| 1. |
- Huang, Miller, et al.
(författare)
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Engineering Genetic Predisposition in Human Neuroepithelial Stem Cells Recapitulates Medulloblastoma Tumorigenesis
- 2019
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Ingår i: Cell Stem Cell. - : CELL PRESS. - 1934-5909 .- 1875-9777. ; 25:3, s. 433-
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Tidskriftsartikel (refereegranskat)abstract
- Human neural stem cell cultures provide progenitor cells that are potential cells of origin for brain cancers. However, the extent to which genetic predisposition to tumor formation can be faithfully captured in stem cell lines is uncertain. Here, we evaluated neuroepithelial stem (NES) cells, representative of cerebellar progenitors. We transduced NES cells with MYCN, observing medulloblastoma upon orthotopic implantation in mice. Significantly, transcriptomes and patterns of DNA methylation from xenograft tumors were globally more representative of human medulloblastoma compared to a MYCN-driven genetically engineered mouse model. Orthotopic transplantation of NES cells generated from Gorlin syndrome patients, who are predis- posed to medulloblastoma due to germline-mutated PTCH1, also generated medulloblastoma. We engineered candidate cooperating mutations in Gorlin NES cells, with mutation of DDX3X or loss of GSE1 both accelerating tumorigenesis. These findings demonstrate that human NES cells provide a potent experimental resource for dissecting genetic causation in medulloblastoma.
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| 2. |
- Lin, Zhen, et al.
(författare)
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Worse Outcomes After Readmission to a Different Hospital After Sepsis : A Nationwide Cohort Study
- 2022
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Ingår i: Journal of Emergency Medicine. - : Elsevier. - 0736-4679 .- 1090-1280. ; 63:4, s. 569-581
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the United States, sepsis accounts for 13% of the total hospital expenses and > 50% of hospital deaths. Moreover, people with sepsis are more likely to be readmitted.OBJECTIVE: The aim of this study was to assess the prevalence and outcomes of different hospital readmissions (DHRs) in patients with sepsis, and the factors associated with DHR.METHODS: We used data from the Nationwide Readmissions Database of the United States in 2017 to identify patients admitted for sepsis. Multivariable logistic regression analysis was used to evaluate the factors associated with DHR; five models were constructed to elucidate the relationship between DHR and in-hospital outcomes.RESULTS: In 2017, 85,120 (21.97%) of all patients with sepsis readmitted within 30 days in the United States were readmitted to a different hospital. The most common reason for readmission was infection irrespective of hospital status. Compared with the patients with sepsis who were readmitted to the same hospital, DHR was associated with higher hospitalization costs ($2264; 95% CI $1755-$2772; p < 0.001), longer length of stay (0.58 days; 95% CI 0.44-0.71 days; p < 0.001), and higher risk of in-hospital mortality (odds ratio 1.63; 95% CI 1.55-1.72; p < 0.001).CONCLUSIONS: DHR occurred in one-fifth of patients with sepsis in the United States. Our findings suggest that patients readmitted to a different hospital within 30 days may experience higher in-hospital mortality, longer length of stay, and higher hospitalization costs. Future studies need to examine whether continuity of care can improve the prognosis of patients with sepsis.
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