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Background: H3 K27M-mutated gliomas were first described as a new grade 4 entity in the 2016 World Health Organization classification. Current studies have focused on its typical appearance in children and young adults, increasing the need to better understand the prognostic factors and impact of surgery on adults. Here, we report a multicentric study of this entity in adults., Methods: We included molecularly confirmed H3 K27M-mutated glioma cases in patients ≥ 18 years diagnosed between 2016 and 2022. Clinical, radiological, and surgical features were analyzed. Univariate and multivariate analyses were performed to identify prognostic factors., Results: Among 70 patients with a mean age of 36.1 years, the median overall survival (OS) was 13.6 ± 14 months. Gross-total resection was achieved in 14.3% of patients, whereas 30% had a subtotal resection and 54.3% a biopsy. Tumors located in telencephalon/diencephalon/myelencephalon were associated with a poorer OS, while a location in the mesencephalon/metencephalon showed a significantly longer OS (8.7 vs. 25.0 months, P = .007). Preoperative Karnofsky-Performance Score (KPS) ≤ 80 showed a reduced OS (4.2 vs. 18 months, P = .02). Furthermore, ATRX loss, found in 25.7%, was independently associated with an increased OS (31 vs. 8.3 months, P = .0029). Notably, patients undergoing resection showed no survival benefit over biopsy (12 vs. 11 months, P = .4006)., Conclusions: The present study describes surgical features of H3 K27M-mutated glioma in adulthood in a large multicentric study. Our data reveal that ATRX status, location and KPS significantly impact OS in H3 K27M-mutated glioma. Importantly, our dataset indicates that resection does not offer a survival advantage over biopsy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Neural-tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is limited. We present an epigenetically defined neural signature of glioblastoma that independently predicts patients' survival. We use reference signatures of neural cells to deconvolve tumor DNA and classify samples into low- or high-neural tumors. High-neural glioblastomas exhibit hypomethylated CpG sites and upregulation of genes associated with synaptic integration. Single-cell transcriptomic analysis reveals a high abundance of malignant stemcell-like cells in high-neural glioblastoma, primarily of the neural lineage. These cells are further classified as neural-progenitor-cell-like, astrocyte-like and oligodendrocyte-progenitor-like, alongside oligodendrocytes and excitatory neurons. In line with these findings, high-neural glioblastoma cells engender neuron-to-glioma synapse formation in vitro and in vivo and show an unfavorable survival after xenografting. In patients, a high-neural signature is associated with decreased overall and progression-free survival. High-neural tumors also exhibit increased functional connectivity in magnetencephalography and resting-state magnet resonance imaging and can be detected via DNA analytes and brain-derived neurotrophic factor in patients' plasma. The prognostic importance of the neural signature was further validated in patients diagnosed with diffuse midline glioma. Our study presents an epigenetically defined malignant neural signature in high-grade gliomas that is prognostically relevant. High-neural gliomas likely require a maximized surgical resection approach for improved outcomes., (© 2024. The Author(s).)

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background : Spondylodiscitis is an infectious disease affecting an intervertebral disc and the adjacent vertebral bodies and is often the complication of a distant focus of infection. This study aims to ascertain the regional and hospital-specific disparities in bacterial patterns and resistance profiles in spontaneous and iatrogenic spondylodiscitis and their implications for patient treatment. Methods: We enrolled patients from two German hospitals, specifically comparing a university hospital (UVH) with a peripheral non-university hospital (NUH). We documented patient demographics, laboratory results, and surgical interventions. Microbiological assessments, antibiotic regimens, treatment durations, and resistance profiles were recorded. Results: This study included 135 patients. Upon admission, 92.4% reported pain, with 16.2% also presenting neurological deficits. The primary microbial species identified in both the UVH and NUH cohorts were S. aureus (37.3% vs. 31.3%) and cog. neg. staphylococci (28.8% vs. 34.4%), respectively. Notably, a higher prevalence of resistant bacteria was noted in the UVH group ( p < 0.001). Additionally, concomitant malignancies were significantly more prevalent in the UVH cohort. Conclusion: Significant regional variations exist in bacterial prevalence and resistance profiles. Consequently, treatment protocols need to consider these nuances and undergo regular critical evaluation. Moreover, patients with concurrent malignancies face an elevated risk of spondylodiscitis.

Patients with glioblastoma (GBM) are at increased risk for arterial and venous thromboembolism (TE). Risk factors include surgery, the use of corticosteroids, radiation, and chemotherapy, but also prothrombotic characteristics of the tumor itself such as expression of tissue factor, vascular endothelial growth factor, or podoplanin. Although distant metastases are extremely rare in this tumor entity, circulating tumor cells (CTCs) have been detected in a significant proportion of GBM patients, potentially linking local tumor growth characteristics to systemic hypercoagulability. We performed post hoc analysis of a study, in which GBM patients had been investigated for CTCs. Information on TE was retrieved from electronic patient charts. In total, 133 patients (median age, 63 years; interquartile range, 53-70 years) were analyzed. During follow-up, TE was documented in 14 patients (11%), including 8 venous and 6 arterial events. CTCs were detected in 26 patients (20%). Four (15%) patients with CTCs had a TE compared with 10 (9%) patients without CTCs. There was no difference in the frequency of TE events between patients with and those without detectable CTCs ( p  = 0.58). In summary, although our study confirms a high risk of TE in GBM patients, it does not point to an obvious association between CTCs and vascular thrombosis., Competing Interests: CB: Invited speaker, personal: AOK Germany; Lectures, personal: Bristol Myers Squipp; Invited speaker, personal: med update; Speaker, personal: Merck Serono, Roche Pharma; Lectures, personal: Sanofi Aventis; Advisory Board, personal: Astra Zeneca, Bayer Healthcare, BioNTech, Bristol Myers Squipp, Merck Serono, Oncology Drug Consult CRO, Sanofi Aventis; Board of Directors: DGHO; Leadership role: Hamburg Cancer Society, National Network of German Cancer Centers; Member of Board of Directors: Northern German Society of Internal Medicine; Advisory role, Board of DGHO Advisors: DGHO; Other financial or non-financial interests: more than 95 clinical trials, Local PI, Institutional, No financial interest, our department is involved in several clincal trials sponsored by industry and cooperative groups where we hold praticipants roles and local PI roles and PI roles.MM, MW, SR and KL have no conflicts of interest.CCR: Grants or contracts from any entity: DFG Research Grant, Roggenbuck-Stiftung, Margarete Clemens Stiftung; Support for attending meetings and/or travel: Pfizer, LFB, CSL Behring.KP: Consulting fees: Menarini, Hummingbird; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events:Agena, Novartis, Illumina, Menarini, Abcam, Sanofi.FK: Support for attending meetings and/or travel: Servier, Gilead, Jazz Pharmaceuticals, Novartis, Amgen; Patents planned, issued or pending: Amgen.FL: Consulting fees: Alexion, Aspen, AstraZeneca, Bayer, BioMarin, Bristol Myers Squibb, Chugai, CSL Behring, Daiichi Sankyo, LEO Pharma, Mitsubishi Tanabe Pharma, Novo Nordisk, Pfizer, Roche, SOBI, Takeda, Viatris; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Alexion, Aspen, AstraZeneca, Bayer, Bristol Myers Squibb, Chugai, CSL Behring, Daiichi Sankyo, Grifols, Janssen-Cilag, LEO Pharma, Mitsubishi Tanabe Pharma, Novo Nordisk, Pfizer, SOBI, Viatris, Werfen;Participation on a Data Safety Monitoring Board or Advisory Board: Alexion, Aspen, AstraZeneca, Bayer, Bristol Myers Squibb, Chugai, CSL Behring, Daiichi Sankyo, Grifols, Janssen-Cilag, LEO Pharma, Mitsubishi Tanabe Pharma, Novo Nordisk, Pfizer, SOBI, Viatris, Werfen; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Secretary of GTH e.V., (Thieme. All rights reserved.)

Introduction: Imposter syndrome (IS), characterized by persistent doubts about one's abilities and fear of exposure as a fraud, is a prevalent psychological condition, particularly impacting physicians. In neurosurgery, known for its competitiveness and demands, the prevalence of IS remains high., Research Question: Recognizing the limited literature on IS within the neurosurgical community, this European survey aimed to determine its prevalence among young neurosurgeons and identify associated factors., Material and Methods: The survey, conducted by the Young Neurosurgeon Committee of the European Association of Neurosurgical Societies, gathered responses from 232 participants. The survey included demographics, the Clance Imposter Phenomenon Survey (CIPS), and an analysis of potential compensatory mechanisms., Results: Nearly 94% of respondents exhibited signs of IS, with the majority experiencing moderate (36.21%) or frequent (40.52%) symptoms. Analyses revealed associations between IS and factors such as level of experience, sex, and board-certification., Discussion and Conclusion: The findings suggest a significant prevalence of IS among young neurosurgeons, with notable associations with sex and level of experience. Compensatory mechanisms, such as working hours, article reading, and participation in events, did not show significant correlations with IS. Notably, male sex emerged as an independent protective factor against frequent/intense IS, while reading more than five articles per week was identified as a risk factor. The identification of protective and risk factors, particularly the influence of gender and reading habits, contributes valuable insights for developing targeted interventions to mitigate IS and improve the well-being of neurosurgeons., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)