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Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered.  相似文献   
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Abstract

Gaining a better grasp on factors related to changes in alcohol use is of particular interest for clinicians. Past research has highlighted a negative link between future time perspective (i.e. a disposition guiding how individuals consider and act regarding their future) and alcohol misuse. However, much remains at stake in the understanding of this association. The objective of this research was to explore bidirectional relationships between future time perspective and severity of alcohol-related problems, in a clinical setting. The sample includes 79 patients followed up in an outpatient alcohol treatment centre. Two measurement times were planned: at entry into care and 6 months later. Multiple linear regression analyses were carried out, controlling for sociodemographic variables. We found that baseline future time perspective predicted level of alcohol-related problems after 6 months in treatment, even when effects of baseline alcohol-related problems and sociodemographic variables were controlled. This study shows that the way patients see and position themselves regarding their future can affect level of alcohol-related problems. It may be useful for clinicians to identify patients with low future time perspective to offer tailored interventions and consider this dimension as a resource for change.  相似文献   
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Objective

Low psoas muscle area is shown to be an indicator for worse postoperative outcome in patients undergoing vascular surgical. Additionally, it has been associated with longer durations of hospital stay in patients with cancer who undergo surgery and subsequently greater health care costs in Europe and the United States. We sought to evaluate this effect on hospital expenditure for patients undergoing vascular repair in a health care system with universal access.

Methods

Skeletal muscle mass was assessed on preoperative abdominal computed tomography scans of patients undergoing open aortic aneurysm repair in a retrospective fashion. The skeletal muscle index (SMI) was used to define low muscle mass. Health care costs were obtained for all patients and the relationship between a low SMI and higher costs was explored using linear regression and cross-sectional analysis.

Results

We included 156 patients (81.5% male) with a median age of 72 years undergoing elective surgery for infrarenal abdominal aortic aneurysm in this analysis. The median SMI for patients with low skeletal muscle mass was 53.21 cm2/kg and for patients without, 70.07 cm2/kg. Hospital duration of stay was 2 days longer in patients with low skeletal muscle mass as compared with patients with normal (14 days vs 11 days; P = .001), as was duration of intensive care stay (3 days vs 1 day; P = .01). The median overall hospital costs were €10,460 higher for patients with a low SMI as compared with patients with a normal physical constitution (€53,739 [interquartile range, €45,007-€62,471] vs €43,279 [interquartile range, €39,509-€47,049]; P = .001). After confounder adjustment, a low SMI was associated with a 14.68% cost increase in overall hospital costs, for a cost increase of €6521.

Conclusions

Low skeletal muscle mass is independently associated with higher hospital as well as intensive care costs in patients undergoing elective aortic aneurysm repair. Strategies to reduce this risk factor are warranted for these patients.  相似文献   
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