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Browsing by Author "Taylor, Michael D."
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Item Impact of Major Residual Lesions on Outcomes after Surgery for Congenital Heart Disease(Elsevier, 2021) Nathan, Meena; Levine, Jami C.; Van Rompay, Maria I.; Lambert, Linda M.; Trachtenberg, Felicia L.; Colan, Steven D.; Adachi, Iki; Anderson, Brett R.; Bacha, Emile A.; Eckhauser, Aaron; Gaynor, J. William; Graham, Eric M.; Goot, Benjamin; Jacobs, Jeffrey P.; John, Rija; Kaltman, Jonathan R.; Kanter, Kirk R.; Mery, Carlos M.; Minich, L. LuAnn; Ohye, Richard; Overman, David; Pizarro, Christian; Raghuveer, Geetha; Schamberger, Marcus S.; Schwartz, Steven M.; Narasimhan, Shanthi L.; Taylor, Michael D.; Wang, Ke; Newburger, Jane W.; Pediatric Heart Network Investigators; Pediatrics, School of MedicineBackground: Many factors affect outcomes after congenital cardiac surgery. Objectives: The RLS (Residual Lesion Score) study explored the impact of severity of residual lesions on post-operative outcomes across operations of varying complexity. Methods: In a prospective, multicenter, observational study, 17 sites enrolled 1,149 infants undergoing 5 common operations: tetralogy of Fallot repair (n = 250), complete atrioventricular septal defect repair (n = 249), arterial switch operation (n = 251), coarctation or interrupted arch with ventricular septal defect (VSD) repair (n = 150), and Norwood operation (n = 249). The RLS was assigned based on post-operative echocardiography and clinical events: RLS 1 (trivial or no residual lesions), RLS 2 (minor residual lesions), or RLS 3 (reintervention for or major residual lesions before discharge). The primary outcome was days alive and out of hospital within 30 post-operative days (60 for Norwood). Secondary outcomes assessed post-operative course, including major medical events and days in hospital. Results: RLS 3 (vs. RLS 1) was an independent risk factor for fewer days alive and out of hospital (p ≤ 0.008) and longer post-operative hospital stay (p ≤ 0.02) for all 5 operations, and for all secondary outcomes after coarctation or interrupted arch with VSD repair and Norwood (p ≤ 0.03). Outcomes for RLS 1 versus 2 did not differ consistently. RLS alone explained 5% (tetralogy of Fallot repair) to 20% (Norwood) of variation in the primary outcome. Conclusions: Adjusting for pre-operative factors, residual lesions after congenital cardiac surgery impacted in-hospital outcomes across operative complexity with greatest impact following complex operations. Minor residual lesions had minimal impact. These findings may provide guidance for surgeons when considering short-term risks and benefits of returning to bypass to repair residual lesions.Item The RNA-Binding Protein Musashi1 Affects Medulloblastoma Growth via a Network of Cancer- Related Genes and Is an Indicator of Poor Prognosis(2012-11) Vo, Dat T.; Subramaniam, Dharmalingam; Remke, Marc; Burton, Tarea L.; Uren, Philip J.; Gelfond, Jonathan A.; Abreu, Raquel de Sousa; Burns, Suzanne C.; Qiao, Mei; Suresh, Uthra; Korshunov, Andrey; Dubuc, Adrian M.; Northcott, Paul A.; Smith, Andrew D.; Pfister, Stefan M.; Taylor, Michael D.; Janga, Sarath Chandra; Anant, Shrikant; Vogel, Christine; Penalva, Luiz O. F.Musashi1 (Msi1) is a highly conserved RNA-binding protein that is required during the development of the nervous system. Msi1 has been characterized as a stem cell marker, controlling the balance between self-renewal and differentiation, and has also been implicated in tumorigenesis, being highly expressed in multiple tumor types. We analyzed Msi1 expression in a large cohort of medulloblastoma samples and found that Msi1 is highly expressed in tumor tissue compared with normal cerebellum. Notably, high Msi1 expression levels proved to be a sign of poor prognosis. Msi1 expression was determined to be particularly high in molecular subgroups 3 and 4 of medulloblastoma. We determined that Msi1 is required for tumorigenesis because inhibition of Msi1 expression by small-interfering RNAs reduced the growth of Daoy medulloblastoma cells in xenografts. To characterize the participation of Msi1 in medulloblastoma, we conducted different high-throughput analyses. Ribonucleoprotein immunoprecipitation followed by microarray analysis (RIP-chip) was used to identify mRNA species preferentially associated with Msi1 protein in Daoy cells. We also used cluster analysis to identify genes with similar or opposite expression patterns to Msi1 in our medulloblastoma cohort. A network study identified RAC1, CTGF, SDCBP, SRC, PRL, and SHC1 as major nodes of an Msi1-associated network. Our results suggest that Msi1 functions as a regulator of multiple processes in medulloblastoma formation and could become an important therapeutic target.Item Standards for writing Society for Cardiovascular Magnetic Resonance (SCMR) endorsed guidelines, expert consensus, and recommendations: a report of the publications committee(Elsevier, 2021-11-04) Uretsky, Seth; Aggarwal, Niti; van Heeswijk, Ruud B.; Rajpal, Saurabh; Rowin, Ethan; Taylor, Michael D.; Verjans, Johan W.; Wokhlu, Anita; Markl, Michael; Raman, Subha V.; Shah, Dipan J.; Medicine, School of Medicine