Neuropathology

Engineered retargeting to overcome systemic delivery challenges in oncolytic adenoviral therapy

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Type of study: Original research (experimental study, engineering approach) First author: Leparc et al. Affiliations:

  • Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
  • Laboratory of Nervous System Disorders and Therapy, GIGA Institute, University of Liège, Liège, Belgium

Journal: Molecular Therapy – Oncolytics Purpose: To engineer adenoviruses with modified tropism for systemic delivery—aiming to reduce off-target accumulation and enhance tumor retention via retargeting strategies.

Conclusions: Engineered vectors exhibited improved immune evasion, diminished sequestration by non-tumor tissues, and improved intratumoral delivery, indicating the feasibility of retargeting modifications for systemic adenoviral therapy.

Critical Review

Methodology: The study lacks transparency in the engineering protocol. Crucial elements such as ligand selection, targeting affinity, and vector modifications are insufficiently described. No rigorous dose-responsiveness or replication kinetics are provided.

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Clinical outcome and deep learning imaging characteristics of patients treated by radio-chemotherapy for a “molecular” glioblastoma

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In a retrospective observational cohort study, Zerbib et al., from the Department of Radiation Oncology, Institut Universitaire du Cancer de Toulouse Oncopole (IUCT-Oncopole), Claudius Regaud; INSERM UMR 1037, Cancer Research Center of Toulouse (CRCT); IRT Saint-Exupéry; Department of Engineering and Medical Physics, IUCT-Oncopole; Biostatistics & Health Data Science Unit, IUCT-Oncopole; Department of Neuroradiology, Hôpital Pierre-Paul Riquet, CHU Purpan; Department of Medical Oncology & Clinical Research Unit, IUCT-Oncopole; Pathology and Cytology Department, CHU Toulouse, IUCT-Oncopole; CerCo, Université de Toulouse, CNRS, UPS, CHU Purpan; Department of Neurosurgery, Hôpital Pierre-Paul Riquet, CHU Purpan; and University Toulouse III – Paul Sabatier, published in The Oncologist, sought to evaluate and compare the clinical outcomes of patients with molecular glioblastoma (molGB) and histological glioblastoma (histGB) treated with standard radio-chemotherapy. They also assessed whether artificial intelligence (AI) models could accurately distinguish molGB without contrast enhancement (CE) from low-grade gliomas (LGG) using MRI FLAIR imaging features.

Conclusion: Patients with molGB and histGB showed similar overall survival under standard treatment.

  • However, molGB without contrast enhancement (CE) demonstrated a significantly better median overall survival (31.2 vs 18 months).
  • AI models based on FLAIR MRI features were able to differentiate non-enhancing molGB from LGG, achieving a best-performing ROC AUC of 0.85.

→ These findings support the clinical relevance of non-enhancing molGB as a distinct subgroup with better prognosis and highlight the potential diagnostic utility of AI tools in radiologically ambiguous cases.

This study presents itself as cutting-edge — mixing radiotherapy outcomes with artificial intelligence — but beneath the polished language and deep learning jargon lies a set of predictable flaws:

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Proposal of a Multiparametric Meningioma (MEN-CCVol) Score for Preoperative Discrimination of World Health Organization Grade 2/3 From Grade 1 Intracranial Meningiomas Based on Patient and MRI Characteristics

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In a retrospective cohort with prospective and DNA methylation-based validation Prajjwal Raj Wagle et al. from the Helios Klinikum Erfurt; Jena University Hospital in the Neurosurgery Journal to develop and validate a multiparametric score (MEN-CCVol) based on preoperative patient and MRI characteristics for differentiating WHO grade 2 meningioma/WHO grade 3 meningioma from WHO grade 3 meningioma. The MEN-CCVol score, incorporating six weighted MRI and demographic variables (male sex, edema, necrosis, convexity location, cysts, volume ≥40 cm³), demonstrated moderate predictive ability for detecting higher-grade Intracranial Meningiomas across three cohorts. A cutoff score of ≥3 offered strong Negative Predictive Value (>90%) but suboptimal Positive Predictive Value, indicating utility as a rule-out tool rather than a definitive diagnostic index 1).

Critical Review

This study attempts to address the perennial challenge of preoperatively identifying higher-grade meningiomas using standard clinical and imaging data. The retrospective derivation cohort (n=463) and subsequent validations (n=211, n=18) bolster the methodological robustness, and the use of logistic regression with the Youden-index provides a solid statistical underpinning.

However, critical limitations remain: – Predictive Limitations: The PPV (35-36%) remains too low for actionable high-risk stratification, reflecting the low prevalence of grade 2/3 lesions and modest specificity (~60%). The tool may overly reassure surgeons or misguide surgical aggressiveness in borderline cases. – Score Simplicity vs. Clinical Complexity: By reducing complex radiological patterns to binary point assignments, the model may oversimplify nuanced features that skilled radiologists already integrate subjectively. – Validation Caveats: The DNA methylation cohort, though forward-thinking, includes only 18 cases, making generalizability speculative at best. – Genomic Oversight: Without incorporating any molecular or epigenetic markers beyond location and imaging, the MEN-CCVol score risks being obsolete as integrated diagnosis (radiology + methylation + histopathology) becomes the standard.

Final Verdict

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Inadvertent intrathecal application of vindesine and its neurological outcome: case report and systematic review of the literature

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In a case report + systematic review Babaee et al. from:

  1. Department of Neurosurgery, University Hospital OWL, Campus Bethel, Bielefeld, NRW, Germany
  2. Institute for Neuroradiology, University Hospital OWL, Campus Bethel, Bielefeld, NRW, Germany

* Journal: Brain & Spine * Purpose: Assess outcomes and optimal management—particularly CSF irrigation—following inadvertent intrathecal administration of vinca alkaloids (vindesine or vincristine). * Conclusions: Intrathecal vinca alkaloids are nearly universally fatal without aggressive intervention; CSF irrigation improves survival odds (40% vs 0%) but survivors suffer severe neurological deficits 1).

This paper offers a sobering update, but several critical flaws undermine its impact:

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Exploring IDH1 and IDH2 Mutations in Paediatric Medulloblastoma

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In a retrospective molecular analysis of 23 pediatric medulloblastoma samples, Motaz Fadul et al. from – King Abdulaziz University, Jeddah – King Faisal Specialist Hospital and Research Center, Jeddah – Umm Al-Qura University, Makkah – King Saud University, Riyadh – King Abdulaziz Medical City, Jeddah – King Fahad General Hospital, Jeddah Published in: Folia Biologica (Praha), 2025;71(2):73-78

This study sought to:

Findings:

  • ❌ No IDH1 or IDH2 mutations were detected in any of the 23 tumor samples.
  • 🧬 β-Catenin expression showed no significant correlation with PFS.
  • 📉 Median PFS was 383 days, suggesting modest clinical outcomes.

These findings reinforce the understanding that IDH mutations, prevalent in adult gliomas, are not typical of paediatric medulloblastomas, possibly due to divergent tumorigenic pathways and distinct cellular origins 2)

**Critical Review**

This study contributes marginally to the existing molecular profiling literature on paediatric medulloblastoma:

  • ✅ Reaffirms known absence of IDH mutations
  • ❗ Sample size (n=23) limits statistical power
  • ❗ Overreliance on β-catenin expression, without subgroup stratification (e.g. WNT/SHH)
  • ❗ Methodology (PCR + Sanger sequencing) lacks genomic depth in the era of next-generation sequencing
  • ❌ No novel biomarkers or clinical correlates were identified

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Fluids, Electrolytes, and Nutrition in the Critically Ill Patient with Neurotrauma

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* Type of Study: Narrative Review * Authors: Thomas et al. * Institution and City: University of Pennsylvania, Philadelphia, PA, USA * Journal: Neurosurgical Clinics of North America*, July 2025 * Purpose: To synthesize current clinical practices and considerations for fluid, electrolyte, and Nutritional Management in Critically Ill Neurotrauma Patients. * Conclusions: Isotonic saline remains the fluid of choice for resuscitation in TBI. Hypertonic saline is increasingly favored over mannitol for hyperosmolar therapy. Electrolyte imbalances are prevalent and necessitate close management. Nutritional optimization requires multidisciplinary coordination due to the elevated metabolic demands in TBI 1).

Critical Peer Review

1. Scientific Rigor & Methodology:

This narrative review lacks systematic methodology, which limits reproducibility and objectivity. There is no explicit discussion of inclusion/exclusion criteria for literature cited, nor a transparency framework for evaluating evidence quality. Future iterations would benefit from at least a semi-structured approach or alignment with PRISMA-ScR guidelines for scoping reviews.

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Multi‑omics analysis of druggable genes to facilitate Alzheimer’s disease therapy: A multi‑cohort machine learning study

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In a computational, multi-omics, machine learning study, Hu et al., published in the Journal of Prevention of Alzheimer’s Disease, aimed to identify druggable genes associated with Alzheimer’s disease (AD) by integrating multi-omics data from brain and blood samples and applying advanced machine learning and Mendelian randomization techniques to facilitate the development of effective therapeutic targets.

They concluded that LIMK2 is a promising druggable gene target for Alzheimer’s disease (AD), as its expression is significantly associated with key AD biomarkers — including Cerebrospinal fluid amyloid-beta, p-tau, and hippocampal atrophy — across both brain and blood datasets.

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Takeaway Message for a Neurosurgeon

Despite its computational complexity, the study by Hu et al. offers no clinically actionable insight for neurosurgeons. While it identifies LIMK2 as a statistically associated gene in Alzheimer’s pathology, there is no mechanistic evidence, no surgical relevance, and no translational pathway that justifies changing diagnostic or therapeutic strategies. Use it as a reminder: Data mining ≠ disease understanding. For neurosurgeons, especially those navigating cognitive decline in surgical candidates, CSF biomarkers and omics correlations remain tools — not decisions.

1. Conceptual Inflation Disguised as Innovation

The article by Hu et al. promises a “multi-cohort, multi-omics, machine learning” roadmap to druggable targets in Alzheimer’s disease (AD), but ultimately delivers a statistical Rube Goldberg machine — impressive in complexity, hollow in clinical consequence. The central narrative is built around the identification of “druggable genes” like LIMK2, but without a mechanistic framework, experimental validation, or translational bridge. The result is computational theater masquerading as biological discovery.

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Factors affecting outcomes following burr hole drainage of chronic subdural hematoma: a single-center retrospective study

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In a retrospective single-center cohort study, Zolnourian et al., from the University Hospital Southampton and Queen’s Hospital, Barking, Havering, & Redbridge University Hospitals NHS Trust, London, United Kingdom, published in the Journal of Neurosurgery, aimed to identify preoperative and perioperative factors that influence clinical outcomes, complications, and hospital length of stay in adult patients undergoing burr hole drainage for chronic subdural hematoma (CSDH), in order to improve patient selection and surgical decision-making.

They concluded that favorable short-term outcomes were primarily associated with nonmodifiable preoperative factors such as age under 80, preadmission independence, higher Glasgow Coma Scale motor score, lower ASA grade, and fewer regular medications. Surgical variables like laterality or the number of burr holes did not significantly impact outcomes. The use of subdural drains was linked to better discharge outcomes but not to recurrence or complications. These findings provide evidence-based criteria to guide surgical decision-making and patient counseling.

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📉 1. Redundancy Rebranded as Discovery

The headline findings — that younger, fitter patients with fewer medications and lower ASA scores fare better — are hardly groundbreaking. These are well-known prognostic factors repeated in countless prior studies. Yet the authors present them as if freshly uncovered, bypassing the fact that any intern with access to the NICE guidelines could have written this paper in a call room.

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Hypoxia-elective prodrug restrains tumor cells through triggering mitophagy and inducing apoptosis

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In a preclinical research, Wang et al. — from the Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University; The Affiliated Hospital of Qingdao University; The First Affiliated Hospital of Jinzhou Medical University; and the Department of Drug Clinical Trials, Zibo Central Hospital — published in the European Journal of Medicinal Chemistry a targeted cancer therapy that leverages tumor hypoxia to maximize antitumor effects while reducing systemic side effects.

They concluded that CHD‑1 functions as a selective prodrug that becomes activated under hypoxia typical of solid tumors. It effectively inhibits tumor cell growth, triggers mitophagy, and induces apoptosis in these hypoxic cancer cells. In vivo, CHD‑1 significantly suppressed HeLa xenograft growth in mice. It also demonstrated a safer toxicity profile compared to the parent compound, based on acute toxicity assessments.

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🧠 Takeaway for Neurosurgeons

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