Genetically modified T cells expressing chimeric antigen receptors (CARs) so far have mostly failed in the treatment of solid tumors owing to a number of limitations, including an immunosuppressive tumor microenvironment and insufficient CAR T cell activation and persistence. Next-generation approaches using CAR T cells that secrete transgenic immunomodulatory cytokines upon CAR signaling, known as TRUCKs (“T cells redirected for universal cytokine-mediated killing”), are currently being explored. As TRUCKs were engineered by the transduction of T cells with two separate vectors, we developed a lentiviral modular “all-in-one” vector system that combines constitutive CAR expression and inducible nuclear factor of activated T cells (NFAT)-driven transgene expression for more efficient production of TRUCKs. Activation of the G_D2-specific CAR via GD2⁺ target cells induced NFAT promoter-driven cytokine release in primary human T cells, and indicated a tight linkage of CAR-specific activation and transgene expression that was further improved by a modified NFATsyn promoter. As proof-of-concept, we showed that T cells containing the “all-in-one” vector system secrete the immunomodulatory cytokines interleukin (IL)12 or IL18 upon co-cultivation with primary human GD2⁺ tumor cells, resulting in enhanced effector cell properties and increased monocyte recruitment. This highlights the potential of our system to simplify application of TRUCK-modified T cells in solid tumor therapy.

Introduction: A multitude of approaches have been postulated for assessing the risk of intracranial aneurysm rupture. However, the amount of potential predictive factors is not applicable in clinical practice and they are rejected in favor of the more practical PHASES score. For the subgroup of multiple intracranial aneurysms (MIAs), the PHASES score might severely underestimate the rupture risk, as only the aneurysm with the largest diameter is considered for risk evaluation. Methods: In this study, we investigated 38 patients harboring a total number of 87 MIAs with respect to their morphological and hemodynamical characteristics. For the determination of the best suited parameters regarding their predictive power for aneurysm rupture, we conducted three phases of statistical evaluation. The statistical analysis aimed to identify parameters that differ significantly between ruptured and unruptured aneurysms, show smallest possible correlations among each other and have a high impact on rupture risk prediction. Results: Significant differences between ruptured and unruptured aneurysms were found in 16 out of 49 parameters. The lowest correlation were found for gamma, aspect ratio (AR1), aneurysm maximal relative residence time (Aneurysm_RRT_max) and aneurysm mean relative residence time. The data-driven parameter selection yielded a significant correlation of only two parameters (AR1 and the Aneurysm_RRT_max) with rupture state (area under curve = 0.75). Conclusion: A high number of established morphological and hemodynamical parameters seem to have no or only low effect on prediction of aneurysm rupture in patients with MIAs. For best possible rupture risk assessment of patients with MIAs, only the morphological parameter AR1 and the hemodynamical parameter Aneurysm_RRT_max need to be included in the prediction model.

Intramedullary schwannomas (IMS) represent exceptional rare pathologies. They commonly present as solitary lesions; only five cases of multiple IMS have been described so far. Here, we report the sixth case of a woman with multiple IMS. Additionally, we performed the first complete systematic review of the literature for all cases reporting IMS. We performed a systematic review of the literature in PubMed, EMBASE and Cochrane Central Register of Controlled (CENTRAL) to retrieve all relevant studies and case reports on IMS. In a second step, we analysed all reported studies with respect to additional cases, which were not identified through the database search. Studies published in other languages than English were included. One hundred nineteen studies including 165 reported cases were included. In only five cases, the patients harboured more than one IMS. Gender ratio showed a ratio of nearly 3:2 (male:female); mean age of disease presentation was 40.2 years; 11 patients suffered from neurofibromatosis (NF) type 1 or 2 (6.6%). IMS are rare. Our first systematic review on this pathology revealed 166 cases, including the here reported case of multiple IMS. Our review offers a basis for further investigation on this disease.

BACKGROUND AND OBJECTIVES: Traditional neurosurgical education has relied heavily on the Halstedian “see one, do one, teach one” approach which is increasingly perceived as inefficient in contemporary settings marked by a steady decline in surgical caseload. In recent years, simulation training has emerged as an effective and accessible training alternative. To date, however, there is no standardized criterion pertaining to the quality and implementation of simulators in neurosurgical education and training. This research aims to compare the efficacy of virtual reality (VR) and Phantom-based simulation training in the context of neurosurgical skill acquisition, with a focus on middle cerebral artery aneurysm clipping. METHODS: An immersive VR clipping tool and a haptic clipping simulator incorporating 3-dimensional printing, additive manufacturing, and rheological analyses were developed. Twenty-two participants, comprising 12 medical students, 6 neurosurgical residents, and 4 experienced neurosurgeons, tested and evaluated both simulators for face and content validity. Construct and predictive validity of the simulators were assessed using an objective structured assessment scale for aneurysm clipping, measuring participants' performances and progress. RESULTS: Both modalities were deemed highly advantageous for educational purposes. Objective evaluations, however, revealed measurable differences in usability, efficacy, and transferability of the learned skills with VR excelling in procedural planning and visualization while Phantom simulation being noticeably superior in conveying surgical skills. CONCLUSION: Simulation training can accelerate the neurosurgical learning curve. The results of this study highlight the importance of establishing standardized criteria for the implementation and assessment of simulation modalities, ensuring consistent quality and efficacy in neurosurgical education.

Purpose: Intracranial aneurysms can be treated micro-surgically. This procedure involves an appropriate head position of the patient and a proper craniotomy. These steps enable a proper access, facilitating the subsequent steps. To train the access planning process, we propose a VR-based training system. Method: We designed and implemented an immersive VR access simulation, where the user is surrounded by a virtual operating room, including medical equipment and virtual staff. The patient’s head can be positioned via hand rotation and an arbitrary craniotomy contour can be drawn. The chosen access can be evaluated by exposing the aneurysm using a microscopic view. Results: The evaluation of the simulation took place in three stages: testing the simulation using the think-aloud method, conducting a survey and examining the precision of drawing the contour. Although there are differences between the virtual interactions and their counterparts in reality, the participants liked the immersion and felt present in the operating room. The calculated surface dice similarity coefficient, Hausdorff distance and feedback of the participants show that the difficulty of drawing the craniotomy is appropriate. Conclusion: The presented training simulation for head positioning and access planning benefits from the immersive environment. Thus, it is an appropriate training for novice neurosurgeons and medical students with the goal to improve anatomical understanding and to become aware of the importance of the right craniotomy hole.