Vascular

pRESET stent retriever

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pRESET stent retriever

https://www.phenox.net/fileadmin/uploads/produkt_pdf/KIF-0005C_Produktflyer_pREset_01.pdf

The pRESET stent retriever is a modern, self-expanding nitinol device designed for mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). This device is part of a growing arsenal of endovascular tools aimed at improving reperfusion outcomes and minimizing neurological damage in stroke patients.

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#### Key Features 1. Self-Expanding Nitinol Design:

  1. Made of nitinol, a material known for its flexibility and memory shape, which aids in navigating tortuous cerebral vessels.
  2. Self-expansion ensures optimal vessel wall apposition and clot engagement.

2. Target Use:

  1. Indicated for cases of AIS caused by LVO in the anterior and posterior circulation.
  2. Designed for deployment through standard microcatheters, compatible with existing endovascular systems.

3. Recanalization Efficiency:

  1. Demonstrates high success rates in recanalizing occluded vessels, both in first-pass and subsequent attempts.
  2. Effective in combination with adjunctive therapies like aspiration.

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#### Clinical Performance A systematic review and meta-analysis (Habibi et al., 2024) evaluated the safety and efficacy of the pRESET device: – Efficacy:

  1. First-pass success: 60% (95% CI: 52%–67%)
  2. Final recanalization success: 90% (95% CI: 83%–95%)
  3. Functional independence (mRS 0-2 at 90 days): 43% (95% CI: 34%–52%)

– Safety:

  1. Overall hemorrhagic complications: 22% (95% CI: 12%–36%)
  2. Parenchymal hemorrhage: 7% (95% CI: 4%–13%)
  3. Subarachnoid hemorrhage: 10% (95% CI: 5%–17%)
  4. Mortality: 18% (95% CI: 12%–25%)

These results suggest that the pRESET device is effective in restoring blood flow and achieving favorable functional outcomes, with complication rates comparable to other stent retrievers.

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#### Advantages 1. High Recanalization Rates:

  1. Achieves similar or better rates compared to other market leaders like Solitaire or Trevo.

2. Versatility:

  1. Effective across a wide range of occlusion sites and clot characteristics.

3. Ease of Use:

  1. Simplified design enhances maneuverability, reducing procedural complexity.

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#### Challenges and Considerations 1. Lack of Head-to-Head Comparisons:

  1. Most available data are observational, with few randomized controlled trials directly comparing pRESET to other stent retrievers.

2. Potential for Complications:

  1. Although within acceptable ranges, hemorrhagic complications remain a concern, underscoring the need for careful patient selection.

3. Limited Adoption:

  1. Despite promising results, broader clinical adoption may depend on further validation in diverse populations and healthcare systems.

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#### Future Directions 1. Comparative Trials:

  1. Randomized controlled trials comparing pRESET with established devices like Solitaire or Trevo could solidify its place in the therapeutic landscape.

2. Real-World Data:

  1. Prospective registry data could provide insights into its performance across different patient demographics and clinical settings.

3. Device Innovation:

  1. Advances in stent retriever technology, such as designs that reduce clot fragmentation or improve safety in fragile vessels, could further enhance outcomes.

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#### Conclusion The pRESET stent retriever is a promising tool for mechanical thrombectomy in LVO-related strokes, with high efficacy and an acceptable safety profile. While its recanalization and functional outcomes are impressive, additional comparative studies are needed to define its role relative to other devices. As evidence accumulates, pRESET has the potential to become a mainstay in endovascular stroke therapy.

Systematic Review and Meta-Analysis

A systematic review and meta-analysis study conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The electronic databases of PubMed, Embase, WoS, and Scopus were systematically reviewed from inception to 8 July 2024.

A total of eight studies involving 1163 patients were included. The pooled mortality rate was 18% with a 95% CI of [12%, 25%]. The rates of any hemorrhagic complication, parenchymal hemorrhage, and subarachnoid hemorrhage were 22% with a 95% CI of [12%, 36%], 7% with a 95% CI of [4%, 13%], and 10% with a 95% CI of [5%, 17%], respectively. The rate of favorable functional outcome (modified Rankin Scale 0-2) at 90 days was 43% with a 95% CI of [34%, 52%]. Successful recanalization rates were 60% with a 95% CI of [52%, 67%] after the first pass and 90% with a 95% CI of [83%, 95%] after the final pass. Rescue devices were used in 13% with a 95% CI of [7%, 24%] of cases.

The pRESET stent retriever demonstrates high recanalization rates and reasonable safety outcomes in patients undergoing mechanical thrombectomy for acute ischemic stroke due to large vessel occlusion. Further randomized trials directly comparing pRESET to other stent retrievers are warranted 1).

In a multicenter, prospective, randomized, controlled, open-label, adaptive, noninferiority trial with blinded primary end point evaluation. Between October 2019 and February 2022, multicenter participation occurred across 19 research hospitals and/or universities in the US and 5 in Germany. Patients with LVO stroke were enrolled and included up to 8 hours after symptom onset.

Interventions: Patients underwent 1:1 randomization to thrombectomy with the pRESET or Solitaire stent retriever.

Main outcomes and measures: The primary outcome was the difference in the rate of 90-day functional independence across the 2 devices, using a -12.5% noninferiority margin for the lower bound of the 1-sided 95% CI of the difference between pRESET and Solitaire retrievers.

Results: Of 340 randomized patients, 170 (50.0%) were female, and the median (IQR) age was 73.0 (64.0-82.0) years. The study procedure was completed in 322 of the 340 randomized patients. The primary end point of 90-day functional independence was achieved by 95 patients (54.9%; 95% CI, 48.7-61.1) in the pRESET group and in 96 (57.5%; 95% CI, 51.2-63.8) in the Solitaire group (absolute difference, -2.57%; 95% CI, -11.42 to 6.28). As the lower bound of the 95% CI was greater than -12.5%, the pRESET retriever was deemed noninferior to the Solitaire retriever. The noninferiority of pRESET over Solitaire was also observed in the secondary clinical end point (90-day shift in modified Rankin Scale score) and in both angiographic end points (Expanded Treatment in Cerebral Infarction [eTICI] score of 2b50 or greater within 3 passes: 146 of 173 [84.4%] vs 149 of 167 [89.2%]; absolute difference, -4.83%; 95% CI, -10.84 to 1.19; eTICI of 2c or greater following the first pass: 76 of 173 [43.7%] vs 74 of 167 [44.3%]; absolute difference, -0.63%; 95% CI, -9.48 to 8.21). Symptomatic intracranial hemorrhage occurred in 0 patients in the pRESET group and 2 (1.2%) in the Solitaire group. Mortality occurred in 25 (14.5%) in the pRESET group and in 24 (14.4%) in the Solitaire group at 90 days. Findings of the per-protocol and as-treated analyses were in concordance with findings of the intention-to-treat analysis.

In this study, among patients with Large Vessel Occlusion (LVO) stroke, thrombectomy with the pRESET stent retriever was noninferior to thrombectomy with the Solitaire stent retriever. Findings suggest that pRESET offers a safe and effective option for flow restoration and disability reduction in patients with LVO stroke 2).

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Habibi MA, Ahmadvand MH, Delbari P, Sabet S, Zare AH, Mirjani MS, Boskabadi AR, Kolur ZA, Bozorgi M. The safety and efficacy of pRESET stent retriever for treatment of thrombo-embolic stroke; a systematic review and meta-analysis. Neuroradiol J. 2024 Nov 27:19714009241303083. doi: 10.1177/19714009241303083. Epub ahead of print. PMID: 39604086.
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Nogueira RG, Lobsien D, Klisch J, Pielenz D, Lobsien E, Sauvageau E, Aghaebrahim N, Möhlenbruch M, Vollherbst D, Ulfert C, Bozorgchami H, Clark W, Priest R, Samaniego EA, Ortega-Gutierrez S, Ghannam M, Lopes D, Billingsley J, Keigher K, Haussen DC, Al-Bayati AR, Siddiqui A, Levy E, Chen M, Munich S, Schramm P, Boppel T, Narayanan S, Gross BA, Roth C, Boeckh-Behrens T, Hassan A, Fifi J, Budzik RF, Tarpley J, Starke RM, Raz E, Brogan G, Liebeskind DS, Hanel RA. Thrombectomy With the pRESET vs Solitaire Stent Retrievers as First-Line Large Vessel Occlusion Stroke Treatment: A Randomized Clinical Trial. JAMA Neurol. 2024 Jan 2. doi: 10.1001/jamaneurol.2023.5010. Epub ahead of print. PMID: 38165690.

Associations of Microvascular Risk Factors with Sporadic Vestibular Schwannoma Outcomes Following Stereotactic Radiosurgery

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The article in *Otolaryngology–Head and Neck Surgery* provides a valuable investigation into how microvascular risk factors might influence outcomes following vestibular schwannoma radiosurgery. By assessing a large cohort of 749 patients treated between 2000 and 2022, the study explores the connections between microvascular risk factors—like hypertension, smoking, obesity, and coronary bypass history—and the efficacy and side effects of SRS 1)

Strengths

1. Large Sample Size and Cohort Design: The authors reviewed a substantial cohort of 749 patients across two decades. This sample size enhances the reliability and generalizability of findings, especially when considering the rare nature of VS.

2. Specific Risk Factors Analysis: The study dives into specific microvascular risk factors, evaluating how each may impact tumor control and adverse outcomes such as facial nerve paresis and hearing loss. This approach allows for a nuanced understanding of the multifactorial risks associated with SRS in VS treatment.

3. Clinical Relevance for Patient Counseling: The findings offer practical implications for clinical counseling. For example, identifying smoking as a risk factor for accelerated hearing loss and hypertension as a predictor for facial nerve weakness can help clinicians guide patients more effectively regarding the potential risks of SRS based on individual health backgrounds.

4. Statistical Approach: The use of Cox proportional hazards regression to assess associations and the adjustment for variables like age and ipsilateral hearing status in hearing loss analysis provide a robust statistical foundation, increasing the validity of the results.

Limitations

1. Lack of Mechanistic Insight: While the study identifies correlations between microvascular risk factors and SRS outcomes, it does not provide insights into the biological mechanisms. The authors hypothesize that microvascular hyalinization and ischemia could play a role in VS tumor control, yet no direct evidence is presented.

2. Limited Data on Tumor Control: Despite a detailed investigation of complications, the study lacks significant findings regarding tumor control in relation to microvascular risk factors. This could be due to limited follow-up on tumor growth or insufficient sensitivity of the study to detect such associations, limiting the applicability of the findings to tumor management.

3. Potential Confounding Factors: Although the study adjusts for age and ipsilateral hearing status, other potential confounding factors such as overall health status, treatment modalities prior to SRS, and specific lifestyle factors were not discussed in detail, which might influence outcomes like hearing loss or facial nerve complications.

4. Limited Generalizability Beyond the Study Setting: Conducted within a single tertiary academic center, results might not fully represent diverse patient populations, especially those managed in non-academic or smaller medical centers where treatment protocols may differ.

Conclusion

This study makes a notable contribution to understanding how microvascular risk factors may affect specific outcomes following SRS for sporadic VS. The association of hypertension and coronary artery bypass surgery history with facial nerve paresis, as well as smoking history with accelerated hearing loss, provides valuable insights for clinical decision-making and patient counseling. However, limitations in mechanistic insight and generalizability, as well as the lack of significant findings on tumor control, suggest the need for further research. Future studies could benefit from exploring the biological mechanisms at play and expanding data collection across multiple centers for broader applicability.

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Dornhoffer JR, Babajanian EE, Khandalavala KR, Marinelli JP, Daher GS, Lohse CM, Link MJ, Carlson ML. Associations of Microvascular Risk Factors with Sporadic Vestibular Schwannoma Outcomes Following Stereotactic Radiosurgery. Otolaryngol Head Neck Surg. 2024 Nov 7. doi: 10.1002/ohn.1038. Epub ahead of print. PMID: 39506614.

Effects of paroxetine, a P2X4 inhibitor, on cerebral aneurysm growth and recanalization after coil embolization: the NHO Drug for Aneurysm Study

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A study, published in the Journal of Neurosurgery, investigates the effect of paroxetine, a P2X4 inhibitor, on the growth and recurrence (recanalization) of cerebral aneurysms following coil embolization. Despite being primarily used as an antidepressant, paroxetine’s inhibition of the P2X4 purinoceptor appears to influence vascular responses, which the authors propose could be protective against aneurysm progression and recurrence 1)

Study Objectives and Rationale The authors address a critical gap in the management of cerebral aneurysms, which, despite increased coil embolization procedures, face a high risk of recurrence compared to surgical clipping. Given that hemodynamic stress on the aneurysm wall is a known factor in aneurysm progression, and P2X4 purinoceptor inhibition appears to counteract these stress responses, this study is scientifically grounded in exploring the secondary effects of paroxetine. Prior animal studies that supported reduced aneurysm induction and growth through P2X4 inhibition provide a basis for this human observational study.

Methodology The study utilized Japan’s J-ASPECT Stroke Registry to analyze data retrospectively, identifying patients who were prescribed paroxetine and who had either unruptured cerebral aneurysms or had undergone coiling. A rigorous approach was taken, comparing these patients against matched controls over a decade, with multivariate and propensity score-matched analyses strengthening the study’s internal validity by reducing confounding variables.

Key Metrics: Growth incidence and growth rate for unruptured aneurysms. Odds ratio (OR) for aneurysm recanalization within one year of coiling. Results The results suggest that paroxetine was significantly associated with reduced aneurysm growth and recanalization:

Aneurysm growth incidence and rate showed reductions, with incidence rate ratios (IRR) substantially favoring paroxetine use (IRR for growth incidence: 0.24; for growth rate: 0.57). Paroxetine lowered the odds of recanalization one year post-coiling (OR: 0.21). Propensity score matching yielded even more striking results, supporting the robustness of the findings (growth incidence IRR: 0.02, and recanalization OR: 0.18). Strengths Large Dataset: Using the extensive J-ASPECT registry allows for a broad patient sample and enhances the study’s statistical power. Robust Statistical Controls: Multivariate analysis and propensity score matching help address potential biases, lending credibility to the associations found. Clinical Applicability: The study opens up a pathway for potential pharmaceutical intervention, especially given paroxetine’s established use and safety profile. Limitations Retrospective Design: Observational studies inherently have limitations in establishing causation, which might limit the clinical applicability of findings without further prospective trials. Selection Bias and Confounders: Despite statistical adjustments, unmeasured confounders related to patient health status, comorbidities, or the precise dosage and adherence to paroxetine may still influence results. Generalizability: This study is based on a Japanese cohort, and cultural or healthcare system differences might impact the generalizability to other populations. Clinical Implications If confirmed through prospective studies, the use of paroxetine or other P2X4 inhibitors could offer a novel approach to managing aneurysm growth and preventing recurrence after coiling, potentially improving patient outcomes. However, the potential side effects and the drug’s primary use as an antidepressant might limit its broad applicability without further targeted research into P2X4 inhibition.

Conclusion This study contributes promising preliminary evidence that paroxetine, as a P2X4 inhibitor, could have a significant role in aneurysm management. Nevertheless, more robust, prospective clinical trials are necessary to confirm these findings and fully establish the drug’s efficacy and safety for this indication.

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Fukuda S, Niwa Y, Ren N, Yonemoto N, Kasahara M, Yasaka M, Ezura M, Asai T, Miyazono M, Korai M, Tsutsumi K, Shigeta K, Oi Y, Nishimura A, Fukuda H, Goto M, Yoshida T, Fukuda M, Yasoda A, Iihara K. Effects of paroxetine, a P2X4 inhibitor, on cerebral aneurysm growth and recanalization after coil embolization: the NHO Drug for Aneurysm Study. J Neurosurg. 2024 Oct 25:1-8. doi: 10.3171/2024.6.JNS24714. Epub ahead of print. PMID: 39454214.

Procedural outcomes of the transradial versus transfemoral approach for diagnostic cerebral angiograms according to BMI: a propensity score-matched analysis

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The study by Roy et al. on the procedural outcomes of transradial access (TR) versus transfemoral (TF) access for diagnostic cerebral angiography by BMI provides initial data suggesting that TR access may offer advantages in reduced procedure time and length of stay (LOS), particularly for obese patients 1)

However, several critical issues in design, analysis, and generalizability undermine the robustness and clinical relevance of its findings.

### 1. Single-Center, Retrospective Design

  1. The retrospective, single-center nature of the study limits generalizability, as it relies on existing records from a single institution. Procedural approaches, patient demographics, and access site expertise vary between institutions, potentially impacting the reported outcomes. A multi-center or randomized design could have yielded broader insights.

### 2. Questionable Clinical Impact of Results

  1. While TR access is associated with reduced procedure time by 10-13 minutes across BMI groups, this difference is relatively small in the context of diagnostic cerebral angiography and may not be meaningful in clinical settings. Additionally, the slightly reduced LOS for obese patients (1.33 days) lacks sufficient exploration into the underlying causes, leaving it unclear if access site alone significantly affects recovery times.

### 3. Propensity Score Matching Limitations

  1. Although propensity score matching was used to reduce selection bias, it cannot control for unmeasured confounding factors inherent in retrospective designs. Important factors, such as operator experience, anatomical variations, or other patient comorbidities, may still bias the results. A randomized trial or more sophisticated statistical methods could have better addressed these complexities.

### 4. BMI as a Central Focus

  1. The emphasis on BMI as a primary stratification factor may be misplaced, as BMI alone is seldom the determining factor in choosing access sites for cerebral angiography. Other variables, such as comorbidities or vascular conditions, might have provided a more clinically relevant framework, and the choice of BMI subgroups without additional analysis on access site suitability limits the depth of the study’s insights.

### 5. Limited Outcome Measures and Follow-Up Data

  1. The study reports immediate procedural outcomes but does not assess long-term safety or vascular health implications of TR versus TF access. Long-term follow-up would be essential to capture delayed complications or recurrent access challenges that might arise, especially given the propensity for repeated angiography in certain patients.

### 6. Statistical and Analytical Shortcomings

  1. The study’s use of basic statistical tools like linear regression and chi-square tests may not capture complex interactions between BMI, access site, and procedural outcomes. More sophisticated modeling could have yielded deeper insights, particularly in understanding how various confounding factors contribute to access site efficacy and safety across different patient populations.

### 7. Limited Contribution to Existing Literature

  1. While the study adds data on TR access safety across BMI groups, its findings do not substantially advance clinical practice due to the limited procedural time savings and lack of evidence that BMI should be a deciding factor in access site selection. The study reiterates existing knowledge on TR access benefits without significantly expanding on their implications in a specialized field like cerebral angiography.

### Conclusion In summary, while this study provides a preliminary comparison of TR versus TF access in diagnostic cerebral angiography, its methodological limitations, reliance on BMI as the main stratification factor, and narrow focus on short-term procedural outcomes reduce its impact. Future studies would benefit from multi-center, prospective designs with randomized control, long-term follow-up, and consideration of broader patient-specific factors to provide a more comprehensive understanding of the ideal access strategies for cerebral angiography across diverse populations.

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Roy JM, Ahmed MT, El Naamani K, Saadat N, Gaskins W, Nguyen A, Gigo M, Fuleihan AA, Amaravadi C, Momin A, Musmar B, Tjoumakaris SI, Gooch MR, Rosenwasser RH, Jabbour PM. Procedural outcomes of the transradial versus transfemoral approach for diagnostic cerebral angiograms according to BMI: a propensity score-matched analysis. J Neurosurg. 2024 Nov 8:1-7. doi: 10.3171/2024.7.JNS241183. Epub ahead of print. PMID: 39504551.

The Effect and Clinical Implications of IL-1β on the Development of Aneurysmal Subarachnoid Hemorrhage

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This study, conducted by Li et al., investigates the impact of interleukin-1 beta (IL-1β) on the progression of aneurysmal subarachnoid hemorrhage (aSAH), a condition associated with high morbidity and mortality. By examining IL-1β expression levels in patients with aSAH and comparing them to a control group of healthy individuals, the authors seek to establish a correlation between IL-1β levels and the development of this type of hemorrhage.

Study Design and Methodology

1. Retrospective Nature: The retrospective design of this study introduces certain limitations, particularly the potential for selection bias and reliance on pre-existing data. Prospective studies may offer a more rigorous approach to understanding the causal relationship between IL-1β and aSAH.

2. Sample Size and Group Composition: The study included 80 participants, divided into a control group of healthy participants and an experimental group of aSAH patients. While the total sample size is relatively small, the study does not mention whether participants were matched on variables such as comorbidities or lifestyle factors, which could influence inflammatory marker levels.

3. Data Collection and Measurement Techniques:

  1. IL-1β Measurement: Blood samples were analyzed using ELISA for IL-1β levels, while western blotting was employed for IL-1β protein analysis. These are reliable methods; however, the timing of sample collection relative to the onset of aSAH was not specified. Since IL-1β levels can fluctuate in response to acute conditions, timing may significantly impact findings.
  2. Imaging Techniques: Digital subtraction angiography (DSA) and computed tomography angiography (CTA) were used to diagnose aSAH. While both are standard imaging techniques, the study does not specify how imaging results were interpreted in relation to IL-1β levels.

Results and Statistical Analysis

1. Baseline Comparability: The authors report no significant differences in gender, age, and medical history between groups, which strengthens the study’s internal validity. However, additional variables that could affect inflammatory response, such as smoking status, alcohol use, or recent infections, were not addressed.

2. Significance of Findings:

  1. The study shows significantly elevated IL-1β levels in the aSAH group (p < 0.05), indicating a potential association between IL-1β upregulation and aSAH. While statistically significant, the study does not discuss the clinical relevance of the absolute increase in IL-1β levels, nor does it provide insights into the threshold IL-1β level that may predict worse outcomes.

3. Potential Mechanistic Insights: The authors suggest that IL-1β may play a role in promoting aSAH development. This aligns with the known pro-inflammatory effects of IL-1β, yet the study does not explore the specific mechanisms by which IL-1β could influence aneurysm formation, rupture, or progression. Experimental studies on IL-1β’s role in vascular inflammation would be valuable for elucidating this pathway further.

Interpretation and Clinical Implications

1. Prognostic Value of IL-1β: The authors propose that IL-1β could serve as a prognostic marker for aSAH. However, the study does not examine patient outcomes following elevated IL-1β levels, nor does it clarify how IL-1β measurement could be practically applied in clinical settings for prognosis or monitoring. Future studies should assess whether interventions that reduce IL-1β levels impact aSAH outcomes.

2. Implications for Treatment: The study briefly suggests IL-1β as a therapeutic target. However, this claim is somewhat premature without experimental evidence of causation. Anti-inflammatory therapies targeting IL-1β, such as IL-1 receptor antagonists, have shown promise in other inflammatory conditions but require rigorous testing within the context of aSAH.

Limitations and Areas for Future Research

1. Study Design: A prospective study with larger sample sizes would provide a stronger basis for establishing a causal relationship between IL-1β and aSAH. Additionally, a control group with a history of other cerebrovascular events (e.g., ischemic stroke) could help isolate IL-1β’s role in aSAH specifically.

2. Longitudinal IL-1β Measurements: Tracking IL-1β levels over time in patients at risk for or recovering from aSAH would offer insights into whether elevated IL-1β is a result of aSAH or contributes to its development. Such data could also clarify if IL-1β levels correlate with outcomes such as rebleeding or recovery.

3. Mechanistic Exploration: Further research into the exact role of IL-1β in cerebrovascular pathology is needed. Animal models or in vitro studies could help uncover how IL-1β mediates vascular inflammation and aneurysm instability.

Conclusion

Li et al.’s study provides valuable preliminary evidence that IL-1β levels are elevated in patients with aSAH, suggesting a possible link between this pro-inflammatory cytokine and the condition. However, the retrospective design, modest sample size, and lack of mechanistic exploration limit the study’s impact. Future research should aim to establish causation, explore potential therapeutic applications, and clarify the clinical utility of IL-1β as a aneurysmal subarachnoid hemorrhage biomarkers

Anti-Inflammatory Thrombolytic JX10 (TMS-007) in Late Presentation of Acute Ischemic Stroke

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The investigational drug TMS-007 (now branded JX10), developed as a novel thrombolytic agent for acute ischemic stroke, has been heralded for its potential to expand the therapeutic window for treatment. However, despite the initial enthusiasm surrounding its clinical development, there are numerous critical flaws in both the study design and the interpretation of the findings that undermine its promise as a groundbreaking stroke therapy.

First, the methodology of the Phase 2a study raises substantial concerns. While the randomized, double-blind, placebo-controlled design is theoretically robust, the small sample size (90 patients) severely limits the generalizability of the findings. With such a small cohort, the study lacks statistical power to make definitive conclusions about the true efficacy and safety of JX10. Moreover, the stratification of patients by dose (1, 3, or 6 mg/kg) and gender (with a skewed distribution of females across doses) introduces an additional layer of complexity and potential bias that goes unaddressed in the analysis. This lack of statistical rigor leaves the results open to question.

The primary endpoint, the incidence of symptomatic intracranial hemorrhage (sICH), demonstrated no significant difference between JX10 and placebo (0% vs. 2.6%, respectively). The authors highlight this as a favorable outcome, but the fact that such a small incidence of sICH was observed in both groups calls into question the clinical relevance of this outcome. With so few patients experiencing a clinically meaningful event, the observed lack of difference between groups is not as compelling as it may initially appear. This failure to show a significant reduction in sICH, an important safety endpoint, undermines the argument that JX10 is substantially safer than existing thrombolytics.

Furthermore, while vessel patency at 24 hours was reportedly improved in patients receiving JX10, the difference between the groups (58.3% vs. 26.7%) was modest at best. The odds ratio of 4.23, while statistically significant, is misleading without further context. The actual clinical significance of such a finding remains uncertain, as vessel reopening does not necessarily equate to improved functional outcomes. The secondary endpoint of modified Rankin Scale scores also demonstrates a modest benefit for JX10, with 40.4% of patients achieving a score of 0-1 versus 18.4% for placebo. While statistically significant, the clinical impact of this difference is questionable given the early nature of stroke treatment, the small sample size, and the inherent variability in patient recovery.

One of the more concerning aspects of the study is the lack of long-term follow-up. Stroke patients who receive thrombolytic treatment face a range of risks, and it is essential to understand the longer-term outcomes of therapies like JX10, including mortality, disability, and quality of life. The absence of these critical data points further weakens the study’s conclusions, as it provides a limited snapshot of the therapy’s true impact.

Finally, the novel mechanism of action for JX10, which involves modulating plasminogen conformation and inhibiting soluble epoxide hydrolase, remains speculative. The proposed benefits of enhanced endogenous fibrinolysis and anti-inflammatory properties are interesting, but there is insufficient evidence to support their clinical relevance in the context of acute ischemic stroke. The mechanism may sound promising in theory, but without more robust data from larger studies, these claims remain unsubstantiated.

In conclusion, while JX10 has shown some potential in expanding the therapeutic window for acute ischemic stroke treatment, the current clinical evidence does not justify the enthusiasm surrounding its future. The small sample size, the lack of meaningful safety and efficacy differences, and the absence of long-term data all point to the need for much more rigorous studies before this drug can be considered a viable treatment option. As it stands, JX10 remains an unproven, underdeveloped therapy with far too many unanswered questions to be hailed as the next generation of stroke treatment.

Endovascular Treatment of Patients With Acute Ischemic Stroke With Tandem Lesions Presenting With Low Alberta Stroke Program Early Computed Tomography Score

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The study “Endovascular Treatment of Patients With Acute Ischemic Stroke With Tandem Lesions Presenting With Low Alberta Stroke Program Early Computed Tomography Score” published in *J Am Heart Assoc* presents a retrospective analysis of endovascular thrombectomy (ET) in patients with acute ischemic stroke and tandem lesions. Despite its timely and relevant focus on a niche aspect of stroke treatment, the article suffers from several critical shortcomings that weaken its impact and utility in advancing clinical practice.

First, the methodology lacks rigor in several areas. While the authors employed inverse probability of treatment weighting (IPTW) to balance groups with different ASPECTS scores, this statistical approach is fraught with challenges. IPTW can only partially adjust for confounding variables and may still introduce biases that distort the relationship between treatment and outcomes. Additionally, the reliance on retrospective data from 16 centers raises concerns about the generalizability of the findings. The data, while extensive, are retrospective and not prospective, which significantly limits the strength of the conclusions.

Second, the outcomes presented, including symptomatic intracranial hemorrhage (sICH) and functional independence, are not analyzed in depth concerning potential confounders such as the timing of thrombectomy, variation in procedural expertise, and differences in patient management. Although the study finds that patients with low ASPECTS (0-5) have lower odds of functional recovery and higher odds of sICH, this oversimplification disregards the nuances that may impact outcomes in real-world clinical settings. The reported odds ratios (ORs) for functional recovery and sICH (0.48 and 3.78, respectively) do little to guide clinical decision-making, as they fail to explore the complexity of individual patient characteristics and treatment variables.

The suggestion that 30% of patients with low ASPECTS may still achieve functional independence should be viewed with caution. This result, while intriguing, is buried in a sea of statistical averages that gloss over the heterogeneity of stroke severity and treatment response. What does this functional independence mean in terms of quality of life for patients with low ASPECTS, and how does it compare to other treatment modalities or supportive care? These critical questions are left unaddressed.

Moreover, the paper glosses over the limitations of the study design, particularly the lack of standardization across the centers involved. Given the variability in treatment protocols and the experience of clinicians at each site, it’s difficult to draw definitive conclusions about the efficacy of ET in this cohort. The authors also fail to explore alternative explanations for the increased risk of sICH observed in the low ASPECTS group, such as the potential role of comorbidities or pre-existing vascular conditions.

The study’s conclusions also need more nuance. While it correctly notes that the low ASPECTS cohort faces worse outcomes, the implication that ET should be withheld from these patients due to “reduced odds of functional recovery” is problematic. Clinical decision-making in acute stroke care must consider the individual patient’s potential for recovery, comorbidities, and the risks associated with other interventions. A blanket recommendation against ET for low ASPECTS patients would be premature and overly simplistic, particularly in light of the 30% functional independence rate reported.

In summary, while the study addresses an important clinical question, its methodological flaws, lack of depth in analysis, and failure to consider confounding factors significantly diminish its value. The paper offers limited insight for clinicians faced with treating patients with low ASPECTS and tandem lesions, and its conclusions require careful interpretation before being applied in practice.