This study aimed to investigate the role of Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase 2 (PLOD2) in glioblastoma (GBM) pathophysiology. To this end, PLOD2 protein expression was assessed by immunohistochemistry in two independent cohorts of patients with primary GBM (n₁ = 204 and n₂ = 203, respectively). Association with the outcome was tested by Kaplan–Meier, log-rank and multivariate Cox regression analysis in patients with confirmed IDH wild-type status. The biological effects and downstream mechanisms of PLOD2 were assessed in stable PLOD2 knock-down GBM cell lines. High levels of PLOD2 significantly associated with (p₁ = 0.020; p₂< 0.001; log-rank) and predicted (cohort 1: HR = 1.401, CI [95%] = 1.009–1.946, p₁ = 0.044; cohort 2: HR = 1.493; CI [95%] = 1.042–2.140, p₂ = 0.029; Cox regression) the poor overall survival of GBM patients. PLOD2 knock-down inhibited tumor proliferation, invasion and anchorage-independent growth. MT1-MMP, CD44, CD99, Catenin D1 and MMP2 were downstream of PLOD2 in GBM cells. GBM cells produced soluble factors via PLOD2, which subsequently induced neutrophils to acquire a pro-tumor phenotype characterized by prolonged survival and the release of MMP9. Importantly, GBM patients with synchronous high levels of PLOD2 and neutrophil infiltration had significantly worse overall survival (p < 0.001; log-rank) compared to the other groups of GBM patients. These findings indicate that PLOD2 promotes GBM progression and might be a useful therapeutic target in this type of cancer.

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.

Intradural spinal cord tumors (IDSCTs) in children and young adults are rare diseases. This present study is aimed to demonstrate our experience with a large series of children and young adults with IDSCT. A total of 50 patients aged <20 years with IDSCT treated in our department between 1990 and 2010 were included in the study. Clinical, histological, and radiological findings, treatment strategies, and clinical outcome were retrospectively assessed. Depending on the relation to the spinal cord, IDSCT were dichotomized into intramedullary SCT (IMSCT) and extramedullary SCT (EMSCT). The functional outcome was evaluated with the Frankel score assessing the longest available follow-up period. Mean age was 10.3 years (range 6 months-19 years). IDSCT surgery was performed in 44 patients (88%). A common first symptom in patients with EMSCT was neck and back pain (41%), whereas monoparesis of arms (43%) were often seen in patients with IMSCT. The main duration of the symptoms was longer in patients with IMSCT. The postoperative functional outcome was generally comparable to the preoperative functional condition, while better for EMSCT (P < 0.01). The functional outcome at last follow-up correlated significantly with the preoperative Frankel score (P < 0.002). Due to the mostly mild impact of the surgery on the functional outcome, the surgical treatment of IDSCT in children and young patients can be uniquely advocated.

Progesterone Receptor Membrane Component 1 (PGRMC1) is a tumour-promoting factor in several types of cancer but its role in brain tumours is poorly characterized thus far. Our study aimed to determine the effect of PGRMC1 on glioblastoma (GBM) pathophysiology using two independent cohorts of IDH wild-type GBM patients and stable knockdown GBM models. We found that high levels of PGRMC1 significantly predicted poor overall survival in both cohorts of GBM patients. PGRMC1 promoted the proliferation, anchorage-independent growth, and invasion of GBM cells. We identified Integrin beta-1 (ITGB1) and TCF 1/7 as potential members of the PGRMC1 pathway in vitro. The levels of ITGB1 and PGRMC1 also correlated in neoplastic tissues from GBM patients. High expression of PGRMC1 rendered GBM cells less susceptible to the standard GBM chemotherapeutic agent temozolomide but more susceptible to the ferroptosis inducer erastin. Finally, PGRMC1 enhanced Interleukin-8 production in GBM cells and promoted the recruitment of neutrophils. The expression of PGRMC1 significantly correlated with the numbers of tumour-infiltrating neutrophils also in tissues from GBM patients. In conclusion, PGRMC1 enhances tumour-related inflammation and promotes the progression of GBM. However, PGRMC1 might be a promising target for novel therapeutic strategies using ferroptosis inducers in this type of cancer.