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Browsing by Subject "Varicose veins"
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Item Machine learning liver histology scores correlate with portal hypertension assessments in nonalcoholic steatohepatitis cirrhosi(Wiley, 2023) Noureddin, Mazen; Goodman, Zachary; Tai, Dean; Chng, Elaine L. K.; Ren, Yayun; Boudes, Pol; Shlevin, Harold; Garcia-Tsao, Guadalupe; Harrison, Stephen A.; Chalasani, Naga P.; Medicine, School of MedicineBackground and aims: In cirrhotic nonalcoholic steatohepatitis (NASH) clinical trials, primary efficacy endpoints have been hepatic venous pressure gradient (HVPG), liver histology and clinical liver outcomes. Important histologic features, such as septa thickness, nodules features and fibrosis area have not been included in the histologic assessment and may have important clinical relevance. We assessed these features with a machine learning (ML) model. Methods: NASH patients with compensated cirrhosis and HVPG ≥6 mm Hg (n = 143) from the Belapectin phase 2b trial were studied. Liver biopsies, HVPG measurements and upper endoscopies were performed at baseline and at end of treatment (EOT). A second harmonic generation/two-photon excitation fluorescence provided an automated quantitative assessment of septa, nodules and fibrosis (SNOF). We created ML scores and tested their association with HVPG, clinically significant HVPG (≥10 mm Hg) and the presence of varices (SNOF-V). Results: We derived 448 histologic variables (243 related to septa, 21 related to nodules and 184 related to fibrosis). The SNOF score (≥11.78) reliably distinguished CSPH at baseline and in the validation cohort (baseline + EOT) [AUC = 0.85 and 0.74, respectively]. The SNOF-V score (≥0.57) distinguished the presence of varices at baseline and in the same validation cohort [AUC = 0.86 and 0.73, respectively]. Finally, the SNOF-C score differentiated those who had >20% change in HVPG against those who did not, with an AUROC of 0.89. Conclusion: The ML algorithm accurately predicted HVPG, CSPH, the development of varices and HVPG changes in patients with NASH cirrhosis. The use of ML histology model in NASH cirrhosis trials may improve the assessment of key outcome changes.Item Risk of variceal hemorrhage and pretransplant mortality in children with biliary atresia(Wiley, 2022) Bass, Lee M.; Ye, Wen; Hawthorne, Kieran; Leung, Daniel H.; Murray, Karen F.; Molleston, Jean P.; Romero, Rene; Karpen, Saul; Rosenthal, Philip; Loomes, Kathleen M.; Wang, Kasper S.; Squires, Robert H.; Miethke, Alexander; Ng, Vicky L.; Horslen, Simon; Jensen, M. Kyle; Sokol, Ronald J.; Magee, John C.; Shneider, Benjamin L.; ChiLDReN; Pediatrics, School of MedicineBackground and aims: The natural history of gastroesophageal variceal hemorrhage (VH) in biliary atresia (BA) is not well characterized. We analyzed risk factors, incidence, and outcomes of VH in a longitudinal multicenter study. Approach and results: Participants enrolled in either an incident (Prospective Database of Infants with Cholestasis [PROBE]) or prevalent (Biliary Atresia Study of Infants and Children [BASIC]) cohort of BA were included. Variceal hemorrhage (VH) was defined based on gastrointestinal bleeding in the presence of varices accompanied by endoscopic or nontransplant surgical intervention. Cumulative incidence of VH and transplant-free survival was compared based on features of portal hypertension (e.g., splenomegaly, thrombocytopenia) and clinical parameters at baseline in each cohort (PROBE: 1.5 to 4.5 months after hepatoportoenterostomy [HPE]; BASIC: at enrollment > 3 years of age). Analyses were conducted on 869 children with BA enrolled between June 2004 and December 2020 (521 in PROBE [262 (51%) with a functioning HPE] and 348 in BASIC). The overall incidence of first observed VH at 5 years was 9.4% (95% CI: 7.0-12.4) in PROBE and 8.0% (5.2-11.5) in BASIC. Features of portal hypertension, platelet count, total bilirubin, aspartate aminotransferase (AST), albumin, and AST-to-platelet ratio index at baseline were associated with an increased risk of subsequent VH in both cohorts. Transplant-free survival at 5 years was 45.1% (40.5-49.6) in PROBE and 79.2% (74.1-83.4) in BASIC. Two (2.5%) of 80 participants who had VH died, whereas 10 (12.5%) underwent transplant within 6 weeks of VH. Conclusions: The low risk of VH and associated mortality in children with BA needs to be considered in decisions related to screening for varices and primary prophylaxis of VH.Item Weighted Gene Co-expression Network Analysis for RNA-Sequencing Data of the Varicose Veins Transcriptome(Frontiers, 2019-03-19) Zhang, Jianbin; Nie, Qiangqiang; Si, Chaozeng; Wang, Cheng; Chen, Yang; Sun, Weiliang; Pan, Lin; Guo, Jing; Kong, Jie; Cui, Yiyao; Wang, Feng; Fan, Xueqiang; Ye, Zhidong; Wen, Jianyan; Liu, Peng; Medicine, School of MedicineObjective: Varicose veins are a common problem worldwide and can cause significant impairments in health-related quality of life, but the etiology and pathogenesis remain not well defined. This study aims to elucidate transcriptomic regulations of varicose veins by detecting differentially expressed genes, pathways and regulator genes. Methods: We harvested great saphenous veins (GSV) from patients who underwent coronary artery bypass grafting (CABG) and varicose veins from conventional stripping surgery. RNA-Sequencing (RNA-Seq) technique was used to obtain the complete transcriptomic data of both GSVs from CABG patients and varicose veins. Weighted Gene Co-expression network analysis (WGCNA) and further analyses were then carried out with the aim to elucidate transcriptomic regulations of varicose veins by detecting differentially expressed genes, pathways and regulator genes. Results: From January 2015 to December 2016, 7 GSVs from CABG patients and 13 varicose veins were obtained. WGCNA identified 4 modules. In the brown module, gene ontology (GO) analysis showed that the biological processes were focused on response to stimulus, immune response and inflammatory response, etc. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis showed that the biological processes were focused on cytokine-cytokine receptor interaction and TNF signaling pathway, etc. In the gray module, GO analysis showed that the biological processes were skeletal myofibril assembly related. The immunohistochemistry staining showed that the expression of ASC, Caspase-1 and NLRP3 were increased in GSVs from CABG patients compared with varicose veins. Histopathological analysis showed that in the varicose veins group, the thickness of vascular wall, tunica intima, tunica media and collagen/smooth muscle ratio were significantly increased, and that the elastic fiber/internal elastic lamina ratio was decreased. Conclusion: This study shows that there are clear differences in transcriptomic information between varicose veins and GSVs from CABG patients. Some inflammatory RNAs are down-regulated in varicose veins compared with GSVs from CABG patients. Skeletal myofibril assembly pathway may play a crucial role in the pathogenesis of varicose veins. Characterization of these RNAs may provide new targets for understanding varicose veins diagnosis, progression, and treatment.