1,720,976 research outputs found
Paediatric inflammatory bowel disease – brief update on current practice
No full textPaediatric inflammatory bowel disease (PIBD), consisting of Crohn’s disease, ulcerative colitis and inflammatory bowel disease unclassified, is a chronic inflammatory condition associated with significant morbidity. The incidence of PIBD is increasing and disease phenotype remains more severe than adult onset disease. Diagnosis of PIBD is often slow and requires referral to specialist services; however, the emergence of faecal calprotectin as a tool for prioritising further investigation, alongside improved use of treatments (including anti-TNF monoclonal antibody therapy) is changing diagnosis and management. Whilst significant challenges remain in the longer-term treatment of PIBD, including growth, nutrition and management of refractory disease there remains a strong research focus on understanding underlying disease pathogenesis and a move towards personalised medicine. This review describes investigations, diagnosis and management of PIBD and presents the most up to date evidence on nutritional and medical management
Challenges in chronic paediatric disease during the COVID-19 pandemic: diagnosis and management of inflammatory bowel disease in children
No full textEpidemiology, management and outcome of ultrashort bowel syndrome in infancy
No full textUltrashort bowel syndrome (USBS) is a group of heterogeneous disorders where the length of small bowel is less than 10 cm or 10% of expected for the age. It is caused by massive loss of the gut which in the neonatal period can be a result of vanishing gastroschisis or surgical resection following mid-gut volvulus, jejunoileal atresia and/or extensive necrotising enterocolitis. The exact prevalence of USBS is not known although there is a clear trend towards increasing numbers because of increased incidence and improved survival. Long-Term parenteral nutrition (PN) is the mainstay of treatment and is best delivered by a multidisciplinary intestinal rehabilitation team. Promoting adaptation is vital to improving long-Term survival and can be achieved by optimising feeds, reducing intestinal failure liver disease and catheter-related bloodstream infections. Surgical techniques that can promote enteral tolerance and hence improve outcome include establishing intestinal continuity and bowel lengthening procedures. The outcome for USBS is similar to patients with intestinal failure due to other causes and only a small proportion of children who develop irreversible complications of PN and will need intestinal transplantation. In this review, we will summarise the available evidence focusing particularly on the epidemiology, management strategies and outcome
Endoscopic versus histological disease extent at presentation of paediatric inflammatory bowel disease
No full textBackground: The Paris classification (PC) of paediatric inflammatory bowel disease (PIBD) categorises disease extent and therefore impacts on treatment decisions Histological (microscopic) disease extent is not incorporated and endoscopic (macroscopic) findings may underrepresent disease extent when compared to histological findings; this study compares disease extent at presentation.Methods: Data were obtained of patients below 17 years of age diagnosed with IBD from 2010-13 at University Hospital Southampton. Data are presented as percentage of patients undergoing endoscopy. PC was performed alongside a modified PC by histological disease location.Results: 172 patients were identified (median age at diagnosis 13.5, 115 male); Crohns disease (CD)- 107, Ulcerative Colitis (UC)- 50, Inflammatory Bowel Disease Unclassified (IBDU)- 15; 159 had undergone upper GI endoscopy, 163 had undergone lower GI endoscopy. Histological disease was more extensive at all points for CD, UC and IBDU.CD; endoscopic ileal disease in 49% of patients compared to histological disease in 71.3%. Comparing PC; a 10% increase in L3 disease (ileocolonic), a 24% increase in L3+L4a disease (ileocolonic plus upper gastrointestinal (GI)) and a 27% increase in all upper GI involvement if histological disease extent was used.UC; the most common disease location was the rectum (endoscopic- 91.5% vs histological- 93.6%) and descending colon (endoscopic- 89.4% vs histological-95.7%). Comparing PC; a 19% increase in E4 disease (pancolitis) if histological disease extent was used.Conclusion: This data confirms that histological disease extent is greater than endoscopic disease extent. This should be considered when the PC is used. Further study is needed to elucidate which classification would better predict disease outcome
Identification of variants in genes associated with single gene inflammatory bowel disease by whole exome sequencing
No full textBackground: Most cases of inflammatory bowel disease (IBD) are caused by complex host–environment interaction. There are a number of conditions associated with a single-gene mutation, most cases are very early onset (aged < 6 yr), present with a unique form of disease and often have atypical features.Methods: Whole-exome data for 147 pediatric patients with IBD were interrogated for a panel of 51 genes associated with monogenic IBD. Observed variation was categorized according to the American College of Medical Genetics (ACMG) guidelines to identify rare, novel, and known variants that might contribute to IBD.Results: Five hundred seventy-four variants were identified across 51 genes. These were categorized in line with ACMG guidance to remove benign variants and to identify “pathogenic” and “likely pathogenic” variants. In 6 patients, we observed 6 pathogenic variants of which CYBA(c.287+2T>C), COL7A1(c.6501+1G>C), LIG4(p.R814X), and XIAP(p.T470S) were known causative mutations, and FERMT1(p.R271Q) and SKIV2L(c.354+5G>A) were novel. In the 3 patients with XIAP, SKIV2L, and FERMT1 variants, individuals' disease features resembled the monogenic phenotype. This was despite apparent heterozygous carriage of pathogenic variation for the latter 2 genes. The XIAP variant was observed in a hemizygous male.Conclusions: Whole-exome sequencing allows for identification of known and de novo potentially causative mutations in genes associated with monogenic IBD. Although these are rare conditions, it is vital to identify causative mutations early to improve prognosis. We postulate that in a subset of IBD, heterozygous mutations (in genes believed to manifest IBD through autosomal recessive inheritance) may contribute to clinical presentation
Genes implicated in thiopurine-induced toxicity: comparing TPMT enzyme activity with clinical phenotype and exome data in a paediatric IBD cohort
No full textThe aim of our study was to assess the utility of next generation sequencing (NGS) for predicting toxicity and clinical response to thiopurine drugs in paediatric patients with inflammatory bowel disease. Exome data for 100 patients were assessed against biochemically measured TPMT enzyme activity, clinical response and adverse effects. The TPMT gene and a panel of 15 other genes implicated in thiopurine toxicity were analysed using a gene based statistical test (SKAT-O test). Nine patients out of 100 (Crohn’s disease- 67, ulcerative colitis- 23 and IBDU-10) had known TPMT mutations associated with deficient enzyme activity. A novel and a highly pathogenic TPMT variant not detectable through standard genotyping, was identified through NGS in an individual intolerant to thiopurines. Of the 14 patients intolerant to thiopurines, NGS identified deleterious TPMT variants in 5 individuals whereas the biochemical test identified 8 individuals as intolerant (sensitivity 35.7% and 57.14%; specificity 93.75% and 50% respectively). SKAT-O test identified a significant association between MOCOS gene and TPMT activity (p=0.0015), not previously reported. Although NGS has the ability to detect rare or novel variants not otherwise identified through standard genotyping, it demonstrates no clear advantage over the biochemical test in predicting toxicity in our modest cohort
The paediatric Crohn’s disease morbidity index (PCD-MI); development of a tool to assess long-term disease burden using a data driven approach
No full textBackground/Objective– Heterogeneity and chronicity of Crohn’s disease (CD) make prediction of outcomes difficult. To date, no longitudinal measure can quantify burden over a patient’s disease course, preventing assessment and integration into predictive modelling. Here, we aimed to demonstrate the feasibility of constructing a data driven, longitudinal disease burden score.Methods– Literature was reviewed for tools used in assessment of CD activity. Themes were identified to construct a paediatric CD morbidity index (PCD-MI). Scores were assigned to variables. Data were extracted automatically from the electronic patient records at Southampton Children’s Hospital, diagnosed from 2012 to 2019 (inclusive). PCD-MI scores were calculated, adjusted for duration of follow up and assessed for variation (ANOVA) and distribution (Kolmogorov-Smirnov).Results– Nineteen clinical/biological features across five themes were included in the PCD-MI including blood/faecal/radiological/endoscopic results, medication usage, surgery, growth parameters and extraintestinal manifestations. Maximal score was 100 after accounting for follow-up duration.PCD-MI was assessed in 66 patients, mean age 12.5 years. Following quality filtering, 9528 blood/faecal test results and 1309 growth measures were included. Mean PCD-MI score was 14.95 (range 2.2-32.5), data were normally distributed (p=0.2) with 25% of patients having a PCD-MI <10. There was no difference in the mean PCD-MI when split by year of diagnosis, F-statistic 1.625, p=0.147.Conclusions– PCD-MI is a calculatable measure for a cohort of patients diagnosed over an 8-year period, integrating a wide-range of data with potential to determine high or low disease burden. Future iterations of the PCD-MI require refinement of included features, optimised scores and validation on external cohorts
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