Multiscale quantification of morphological heterogeneity with creation of a predictor of longer survival in glioblastoma

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.     

Explicit Finite Element Models Accurately Predict Subject-Specific and Velocity-Dependent Kinetics of Sideways Fall Impact

The majority of hip fractures in the elderly are the result of a fall from standing or from a lower height. Current injury models focus mostly on femur strength while neglecting subject-specific loading. This article presents an injury modeling strategy for hip fractures related to sideways falls that takes subject-specific impact loading into account. Finite element models (FEMs) of the human body were used to predict the experienced load and the femoral strength in a single model. We validated these models for their predicted peak force, effective pelvic stiffness, and fracture status against matching ex vivo sideways fall impacts (n = 11) with a trochanter velocity of 3.1 m/s. Furthermore, they were compared to sideways impacts of volunteers with lower impact velocities that were previously conducted by other groups. Good agreement was found between the ex vivo experiments and the FEMs with respect to peak force (root mean square error [RMSE] = 10.7%, R² = 0.85) and effective pelvic stiffness (R² = 0.92, RMSE = 12.9%). The FEMs were predictive of the fracture status for 10 out of 11 specimens. Compared to the volunteer experiments from low height, the FEMs overestimated the peak force by 25% for low BMI subjects and 8% for high BMI subjects. The effective pelvic stiffness values that were derived from the FEMs were comparable to those derived from impacts with volunteers. The force attenuation from the impact surface to the femur ranged between 27% and 54% and was highly dependent on soft tissue thickness (R² = 0.86). The energy balance in the FEMS showed that at the time of peak force 79% to 93% of the total energy is either kinetic or was transformed to soft tissue deformation. The presented FEMs allow for direct discrimination between fracture and nonfracture outcome for sideways falls and bridge the gap between impact testing with volunteers and impact conditions representative of real life falls. © 2019 American Society for Bone and Mineral Research.     

Notärztliches Atemwegsmanagement in Abhängigkeit von Fachrichtung und Weiterbildung

Die Anaesthesiologie - Das Management des schwierigen Atemwegs ist eine präklinische Schlüsselqualifikation. Für Notärzte mit hohem Erfahrungsgrad im Atemwegsmanagement sind...     

Factors predicting tracer uptake in somatostatin receptor and MIBG scintigraphy of metastatic gastroenteropancreatic neuroendocrine tumors.

Radiolabeled octreotide analogs (Oct) and metaiodobenzylguanidine (MIBG) offer 2 different approaches for imaging and targeting metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NET). Despite successful establishment of the revised World Health Organization (WHO) classification, which distinguishes between low- and high-grade malignant GEP-NET, there is a lack of scintigraphic studies comparing uptake behavior on the basis of this categorization. This study aims to define predisposing factors of tracer uptake for both imaging principles implementing the updated tumor criteria of the current WHO classification. METHODS: Fifty-seven consecutive patients with histologically confirmed metastatic GEP-NET evaluated with both 111In-pentetreotide and 123I/131I-MIBG scintigraphy were included in this study. Intensity of tracer uptake was graded according to the different metastatic regions. Patients were classified as overall positive when avid uptake in the clinically relevant tumor lesions was present. Correlation was tested between the proportion of positive patients and tumor origin, function, and malignancy. RESULTS: Overall, 52 patients (91.2%) were Oct positive and 28 patients (49.1%) were MIBG positive. The proportion of tracer-positive patients was significantly higher (P < 0.05) in low-grade malignant tumors for both tracers and in functioning as well as in gastroenteral NET for MIBG. Five patients were negative for both tracers. None of the Oct-negative patients proved to be MIBG positive. CONCLUSION: Oct affinity is observed with high frequency throughout the subgroups of metastatic GEP-NET, whereas corresponding MIBG uptake is overall less prevalent and more group dependent. Tumor differentiation significantly impacts both Oct and MIBG uptake, whereas functionality predisposes only for MIBG accumulation. Though clearly inferior to Oct-based radioimaging in most GEP-NET, MIBG achieves a remarkable rate of radioligand accumulation in functioning midgut enterochromaffin cell metastases (>80% of patients positive). These results may have implications for patient management and potentially for selection and performance of targeted therapy.     

Fetal growth in hypertensive women]

The Authors examine the correlation between hypertensive disorders of pregnancy and fetal growth. The results of a study of 342 pregnancies, confirm a significant correlation between hypertension and fetal growth retardation. These findings, so evident in moderate and severe hypertension, have also been confirmed in cases of mild hypertension. The medical treatment also in the pregnancies with mild hypertension, and a larger utilisation of operative deliveries, determined a decrease in perinatal mortality and morbidity.     

Microtuboplasty as an outpatient procedure

Fifteen cases of microtuboplasty were done as outpatient procedures at low cost and with increased patient convenience. Advances in outpatient surgery at free-standing surgery centers have allowed many new patient care innovations, and microsurgery should now be considered an outpatient procedure for gynecologic patients. Outpatient microtuboplastic surgery is not only feasible but perhaps preferable to that done as an inpatient procedure.     

Use of the inferior epigastric artery as a free graft for myocardial revascularization

From March 1990 through January 1991, 47 patients undergoing myocardial revascularization had one (37) or both (10) inferior epigastric arteries (IEA) used as a conduit for bypass with 62 distal anastomoses. The internal thoracic artery (ITA) was used bilaterally in 41 patients and unilaterally in 6 with 100 distal anastomoses. Five patients had a single saphenous vein graft. In total, 167 anastomoses (3.55 per patient) were performed. Single IEA grafts were harvested through a paramedian incision and bilateral grafts, a midline incision. Harvest time was 36.5 minutes for IEA grafts and 29.6 minutes for ITA grafts (p less than 0.0001). Graft length was 11.9 cm for IEA grafts and 16.5 cm for ITA grafts (p less than 0.0001). Distal graft diameter was 2.0 mm for IEA grafts and 2.1 mm for ITA grafts (p less than 0.01). Graft flow was 49.7 mL/min for IEA grafts and 48.7 mL/min for ITA grafts. Microscopic assessment of segments of both the IEA and ITA from 14 patients revealed similar internal elastic laminae and an equal number of fenestrations. Combined intimal and medial thickness was comparable in both conduits. Medial elastic tissue was more prominent in ITA grafts and lacking in eight of the 14 IEA grafts. Gross plaque formation was noted in the proximal 1 to 3 cm of 50% of IEA grafts, but the lumen was not compromised and microscopic thickening was minimal. An unexpected finding was medial calcifications (M?nckeberg's disease) in two of the 14 IEAs without associated atherosclerosis. There was one hospital death, one abdominal wound infection, and one instance of fat necrosis superficial to the sternum.(ABSTRACT TRUNCATED AT 250 WORDS)