BackgroundAlthough complete resolution and recovery occurs in most children with an initial attack of acute pancreatitis (AP), a subset of children may progress to recurrent AP (RAP). RAP has serious effects to the individual and the socioeconomic burden. The aim of this project was to identify the independent risk factors for pediatric RAP so as to provide evidence for its prevention, early diagnosis and treatment.MethodsA retrospective cohort study of children discharged from Tianjin Children’s Hospital from June 2017 to January 2020 was performed. Demographic and clinical variables, treatment strategies, clinical course and outcomes were collected. Independent risk factors of RAP were identified using the logistic regression model.ResultsOf the total 96 enrolled children, 30 (31.3%) developed RAP during the follow-up period. The majority (27/30, 90%) of the children with AP developed RAP within 6 months of their first AP attack. The presence of systemic inflammatory response syndrome (SIRS) [odds ratio (OR)=6.652, 95% confidence interval (CI) 1.989 to 22.247], fasting time (OR=1.267, 95% CI 1.104 to 1.583), whether meet all three AP diagnostic criteria (OR=7.438, 95% CI 1.346 to 41.103) and abnormal amylase/lipase value on the seventh day of hospitalization (OR=3.601, 95% CI 0.972 to 13.342) were independent risk factors of RAP in children.ConclusionsMost children who developed RAP had progressed within 6 months after their first episode of AP. RAP was more common in children who met all three AP diagnostic criteria at initial attack and in children with SIRS, long fasting time and abnormal amylase/lipase value on the seventh day of hospitalization.
Purpose
Based on a public gene expression database, this study established the immune-related genetic model that distinguished BA from other cholestasis diseases (DC) for the first time. We explored the molecular mechanism of BA based on the gene model.
Methods
The BA microarray dataset GSE46960, containing BA, other cause of intrahepatic cholestasis than biliary atresia and normal liver gene expression data, was downloaded from the Gene Expression Omnibus (GEO) database. We performed a comprehensive bioinformatics analysis to establish and validate an immune-related gene model and subsequently identified hub genes as biomarkers associated with the molecular mechanisms of BA. To assess the model's performance for separating BA from other cholestasis diseases, we used receiver operating characteristic (ROC) curves and the area under the curve (AUC) of the ROC. Independent datasets GSE69948 and GSE122340 were used for the validation process.
Results
The model was built using eight immune-related genes, including EDN1, HAMP, SAA1, SPP1, ANKRD1, MMP7, TACSTD2, and UCA1. In the GSE46960 and validation group, it presented excellent results, and the prediction accuracy of BA in comparison to other cholestasis diseases was good. Functional enrichment analysis revealed significant immunological differences between BA and other cholestatic diseases. Finally, we found that the TNFα- NF-κB pathway is associated with EDN1 gene expression and may explain fibrosis progression, which may become a new therapeutic target.
Conclusion
In summary, we have successfully constructed an immune-related gene model that can distinguish BA from other cholestatic diseases, while identifying the hub gene. Our exploration of immune genes provides new clues for the early diagnosis, molecular mechanism, and clinical treatment of biliary atresia.
Background: Hepato-pancreato-biliary (HPB) disease has different causes and types between children and adults, which have been diagnosed increasingly in the pediatric group. Endoscopic retrograde cholangiopancreatography (ERCP) has been gradually considered as a therapeutic method in adults, while in pediatric patients, there are not many reports of its usage. This systematic review and meta-analysis aims to assess the use condition of therapeutic ERCP in the management of pediatric HPB diseases.Methods: This systematic literature search was conducted in the PubMed、Embase、Web of Science and the Cochrane library databases to identify all relevant articles published from inception to February 2022 that evaluated therapeutic ERCP in pediatric patients with Hepato-Pancreato-Biliary diseases. The researchers included studies that patients were less than 18 years old and underwent therapeutic ERCP procedures. A random-effects model was used to analyze the usage rate of therapeutic ERCP-procedures, procedural success rates, adverse events rates, and the rate of different therapeutic procedures. Subgroup analysis, sensitivity analysis, and meta-regression were conducted to analyze the source of heterogeneity.Results: A total of 33 articles were included. After homogenization, the overall usage of therapeutic interventions accounts for 77% (95%CI74%-81%) in all ERCP procedures. After excluding outlier studies, the estimation of therapeutic procedure success rate is 74% (95% CI 69 %-79%), adverse events rate is 8% ( 95% CI 6 %-10%). In our study, stent placement is the most common procedure which makes up 75% (95%CI 65%-86%) of all therapeutic procedures. In addition, the usage proportion of sphincterotomy (ST), stone extraction/removal, bougienage/Balloon dilation is respectively 46% (95% CI 39 %-53%), 34% (95% CI 31%-38%), and 26% (95% CI 22%-29%).Conclusions: ERCP procedure is gradually considered as a therapeutic technique in pediatric patients, the proportion of therapeutic ERCP is 77% of total usage, which is increasing by the year. Meanwhile, its success rate is relatively high. It reflects that this operation modality is promising in the treatment of Hepato-pancreato-biliary disorders and is gradually expanded as more branch technologies are being used. A variety of operations can be achieved through ERCP procedures, and more functions should be developed in the future.
ObjectiveBiliary atresia (BA) presents as a severe infantile cholangiopathy disease, characterized by progressive liver fibrosis and the resulting poor prognosis. Leukocyte cell-derived chemotaxin 2 (LECT2) was proposed as the key gene associated with hepatic fibrosis in BA, but the molecular mechanism is unclear. This study aims to investigate the function of LECT2 in BA.MethodsA total of 53 patients were enrolled in this study; 36 patients with BA, and 17 control patients with cholestasis, including congenital biliary dilations, biliary hypoplasia, and inspissated bile syndrome. The role of LECT2 in BA was analyzed using histological and cytological tests. The correlation between LECT2 and infiltrating immune cells was further analyzed by bioinformatics. The analyses were conducted using correlational analyses and ROC curves.ResultsLECT2 was highly expressed in infants with BA and positively related with fibrosis (0.1644 ± 0.0608 vs. 0.0779 ± 0.0053, p < 0.0001; rs = 0.85, p < 0.0001). Serum levels of LECT2 showed high distinguishing features for patients with BA having an AUC of 0.95 (95% CI: 0.90–1.00). CD163 was highly expressed in the aggravation of fibrosis (0.158 ± 0.062 vs. 0.29 ± 0.078, p < 0.0001), and the expression of LECT2 was positively correlated with the accumulation of CD163+ macrophages (r = 0.48, p = 0.003). The bioinformatic analysis also showed that LECT2 was positively correlated with macrophage M2 (r = 0.34, p = 0.03). TGF-β1 and CD163 colocalized to the portal area in the livers of patients with BA. Moreover, TGF-β1 upregulated the expression of LECT2.ConclusionLECT2 is highly expressed in both BA liver tissue and serum, and serum LECT2 is a potential diagnostic biomarker of BA. Meanwhile, TGF-β1 is secreted by macrophages to regulate LECT2 associated with BA liver fibrosis.
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