%) of them. The GERD (+) and GERD (-) subgroups differed mainly in their esophageal exposure to acid content (2.9 vs. 1.0%, p = 0.02) and bolus exposure (3.0 vs. 1.4%, p < 0.0001), as well as total number of GER (72.5 vs. 42.0 p = 0.0004), acid GER (35.5 vs. 15.0 p = 0.004), and acid proximal GER (21.0 vs. 12.0 p = 0.02). There were no differences in the number of proximal GER comparing GERD (+) and GERD (-) subgroups. CONCLUSIONS: The frequency of GERD seems to be relatively high in the population of children with chILD used in this study. However, it has not demonstrated an association between proximal GER and GERD diagnosis in chILD, which casts uncertainty over the microaspiration theory proposed to link the two diseases. The latter conclusion, however, needs to be confirmed using more accurate aspiration assessment methods.

Old but Fancy: Curcumin in Ulcerative Colitis-Current Overview.

Ulcerative colitis (UC) is one of the inflammatory bowel diseases (IBD). It is a chronic autoimmune inflammation of unclear etiology affecting the colon and rectum, characterized by unpredictable exacerbation and remission phases. Conventional treatment options for UC include mesalamine, glucocorticoids, immunosuppressants, and biologics. The management of UC is challenging, and other therapeutic options are constantly being sought. In recent years more attention is being paid to curcumin, a main active polyphenol found in the turmeric root, which has numerous beneficial effects in the human body, including anti-inflammatory, anticarcinogenic, and antioxidative properties targeting several cellular pathways and making an impact on intestinal microbiota. This review will summarize the current knowledge on the role of curcumin in the UC therapy.

A New Viscous Budesonide Formulation for the Treatment of Eosinophilic Esophagitis in Children: A Preliminary Experience and Review of the Literature.

Eosinophilic esophagitis (EoE) is a chronic disease, characterized clinically by esophageal disfunction. Topical corticosteroids (tCS), predominantly fluticasone and budesonide, are considered the effective first line treatment, as well as an option of maintenance therapy in EoE. The way that tCS are administered significantly affects their effectiveness. There is still no ready-to-use steroid drug to be applied topically to the esophagus in children-a few experimental viscous slurries (mainly of budesonide) have been shown in trials to be more effective than steroids administered via metered dose inhalers (MDIs) and swallowed. The best examined steroid solvent of all is sucralose, a high-intensity artificial sweetener. Although it has been shown in a critical review that it is non-toxic and safe for all consumers, there are still some concerns among patients about its potential adverse effect on humans. Due to that fact, we developed a new viscous formulation and evaluated its effectiveness in the treatment of children with EoE. In an open, prospective, single-center study, we administered our new formulation of viscous budesonide twice daily for 8 weeks in patients with an active EoE. After treatment, we performed a control gastroscopy with the collection and evaluation of histopathological samples. We have proven our formulation effectiveness at 64%, as far as histological remission is concerned. We have also shown a reduction in the mean endoscopic reference score (EREFS) from 3.1 points at the beginning of the study to 1.6 points at the end of the study. Bearing in mind how important the acceptance of the solvent is for long-time compliance, especially among children, we also decided to assess the taste of the formulation. Therefore, we asked 46 adults and 10 children to swallow a sample of the solvent and fill in a short anonymous questionnaire about its taste, smell, consistency and easiness of swallowing. General acceptance for the proprietary solvent was high, reaching 7.5/10 among adults and 6.5/10 in children. To be able to compare the results of our preliminary experience, we reviewed the studies which evaluated substances that have been used so far as steroid solvents for the treatment of EoE. The overall effectiveness of the oral viscous budesonide (OVB) ranged from 65% to 90%, which is consistent with the results obtained in our study. Unfortunately, the high heterogeneity of the studies did not allow us to draw reliable conclusions.

C-Reactive Protein/Albumin Ratio at Diagnosis of Pediatric Inflammatory Bowel Disease: A Retrospective Multi-Center Study.

BACKGROUND This study aimed to evaluate the C-reactive protein-to-albumin (CRP/albumin) ratio at diagnosis of pediatric inflammatory bowel disease (IBD). MATERIAL AND METHODS Serum CRP/albumin ratio was calculated for patients with Crohn's disease (CD; n=186) and ulcerative colitis (UC; n=159) aged 3-18 years. RESULTS Patients with CD differed in CRP/albumin ratio at diagnosis in groups with quiescent, mild, moderate, and severe disease (P=0.011). CRP/albumin ratio at diagnosis was significant in differentiating patients with severe CD from quiescent disease at diagnosis (area under the curve (AUC)=0.94, odds ratio (OR)=63.4, 95% confidence interval (CI) 7.1-569.1, P<0.0001). CRP/albumin ratio at diagnosis could moderately differentiate penetrating from non-penetrating disease behavior in CD at diagnosis (AUC=0.73, OR=6.3, 95% CI 2.0-19.3, P<0.001). Furthermore, CRP/albumin ratio at diagnosis weakly differentiated IBD patients in need of biological treatment in a step-up procedure (AUC=0.58, OR=2.1, 95% CI 1.3-3.4, P=0.022) and in need of surgery (AUC=0.63, OR=3.1, 95% CI 1.4-7.2, P=0.006). For the IBD, CRP/albumin ratio at diagnosis was weakly correlated with age at first immunosuppressive treatment (rho=0.20, P=0.018), time from diagnosis to first biological treatment (rho=-0.37, P<0.001), days spent in hospital (rho=0.26, P=0.007), number of severe relapses (rho=0.31, P=0.001), and Pediatric Crohn's Disease Activity Index (rho=0.38, P=0.002). CONCLUSIONS The present findings add to previous studies carried out in adult patients and show that the CRP/albumin ratio at diagnosis was not significantly associated with the course of either CD or UC in children. However, CRP/albumin ratio could differentiate patients with severe CD from those with quiescent disease.

Metronidazole-Induced Encephalopathy in a 16-Year-Old Girl with Crohn's Disease: Case Report and Review of the Pediatric Literature.

Metronidazole-induced encephalopathy (MIE) is a rare and unpredictable complication that is most commonly reported in adults. Here, we present the case of MIE in a patient treated with rectal, oral, and intravenous metronidazole. This is the first case of MIE reported after suppositories. A 16-year-old girl with Crohn's disease treated with mesalazine and exclusive enteral nutrition was operated on due to perianal fistulas and abscesses. She received oral metronidazole for 25 days and rectal metronidazole for 15 days as an adjuvant before surgery. Moreover, 2.5 g of intravenous metronidazole was administrated during the perioperative period. The second day after the surgery, symptoms of cerebellar syndrome appeared. She presented with an inability to coordinate balance and gait. Although she showed accurate verbal responses, her speech was slow, slurred, and scanning. The finger-nose test was positive. The T2-weighted magnetic resonance imaging revealed an increased symmetrical signal within the dentate nuclei of the cerebellum and in the corpus callosum. The changes were characterized by restricted diffusion. Based on the clinical picture and magnetic resonance imaging findings, MIE was diagnosed. Treatment with metronidazole was discontinued. The cumulative dose of metronidazole that she received for 29 days was 54 g: 38 g p.o., 13.5 g p.r., and 2.5 g i,v. The first symptoms appeared on the 28th day of antibiotic therapy after receiving 52 g of metronidazole. The neurological symptoms resolved after six days; however, three days after the resolution, paresthesia appeared in the distal phalanges of both feet and lasted for approximately two months. Our report highlights that neurologic symptoms related to metronidazole treatment should raise the suspicion of MIE.

Methylation of RUNX3 Promoter 2 in the Whole Blood of Children with Ulcerative Colitis.

Ulcerative colitis (UC) results from a complex interplay between the environment, gut microbiota, host genetics, and immunity. Runt-related transcription factor 3 (RUNX3) regulates Th1/Th2 balance and, thus, the synthesis of cytokines and inflammation. We aimed to analyze the dependence of RUNX3 promoter 2 (P2) methylation level on: age, sex, body mass index (BMI), C-reactive protein (CRP), serum albumin, disease duration, Pediatric Ulcerative Colitis Activity Index (PUCAI), the Paris classification, and exposure to medications. This multicenter, cross-sectional study recruited hospitalized children with UC. Methylation of RUNX3 P2 was measured with methylation-sensitive restriction enzymes in the whole blood DNA. Sixty-four children were enrolled, with a mean age of 14.5 ± 2.8 years. Half of them were female (51.6%), and the average BMI Z-score was -0.44 ± 1.14. The mean methylation of RUNX3 P2 was 54.1 ± 13.3%. The methylation level of RUNX3 P2 did not correlate with age, sex, nutritional status, CRP, albumin, PUCAI, or the extent of colitis (Paris E1-E4). RUNX3 P2 methylation did not differ between patients recruited within two and a half months of diagnosis and children who had UC for at least a year. Current or past exposure to biologics, immunosuppressants, or steroids was not associated with RUNX3 P2 methylation. Methylation of RUNX3 promoter 2 in whole blood DNA does not seem to be associated with the characteristics of UC in children.

Sodium Butyrate Effectiveness in Children and Adolescents with Newly Diagnosed Inflammatory Bowel Diseases-Randomized Placebo-Controlled Multicenter Trial.

BACKGROUND: Butyric acid's effectiveness has not yet been assessed in the pediatric inflammatory bowel disease (IBD) population. This study aimed to evaluate the effectiveness of oral sodium butyrate as an add-on to standard therapy in children and adolescents with newly diagnosed IBD. METHODS: This was a prospective, randomized, placebo-controlled multicenter study. Patients aged 6-18 years with colonic Crohn's disease or ulcerative colitis, who received standard therapy depending on the disease's severity, were randomized to receive 150 mg sodium butyrate twice a day (group A) or placebo (group B). The primary outcome was the difference in disease activity and fecal calprotectin concentration between the two study groups measured at 12 weeks of the study. RESULTS: In total, 72 patients with initially active disease completed the study, 29 patients in group A and 43 in group B. At week 12 of the study, the majority of patients achieved remission. No difference in remission rate or median disease activity was found between the two groups (p = 0.37 and 0.31, respectively). None of the patients reported adverse events. CONCLUSIONS: A 12-week supplementation with sodium butyrate, as adjunctive therapy, did not show efficacy in newly diagnosed children and adolescents with IBD.

Early Enteral Nutrition in Paediatric Acute Pancreatitis-A Review of Published Studies.

Nowadays, nutrition is said to be an integral aspect of acute pancreatitis (AP) treatment. Early enteral nutrition (EEN) is safe and beneficial for patients. This was confirmed by clinical experience and can be found in guidelines on managing adults with AP. Furthermore, paediatric recommendations encourage EEN use in AP. However, paediatric guidelines are based exclusively on studies in adults. Therefore, we present a review of published studies on the time of nutritional interventions in children with AP. A search was independently conducted in April 2022 by two of the authors. Only full-text papers published in English involving children between 0-21 were considered. Only four papers met our inclusion criteria: one randomised-control trial (RCT), one prospective study with retrospective chart review, and two retrospective chart reviews. All studies supported EEN and there was no recommendation of any delay in its initiation. The results of all four papers suggested EEN with a regular, normal-fat diet. EEN is safe in children with mild or moderately severe AP and may decrease the length of hospitalisation. Unfortunately, all the conclusions are based on a small amount of heterogeneous data that are mostly retrospective. Future prospective RCTs are needed.

Three-dimensional High-resolution Anorectal Manometry in Children With Non-retentive Fecal Incontinence.

Background/Aims: Three-dimensional high-resolution anorectal manometry (3D-HRAM) is a precise tool to assess the function of the anorectum. Our aim is to evaluate children diagnosed with non-retentive fecal incontinence (NRFI) using 3D-HRAM. Methods: In all children diagnosed with NRFI, manometric parameters and 3-dimensional reconstructions of the anal canal subdivided into 8 segments were recorded. All data were compared to raw data that were obtained from asymptomatic children, collected in our laboratory and published previously (C group). Results: Forty children (31 male; median age, 8 years; range, 5-17) were prospectively included in the study. Comparison of the NRFI group and C group revealed lower values of mean resting pressure (74.4 mmHg vs 89.2 mmHg, P > 0.001) and maximum squeeze pressure (182 mmHg vs 208.5 mmHg, P = 0.018) in the NRFI group. In the NRFI group, the thresholds of sensation, urge and discomfort (40 cm3, 70 cm3, and 140 cm3, respectively) were significantly higher than those in the C group (20 cm3, 30 cm3, and 85 cm3, respectively; P > 0.001). In the NRFI group, 62.5% presented a mean resting pressure above the fifth percentile, and 82.5% of patients presented a maximum squeeze pressure above the fifth percentile. The comparisons between segments obtained from these patients and those obtained from the C group revealed several segments with significantly decreased pressure values in the NRFI group. Conclusions: Our study demonstrated lower pressure parameters in children with NRFI. In patients with normal resting pressures, 3D-HRAM may reveal segments with decreased pressures, which may play a potential role in the pathomechanism of incontinence.

Comparison of Anorectal Function as Measured with High-Resolution and High-Definition Anorectal Manometry.

INTRODUCTION: Anorectal manometry (ARM) provides comprehensive assessment of pressure activity in the rectum and anal canal. Absolute pressure values might depend on the catheter used. OBJECTIVE: Our aim was to compare the results obtained by different anorectal catheters in children with functional anorectal disorders. METHODS: Children diagnosed with functional defecation disorders based on the Rome IV criteria were prospectively enrolled. ARM was performed in the supine position successively using 2 different probes in each patient in random order. Resting, squeeze pressures, and bear-down maneuver variables obtained by high-resolution (2-dimensional [2D]) and high-definition (3-dimensional [3D]) catheters were compared. RESULTS: We prospectively included 100 children {mean age 7.5 [standard deviation (SD) ± 4.3] years; 62 boys}. Mean resting pressures were significantly higher when measured with the 3D than with the 2D catheter (71 [SD ± 19.4] vs. 65 [SD ± 20.1] mm Hg, respectively; p = 0.000). Intrarectal pressure measured by 3D and 2D catheters was similar (35 vs. 39 mm Hg, respectively; p = 0.761), but the percent of anal relaxation appeared to be higher for the 3D than for the 2D probe (12 vs. 5%, respectively; p = 0.002). Dyssynergic defecation (DD) was diagnosed in 41/71 patients (57.7%) using the 3D probe and in 51/71 children (71.8%) using the 2D probe (p = 0.044). Cohen's kappa showed only fair agreement between the catheters (κ = 0.40) in diagnosis of DD. CONCLUSIONS: Our study demonstrated significantly different values of pressures obtained with different types of catheters. Normal ranges for conventional manometry cannot be applied to high-resolution systems, and results obtained by different types of manometry cannot be compared without adjustments (NCT02812823).

HLA-DQA1*05 Associates with Extensive Ulcerative Colitis at Diagnosis: An Observational Study in Children.

The human leukocyte antigen (HLA) allele group HLA-DQA1*05 predisposes to ulcerative colitis (UC) and is associated with the development of antibodies against infliximab in patients with inflammatory bowel disease (IBD). Therefore, we hypothesized that the presence of HLA-DQA1*05 correlates with characteristics of pediatric IBD. Within a multi-center cohort in Poland, the phenotype at diagnosis and worst flare was established and HLA-DQA1*05 status was assessed enabling genotype-phenotype analyses. HLA-DQA1*05 was present in 221 (55.1%) out of 401 children with IBD (UC n = 188, Crohn's disease n = 213). In UC, the presence of HLA-DQA1*05 was moderately associated with a large extent of colonic inflammation at diagnosis (E4 55% more frequent in HLA-DQA1*05-positive patients, p = 0.012). PUCAI at diagnosis (p = 0.078) and the time from UC diagnosis to the first administration of biologic treatment (p = 0.054) did not differ depending on HLA-DQA1*05 status. The number of days of hospitalization for exacerbation was analyzed in 98 patients for whom sufficient follow-up was available and did not differ depending on HLA-DQA1*05 carriership (p = 0.066). HLA-DQA1*05 carriers with CD were less likely to present with both stenosing and penetrating disease (B2B3, p = 0.048) and to have active disease proximal to the ligament of Treitz (L4a) at the worst flare (p = 0.046). Future research focusing on explaining and preventing anti-TNF immunogenicity should take into account that ADA may develop not only as an isolated reaction to anti-TNF exposure but also as a consequence of intrinsic differences in the early course of UC.

Genetic Variants of DMBT1 and SFTPD and Disease Severity in Paediatric Inflammatory Bowel Disease-A Polish Population-Based Study.

Deleted in malignant brain tumours 1 protein (DMBT1) and surfactant protein D (SFTPD) are antimicrobial peptides previously linked to inflammatory bowel disease (IBD) susceptibility. This study attempts to link the most potential IBD-associated polymorphisms in DMBT1 and SFTPD with the disease severity in children. A total of 406 IBD patients (Crohn's disease (CD) n = 214 and ulcerative colitis (UC) n = 192) were genotyped using hydrolysis probe assay. Clinical expression was described by disease activity scales, albumin and C-reactive protein levels, localisation and behaviour (Paris classification), systemic steroid, immunosuppressive, biological, and surgical treatment, number of exacerbation-caused hospitalisations, relapses and nutritional status. IBD patients with the risk genotype (AA) in DMBT1 rs2981804 had more frequent biological treatment (AA: vs. AG/GG; p = 0.012), concomitant diseases (AA vs. AG vs. GG; p = 0.015) and cutaneous manifestations (AA vs. AG/GG, p = 0.008). In UC, rs2981804 genotypes might be linked with albumin concentrations at diagnosis (AA vs. AG vs. GG; p = 0.009). In CD, DMBT1 rs2981745 was significantly associated with the number of severe relapses per year of disease (p = 0.020) and time-to-immunosuppression (p = 0.045). SFTPD was seemingly found to be associated with age at first immunosuppression in IBD (CC vs. CT vs. TT; p = 0.048). In conclusion, selected polymorphisms of DMBT1 and SFTPD might be associated with some disease severity measures in children with IBD. However, the magnitude of associations and their clinical relevance might be minor.

Recurrent gastrointestinal bleeding due to vascular malformations in a girl with Turner syndrome.

Turner syndrome (TS) is a genetic defect accompanied by gonadal dysgenesis, short stature, characteristic dysmorphic features, congenital heart and kidneys defects, and other diseases. One of the less common are vascular malformations in the gastrointestinal (GI) tract. They are asymptomatic in some patients, but can also cause GI bleeding. We present a description of a 12-year-old patient with TS and vascular malformations in the GI tract who was admitted to the hospital because of recurrent microcytic anemia. At the age of 15, she started estrogen therapy due to hypogonadism. Since then, the bleeding has stopped and the number of malformations on follow-up colonoscopy has been significantly decreased. In TS patients with iron deficiency anemia, the differential diagnostics should include vascular defects in the GI. There are evidences, that estrogen therapy may limit the number of lesions and reduce the risk of bleeding.

Exploring Physicians' Perspectives on the Introduction of Complementary Foods to Infants and Toddlers.

Complementary feeding is the subject of many recommendations regarding the benefits of its use, illustrating its crucial impact on further health. However, it still poses a significant problem for caregivers, and thus for doctors. This survey focused on nutritional problems faced by the parents of infants and toddlers, as well as how physicians deal with these problems. Based on the responses from 303 doctors, it was determined that the time and sequence of introducing complementary foods raise the greatest doubts in parents. This study also found that at least one-third of pediatricians experience difficulties in providing effective nutritional counseling. Increasing the nutritional awareness of physicians can allow them to provide more appropriate support to parents.