Plos One
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Multicenter Study
Lessons learned from whole exome sequencing in multiplex families affected by a complex genetic disorder, intracranial aneurysm.
Genetic risk factors for intracranial aneurysm (IA) are not yet fully understood. Genomewide association studies have been successful at identifying common variants; however, the role of rare variation in IA susceptibility has not been fully explored. In this study, we report the use of whole exome sequencing (WES) in seven densely-affected families (45 individuals) recruited as part of the Familial Intracranial Aneurysm study. ⋯ We demonstrate that sequencing of densely affected families permits exploration of the role of rare variants in a relatively common disease such as IA, although there are important study design considerations for applying sequencing to complex disorders. In this study, we explore methods of WES variant prioritization, including the incorporation of unaffected individuals, multipoint linkage analysis, biological pathway information, and transcriptome profiling. Further studies are needed to validate and characterize the set of variants and genes identified in this study.
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Multicenter Study
National Trends in Hospital Readmission Rates among Medicare Fee-for-Service Survivors of Mitral Valve Surgery, 1999-2010.
Older patients who undergo mitral valve surgery (MVS) have high 1-year survival rates, but little is known about the experience of survivors. Our objective was to determine trends in 1-year hospital readmission rates and length of stay (LOS) in these individuals. ⋯ Among older adults surviving MVS to 1 year, slightly fewer than half experience a hospital readmission. There has been a modest decline in both the readmission rate and LOS over time, with worse outcomes in women and blacks.
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Multicenter Study Clinical Trial
Albumin Kinetics in Patients Undergoing Major Abdominal Surgery.
The drop in plasma albumin concentration following surgical trauma is well known, but the temporal pattern of the detailed mechanisms behind are less well described. The aim of this explorative study was to assess changes in albumin synthesis and transcapillary escape rate (TER) following major surgical trauma, at the time of peak elevations in two well-recognized markers of inflammation. ⋯ Two days after major abdominal surgery, at the time-point when two biomarkers of generalised inflammation were at their peak and the plasma albumin concentration had decreased by 33%, we were unable to show any difference in the absolute synthesis rate of albumin, TER and plasma volume as compared with values obtained immediately pre-operatively. This suggests that capillary leakage, if elevated postoperatively, had ceased at that time-point. The temporal relations between albumin kinetics, capillary leakage and generalised inflammation need to be further explored.
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Multicenter Study
Decreased and Increased Anisotropy along Major Cerebral White Matter Tracts in Preterm Children and Adolescents.
Premature birth is highly prevalent and associated with neurodevelopmental delays and disorders. Adverse outcomes, particularly in children born before 32 weeks of gestation, have been attributed in large part to white matter injuries, often found in periventricular regions using conventional imaging. To date, tractography studies of white matter pathways in children and adolescents born preterm have evaluated only a limited number of tracts simultaneously. ⋯ These findings indicate that prematurity-related white matter differences in later childhood and adolescence do not affect all tracts in the periventricular zone and can involve both decreased and increased FA. Differences in the patterns of radial diffusivity and axial diffusivity suggest that the tissue properties underlying group FA differences may vary within and across white matter tracts. Distinctive diffusion properties may relate to variations in the timing of injury in the neonatal period, extent of white matter dysmaturity and/or compensatory processes in childhood.
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Multicenter Study Clinical Trial
Acute Kidney Injury in Severe Sepsis and Septic Shock in Patients with and without Diabetes Mellitus: A Multicenter Study.
Whether diabetes mellitus increases the risk of acute kidney injury (AKI) during sepsis is controversial. ⋯ In patients with severe sepsis or septic shock, diabetes is not associated with occurrence of AKI or need for RRT but is an independent risk factor for persistent renal dysfunction in patients who experience AKI during their ICU stay.