Changes to the upper gastrointestinal microbiotas of children with reflux oesophagitis and oesophageal metaplasia.

Little is known of the relationships among paediatric upper gastrointestinal microbiotas, and the impact of medication use and disease on their diversity. Here, we investigated the diversity of three microbiotas in the upper gastrointestinal tract of paediatric patients in relation to each other and to host factors. Oral, oesophageal and gastric microbiotas from a prospective paediatric cohort (n=54) were profiled using the 16S rRNA gene and ITS2 amplicon sequencing. 16S rRNA gene amplicon sequencing of oesophageal biopsies from a retrospective paediatric cohort (n=96) and shotgun metagenomics data from oesophageal brushings (n=88) were employed for genomic signature validation. Bacterial diversity and composition showed substantial differences across oral, oesophageal and gastric fluid samples that were not replicated for fungi, and the presence of reflux led to increased homogeneity in the bacterial component of these three microbiotas. The oral and oesophageal microbiotas were associated with age, sex, history of oesophageal atresia and presence of oesophageal metaplasia, with the latter characterized by Prevotella enrichment. Proton pump inhibitor use was associated with increased oral bacterial richness in the gastric fluid, and this correlated with increased levels of gastric pro-inflammatory cytokines. Profiling of oesophageal biopsies from a retrospective paediatric cohort confirmed an increased Prevotella prevalence in samples with metaplasia. Analysis of metagenome-derived oesophageal Prevotella melaninogenica genomes identified strain-specific features that were significantly increased in prevalence in samples with metaplasia. Prevotella enrichment is a signature associated with paediatric oesophageal metaplasia, and proton pump inhibitor use substantially alters the paediatric gastric microenvironment.

Isolated positive deamidated gliadin peptide-IgG has limited diagnostic utility in coeliac disease.

AIM: Deamidated gliadin peptide-IgG (DGP-IgG) antibody serology testing is widely utilised in screening for coeliac disease in Australia; however, it is used sparingly in Europe. The aim of this study was to assess the diagnostic value of a positive DGP-IgG in the setting of a negative tissue transglutaminase-IgA (tTG-IgA) for gastrointestinal pathology among paediatric patients. METHODS: We conducted a retrospective cohort study of all children with an elevated DGP-IgG in the setting of a negative tTG-IgA who underwent gastroscopy over a 48-month period (January 2015-December 2018) at a tertiary paediatric centre. They were identified utilising the electronic pathology database and demographic and clinical data were collected from electronic medical records. Patients who had previously been diagnosed with coeliac disease were on a gluten-free diet or over the age of 18 were excluded from the study. RESULTS: Twenty-six patients with an elevated DGP-IgG in the setting of a negative tTG-IgA underwent gastroscopy. Our study yielded a positive predictive value of 1/26 (3.9% CI 95% 0.7%, 18.9%) for the diagnosis of coeliac disease. Overall, there were 25 histopathological diagnoses including 1 diagnosis of coeliac disease among the total 26 patients who were positive DGP-IgG and negative tTG-IgA and underwent gastroscopy. CONCLUSIONS: Our findings suggest that an isolated positive DGP-IgG has a very low diagnostic yield for coeliac disease in children and may be indicative of other gastrointestinal pathology.

Acute-on-chronic liver failure: A 20-year retrospective review of a tertiary paediatric liver centre.

AIM: Acute-on-chronic liver failure (ACLF) is an acute deterioration of pre-existing chronic liver disease related to a precipitating event. We characterised paediatric ACLF at Birmingham Children's Hospital (BCH) utilising European Association of Liver Disease CLIF criteria, including prevalence, triggers and outcomes. METHODS: All BCH patients from 2000 to 2020 with CLD who underwent initial liver transplant or died on the transplant waiting list or whilst too unwell to be listed were reviewed. RESULTS: From 2000 to 2020, 24 (4%) children with ACLF were identified. Death occurred in 18 (75%). Transplant occurred in 9 (36%), 3 of which died. ACLF triggers were sepsis organism negative 11 (46%), sepsis organism positive 8 (33%) and GI bleed 5 (17%). Bilirubin at the time of transplant/death in those with ACLF who lived compared with those who died was 529 umol/L (381) versus 665 (210) (p=0.38), creatinine 138 umol/L (147) versus 67 (46) (p=0.41), PT 33 sec (14) versus (32 (15) (p = 0.72), Grade 3, 4 hepatic encephalopathy 1 (17%) versus 10 (56%) (p = 0.17), vasopressor use 1 (17%) versus 17 (94%) (p = 0.001) and ventilation 3 (50%) versus 17 (94%) (p = 0.035). CONCLUSION: Acute-on-chronic liver failure whilst infrequent has high rates of mortality. The use of vasopressors and ventilation is more frequent in those who die from ACLF.

Late Bleeding Episodes Following Intestinal Transplantation: It Is Not Always Rejection or Infection.

Ectopic varices have been reported in 5% of children presenting with variceal bleeding and are defined as portosystemic venous collaterals occurring anywhere in the abdomen except in the cardioesophageal region. The liver-intestinal transplant or isolated liver-intestinal transplant patient presenting several years post-transplant with ectopic variceal bleeding as a consequence of portal hypertension is a seldom reported complication. Etiologies such as rejection or infection are a more common source of bleeding, and only after excluding these can differentials such as portal hypertension secondary to a blocked portacaval shunt or native liver disease be considered.

Pulp Regeneration in an Immature Maxillary Central Incisor Using Hyaluronic Acid Hydrogel.

Pulp regenerative procedure is one of the treatment options for endodontically involved immature permanent teeth. The regenerative endodontic procedure was performed in a child of 9 years. After thorough canal disinfection using triple antibiotic paste for 21 days, bleeding was induced from the apex to provide for the stem cells. After that hyaluronic acid (HA) hydrogel was introduced into the canal space to act as injectable scaffold for pulp regeneration. This was followed by mineral trioxide aggregate placement to provide tight seal from the coronal aspect. Later, the tooth was restored with composite restoration. This approach offers the clinicians great opportunity to physiologically strengthen the immature root walls. The present report presents a regenerative endodontic procedure with HA hydrogel for a traumatized central incisor with arrested root development. The continued root development in the present case suggests that this treatment option may be able to resume the root maturation process in immature teeth with open apices.

Emergency Presentations for Gastrostomy Complications Are Similar in Adults and Children.

ABSTRACT: Gastrostomy tube (GT) complications are often managed in the Emergency Department (ED). We aimed to characterize and compare the pattern of ED presentations of GT complications in adults and children. A retrospective chart review of patients with GT complications presenting to 3 Australian EDs in 2 years was undertaken. ED visits for GT complications occurred in 70 GT patients (36 adults, 34 children) with 122 presentations. When comparing adults to children, infections occurred in 21% versus 36%, respectively; P = 0.08, mechanical issues in 48% versus 52%; P = 0.86, vomiting in 23% versus 8%; P = 0.02, and other issues in 7% versus 5%; P = 0.7. Presentation to ED within 28 days of initial GT insertion occurred in 3 (8%) adults and 3 (9%) children, predominantly with tube dislodgement. GT complications seen in ED are predominantly infectious and mechanical in nature, with an increased frequency of vomiting in adults when compared with children.

Presence of Gastric Pepsinogen in the Trachea Is Associated with Altered Inflammation and Microbial Composition.

Gastroesophageal reflux is a common gastrointestinal issue that can lead to aspiration and contribute to respiratory problems. Little is known about how reflux can alter the respiratory microenvironment. We aimed to determine if the presence of gastric pepsinogen in the trachea was associated with changes in the microbial and inflammatory microenvironment. A pediatric cohort at high risk of reflux aspiration was prospectively recruited, and the tracheal microenvironment was examined. Pepsinogen A3 (PGA3) and cytokines were measured. The microbiome (bacterial and fungal) was profiled using 16S rRNA and internal transcribed spacer 2 (ITS2) amplicon sequencing. Increased bacterial richness and an altered composition driven by an enrichment of Prevotella correlated with high PGA3 levels. Fungal richness increased with PGA3, with higher Candida relative abundances observed in a subset of samples with high PGA3 levels. Source tracking of tracheal microbial taxa against taxa from matched oral and gastric samples revealed a significantly greater contribution of oral than of gastric taxa with higher PGA3 levels. Tracheal cytokines were differentially produced when stratified according to PGA3, with higher levels of interleukin-1 (IL-1)-related cytokines and IL-8 being associated with high PGA3 levels. Network analysis across cytokine and microbiome measures identified relationships between IL-1-related proteins and microbial taxa, with the presence of respiratory issues associated with higher levels of IL-1ß, IP-10, and Prevotella In conclusion, PGA3 levels in the trachea are correlated with increases in specific microbial taxa and inflammatory molecules, with an increase in oral microbes with increasing PGA3.

Early Feeding in Acute Pancreatitis in Children: A Randomized Controlled Trial.

BACKGROUND: Studies have increasingly challenged the traditional management of acute pancreatitis (AP) with bowel rest. However, these studies used a low-fat diet or transgastric feeding and only included adults. Aiming to generate higher-quality prospective pediatric data, we compared the traditional approach of fasting and intravenous fluids and early enteral feeding with standard diet or formula. METHODS: Randomized controlled trial of children (2-18 years) with mild-moderate AP. Patients were randomly assigned 1:1 to initial fasting and intravenous fluids or an immediate, unrestricted diet. Pain scores, blood measures, and cross-sectional imaging were recorded throughout admission and follow-up. The primary outcome was time to discharge, and secondary outcomes were clinical and biochemical resolution and local and systemic complication rates. RESULTS: Of 33 patients (17 [52%] boys, mean age of 11.5 [±4.8] years), 18 (55%) were randomly assigned to early feeding and 15 (45%) were randomly assigned to initial fasting. We recorded the median (interquartile range [IQR]) time to discharge (2.6 [IQR 2.0 to 4.0] vs 2.9 [IQR 1.8 to 5.6]; P = .95), reduction in serum lipase levels by day 2 (58% [IQR 2% to 85%] vs 48% [IQR 3% to 71%]; P = .65), and readmission rates (1 of 18 [6%] vs 2 of 15 [13%]; P = .22) between the early feeding and fasting cohorts, respectively. Immediate or delayed complication rates did not differ. Patients randomly assigned to early feeding had weight gain of 1.3 kg (IQR 0.29 to 3.6) at follow-up, compared with weight loss of 0.8 kg (IQR -2.1 to 0.7) in fasted patients (P = .028). CONCLUSIONS: This is the first randomized controlled trial in pediatric AP. There was no difference between early commencement of a standard oral diet and initial fast in any of the major outcome measures.

Cystic Fibrosis-related Liver Disease is Associated With Increased Disease Burden and Endocrine Comorbidities.

BACKGROUND: Cystic fibrosis-related liver disease (CFLD) is the leading nonpulmonary cause of mortality in cystic fibrosis (CF). We evaluated and compared the burden of disease and nonrespiratory comorbidities of those with severe CFLD and those without (noCFLD). METHODS: A retrospective nationwide (Australia) longitudinal review (from 1998 to 2016) of severe CFLD patients compared with noCFLD controls (matched 1 : 1 for age, genotype, pancreatic insufficiency, and center). RESULTS: One hundred sixty-six patients with severe CFLD and 166 with noCFLD were identified. Forced expiratory volume in 1 second percentage of predicted (FEV1%) was significantly lower in CFLD than noCFLD across all ages (estimate [SE] -6.05% [2.12]; P = 0.004). Median (IQR) hospitalizations per patient per year were higher in CFLD than noCFLD for: respiratory indications (0.6 [0.2-1.3] vs 0.4 [0.1-0.9]; P = 0.002); gastrointestinal indications (0.09 [0-0.2] vs 0 [0-0.05]; P < 0.001); and other indications (0.05 [0-0.2] vs 0 [0-0.1]; P = 0.03). In the CFLD cohort, there was increased use of nasogastric (12.6% vs 5.4%; OR 2.51 [95% CI 1.06-6.46]; P = 0.03) and gastrostomy nutritional supplementation (22.9% vs 13.2%; OR 1.93 [95% CI 1.05-3.63]; P = 0.03). Additionally, the CFLD cohort had a higher frequency of bone diseases, osteopenia (26.5% vs 16.8%; OR 1.77 [95%CI 1.01-3.15]; P = 0.04) and osteoporosis (16.2% vs 8.4%; OR 2.1 [95% CI 1.01-4.52]; P = 0.04), as well as CF-related diabetes (38.5% vs 19.2%; OR 2.61 [95% CI 1.55-4.47]; P = 0.001). CONCLUSIONS: Patients with severe CFLD have greater disease burden, with higher number of hospitalizations (both respiratory and nonrespiratory indications), nutritional interventions, and are at higher risk of CF-related bone disease and diabetes.

Pepsin as a Marker of Reflux Aspiration in Children With Esophageal Atresia: A Pilot Study.

Background: Reflux aspiration secondary to gastroesophageal reflux disease (GERD) is one of the causes of chronic gastrointestinal and respiratory morbidity in children with esophageal atresia (EA). Currently there are no simple, validated non-invasive tests for the diagnosis of reflux aspiration in children. Objectives: The aim of this pilot study was to investigate pepsin detected in exhaled breath condensate (EBC) and saliva as a potential non-invasive marker of reflux aspiration in children with EA. Methods: EBC and saliva samples were prospectively collected from children with EA aged between 5 and 18 years attending a multidisciplinary EA Clinic. Pepsin in the samples was assayed by two methods, a commercial lateral flow device, the Peptest™ and an enzyme-linked immunosorbent assay (ELISA) and correlated with validated gastrointestinal and respiratory symptom questionnaires and objective measures of GERD and respiratory function. Results: EBC were collected from 18 children with EA, 15/18 also provided salivary samples. Pepsin was not detected in any of the EBC samples using the Peptest™ and only 1/14 (7.1%) samples by the ELISA. However, pepsin was detected in 33 and 83% of saliva samples when analyzed with Peptest™ and the ELISA respectively. Salivary pepsin levels were significantly higher in children with reflux symptoms or wheeze. Pepsin was detected by the Peptest™ in the saliva of 5/5 (100%) children with histological evidence of reflux esophagitis compared with 0/2 (0%) in children with normal histology (p = 0.048). Conclusions: Salivary pepsin was detected in a large proportion of children with EA and was significantly associated with GERD symptoms or wheeze. The role of salivary pepsin as a potential non-invasive marker of reflux aspiration in children with EA needs further validation in future studies with larger cohorts.

A comparative evaluation of the efficacy of erbium: yttrium-aluminum-garnet and diode lasers in smear layer removal and dentin permeability of root canal after biomechanical preparation - A scanning electron microscopy study.

INTRODUCTION: The chemomechanical preparation of root canal dentin with hand or rotary instruments creates debris and a smear layer. Root canal preparation (RCP) along with irrigants is not effective in cleaning apical portions, and hence, different laser activation systems were used for better cleaning in the apical third. Aim: The aim of this study is to compare the efficacy of erbium: yttrium-aluminum-garnet (Er:YAG) and diode laser irradiation in smear layer removal and dentin permeability after biomechanical preparation using scanning electron microscopic investigation. Material and Methods: Thirty sound single-rooted human teeth were distributed randomly and equally into three groups (n = 10 each) based upon the type of laser irradiation after RCP: Group I (control group) - RCP with ProTaper rotary system using the standard irrigating protocol; Group II - RCP with ProTaper rotary system using the standard irrigating protocol followed by diode laser irradiation; and Group III - RCP with ProTaper rotary system using the standard irrigating protocol followed by Er:YAG laser irradiation. After root sectioning, specimens were dehydrated, then gold plated and observed using a scanning electron microscopy. Then, the smear layer scores were recorded and performed using the statistical analysis. Results: Smear layer removal efficacy of Er:YAG laser was more at coronal, middle, and apical third when compared to Group I and Group II. Debris removal score of Group III (Er:YAG) was better than Group I (17% ethylenediaminetetraacetic acid) and Group II (diode). Conclusion: Er:YAG laser-activated RCP was comparatively efficient in cleaning the smear layer and dentinal tubules opening.

Recurrent Abdominal Pain in Children: Is Colonoscopy Indicated?

Recurrent abdominal pain (RAP) in children is common, with most functional in origin. Colonoscopy has sometimes been performed to exclude pathology but its role is unclear. Our aim therefore was to assess the diagnostic yield and role of colonoscopy in these children. Retrospective review of consecutive colonoscopies in a tertiary pediatric hospital between November 2011 and October 2015 was undertaken. Only those with RAP as an indication for procedure were included. Chart review of patients with pain was undertaken to ensure they fulfilled Rome IV criteria. Patient demographics, indication for procedure, and adjunct preprocedure tests were noted. Statistical analyses were performed with SPSS software. A total of 652 colonoscopies were performed, of which 68 (10%) had abdominal pain as one of the indications, and was the sole indication in 15 (2%) patients. All 68 patients had preprocedure serum inflammatory markers measured and 53% (36/68) had stool calprotectin. Positive histology was found in 10% (7/68) including Crohn disease (n = 3), polyps (n = 2), and microscopic colitis (n = 2). The remaining 61 patients had normal colonoscopy and ileocolonic biopsies. Of the 36 patients 5 had raised fecal calprotectin, and all had abnormal histology. Serum inflammatory markers were raised in 4 patients and all also had abnormal calprotectin. No patient with isolated abdominal pain had positive histology. Rectal bleeding was the only associated indication to predict abnormal histology (P = 0.019). Colonoscopy is likely not warranted in children with RAP without bleeding, weight loss, or altered bowel habit. Fecal calprotectin is useful in helping predict positive findings.

Paediatric constipation: An approach and evidence-based treatment regimen

BACKGROUND: Constipation affects 5-30% of children and is responsible for 3% of primary care visits. General practitioners (GPs) are frequently the first medical encounter for concerned parents regarding their child's bowel habit. OBJECTIVE: The aim of this article is to review the assessment and management of children with constipation to empower GPs to initiate treatment and know when to refer to a paediatrician. DISCUSSION: In the absence of organic aetiology, childhood constipation is almost always functional and often due to painful bowel movements that prompt the child to withhold stool. It is important to initiate a clear management plan for the family, as what is an easily treatable condition can escalate into a vicious cycle of pain if not addressed early. The medical approach should consider organic disease, the use of appropriate toileting habits, and dietary modifications. Laxatives are often required to re-establish regular, painless defaecation.

Evolving Practice and Changing Phenotype in Pediatric Autoimmune Liver Disease: Outcomes From an Australian Center.

OBJECTIVES: Autoimmune liver disease (AILD) incorporates primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), and autoimmune sclerosing cholangitis (ASC). ASC is a condition that includes overlap of AIH and PSC. We investigate changes in practice in relation to diagnosis and phenotype over 2 time periods. METHODS: Retrospective chart review was conducted from January 2000 to 2016. Data were divided into two 8-year cohorts, CI and C2. RESULTS: Data were collected in 75 children, 29 in 2000-2007 (C1) and 46 in 2008-2016 (C2). Presenting AILD type was AIH in 59%, ASC in 10%, and PSC in 31%. Final AILD type was AIH in 53%, ASC in 16%, and PSC in 31%. When comparing C1 to C2, those with AIH decreased (65% vs 45%) and those with ASC increased (14% vs 18%). Use of magnetic resonance cholangio-pancreatography increased from 34% in C1 to 65% in C2. Advanced liver disease on biopsy was noted in 53% of all children at presentation. Only 5 female children progressed to liver transplant (3 ASC-IBD [inflammatory bowel disease]; 1 PSC-IBD; 1 AIH). Colonoscopy performance increased from 48% in C1 to 63% in C2 with diagnosis of AILD-IBD increasing from 31% to 52%. Right-sided disease was present in 46% and macroscopic rectal sparing in 36% of those with ulcerative colitis (UC). Colectomy was required in 3 children with large duct PSC-IBD. CONCLUSIONS: PSC and ASC are increasing in relevance along with IBD and reflect increasing performance of magnetic resonance cholangio-pancreatography and colonoscopy. Large duct PSC and ASC with IBD are risk factors for colectomy and along with female gender, for liver transplant.

Research during medical school: is it particularly difficult in developing countries compared to developed countries?

OBJECTIVES: Medical student involvement in research has been declining over the years. We reviewed the factors that hinder participation in research with a focus on developing countries. METHODS: Literature search was performed using PubMed, MEDLINE and Cochrane Library. Peer-reviewed articles published between 1995 and 2017 were screened for relevance to identify key factors affecting medical student involvement in research with a particular focus on developing world. Analytical review is presented here in this article in relation to commonly reported aspects related to research during medical school. RESULTS: This search revealed varied contributing factors that hinder students' growth and interest in research. It commonly highlighted few aspects in relation to research during medical school, and they were "variability in research uptake among students and issues related to them, their knowledge and attitude toward research and organizational input and its influence on students". CONCLUSION: While early introduction to research by inculcating a mindset aimed at research has been proposed, it has not been seen in practice during either the medical school or beyond to an extent that was expected. It appears that developing countries, while they share some of the reasons with developed countries, have their own set of difficulties, which are influenced by culture, beliefs and priorities.