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
Die Anaesthesiologie - Die Anlage einer Magensonde im OP oder auf einer Intensivstation (ITS) stellt eine alltäglich durchgeführte Prozedur dar. Obwohl die Sonde häufig durch... 相似文献
Cutaneous leiomyomas are rare benign smooth‐muscle tumors. These lesions are distinguished based on their cell of origin and are subclassified as pilar leiomyoma, angioleiomyoma, and genital‐type leiomyoma. Nipple leiomyoma is the least common genital‐type leiomyoma, arising from the dartoic muscle cell of the nipple. Histologic examination of the lesion is necessary for definitive diagnosis, and these uncommon tumors can pose a diagnostic challenge. We describe herein a series of six nipple leiomyomas with a spectrum of histologic appearances. 相似文献
Introduction: The Hedgehog (HH) pathway constitutes a collection of signaling molecules which critically influence embryogenesis. In adults, however, the HH pathway remains integral to the proliferation, maintenance, and apoptosis of adult stem cells including hematopoietic stem cells.
Areas covered: We discuss the current understanding of the HH pathway as it relates to normal hematopoiesis, the pathology of acute myeloid leukemia (AML), the rationale for and data from combination therapies including HH pathway inhibitors, and ultimately the prospects that might offer promise in targeting this pathway in AML.
Expert opinion: Efforts to target the HH pathway have been focused on impeding this disposition and restoring chemosensitivity to conventional myeloid neoplasm therapies. The year 2018 saw the first approval of a HH pathway inhibitor (glasdegib) for AML, though for an older population and in combination with an uncommonly-used therapy. Several other clinical trials with agents targeting modulators of HH signaling in AML and MDS are underway. Further study and understanding of the interplay between the numerous aspects of HH signaling and how it relates to the augmented survival of AML will provide a more reliable substrate for therapeutic strategies in patients with this poor-risk disease. 相似文献
ABSTRACTObjective: Dry eye is reported to be associated with several neurological diseases. The aim of this study is to evaluate the patients with hemiplegia after stroke for dry eye and compare their results with a control group. Materials and methods: Forty-five patients with hemiplegia and 45 individuals as the control group were included in the study. Tear function tests (Schirmer and tear breakup time) and a dry eye questionnaire for dry eye symptoms (ocular surface disease index) were performed and the results of the two groups were compared. Results: Schirmer test results were significantly lower in the post-stroke hemiplegia group compared to the control group (11.3 ± 8.2 mm and 20.6 ± 11.6 mm, respectively, p < .001). Tear breakup time results were significantly lower in the post-stroke hemiplegia group compared to the control group (7.9 ± 3.1 s and 12.1 ± 4.3 s, respectively, p < .001). Ocular surface disease index scores were not significantly different between hemiplegia and control groups (21.6 ± 20.0 and 19.8 ± 13.9, respectively, p = .635). Schirmer scores lower than 10 mm (60% and 30%, p < .001) and tear breakup time results lower than 10 s (65.6% and 28.9%, p < .001) were also higher in the hemiplegia group compared to control group. Conclusion: We found lower Schirmer test and tear breakup time results and similar OSDI scores in hemiplegia patients compared to controls. Hemiplegia patients may have dry eye without typical symptoms. This should be taken into consideration in the follow-up and rehabilitation of post-stroke hemiplegia patients. 相似文献
Monitoring variations in the functioning of the autonomic nervous system may help personalize training of runners and provide more pronounced physiological adaptations and performance improvements. We systematically reviewed the scientific literature comparing physiological adaptations and/or improvements in performance following training based on responses of the autonomic nervous system (ie, changes in heart rate variability) and predefined training. PubMed, SPORTDiscus, and Web of Science were searched systematically in July 2019. Keywords related to endurance, running, autonomic nervous system, and training. Studies were included if they (a) involved interventions consisting predominantly of running training; (b) lasted at least 3 weeks; (c) reported pre- and post-intervention assessment of running performance and/or physiological parameters; (d) included an experimental group performing training adjusted continuously on the basis of alterations in HRV and a control group; and (e) involved healthy runners. Five studies involving six interventions and 166 participants fulfilled our inclusion criteria. Four HRV-based interventions reduced the amount of moderate- and/or high-intensity training significantly. In five interventions, improvements in performance parameters (3000 m, 5000 m, Loadmax, Tlim) were more pronounced following HRV-based training. Peak oxygen uptake () and submaximal running parameters (eg, LT1, LT2) improved following both HRV-based and predefined training, with no clear difference in the extent of improvement in . Submaximal running parameters tended to improve more following HRV-based training. Research findings to date have been limited and inconsistent. Both HRV-based and predefined training improve running performance and certain submaximal physiological adaptations, with effects of the former training tending to be greater. 相似文献
Compression fractures of the cuboid bone in children and adolescents are rare. Fracture morphology, associated lesions, treatment options and long-term outcomes of this very rare injury are published in a few case reports. This study with review of the literature aims to support the understanding of fracture pattern and optimize pathways of decision making.
Material and Methods
A retrospective two-center study was performed in a patient cohort treated between 2001 and 2016. All patients aged less than 18 years who sustained a cuboid fracture were included. Age, gender, mechanism of injury, fracture morphology, amount of displacement, associated injuries, and therapy were analyzed. In the follow-up (FU), the AOFAS Midfoot Scale was investigated.
Results
Fractures of the cuboid bone were diagnosed in 7 boys and 9 girls. The mean age of the patients was 10 years (range: 2.2–16.1 years). According to the classification of Fenton we detected 11 (69%) type 2, 2 (12%) type 3 and 3 (19%) type 5b fractures. Other fracture types according to Fenton were not observed. All children under 10 years sustained a type 2 fracture. Open reduction and internal fixation was performed in 5 (31%) patients. Bone grafting was not necessary. FU was performed in 14/16 patients on average after 9 years (mean; range: 1.4–16.2 years). The mean AOFAS Midfoot Scale at FU for extra-articular type 2 fractures was 100 points, whereas in intra-articular fractures (Type 3) and fractures associated with mid-tarsal disruption (type 5b) worse results were found (95 and 66 points, accordingly).
Conclusion
This rare injury shows inhomogenous morphologies and offers different treatment approaches. Extra-articular Fenton type 2 lesions are the most common type of cuboid fracture in children (69%). A potential loss of length of the lateral column must be considered. In contrast to adults, type 1, 4, and 5a fractures were not found in our cohort of children and adolescents. Lower scores of the AOFAS Midfoot Scale were found with either intra-articular involvement or associated midfoot lesions. 相似文献