Bystander killing by anti-PTPRZ1 CAR-T cells using additional tumor cell lines and scFv

The European Association of Neurosurgical Societies (EANS) has long been committed to advancing neurosurgical care through training, education, and research. The creation of the EANS Foundation represents a strategic step toward strengthening this mission by enabling structured philanthropic support. This editorial outlines the Foundation’s origins, governance, and early achievements, including its first flagship fundraising event, initiatives in neurotrauma research, and contributions to global neurosurgical education. By fostering collaboration between the neurosurgical community, philanthropic partners, and society at large, the EANS Foundation aims to promote sustainable progress in neurosurgical care across Europe and beyond.

Primer pairs for CAR-T cell phenotyping by qPCR

Objective In brain tumor surgery, gross total and supramarginal resections are sought to maximize survival, while maintaining neurological integrity. Cortico-cortical evoked potentials (CCEPs), initially introduced for intraoperative mapping of language pathways during awake surgery, have been recently applied to asleep procedures. The present work reports a review on CCEPs and subcortico-cortical evoked potentials (SCEPs) performed in brain surgery under general anesthesia. Methods PRISMA guidelines were applied. All records published up to March 2025, were searched through PubMed, Cochrane Library, Web of Science, and Google Scholar databases, with detailed search strings. Results Fourteen studies were found to which five were added because they also contained the search strings. Among them, thirteen focused on the language pathway, particularly the arcuate fasciculus, and four on the visual pathway. Seven studies investigated the SCEPs, while fifteen reported CCEPs. All studies applied single electrical pulse stimulation (SPES), 0.3-1 ms in duration, if monophasic, alternating their polarity, repeated at a rate of 0.3-9 pulses per second, usually in bipolar configuration. The recordings were usually done from subdural electrodes. The N1 peak latencies were shown to be dependent on the stimulation and recording sites. In addition, under general anesthesia, the latter N2 peak latencies were not detected. Conclusions The present work highlights the feasibility of CCEPs and SCEPs during general anesthesia, in their different roles: monitoring the integrity of the tracts with CCEPs and detecting their proximity with SCEPs. Significance CCEPs and SCEPs are promising tools for monitoring eloquent cognitive functions that may be at risk during neurosurgery performed under general anesthesia.

Percutaneous endoscopic spine surgery and tubular minimally invasive surgery (MIS) each offer distinct advantages but also important limitations. We describe a proof-of-concept study of a hybrid technique—tubular endoscopic spine surgery (TESS)—combining a tubular retractor with a 30° endoscope and continuous irrigation, aiming to integrate the advantages of both approaches. TESS was first evaluated in a cadaveric L4–L5 model and subsequently applied in a single clinical case of L4–L5 lumbar stenosis with right L5 radiculopathy. The technique uses a standard tubular retractor to establish a single paramedian muscle-splitting corridor. A 30° endoscope is introduced through the tube with continuous irrigation, while standard microsurgical instruments are used through the working channel. The tubular retractor provided a stable, reproducible single-incision transmuscular corridor to the interlaminar space. The addition of the endoscope with irrigation ensured a consistently clear operative field, while maintaining the ergonomics and simplicity of a single working channel. Instrument handling and exchange were straightforward, and no specific technical difficulties were encountered. In the clinical case, adequate decompression was achieved with complete symptom resolution at 6 and 12 months. TESS is a feasible hybrid technique that combines the familiar ergonomics of tubular MIS surgery with the dynamic visualization of endoscopic systems using irrigation. Further studies are needed to evaluate its clinical value before widespread clinical adoption.

BACKGROUND:Evidence regarding the clinical course of unruptured giant intracranial aneurysms (GIAs) after conservative management (CON), microsurgical treatment (SURG) or endovascular treatment (EVT) remains limited. We aimed to assess mortality, functional outcome, symptom course and retreatment rates after different management strategies. METHODS:In this prospective, multinational registry, patients with unruptured GIAs treated at 37 neurovascular centres between 2008 and 2018 were included. Outcomes after CON, EVT or SURG were analysed with standardised 3-year follow-up. The study is registered at ClinicalTrials.gov. RESULTS:We included 339 patients of whom 22.7% received CON, 42.8% EVT and 34.5% SURG. Three-year survival was 64.0% (95% CI 53.73% to 76.20%) in the CON group, 82.0% (95% CI 75.42% to 89.17%) in the EVT group and 93.5% (95% CI 88.91% to 98.28%) in the SURG group (p<0.001). Favourable neurological outcome (modified Rankin Scale 0-2) declined to 53.0%, 66.9% and 75.7% in the CON, EVT and SURG groups, respectively (p<0.01). Symptom improvement at 3 years occurred in 10.3% of CON, 22.1% of EVT and 11.1% of SURG patients, while deterioration was observed in 7.7%, 8.5% and 15.8%, respectively. Retreatment was required in 22.8% of EVT patients and 6.2% of SURG patients (p<0.01). CONCLUSIONS:EVT and SURG were associated with significantly improved survival and functional outcomes compared with conservative management of unruptured GIAs. In patients eligible for intervention, both treatment modalities represent reasonable and effective options, with a high proportion of patients achieving favourable clinical outcomes. TRIAL REGISTRATION NUMBER:NCT02066493.

Anti-PTPRZ1 CAR-T cell effector function after incubation with the Ge1302_PTPRZ1-KI cells

BACKGROUND:Unruptured intracranial aneurysms (UIAs) affect 3 %-5 % of the population and are increasingly detected incidentally. Although rupture risk is low, UIAs pose clinical challenges, as rupture can cause severe disability or death, and treatments carry complications. OBJECTIVE:To investigate how management strategy and patient characteristics affect longitudinal patient outcomes measured as modified Rankin Scale (mRS) in individuals with an asymptomatic, saccular, incidentally detected, unruptured, solitary intracranial aneurysm (ASIS). METHODS:We analysed a prospective, non-randomized ASIS cohort of 487 patients from Geneva University Hospitals at three time-points, including one-year follow-up. Conway-Maxwell-Poisson (CMP) regression was used for outcome modelling, inverse probability weighting (IPW) to estimate treatment effect expressed as an incidence rate ratio (IRR), and additive Bayesian networks (ABNs) to explore dependencies among variables, including patients' conditions. Missing baseline data were imputed using multiple imputation by chained equations (MICE) with covariate shift adjustment. RESULTS:Age significantly influenced one-year mRS (IRR 1.43, 95 % CI 1.16-1.77, p = 0.0009) and interacted with management strategy (p = 0.04). Average treatment effects (risk ratios) were estimated to be 0.77 (0.45-1.31) for endovascular vs observation and 1.28 (0.76-2.15) for microneurosurgery. ABN analysis reassured that age and prior mRS directly affect one-year outcomes. CONCLUSION:Age and baseline mRS are key determinants of one-year outcome. The absence of evidence for other variables' effects on treatment impact may reflect the limited sample size. The findings highlight the central role of patient-specific factors in guiding UIA management decisions. TRIAL REGISTRATION:ClinicalTrials.gov: NCT05526352, registered 31.08.2022.

In vivo anti-tumor activity of anti-PTPRZ1 CAR-T cells

This study conducts a clinical evaluation of a secure, locally deployed, quantized large language model (LLM) for automating modified Rankin Scale (mRS) score extraction from unstructured neurosurgical notes. We retrospectively selected 103 authentic clinical letters (2007–2025) from aneurysm patients at a tertiary neurosurgical centre. To comply with data privacy constraints, an open-source reasoning LLM (Qwen3-32B) with 4-bit quantization was deployed entirely on-premises. The LLM extracted mRS scores using a zero-shot approach with custom logits processors to enforce strict JSON formatting. Performance was compared to a reference standard (attending neurosurgeons’ consensus) and parallel scoring by medical residents and students. The LLM achieved excellent agreement with the attending consensus (QWK 0.95), matching the reliability of medical students (QWK 0.95) and residents (QWK 0.93). Exact agreement was 75%, and agreement within ±1 mRS point was 96%. Bayesian analysis strongly supported statistical equivalence between the model and human raters. The computationally optimized LLM demonstrated human-level classification reliability without task-specific fine-tuning. This approach successfully addresses key patient data privacy barriers and the formatting inconsistencies typical of open-ended generative models. Securely deploying a general-purpose, quantized LLM provides a scalable pathway for extracting functional outcomes and supports FAIR-aligned data systems.

Background: Temporal lobe epilepsy (TLE) often originates from focal hippocampal injury but progressively evolves into a bilateral epileptic network engaging both hippocampi and distributed cortical regions. A mechanistic understanding of how this network emerges, and whether early perturbation of specific nodes can alter its trajectory, is essential for developing network-level therapeutic strategies. Objective: We used a kainate-induced rodent model of TLE to (1) characterize the spatiotemporal emergence of epileptic discharges during the latent phase, (2) determine how bilaterally synchronized events develop, and (3) test whether transient chemogenetic silencing of either the ipsilateral epileptogenic focus (EF) or the contralateral hippocampus (CH) modifies large-scale epileptogenesis. Methods: Freely moving mice were implanted with multisite electrodes spanning bilateral hippocampal subfields (dentate gyrus, CA1, subiculum) and cortical regions (M2, Cg1, PrL, V1, entorhinal cortex). Longitudinal LFP recordings were performed every other day during the latent and early chronic phases following KA or saline injection. DREADD-based chemogenetic inhibition of glutamatergic neurons was applied between days 2-7 post-KA. Epileptiform events were quantified via spike rates, waveform metrics, high-frequency oscillations (HFOs), and short-latency interregional co-spiking. Results: Early after KA, epileptic spiking emerged locally in the ipsilateral dentate gyrus and progressively organized into HFO-coupled discharges. Contralateral hippocampal recruitment followed a distinctive biphasic time course, characterized by transient early activation, subsequent suppression, and later re-emergence with increasing bilateral coactivation. Cortical regions gradually developed higher spike rates and enhanced DG-related co-spiking, indicating large-scale network integration. Ipsilateral silencing modified local spike composition but did not prevent global network progression, whereas contralateral silencing accelerated ipsilateral epileptogenesis and strengthened pathological HFO expression. Conclusion: Epileptogenesis in the KA model reflects a transition from a focal hippocampal insult to a resilient, bilateral cortico-hippocampal network. Targeting a single hippocampal node, even at early latent stage, is insufficient to halt this progression, highlighting the need for network-level therapeutic strategies. ### Competing Interest Statement The authors have declared no competing interest.

This study examines the demographic, temporal, and spatial patterns of traumatic brain injury (TBI) hospitalizations in the canton of Geneva, Switzerland, between 2012 and 2024. Particular attention is given to differences between seniors (≥60 years) and the younger or working-age population (15–59 years). Hospital discharge data were analyzed in combination with geographic information systems (GIS) to explore incidence, severity, and clinical outcomes. Temporal trends were assessed across seasons and days of the week. Spatial distribution was investigated using Join Count and SPARR methods to detect clustering. Multivariate clustering further integrated socio-clinical characteristics, including age, autonomy, residential setting, and hospital trajectory. Seniors accounted for more than half of all TBI hospitalizations. Advanced age and institutional residence were strongly associated with reduced likelihood of returning home post-discharge (statistical values). Temporal analyses showed a marked increase in TBI incidence among seniors during autumn and at the beginning of the week, patterns not observed in the working-age group. Spatial analyses revealed non-random clustering of cases, with high-risk zones concentrated in specific areas, particularly for older adults. Multivariate clustering identified distinct socio-clinical profiles in both age groups, shaped by residential environment, autonomy level, and care pathways. The findings underscore the dual clinical and territorial dimensions of TBI, highlighting significant age-related and spatial disparities. Tailored prevention strategies, safer environmental design, and integrated care pathways are needed to reduce inequalities and improve outcomes. Addressing TBI through both a medical and public health lens is essential to support at-risk populations, particularly seniors.

Use of Jurkat triple reporter cells to assess CAR tonic signaling and specificity

Systematic review. X-linked hypophosphatemia (XLH) is a rare genetic disorder characterized by impaired phosphate homeostasis due to renal phosphate wasting. It leads to osteomalacia and skeletal abnormalities and represents the most common inherited cause of vitamin D-resistant rickets. In some patients, heterotopic ossification of the ligamentum flavum and paravertebral ligaments may result in spinal cord compression and myelopathy. Due to its rarity, large case series evaluating patient characteristics and surgical outcomes are lacking. We conducted a PRISMA-P based systematic review on spine surgery and X-linked hypophosphatemia from 1960 to 2022. Twenty-five studies were included, comprising 32 clinical cases. An illustrative case is also presented. Thirty-two patients (16 females and 16 males) with spinal cord compression due to XLH were included in this systematic review. Thirty out of 32 patients underwent surgery (one death and one refusal of surgery). The mean age of onset of symptoms was 41 years. 83

Bystander killing by 471_28z CAR-T cells depends on soluble mediators and does not affect macrophages

Expression of effector/memory and activation/exhaustion markers by CAR-T cells in pre- vs. post-thawing samples

Objective: Spinal infection (SI) is associated with substantial morbidity and mortality, and optimal treatment strategies remain debated, particularly in medically fragile patients. The Mortality in Spinal Infection (MSI-20) score was developed as the first dedicated prognostic tool for mortality risk estimation, but external validation in large cohorts has been lacking. This study aimed to externally validate the MSI-20 in a large multicenter registry cohort and assess its performance, clinical thresholds, and generalizability.Methods: This retrospective multi-institutional registry study included 1,122 adult patients with clinically, radiologically, and laboratory-confirmed SI treated at 6 tertiary referral centers between 2010 and 2023. The multicenter registry design enabled robust analysis of this relatively rare outcome. MSI-20 scores were calculated according to the original definition. Predictive performance was evaluated using receiver operating characteristic (ROC) analysis with 95% confidence intervals. Mortality across score strata and center-wise performance were analyzed, with exploratory assessment of additional baseline predictors.Results: Mean age was 66.4±13.1 years, and overall mortality was 18.3%. The MSI-20 demonstrated fair discriminative ability (area under the curve [AUC], 0.68; 95% confidence interval [CI], 64–72). The optimal ROC threshold was 3.5; a cutoff ≥4 yielded sensitivity 0.49 and specificity 0.74 (F1 score, 0.38). Mortality increased progressively, approaching 50% (47.4%) at scores ≥9. Performance was consistent across centers (AUC, 0.60–0.75). Exploratory univariable analyses did not identify additional baseline variables with consistent strong associations beyond the MSI-20 components.Conclusion: This large multicenter registry study provides the first external validation of the MSI-20, confirming reproducibility and generalizability. The score demonstrated fair discrimination and a clear risk gradient across increasing score categories. Given its simplicity and high negative predictive value, the MSI-20 may serve as an adjunctive tool to support risk communication, multidisciplinary discussion, patient counseling, and preoperative optimization in spinal infection.

PTPRZ1 expression at the mRNA level according to different GBM clinicopathologic features

Background: The atlanto-axial segment is highly mobile and, therefore, prone to instability in the setting of inflammatory disease, infection, tumor or trauma. While minimally invasive surgical (MIS) techniques have gained acceptance in the thoracolumbar spine due to their advantages over traditional approaches, their use at the atlanto-axial segment is controversial due to the surgical risk associated with its complex anatomy. To evaluate the current evidence on MIS atlanto-axial fixation, we carried out a systematic review of the literature and compared the reported results with those of open procedures. Methods: This systematic review follows PRISMA-DTA 2020 guidelines. A comprehensive search was conducted in November 2023 across PubMed/Medline, Google Scholar and clinicaltrials.gov using specific keywords related to minimally invasive atlanto-axial fixation. Data regarding study characteristics, patient demographics, surgical techniques, and outcomes were extracted from included studies. Results: This systematic review included 13 articles reporting on the results of surgery in 305 patients, in whom a total of 683 screws were inserted through a posterior MIS approach. N = 162 screws were inserted using the Harms–Goel technique, while N = 521 were placed using the Magerl technique. N = 40 screws were inserted using navigation guidance, while N = 643 were introduced with fluoroscopy assistance. Eight screws were misplaced. A Vertebral Artery (VA) injury was reported in three patients. With a mean value of 26.2 ± 15.3 months, the rate of fusion ranged between 80% and 100%. Conclusions: This study highlights the potential of MIS for posterior atlanto-axial fixation, which was achieved using Magerl transarticular screws in a large majority of cases. Despite technical challenges, MIS approaches appear to achieve satisfactory clinical and radiological outcomes with complication rates similar to those of open techniques. Future studies may help refine the indications for MIS and identify those cases better suited for open approaches.

Background/Objectives: Sacral chordomas are rare, locally invasive tumors that pose significant surgical and oncological challenges due to their anatomical complexity, proximity to critical structures, and resistance to conventional therapies. Methods: A literature search focused on contemporary multidisciplinary management of sacral chordoma was conducted. An illustrative case of such a multidisciplinary approach is presented. Results: Achieving optimal outcomes necessitates a multidisciplinary approach that balances en-bloc resection with negative margins and preservation of biomechanical stability and neurological function. Negative resection margins are a key determinant of long-term survival and reduced recurrence, particularly for tumors involving the upper sacrum (S1–S2). While postoperative radiation therapy provides adjunctive benefits, precision in surgical planning and execution remains paramount. Emerging technologies, such as augmented reality and 3D-printed anatomical models, are enhancing surgical precision, while the role of multidisciplinary surgical teams in improving outcomes requires further study. Conclusions: This review highlights the complexities of sacral chordoma management, focusing on surgical strategies, functional trade-offs, and future directions to optimize oncological and functional outcomes.