Comparison of survival benefit and safety profile between lenvatinib and donafenib as conversion therapy in patients with hepatocellular carcinoma 

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In a retrospective comparative cohort study, Hou et al. 1) published in the American Journal of Translational Research, the authors—affiliated with the Department of Oncology, Department of Gynaecology and Obstetrics, and Department of Neurosurgery at Shijiazhuang People’s Hospital (Hebei, China), as well as Beijing Water Conservancy Hospital—compared the survival benefit and safety profile of lenvatinib versus donafenib as conversion therapy in patients with hepatocellular carcinoma (HCC) at China National Liver Cancer (CNLC) stages I–III.

Lenvatinib demonstrated significantly superior survival outcomes—both in overall survival and progression-free survival—compared to donafenib. It also showed better tolerability, with fewer grade ≥3 adverse events.

❌ 1. Study Design: Retrospective = Weak Evidence

This is yet another retrospective single-center analysis, plagued by inherent biases—selection, reporting, and confounding—that no amount of statistical massaging can resolve. No randomization, no blinding, and no control for treatment timing or physician discretion. In oncology, where treatment nuances matter, such designs should be considered hypothesis-generating at best, not guidance for clinical practice.

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Fighting the Fracture Cascade: Early and Repeated Balloon Kyphoplasty as a Bridge Until the Effects of Osteoporosis Treatment Become Apparent in a Super-Aged Patient

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In a case report by Tanaka et al., published in Cureus in May 2025, and authored by clinicians from the Departments of Neurosurgery at the International University of Health and Welfare Narita Hospital (Narita), Shiroishi Kyoritsu Hospital (Shiroishi), Shojima Neurosurgery (Saga), Imari Arita Kyoritsu Hospital (Arita), and the Department of Neurology at Shiroishi Kyoritsu Hospital, the authors describe the management of an 87-year-old patient with a cascade of adjacent osteoporotic vertebral fractures. The purpose of the report is to highlight the role of early and repeated balloon kyphoplasty (BKP) as an effective bridging strategy to preserve mobility, spinal alignment, and independence in super-aged patients, until the delayed therapeutic effects of pharmacologic osteoporosis treatments, such as teriparatide, become evident 1)

1. Overinterpretation of a Single Case

The fundamental flaw of this report is its excessive generalization from a single anecdotal case. No matter how long the follow-up, one patient’s trajectory cannot justify broad clinical recommendations, especially regarding a high-cost and procedure-intensive strategy like repeated BKP.

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Pituitary apoplexy: surgical or conservative? A meta-analytical insight.

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In a Systematic Review and Meta-Analysis, Xia et al., from the First College of Clinical Medical Science, Three Gorges University & Yichang Central People’s Hospital, Yichang, Hubei, China, published in Frontiers in Surgery. The authors compared recovery outcomes of neurosurgical vs. conservative treatment in patients with pituitary apoplexy, aiming to provide evidence-based guidance for clinical decision-making.

Recovery from ophthalmoplegia improved wih surgery 3).

The authors claim to provide evidence-based guidance for choosing between surgical and conservative treatment in pituitary apoplexy through a meta-analysis of 33 years of literature.

They conclude that surgery significantly improves ocular muscle paralysis but yields no benefit over conservative management for visual acuity, visual field, or endocrine outcomes.

💣 Critical Issues

1. Methodological Superficiality

Despite claiming a rigorous meta-analysis, the study relies on a fixed-effects model—a questionable choice given the expected heterogeneity across decades of heterogeneous, mostly retrospective, observational studies. This choice artificially narrows confidence intervals and potentially overstates precision. No rationale is given for not using a random-effects model, which is standard in clinical meta-analyses dealing with variable populations and treatment protocols.

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Systematic Review of the predictive value of negative brain or low probability brain MRIs in patients with CSF venous fistulas

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The article titled “Systematic Review of the Predictive Value of Negative Brain or Low Probability Brain MRIs in Patients with CSF Venous Fistulas” (American journal of neuroradiology) is a systematic review analyzing data from nine studies (898 patients) to assess how reliably negative brain MRI or low-probability MRI scores (Bern, Mayo) can rule out cerebrospinal fluid (CSF) venous fistulas, a surgically treatable cause of spontaneous intracranial hypotension (SIH) 1).

The authors found that although negative brain MRI has a high negative predictive value (89%), CVFs were still identified in a notable number of patients—especially when using the Mayo score (NPV only 65%).

The authors conclude that negative imaging does not exclude CVF, and invasive spinal imaging (e.g., DSM, dynamic CT myelography) should be considered in cases with strong clinical suspicion. This is especially relevant for neurosurgeons, as surgical ligation of CVFs may be necessary.

All authors are affiliated with Cedars-Sinai Medical Center (Los Angeles), with Dr. Wouter I. Schievink, a neurosurgeon, being a leading expert in the field of CSF leaks.

This so-called systematic review by Tay et al. (AJNR, June 2025) ambitiously sets out to clarify the diagnostic value of negative brain MRI in detecting cerebrospinal fluid venous fistulas (CVFs), yet ends up as a textbook example of how quantitative gloss can’t save a weak clinical premise.

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Temporal trends and risk factors associated with stroke mortality among cancer patients

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In a retrospective cohort study published in the Journal of Clinical Neuroscience, Ahmed et al. with Cleveland Clinic Cerebrovascular Center, West Virginia University participation 1) analyzed data from over 5.9 million patients diagnosed with a first primary cancer, based on the SEER database (2000–2020). The study aimed to quantify the risk of stroke-related death (SD) in cancer patients and to identify temporal trends and associated clinical and demographic risk factors. Stroke-related mortality (SD) among cancer patients has significantly declined over the past two decades across all cancer types and both sexes. However, older age, non-white race, male sex, and specific cancer types—notably nervous system, respiratory, and head and neck cancers—are associated with a higher risk of stroke death. Conversely, patients receiving chemotherapy or radiotherapy had a lower risk of SD compared to those who received no treatment.

⚠️ Fatal Methodological Flaws

No Clinical Stroke Classification

The authors report on “stroke mortality” without differentiating ischemic vs. hemorrhagic strokes, nor providing stroke etiology or timing relative to cancer diagnosis or cancer treatment—rendering any mechanistic or preventative inference purely speculative.

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Global burden and trend of stroke attributable to metabolic risks among young adults (20–39 years old) from 1990 to 2021

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In a retrospective secondary analysis based entirely on data from the Global Burden of Disease Study (GBD) 2021 — with no original dataset, no prospective design, and no hypothesis testing — Liu et al., from the Department of Neurosurgery, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, China, published in Frontiers in Cardiovascular Medicine an assessment of the global burden and long-term trends of stroke among young adults (ages 20–39) attributable to metabolic risk factors. The authors identify regional disparities and support the call for targeted prevention strategies.

The study concludes that the global burden of stroke attributable to metabolic risk factors among young adults (20–39 years old) has significantly increased from 1990 to 2021, both in terms of absolute numbers and age-standardized rates. The major contributors to this burden are high body mass index (BMI), high fasting plasma glucose, and high systolic blood pressure. The authors emphasize the need for targeted, age-specific public health interventions to reduce these modifiable risks and prevent early-onset stroke.

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Main Limitation

The study merely visualizes model-generated data without offering critical interpretation, clinical insight, or actionable public health strategies.

📉 Main Criticisms

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The impact of DRG payment reform on inpatient costs for different surgery types: an empirical analysis based on Chinese tertiary hospitals

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In a retrospective observational econometric analysis Luo et al. from the Panzhihua Central Hospital, Sichuan Provincial People’s Hospital, Chengdu, Sichuan, China 1) in Frontiers in Public Health attempt to quantify the cost-containment effects of DRG-based payment systems in China hospitals using advanced statistical tools. They claim significant cost reductions (especially in drug and material expenditures) and more “concentrated” cost distribution post-reform.

Major Criticisms

1. **Shallow Econometric Sophistication Masquerading as Rigor**

While Propensity Score Matching (PSM) and Difference-in-Differences (DiD) models are commonly used to infer causal effects, their validity hinges on critical assumptions — none of which are addressed with sufficient care here. The authors provide no robustness checks, falsification tests, or sensitivity analyses. The technical glitter hides conceptual rust.

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Early clinical experience with the Emboguard Balloon Guide Catheter: impact on technical success and patient outcomes in large vessel occlusion thrombectomy

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In a retrospective observational cohort study published in the Journal of NeuroInterventional Surgery, Mahat et al.—with participation from the Department of Neurosurgery at the University of Pittsburgh School of Medicine—evaluated the early clinical performance of the Emboguard Balloon Guide Catheter (EBGC) in anterior circulation large vessel occlusion (LVO) strokes treated with endovascular thrombectomy. The analysis relied on a prospectively maintained thrombectomy database, yet lacked a control group, randomization, or blinding, limiting its internal validity.

The study sought to assess:

Technical outcomes: rates of successful (mTICI 2b/3) and complete (mTICI 2c/3) recanalization, number of passes, and first-pass effect (FPE).

Clinical outcomes: NIHSS at discharge and functional status at 90 days (mRS).

Safety outcomes: incidence of symptomatic intracranial hemorrhage (sICH) and all-cause mortality.

While the reported results appear favorable, the commercial tone, lack of methodological rigor, and extensive conflicts of interest raise concerns that the study may serve more as an early promotional endorsement of the device rather than a robust, independent scientific evaluation. 1)

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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.

Use of N-hexyl Cyanoacrylate Monomers for the Treatment of Intra- and Extracranial Arteriovenous Malformations: A Single-Center Experience

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In a retrospective single-center case series (n=22 patients, 24 procedures) with no control group or comparison, Murias Quintana et al. from the Hospital Universitario Central de Asturias, Oviedo, Hospital Clínic de Barcelona, Hospital Universitario Marqués de Valdecilla, Santander, Alfried Krupp Krankenhaus, Essen, Hospital Universitario de Salamanca 1) aim to describe outcomes after the use of N-hexyl cyanoacrylate (NHCA, “Magic Glue”) for AVM embolization. Despite its stated aim of evaluating “strengths and limitations,” the article offers a one-sided, promotional narrative that lacks critical analysis.

🧱 Structural and Conceptual Weaknesses

1. Journal-Level Issues: “Cureus Syndrome”

The journal *Cureus* is increasingly known for:

This paper reinforces that reputation, providing more of a procedural diary than a peer-reviewed study. It embodies editorial complacency and academic dilution.

2. Lowest Tier of Evidence

A retrospective case series offers no comparative insight. There is:

This is not hypothesis–testing research — it’s purely observational, anecdotal reporting.

📉 Methodological Limitations

3. “Success” Is Redefined to Mean Nothing

The paper defines technical success as “the outcome achieved based on objective.” This is circular reasoning and renders the concept of success meaningless.

4. Data Dump of Technical Details

Injection times and catheter models are listed with obsessive detail:

  • HeadWay Duo 167 cm in 70.8%
  • Magic 1.2F in the rest
  • Injection times: 27 seconds to 9 minutes 38 seconds

Yet none of these details translate to improved patient care or clinical insight.

5. Zero Complications ≠ Safety

No adverse events in 24 procedures cannot be extrapolated as “safe.” This cohort is underpowered to detect rare but serious complications — a classic false sense of security.

🤹 Interpretation Bias and Overreach

6. 12.5% Success = “Effective”?

Only '3 out of 24 cases (12.5%)‘ achieved complete occlusion with a single NHCA injection. The authors still call it “effective.” This is an example of:

  • ::unjustified enthusiasm::
  • ::intellectual dishonesty::

7. Promotional Tone

Frequent use of the term “Magic Glue” and positive adjectives for NHCA give this paper the tone of a product brochure, not a neutral scientific analysis.

🧠 What’s Missing?

Key omissions include:

  • No clinical or imaging follow-up data
  • No outcome measures beyond technical success
  • No comparison with other embolic agents (Onyx, PHIL, Squid)
  • No cost-benefit analysis
  • No discussion of failure cases or limitations in complex AVMs

🧾 Conclusion

This paper does not meet the standards of a rigorous scientific study. It provides:

  • No high-quality evidence
  • No clinically useful guidance
  • No long-term data

It reinforces the perception of *Cureus* as a platform for uploading technically correct but scientifically irrelevant work. A procedural note disguised as research, this article is a missed opportunity to meaningfully contribute to the field of neurointerventional radiology.

Final Verdict: This is not a “study” — it is a technical anecdote polished with promotional language and framed in a journal that too often rewards upload volume over scientific substance.

📎 References

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Murias Quintana E, Rodríguez Castro J, Puig J, Gil García A, Chapot R, Maestro V, Llibre JC, Gutiérrez Morales JC, García Arias F, Vega P. Use of N-hexyl Cyanoacrylate Monomers for the Treatment of Intra- and Extracranial Arteriovenous Malformations: A Single-Center Experience. Cureus. 2025 May 17;17(5):e84290. doi: 10.7759/cureus.84290. PMID: 40525034; PMCID: PMC12169607.