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1.
Georg Prokop Benedikt Wiestler Daniel Hieber Fynn Withake Karoline Mayer Jens Gempt Claire Delbridge Friederike Schmidt-Graf Nicole Pfarr Bruno Märkl Jürgen Schlegel Friederike Liesche-Starnecker 《International journal of cancer. Journal international du cancer》2023,153(9):1658-1670
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
2.
Boffa Joseph W. Tock Jamie L. Morabito Danielle M. Schmidt Norman B. 《Cognitive therapy and research》2022,46(5):1016-1029
Cognitive Therapy and Research - Despite interest in psychological inflexibility as a marker of suicide risk, no measure of psychological inflexibility specific to SI exists. The present study... 相似文献
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Anders Elm Pedersen Esben Gjerløff Wedebye Schmidt Jesper Freddie Sørensen Carsten Faber Boye Schnack Nielsen Kim Holmstrøm Silje Haukali Omland Peter Tougaard Søren Skov Bo Bang 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2015,123(7):547-555
TL1A is a TNF‐like cytokine which has been shown to co‐stimulate TH1 and TH17 responses during chronic inflammation. The expression of this novel cytokine has been investigated in inflammatory disorders like rheumatoid arthritis and inflammatory bowel disease, but little is known about expression and induction in psoriasis. Indeed, the pathogenesis in psoriasis is still not fully understood and it is speculated that cytokines other than TNF‐α are important in subsets of patients. Also, for patients with severe disease that are treated with systemic anti‐TNF‐α blockade, novel candidates to be used as disease and response biomarkers are of high interest. Here, we demonstrate TL1A expression in biopsies from psoriatic lesions. Also, we investigated spontaneous and induced TL1A secretion from PBMCs and blood levels from a cohort of psoriasis patients. Here, increased spontaneous secretion from PBMCs was observed as compared to healthy controls and a small subset of patients had highly elevated TL1A in the blood. Interestingly, activation of PBMCs with various cytokines showed a decreased sensitivity for TL1A activation in psoriasis patients compared to healthy controls.TL1A levels in blood and biopsies could not be correlated with disease activity with this patient cohort. Thus, additional large‐scale studies are warranted to investigate TL1A as a biomarker. 相似文献
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Stephan Koter Tina U. Cohnert Korbinian B. Hindermayr Jörg Lindenmann Maximilian Brückner Wolfgang K. Oswald Georg Werkgartner Doris Wagner 《Journal of vascular surgery》2019,69(4):1227-1232
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7.
8.
Judith Brock Andreas Schmid Thomas Karrasch Petra Pfefferle Jutta Schlegel Inga Busse Annette Hauenschild Barbara Schmidt Maria Koukou Efthymia Arapogianni Andreas Schultz Miriam Thomalla Secil Akinci Johannes Kruse Winfried Padberg Andreas Schffler Jens Albrecht 《Clinical endocrinology》2019,91(3):400-410
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Anna C. Rienmüller Sandro M. Krieg Franziska A. Schmidt Elias L. Meyer Bernhard Meyer 《The spine journal》2019,19(1):113-120