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BMC Pediatrics Feb 2024Biliary atresia (BA) is a severe neonatal disease with progressive intra- and extra-hepatic bile ducts inflammation and hepatic fibrosis. Characterization of gut...
BACKGROUND
Biliary atresia (BA) is a severe neonatal disease with progressive intra- and extra-hepatic bile ducts inflammation and hepatic fibrosis. Characterization of gut microbiome profiles in infants with biliary atresia can provide valuable information and potential disease biomarkers. Our study aims to explore the relationship between gut microbiota and biliary atresia.
METHODS
16 S ribosomal RNA (rRNA) gene sequencing was carried out to identify the differences in composition and diversity of gut microbiota between infants with BA and healthy subjects. A total of 31 infants with biliary atresia and 20 healthy subjects were recruited.
RESULTS
The composition of gut microbiota in BA group was significantly different with the normal control group (P < 0.05) and the abundance ratio of Klebsiella/Bifidobacterium showed great potential for identification of BA (P < 0.01). In addition, the differential bacterial taxa were involved in lipid and vitamins metabolism.
CONCLUSION
Our results could provide potential non-invasive biomarker for identification of biliary atresia and contribute to the treatment in terms of ameliorating microbiota dysbiosis.
Topics: Infant, Newborn; Infant; Humans; Gastrointestinal Microbiome; Biliary Atresia; RNA, Ribosomal, 16S; Microbiota; Bacteria
PubMed: 38355416
DOI: 10.1186/s12887-024-04582-9 -
Scientific Reports Feb 2024Single cell and spatially resolved 'omic' techniques have enabled deep characterization of clinical pathologies that remain poorly understood, providing unprecedented...
Single cell and spatially resolved 'omic' techniques have enabled deep characterization of clinical pathologies that remain poorly understood, providing unprecedented insights into molecular mechanisms of disease. However, transcriptomic platforms are costly, limiting sample size, which increases the possibility of pre-analytical variables such as tissue processing and storage procedures impacting RNA quality and downstream analyses. Furthermore, spatial transcriptomics have not yet reached single cell resolution, leading to the development of multiple deconvolution methods to predict individual cell types within each transcriptome 'spot' on tissue sections. In this study, we performed spatial transcriptomics and single nucleus RNA sequencing (snRNAseq) on matched specimens from patients with either histologically normal or advanced fibrosis to establish important aspects of tissue handling, data processing, and downstream analyses of biobanked liver samples. We observed that tissue preservation technique impacts transcriptomic data, especially in fibrotic liver. Single cell mapping of the spatial transcriptome using paired snRNAseq data generated a spatially resolved, single cell dataset with 24 unique liver cell phenotypes. We determined that cell-cell interactions predicted using ligand-receptor analysis of snRNAseq data poorly correlated with cellular relationships identified using spatial transcriptomics. Our study provides a framework for generating spatially resolved, single cell datasets to study gene expression and cell-cell interactions in biobanked clinical samples with advanced liver disease.
Topics: Humans; Transcriptome; Liver Diseases; Digestive System Diseases; Gene Expression Profiling; Liver Cirrhosis; Single-Cell Analysis
PubMed: 38351241
DOI: 10.1038/s41598-024-53993-2 -
Surgical Neurology International 2024A ventriculoatrial shunt (VAS) proves to be an excellent alternative in the treatment of hydrocephalus. Its usage is a viable option when ventriculoperitoneal shunt...
BACKGROUND
A ventriculoatrial shunt (VAS) proves to be an excellent alternative in the treatment of hydrocephalus. Its usage is a viable option when ventriculoperitoneal shunt (VPS) is contraindicated in any age of patients.
CASE DESCRIPTION
This report highlights a successful case involving a 6-month-old patient who underwent VAS catheter positioning. The child presented with hydrocephalus and biliary atresia, making him a candidate for a liver transplant. Notably, a VPS was considered a relative contraindication in this scenario.
CONCLUSION
The VAS emerges as a viable option for patients in whom a VPS might be contraindicated. This case demonstrates the successful application of a VAS in a pediatric patient.
PubMed: 38344081
DOI: 10.25259/SNI_724_2023 -
Translational Pediatrics Jan 2024Kasai procedure and liver transplantation are effective ways to save the life of children with biliary atresia (BA). However, with the gradual development of liver...
BACKGROUND
Kasai procedure and liver transplantation are effective ways to save the life of children with biliary atresia (BA). However, with the gradual development of liver transplantation technology, scholars have questioned the necessity of the Kasai procedure. Therefore, we conducted a meta-analysis to evaluate the effect of previous Kasai procedures on liver transplantation in children with BA.
METHODS
Seven databases were searched and screened from the establishment of the database to May 3, 2023. The data in the included literature were extracted for meta-analysis to compare the differences between the Kasai group and the non-Kasai group. Finally, a publication bias test, sensitivity analysis, subgroup analysis, and systematic review were performed.
RESULTS
A total of 26 studies were included in which 6,522 children with BA underwent liver transplantation, including 4,989 in the Kasai group. Compared with the non-Kasai group, the Kasai group had older age [standardized mean difference (SMD) =0.64; 95% confidence interval (CI): 0.46, 0.82; P<0.001] (I=78.6%), heavier weight (SMD =0.41; 95% CI: 0.33, 0.48; P<0.001) (after sensitivity analysis, I=0.0%), lower pediatric end-stage liver disease (PELD) (SMD =-0.41; 95% CI: -0.48, -0.35; P<0.001) (I=20.1%), longer operation time (SMD =0.33; 95% CI: 0.01, 0.65; P<0.001) (I=83.2%), more intraoperative blood loss (SMD =0.26; 95% CI: 0.06, 0.46; P=0.012) (I=19.1%), shorter intensive care unit (ICU) stay (SMD =-0.09; 95% CI: -0.34, 0.15; P=0.027) (I=68.6%) and higher incidence of intestinal perforation [odds ratio (OR) =1.96; 95% CI: 1.20, 3.18; P=0.007] (I=7.4%) and biliary complications (OR =1.41; 95% CI: 1.05, 1.89; P=0.024) (I=31.4%). In the "Asia" subgroup, the Kasai group was older (SMD =0.68; 95% CI: 0.52, 0.84; P<0.001) (I=28.2%). In the "Cases since 2000" subgroup, there was no significant difference in operation time between the two groups (I=28.5%). In the "Other" and the "non-Asia" subgroup, there was no significant difference in length of intensive care unit (ICU) stay between the two groups (I=0.0%). However, there were no significant differences in other postoperative complications and prognostic indicators between the two groups.
CONCLUSIONS
For children with BA undergoing liver transplantation, although previous Kasai procedure may increase the risk of intraoperative bleeding, biliary complications, and intestinal perforation, it does not affect the main clinical outcomes, and can even delay the timing of liver transplantation and improve the preoperative status of children. Therefore, when BA children have no obvious contraindications to Kasai procedure, the sequential treatment of Kasai procedure-liver transplantation should be supported first.
PubMed: 38323176
DOI: 10.21037/tp-23-504 -
Frontiers in Pediatrics 2024Biliary atresia (BA) is a cholestatic hepatopathy caused by fibrosing destruction of intrahepatic and extrahepatic bile ducts, and its etiology has not been clearly...
INTRODUCTION
Biliary atresia (BA) is a cholestatic hepatopathy caused by fibrosing destruction of intrahepatic and extrahepatic bile ducts, and its etiology has not been clearly revealed. In BA, liver fibrosis progression is often observed even after Kasai portoenterostomy (KPE), and more than half of cases require liver transplantation in their lifetime in Japan. Macrophages play an important role in liver fibrosis progression and are classically divided into proinflammatory (M1) and fibrotic macrophages (M2), whose phenotypic transformation is called "macrophage polarity." The polarity has been reported to reflect the tissue microenvironment. In this study, we examined the relationship between macrophage polarity and the post-KPE clinical course.
MATERIALS AND METHODS
Thirty BA patients who underwent KPE in our institution from 2000 to 2020 were recruited. Multiple immunostainings for CD68, CD163, CK19, and α-SMA were carried out on liver biopsy specimens obtained at KPE. ROC curves were calculated based on each clinical event, and the correlation with the clinical data was analyzed.
RESULTS AND DISCUSSION
The M2 ratio, defined as the proportion of M2 macrophages (CD163-positive cells), was correlated inversely with the occurrence of postoperative cholangitis (AUC: 0.7602). The patients were classified into M2 high ( = 19) and non-high ( = 11) groups based on an M2 ratio value obtained from the Youden index ( = 0.918). As a result, pathological evaluations (Metavir score, αSMA area fraction, and CK19 area fraction) were not significantly different between these groups. In mild liver fibrosis cases (Metavir score = 0-2), the M2 non-high group had a significantly lower native liver survival rate than the high group (= 0.02). Moreover, 4 out of 8 cases in the M2 non-high group underwent early liver transplantation within 2 years after KPE.
CONCLUSIONS
Non-M2 macrophages, including M1 macrophages, may be correlated with postoperative cholangitis, and the M2 non-high group in mild liver fibrosis cases had a significantly lower native liver survival rate than the high group, requiring early liver transplantation in this study. Preventing advanced liver fibrosis is a key factor in improving native liver survival for BA patients, and liver macrophages may play important roles in liver homeostasis and the promotion of inflammation and fibrosis.
PubMed: 38318455
DOI: 10.3389/fped.2024.1338131 -
Experimental and Therapeutic Medicine Mar 2024Circular RNAs (circRNAs) serve an essential role in the occurrence and development of cholangiocarcinoma, but the expression and function of circRNA in biliary atresia...
Circular RNAs (circRNAs) serve an essential role in the occurrence and development of cholangiocarcinoma, but the expression and function of circRNA in biliary atresia (BA) is not clear. In the present study, circRNA expression profiles were investigated in the liver tissues of patients with BA as well as in the choledochal cyst (CC) tissues of control patients using RNA sequencing. A total of 78 differentially expressed circRNAs (DECs) were identified between the BA and CC tissues. The expression levels of eight circRNAs (hsa_circ_0006137, hsa_circ_0079422, hsa_circ_0007375, hsa_circ_0005597, hsa_circ_0006961, hsa_circ_0081171, hsa_circ_0084665 and hsa_circ_0075828) in the liver tissues of the BA group and control group were measured using reverse transcription-quantitative polymerase chain reaction. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis demonstrated that the identified DECs are involved in a variety of biological processes, including apoptosis and metabolism. In addition, based on the GO and KEGG pathway enrichment analyses, it was revealed that target genes that can be affected by circRNAs regulatory network were enriched in the TGF-β signaling pathway, EGFR tyrosine kinase inhibitor resistance pathway and transcription factor regulation pathway as well as other pathways that may be associated with the pathogenesis of BA. The present study revealed that circRNAs are potentially implicated in the pathogenesis of BA and could help to find promising targets and biomarkers for BA.
PubMed: 38313582
DOI: 10.3892/etm.2024.12383 -
Cureus Dec 2023It is uncertain whether prior Kasai procedures negatively impact the outcomes of liver transplantation (LT). The prior meta-analysis did not distinguish between Kasai... (Review)
Review
It is uncertain whether prior Kasai procedures negatively impact the outcomes of liver transplantation (LT). The prior meta-analysis did not distinguish between Kasai early failure (K-EF) and late failure (K-LF). Numerous studies have been recently published; therefore, we perform a systematic review and meta-analysis. We searched PubMed and Embase databases to identify studies comparing the outcomes of biliary atresia (BA) patients undergoing primary LT versus patients with prior Kasai procedures. Subgroup analysis was done at the time of Kasai failure (early vs. late). Twenty-five studies comprising 6,408 patients receiving LT were included in the analysis. We found a statistically significant increase in one-year graft survival in K-LF versus primary liver transplant (pLT) (P = 0.0003). One-year patient survival was also increased in K-LF, although not statistically significant (P = 0.09). No difference in the one- and five-year graft and patient survival, reoperation rate, infection, and biliary complication was seen in pLT vs overall prior Kasai (K-EF and K-LF). These results suggest that prior kasai procedure does not negatively impact the outcome of LT. In addition, BA patients with prior Kasai undergoing LT later in life tend to perform better than primary liver transplants.
PubMed: 38299129
DOI: 10.7759/cureus.51424 -
Scientific Reports Jan 2024Bile acids have received increasing attention as a marker of the long-term prognosis and a potential therapeutic target in patients with biliary atresia, which is a...
Bile acids have received increasing attention as a marker of the long-term prognosis and a potential therapeutic target in patients with biliary atresia, which is a progressive disease of the hepatobiliary system. A detailed analysis of serum and urinary bile acid compositions was conducted to assess the characteristics of bile acid profiles and the correlation between bile acid profiles and liver fibrosis markers in adult patients with biliary atresia who achieved bilirubin normalization. Serum total bile acids and glucuronide-conjugated (glyco- and tauro-) cholic acids (GCA and TCA) and chenodeoxycholic acids (GCDCA and TCDCA) were significantly higher in patients with biliary atresia than in healthy controls, whereas unconjugated CA and CDCA showed no significant difference. There were no significant differences in CA to CDCA ratios and glycine-to-taurine-conjugated ratios. Urinary glycocholic acid 3-sulfate (GCA-3S) was significantly higher in patients with biliary atresia. Serum GCDCA showed a strong positive correlation with Mac-2 binding protein glycosylation isomer (M2BPGi). These results demonstrate that bile acid congestion persists into adulthood in patients with biliary atresia, even after cholestasis has completely improved after Kasai portoenterostomy. These fundamental data on bile acid profiles also suggest the potential value of investigating bile acid profiles in patients with biliary atresia.
Topics: Humans; Biliary Atresia; Bile Acids and Salts; Liver; Portoenterostomy, Hepatic; Cholestasis; Chenodeoxycholic Acid
PubMed: 38291117
DOI: 10.1038/s41598-024-52969-6 -
European Journal of Pediatric Surgery :... Apr 2024Patient-reported outcome measures (PROMs) can be employed in both research and clinical care to enhance our understanding of outcomes that matter to patients. This... (Review)
Review
A Narrative Review of Patient-Reported Outcome Measures and Their Application in Recent Pediatric Surgical Research: Advancing Knowledge and Offering New Perspectives to the Field.
INTRODUCTION
Patient-reported outcome measures (PROMs) can be employed in both research and clinical care to enhance our understanding of outcomes that matter to patients. This narrative review aims to describe PROM use in recent pediatric surgical research, identify and describe psychometrically robust PROMs, providing an overview of those derived from pediatric patient input, and make recommendations for future research.
MATERIALS AND METHODS
A search was conducted to identify articles published from 2021 to August 2023 describing the availability and/or use of at least one valid or reliable PROM in children with conditions including anorectal malformations, biliary atresia, congenital diaphragmatic hernia, duodenal atresia, esophageal atresia, abdominal wall defects, Hirschsprung's disease, sacrococcygeal teratoma, and short bowel syndrome. Articles were categorized based on their objectives in applying PROMs. Psychometrically robust PROMs were identified and described.
RESULTS
Out of the 345 articles identified, 49 met the inclusion criteria. Seventeen focused on esophageal atresia and 14 on Hirschsprung's disease. Twenty-nine PROMs were identified, with 12 deemed psychometrically robust. Seven psychometrically robust PROMs were developed using patient input in the primary item generation. Most PROMs were applied to advance understanding of conditions and/or treatment and fewer were developed or psychometrically evaluated. No PROMs were assessed for their impact or incorporated into an implementation study.
CONCLUSIONS
This review reveals gaps in the application of PROMs in recent pediatric surgical research. Emphasis should be placed on the development and utilization of psychometrically robust PROMs, broadening the scope of covered diseases, conducting impact assessments, and evaluating implementation strategies.
Topics: Humans; Child; Quality of Life; Hirschsprung Disease; Patient Reported Outcome Measures; Short Bowel Syndrome
PubMed: 38272041
DOI: 10.1055/s-0043-1778108 -
BMC Medicine Jan 2024A previously trained deep learning-based smartphone app provides an artificial intelligence solution to help diagnose biliary atresia from sonographic gallbladder...
BACKGROUND
A previously trained deep learning-based smartphone app provides an artificial intelligence solution to help diagnose biliary atresia from sonographic gallbladder images, but it might be impractical to launch it in real clinical settings. This study aimed to redevelop a new model using original sonographic images and their derived smartphone photos and then test the new model's performance in assisting radiologists with different experiences to detect biliary atresia in real-world mimic settings.
METHODS
A new model was first trained retrospectively using 3659 original sonographic gallbladder images and their derived 51,226 smartphone photos and tested on 11,410 external validation smartphone photos. Afterward, the new model was tested in 333 prospectively collected sonographic gallbladder videos from 207 infants by 14 inexperienced radiologists (9 juniors and 5 seniors) and 4 experienced pediatric radiologists in real-world mimic settings. Diagnostic performance was expressed as the area under the receiver operating characteristic curve (AUC).
RESULTS
The new model outperformed the previously published model in diagnosing BA on the external validation set (AUC 0.924 vs 0.908, P = 0.004) with higher consistency (kappa value 0.708 vs 0.609). When tested in real-world mimic settings using 333 sonographic gallbladder videos, the new model performed comparable to experienced pediatric radiologists (average AUC 0.860 vs 0.876) and outperformed junior radiologists (average AUC 0.838 vs 0.773) and senior radiologists (average AUC 0.829 vs 0.749). Furthermore, the new model could aid both junior and senior radiologists to improve their diagnostic performances, with the average AUC increasing from 0.773 to 0.835 for junior radiologists and from 0.749 to 0.805 for senior radiologists.
CONCLUSIONS
The interpretable app-based model showed robust and satisfactory performance in diagnosing biliary atresia, and it could aid radiologists with limited experiences to improve their diagnostic performances in real-world mimic settings.
Topics: Infant; Child; Humans; Gallbladder; Mobile Applications; Artificial Intelligence; Biliary Atresia; Retrospective Studies; Radiologists
PubMed: 38267950
DOI: 10.1186/s12916-024-03247-9