Neurosurgery

Engineering of CD63 Enables Selective Extracellular Vesicle Cargo Loading and Enhanced Payload Delivery.

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In a preclinical experimental study, Obuchi et al. (2025)—with contributions from the Department of Neurosurgery at Leiden University Medical Center—engineered extracellular vesicles for selective cargo loading and enhanced functional delivery, using a modified CD63 scaffold and VSV-G fusion, with in vivo validation in mouse brain models. 1)

🚫 1. Rebranding Complexity as Innovation The authors tout a modular EV engineering system using CD63, mCherry, FLAG-tags, nanobody fusions, and VSV-G. But this is not scientific ingenuity—it’s molecular bricolage. Each component is repurposed from older literature and glued together without real conceptual novelty. The result? A bloated acronym soup with more moving parts than scientific value.

⚠️ What’s pitched as a breakthrough is closer to a tech demo in search of a clinical rationale.

❌ 2. Absence of Disease-Relevant Application Despite name-dropping CRISPR, Cre, and Cas9, no disease context is addressed. No glioma model. No neurodegenerative target. No proof that the cargo accomplishes anything biologically meaningful in the recipient tissue. The mouse brain “validation” is just a fluorescent readout, not a therapeutic outcome.

The cargo arrives, but so what? This is payload delivery without a payload purpose.

🧪 3. Methodological Blind Spots No quantification of EV heterogeneity or functional subpopulations.

No rigorous comparison with alternative delivery systems (e.g., AAVs, lipid nanoparticles).

No evidence of endosomal escape for actual cytoplasmic/nuclear action.

No dose-response curves, toxicity profiling, or repeatability metrics.

This is a biotech prototype, not a therapy-in-the-making.

🔥 4. VSV-G: The Short-Term High, Long-Term Problem The use of VSV-G, a viral fusogen with broad tropism and high immunogenicity, is particularly careless. While it boosts in vitro uptake and helps “sell” delivery efficiency, it introduces a critical translational liability: poor specificity, potential immune activation, and unsuitability for clinical use.

❝Putting VSV-G on EVs is like installing a rocket engine on a paper boat—it moves faster, but it’s doomed to burn out or sink.❞

🧱 5. Structural Inefficiency and Complexity The system requires:

Engineering CD63 with dual tags

Fusing cargo to a nanobody

FLAG-based purification

VSV-G pseudotyping

TEV protease cleavage

This is logistically unscalable for clinical or industrial production and riddled with points of failure. The more components you bolt on, the more it resembles a lab curiosity, not a deliverable platform.

📉 6. Journal Inflation and Institutional Complacency The publication in J Extracell Vesicles is not a mark of impact, but rather a reflection of how EV journals have drifted into translational cosplay, applauding synthetic elegance over clinical relevance. The heavyweight affiliations (MGH, Harvard, etc.) likely ensured acceptance despite the absence of therapeutic depth or mechanistic rigor.

🧠 Conclusion: A study more interested in showing what’s technically possible than what’s biologically meaningful. It trades therapeutic relevance for engineering flair, while ignoring the hard questions of targeting, safety, scalability, and necessity.

This is not a step toward Evidence-based medicine—it’s a flashy side road to nowhere.

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Obuchi W, Zargani-Piccardi A, Leandro K, Rufino-Ramos D, Di Lanni E, Frederick DM, Maalouf K, Nieland L, Xiao T, Repiton P, Vaine CA, Kleinstiver BP, Bragg DC, Lee H, Miller MA, Breakefield XO, Breyne K. Engineering of CD63 Enables Selective Extracellular Vesicle Cargo Loading and Enhanced Payload Delivery. J Extracell Vesicles. 2025 Jun;14(6):e70094. doi: 10.1002/jev2.70094. PMID: 40527733.

Epithelioid angiosarcoma of the cervical spine: A case report.

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Nan et al. 1) describe a rare case of epithelioid angiosarcoma (EA) involving the cervical spine, presenting with pathological fracture and kyphotic deformity, and document the surgical and adjuvant management as well as the clinical outcome in the World Journal of Clinical Cases.

1. Predictable Yet Pointless

The authors claim novelty by describing a rare anatomical presentation of EA. However, this degenerates into a predictable narrative with no new pathophysiological insights, no hypothesis generated, and no clinical paradigm challenged. It is the kind of “rare case” that proliferates in low-barrier journals precisely *because* it demands no intellectual risk.

2. Zero Diagnostic Value

The authors bypass the opportunity to deepen our understanding of the radiological-morphological signature of EA in the spine. No comparative imaging, no differential diagnostic flowchart, no histopathological discussion beyond standard CD31/CD34 immunostaining. If this case had been published in 1995, it would be equally uninformative.

3. Therapeutic Confusion Disguised as Aggressiveness

Two major spine surgeries (posterior decompression + anterior corpectomy) followed by immediate radiotherapy in a moribund patient demonstrate therapeutic overreach without oncological strategy. There is no discussion on multidisciplinary planning, palliative thresholds, or whether delaying surgery or avoiding the second procedure might have prevented ARDS. The reader is left with the impression of a surgical reflex, not an evidence-based decision.

4. No Discussion of Differential Diagnosis or Biomarkers

In a tumor type notorious for being misdiagnosed as metastasis, chordoma, or sarcoma NOS, the absence of a differential diagnostic framework or advanced markers (ERG, FLI1, HHV-8, etc.) is alarming. Histological laziness cloaked in “rare disease” rhetoric.

5. Outcome Reporting: Conveniently Truncated

The patient dies 3 weeks after surgery, yet the discussion fails to draw any causal or cautionary link between the interventions and the fatal ARDS. No autopsy data, no postmortem imaging, no pulmonary workup. This omission sterilizes the clinical narrative, reducing it to anecdote.

6. Ethically Murky

The case implicitly raises an ethical dilemma—should maximal surgery be performed in aggressive, terminal tumors without demonstrated systemic control? Yet the authors shy away from even mentioning this, let alone framing it for academic discussion.

7. Journal Choice Reflects the Paper’s Weakness

Published in a journal known for minimal peer review stringency, the article offers no citations of recent molecular or targeted therapy advances, no engagement with broader oncological guidelines, and no rationale for the treatment decisions beyond procedural listing.

Definitions (for Teaching Purposes)

  • Histological laziness: Failing to provide in-depth pathology discussion beyond CD31/CD34 and H&E staining in vascular tumors.
  • Surgical reflex: The tendency to operate based on mechanical findings (compression, fracture) without integrating prognosis or systemic disease behavior.
  • Ethical sterilization: Avoiding uncomfortable questions about futility, risk-benefit tradeoffs, and overtreatment in end-stage patients.
  • Postmortem evasion: Reporting a perioperative death without diagnostic closure (autopsy, imaging, or medical reflection).

Conclusion

This case report is an example of procedural reporting devoid of scientific merit, clinical reflection, or ethical introspection. It contributes nothing to the understanding of EA, its diagnosis, biology, or management—beyond reiterating its rarity. In its current form, it is neither hypothesis-generating nor practice-changing, and serves as a cautionary tale on how not to write a case report.

Suggested Revisions

  • Include comparative radiology with metastatic disease and primary bone tumors.
  • Provide autopsy findings or detailed explanation of respiratory decline.
  • Discuss therapeutic alternatives (e.g., single-stage surgery, biopsy + RT, palliative care).
  • Frame the case within an oncological decision-making algorithm.
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Nan YH, Chiu CD, Chen WL, Chen LC, Chen CC, Cho DY, Guo JH. Epithelioid angiosarcoma of the cervical spine: A case report. World J Clin Cases. 2025 Jun 16;13(17):101593. doi: 10.12998/wjcc.v13.i17.101593. PMID: 40524767; PMCID: PMC11866273.

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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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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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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