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- 2019
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Tidskriftsartikel (refereegranskat)
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- Barretina, Jordi, et al.
(författare)
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Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy.
- 2010
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:8, s. 715-21
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Tidskriftsartikel (refereegranskat)abstract
- Soft-tissue sarcomas, which result in approximately 10,700 diagnoses and 3,800 deaths per year in the United States, show remarkable histologic diversity, with more than 50 recognized subtypes. However, knowledge of their genomic alterations is limited. We describe an integrative analysis of DNA sequence, copy number and mRNA expression in 207 samples encompassing seven major subtypes. Frequently mutated genes included TP53 (17% of pleomorphic liposarcomas), NF1 (10.5% of myxofibrosarcomas and 8% of pleomorphic liposarcomas) and PIK3CA (18% of myxoid/round-cell liposarcomas, or MRCs). PIK3CA mutations in MRCs were associated with Akt activation and poor clinical outcomes. In myxofibrosarcomas and pleomorphic liposarcomas, we found both point mutations and genomic deletions affecting the tumor suppressor NF1. Finally, we found that short hairpin RNA (shRNA)-based knockdown of several genes amplified in dedifferentiated liposarcoma, including CDK4 and YEATS4, decreased cell proliferation. Our study yields a detailed map of molecular alterations across diverse sarcoma subtypes and suggests potential subtype-specific targets for therapy.
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- Lim, Lee Ling, et al.
(författare)
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Aspects of Multicomponent Integrated Care Promote Sustained Improvement in Surrogate Clinical Outcomes: A Systematic Review and Meta-analysis.
- 2018
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Ingår i: Diabetes care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 41:6, s. 1312-1320
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Tidskriftsartikel (refereegranskat)abstract
- The implementation of the Chronic Care Model (CCM) improves health care quality. We examined the sustained effectiveness of multicomponent integrated care in type 2 diabetes.We searched PubMed and Ovid MEDLINE (January 2000-August 2016) and identified randomized controlled trials comprising two or more quality improvement strategies from two or more domains (health system, health care providers, or patients) lasting ≥12 months with one or more clinical outcomes. Two reviewers extracted data and appraised the reporting quality.In a meta-analysis of 181 trials (N = 135,112), random-effects modeling revealed pooled mean differences in HbA1c of -0.28% (95% CI -0.35 to -0.21) (-3.1 mmol/mol [-3.9 to -2.3]), in systolic blood pressure (SBP) of -2.3 mmHg (-3.1 to -1.4), in diastolic blood pressure (DBP) of -1.1 mmHg (-1.5 to -0.6), and in LDL cholesterol (LDL-C) of -0.14 mmol/L (-0.21 to -0.07), with greater effects in patients with LDL-C ≥3.4 mmol/L (-0.31 vs. -0.10 mmol/L for <3.4 mmol/L; Pdifference = 0.013), studies from Asia (HbA1c -0.51% vs. -0.23% for North America [-5.5 vs. -2.5 mmol/mol]; Pdifference = 0.046), and studies lasting >12 months (SBP -3.4 vs. -1.4 mmHg, Pdifference = 0.034; DBP -1.7 vs. -0.7 mmHg, Pdifference = 0.047; LDL-C -0.21 vs. -0.07 mmol/L for 12-month studies, Pdifference = 0.049). Patients with median age <60 years had greater HbA1c reduction (-0.35% vs. -0.18% for ≥60 years [-3.8 vs. -2.0 mmol/mol]; Pdifference = 0.029). Team change, patient education/self-management, and improved patient-provider communication had the largest effect sizes (0.28-0.36% [3.0-3.9 mmol/mol]).Despite the small effect size of multicomponent integrated care (in part attenuated by good background care), team-based care with better information flow may improve patient-provider communication and self-management in patients who are young, with suboptimal control, and in low-resource settings.
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