Glioblastoma multiforme (GBM) is one of the most aggressive brain tumors. GBM cell lines used in laboratory studies are frequently passaged in various culture media at high proliferation rates, resulting in significant genetic and molecular alterations. Thus, data obtained in cell lines are often inapplicable to patient tumors. Furthermore, recent studies suggest that there is a stem cell–like hierarchy among GBM cell populations and a crucial role for tumor vasculature in stem cells, as well as tumor growth, which cannot be reproduced in cell line cultures. Our laboratory has developed a novel three‐dimensional (3D) organotypic “explant” system of surgical GBM specimens that preserves tumor cells in their original milieu, as well as the cytoarchitecture of the tumor stroma. Our previous study on the role of Notch inhibition has demonstrated a definitive effect on the tumor endothelium that could only be highlighted by this system. In this unit, we describe a detailed protocol for preparing GBM explants, and discuss strengths, as well as limitations of the explant system as an in vitro 3D model of GBM. Curr. Protoc. Stem Cell Biol. 19:3.5.1‐3.5.9. © 2011 by John Wiley & Sons, Inc.

Lacking previous description, the deep inferior epigastric lymph node basin is a readily accessible donor site with significant anatomic advantages for potential VLNT during autologous breast reconstruction.

Background Through targeted medication alerts, clinical decision support systems (CDSS) help users to identify medication errors such as disregarded drug–drug interactions (DDIs). Override rates of such alerts are high; however, they can be mitigated by alert tailoring or workflow-interrupting display of severe alerts that need active user acceptance or overriding. Yet, the extent to which the displayed alert interferes with the prescribers' workflow showed inconclusive impact on alert acceptance. Objectives We aimed to assess whether and how often prescriptions were changed as a potential result of interruptive alerts on different (contraindicated) prescription constellations with particularly high risks for adverse drug events (ADEs). Methods We retrospectively collected data of all interruptive alerts issued between March 2016 and August 2020 in the local CDSS (AiDKlinik) at Heidelberg University Hospital. The alert battery consisted of 31 distinct alerts for contraindicated DDI with simvastatin, potentially inappropriate medication for patients > 65 years (PIM, N = 14 drugs and 36 drug combinations), and contraindicated drugs in hyperkalemia (N = 5) that could be accepted or overridden giving a reason in free-text form. Results In 935 prescribing sessions of 500 274 total sessions, at least one interruptive alert was fired. Of all interruptive alerts, about half of the sessions were evaluable whereof in total 57.5% (269 of 468 sessions) were accepted while 42.5% were overridden. The acceptance rate of interruptive alerts differed significantly depending on the alert type (p <0.0001), reaching 85.7% for DDI alerts (N = 185), 65.3% for contraindicated drugs in hyperkalemia (N = 98), and 25.1% for PIM alerts (N = 185). Conclusion A total of 57.5% of the interruptive medication alerts with particularly high risks for ADE in our setting were accepted while the acceptance rate differed according to the alert type with contraindicated simvastatin DDI alerts being accepted most frequently.

A clinical implementation of ion-beam radiography (iRAD) is envisaged to provide a method for on-couch verification of ion-beam treatment plans. The aim of this work is to introduce and evaluate a method for quantitative waterequivalent thickness (WET) measurements for a specific helium-ion imaging system for WETs that are relevant for imaging thicker body parts in the future. Methods: Helium-beam radiographs (𝛼Rads) are measured at the Heidelberg Ion-beam Therapy Center with an initial beam energy of 239.5 MeV/u. An imaging system based on three pairs of thin silicon pixel detectors is used for ion path reconstruction and measuring the energy deposition (dE) of each particle behind the object to be imaged. The dE behind homogeneous plastic blocks is related to their well-known WETs between 280.6 and 312.6 mm with a calibration curve that is created by a fit to measured data points. The quality of the quantitative WET measurements is determined by the uncertainty of the measured WET of a single ion (single-ion WET precision) and the deviation of a measured WET value to the well-known WET (WET accuracy). Subsequently, the fitted calibration curve is applied to an energy deposition radiograph of a phantom with a complex geometry. The spatial resolution (modulation transfer function at 10 % -MTF 10% ) and WET accuracy (mean absolute percentage difference-MAPD) of the WET map are determined. Results: In the optimal imaging WET-range from ∼280 to 300 mm, the fitted calibration curve reached a mean single-ion WET precision of 1.55 ± 0.00%. Applying the calibration to an ion radiograph (iRad) of a more complex WET distribution, the spatial resolution was determined to be MTF 10% = 0.49 ± 0.03 lp/mm and the WET accuracy was assessed as MAPD to 0.21 %. Conclusions: Using a beam energy of 239.5 MeV/u and the proposed calibration procedure, quantitative 𝛼Rads of WETs between ∼280 and 300 mm can be measured and show high potential for clinical use. The proposed approach with the resulting image qualities encourages further investigation toward the clinical application of helium-beam radiography.