Study Of Disease Characteristics And Its Association With Fecal Microbiota In Paediatric Inflammatory Bowel Disease | | Posted on:2019-07-18 | Degree:Doctor | Type:Dissertation | | Country:China | Candidate:X Q Wang | Full Text:PDF | | GTID:1364330590990048 | Subject:Internal Medicine | | Abstract/Summary: | PDF Full Text Request | | Section One[Objective] To investigate progression of pediatric Inflammatory Bowel Disease(IBD),we present data showing correlation between the disease phenotype and its prognosis for different ages.[Methods] We collected data from patients diagnosed with IBD(with ulcerative colitis(UC),with Crohn’s disease(CD)) from 2002 to 2016.Anatomic locations and behavior were assessed according to Paris classification.Risk factor of surgery,mortality and relapse were analyzed by Cox proportional hazard models.[Results] Of the 143 patients,there were 113 CD cases and 30 UC cases,89 males and 54 females with median age of 9 years(y).13 patients in the 0-2 y category had monogenic disorders,and this disorder was significantly more in this age group compared to 3-9 and 10-16 y patients.Some 0-2 y patients had mutations in IL-10 receptor A.Risk factor of surgery was B3 phenotype and risk factors of death were age of 0-2 y and B3 phenotype.[Conclusions] Clinical manifestation of infantile or toddler onset IBD(0-2 y)was extensive and aggressive.It has association with early relapse and patients’ death.Since some patients showed monogenic disorders,introduction of genetic tests is essential for these patients.Section Two[Objective] It’s still lack the easy and non-invasive way to diagnosis pediatrics IBDs.Regarded as the second set of human genes,intestinal flora may play an important role in the pathogenesis of IBD.This study aims to identify the difference between IBD and the healthy children and find some new markers for IBD diagnosis.[Methods] The clinical data and stool samples of IBD patients were collceted from December 2016 to August 2017 in our hospital.At the same time,we collected the agerelated healthy children’s stool samples in the community.The patient’s intestinal flora database was established by detecting the 16S rRNA sequences of each specimen.The profile of intestinal flora and different between IBD patients and healthy children were analyzed.[Results] A total of 66 IBD patient specimens and 27 healthy children specimens were collected.Through second-generation sequencing and statistical findings,the richness,diversity and uniformity of intestinal flora in patients with IBD were lower than healthy children.The Proteobacteria increased dominantly in IBD patients,while the Actinobacteria,Bacteroides and Firmicutes decreased.Among the the genus of Proteobacteria,E.coliSalmonella increased significantly.Enterococci also increased.Bifidobacteria of Actinobacteria,were decreased in IBD patients.Based on these findings of random forest analysis,the five most important OTUs that distinguish between IBD and healthy children are obtained,and a predictive model is established,which has a high predictive value,AUC=0.84.[Conclusions] The intestinal flora of IBD patients changed significantly.Its specifical change in flora can be used as a biomarker for the diagnosis of IBD and also useful in observation of therapeutic efficacy.Section ThreeObjectives: Few studies have examined the efficacy and safety of infliximab(IFX)in pediatric Crohn’s disease(CD)in China.This study aimed to investigate the response and remission rate of IFX,as well as the associated adverse events.Methods: We collected data from CD patients who had received IFX 2 or more times from three hospitals in Shanghai from January 2007 to December 2016.The efficacy of IFX was observed,as well as the adverse events,relapse rate and retreatment efficacy.The overall risk factors related to IFX were also evaluated.Results: Eighty-six patients participated in the study.With treatment,the patients demonstrated improved growth and nutrition indices and decreased disease activity.The clinical response rate was 91.9% and 88.2% at weeks 10 and 34,respectively.The sustained remission rates were 69.8% and 67.6% at weeks 10 and 34,respectively.The mucous healing rate was 19.3% at week 10 and 25.7% at week 34.Finally,45 patients(66.2%)d emonstrated durable responses,and 23(33.8%) showed complete LOR.Adverse events related to IFX including allergic reactions in 17.4% and infections in 41.9%.Univariate analysis showed that a high pediatric clinical disease activity index score prior to IFX administration was a risk factor for IFX response.Continuation of concomitant azathioprine beyond induction was a protective factor for durable response.Conclusions: IFX is an effective treatment for CD in Chinese children;however,adverse events can occur.A comprehensive evaluation must be performed before each IFX infusion. | | Keywords/Search Tags: | Inflammatory bowel disease, Children, infantile or toddler onset IBD, Paris classification, Prognosis, intestinal flora, biomarker, 16S rRNA, adverse events, children, Crohn’s disease, efficacy, infliximab | PDF Full Text Request | Related items |
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