Ischemia reperfusion injury (I/RI) is a common complication of cardiovascular diseases. Resolution of detrimental I/RI-generated prothrombotic and proinflammatory responses is essential to restore ...homeostasis. Platelets play a crucial part in the integration of thrombosis and inflammation. Their role as participants in the resolution of thromboinflammation is underappreciated; therefore we used pharmacological and genetic approaches, coupled with murine and clinical samples, to uncover key concepts underlying this role.
Middle cerebral artery occlusion with reperfusion was performed in wild-type or annexin A1 (AnxA1) knockout (AnxA1
) mice. Fluorescence intravital microscopy was used to visualize cellular trafficking and to monitor light/dye-induced thrombosis. The mice were treated with vehicle, AnxA1 (3.3 mg/kg), WRW4 (1.8 mg/kg), or all 3, and the effect of AnxA1 was determined in vivo and in vitro.
Intravital microscopy revealed heightened platelet adherence and aggregate formation post I/RI, which were further exacerbated in AnxA1
mice. AnxA1 administration regulated platelet function directly (eg, via reducing thromboxane B
and modulating phosphatidylserine expression) to promote cerebral protection post-I/RI and act as an effective preventative strategy for stroke by reducing platelet activation, aggregate formation, and cerebral thrombosis, a prerequisite for ischemic stroke. To translate these findings into a clinical setting, we show that AnxA1 plasma levels are reduced in human and murine stroke and that AnxA1 is able to act on human platelets, suppressing classic thrombin-induced inside-out signaling events (eg, Akt activation, intracellular calcium release, and Ras-associated protein 1 Rap1 expression) to decrease α
β
activation without altering its surface expression. AnxA1 also selectively modifies cell surface determinants (eg, phosphatidylserine) to promote platelet phagocytosis by neutrophils, thereby driving active resolution. (n=5-13 mice/group or 7-10 humans/group.) Conclusions: AnxA1 affords protection by altering the platelet phenotype in cerebral I/RI from propathogenic to regulatory and reducing the propensity for platelets to aggregate and cause thrombosis by affecting integrin (α
β
) activation, a previously unknown phenomenon. Thus, our data reveal a novel multifaceted role for AnxA1 to act both as a therapeutic and a prophylactic drug via its ability to promote endogenous proresolving, antithromboinflammatory circuits in cerebral I/RI. Collectively, these results further advance our knowledge and understanding in the field of platelet and resolution biology.
Abstract Background Endovascular treatment in the present form, has almost taken over the management of posterior circulation aneurysms. However, superior cerebellar artery (SCA) aneurysms are among ...the few that are said to be “surgeon friendly” with comparable outcome with microsurgery. This study includes a comparative analysis of the SCA aneurysms treated with microsurgery and endovascular techniques at our institute along with a pooled analysis of available literature on overall outcomes in these two forms of treatment Methods This retrospective study included our patients with SCA aneurysms from 2000 to 2015. Clinical outcomes were assessed by the Glasgow outcome scale (GOS) at discharge and Modified Rankin scale (mRS) at follow-up. A literature review was performed for clinical series on SCA aneurysms from 1991 to 2015 describing more than 10 patients for pooled analysis. Results Among the twenty patients (microsurgery=12, endovascular=8), 66% from microsurgery and 75% from endovascular arm had good outcomes (GOS score >3 and mRS score <3) (p=0.54). Microsurgery had 88.8% complete occlusion rate as compared to 75% in endovascular treatment (p=0.45). Pooled analysis of 12 studies showed endovascular coiling is significantly associated with good clinical outcome (88.1% vs 76.9%; p=0.003). Microsurgery provides better radiological outcome in terms of complete occlusion rate (90.1% vs 67.4%; p=0.0001) and lower recurrence rate (0% vs 11.8%; p=0.005). Conclusion Individual series on SCA aneurysms have not proven any outcome benefit of either treatment modality over the other. However, pooled analysis suggests that microsurgery provides complete and sustainable aneurysm occlusion, though with an inferior clinical outcome.
Aneurysmal persistence after flow diversion (FD) occurs in 5% to 25% of aneurysms, which may necessitate retreatment. There are limited data on safety/efficacy of repeat FD-a frequently utilized ...strategy in such cases.
A series of consecutive patients undergoing FD retreatment from 15 centers were reviewed (2011-2019), with inclusion criteria of repeat FD for the same aneurysm at least 6 months after initial treatment, with minimum of 6 months post-retreatment imaging. The primary outcome was aneurysmal occlusion, and secondary outcome was safety. A multivariable logistic regression model was constructed to identify predictors of incomplete occlusion (90%-99% and <90% occlusion) versus complete occlusion (100%) after retreatment.
Ninety-five patients (median age, 57 years; 81% women) harboring 95 aneurysms underwent 198 treatment procedures. Majority of aneurysms were unruptured (87.4%), saccular (74.7%), and located in the internal carotid artery (79%; median size, 9 mm). Median elapsed time between the first and second treatment was 12.2 months. Last available follow-up was at median 12.8 months after retreatment, and median 30.6 months after the initial treatment, showing complete occlusion in 46.2% and near-complete occlusion (90%-99%) in 20.4% of aneurysms. There was no difference in ischemic complications following initial treatment and retreatment (4.2% versus 4.2%;
>0.99). On multivariable regression, fusiform morphology had higher nonocclusion odds after retreatment (odds ratio OR, 7.2 95% CI, 1.97-20.8). Family history of aneurysms was associated with lower odds of nonocclusion (OR, 0.18 95% CI, 0.04-0.78). Likewise, positive smoking history was associated with lower odds of nonocclusion (OR, 0.29 95% CI, 0.1-0.86). History of hypertension trended toward incomplete occlusion (OR, 3.10 95% CI, 0.98-6.3), similar to incorporated branch into aneurysms (OR, 2.78 95% CI, 0.98-6.8).
Repeat FD for persistent aneurysms carries a reasonable success/safety profile. Satisfactory occlusion (100% and 90%-99% occlusion) was encountered in two-thirds of patients, with similar complications between the initial and subsequent retreatments. Fusiform morphology was the strongest predictor of retreatment failure.
The effectiveness of mechanical thrombectomy (MT) was demonstrated in five landmark trials published in2015.Mechanical thrombectomy is now standard of care for acute ischemic stroke and has been ...growing in popularity after publication of landmark trials.
To analyze outcomes and trends of the use of MT and intravenous thrombolysis (IVT) in patients with acute ischemic stroke in US hospitals before and after publication of these trials.
Patients discharged with a diagnosis of ischemic stroke between 2012 to 2017 were diagnosed using ICD codes from the National Inpatient Sample. Thereafter, patients given acute stroke treatment were identified using the corresponding procedure codes for IVT and MT. The primary clinical outcomes of in-hospital mortality and disability were then compared between two time periods: 2012-2014 (pre-landmark trials) and 2015-2017 (post-landmark trials). Binary logistic regression and Χ
tests were used for statistical analysis.
A total of 57 675 patients (median age 68.9 years (range 18-90), 50.1% female) were identified with acute procedures. Of these patients, 57.6% were from the post-landmark trials time period. Despite an increased number of cases, the rate of IVT decreased from 84.3% to 75.9% and the rate of IVT+MT decreased from 7.1% to 6.3%. After publication of the pivotal trials in 2015, the rates of MT increased from 8.7% to 17.8%. Significant reductions of in-hospital mortality (7.1% vs 8.7%, p<0.001) and disability (64% vs 66.2%, p<0.001) were noted.
The analysis showed a significant increase in the proportion of patients receiving MT after 2015. This has translated into reduction of in-hospital mortality and improvement in disability.
Background Advancements in flow diversion technology have revolutionized the treatment of intracranial aneurysms. The pipeline embolization device (PED) and the flow redirection endoluminal device ...(FRED) have emerged as prominent tools in this field. This study aims to compare the safety and efficacy profiles of PED and FRED in the treatment of intracranial aneurysms. Methods Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive literature search was conducted across PubMed, Web of Science, and Scopus databases. Studies comparing PED and FRED were included and data extraction focused on study characteristics, patient demographics, and clinical and radiological outcomes. Primary outcomes were favorable outcomes, described as modified Rankin scale (mRS) 0–2 score, and complete/near-complete occlusion, while secondary outcomes included retreatment rate and thromboembolic and hemorrhagic complications. Results Five studies, comprising 1238 patients, were included. No significant differences were found between PED and FRED in terms of complete occlusion at 6 months and 1 year, complete/near-complete occlusion at the last follow up, retreatment rates, and thromboembolic, in-stent thrombosis and hemorrhagic complications. However, FRED was significantly associated with higher favorable outcomes compared to PED (odds ratio: 0.37; confidence interval: 0.17 to 0.81; p = 0.01). Conclusion This study showed that both PED and FRED had comparable rates of complete occlusion, retreatment and complications, and FRED also demonstrated a higher likelihood of achieving favorable outcomes. The study underscores the need for further research with larger cohorts and longer follow up to consolidate these findings.
Objective The proximal segment of the anterior cerebral artery (A1) is among the most uncommon locations for occurrence of an intracranial aneurysm. These aneurysms may be missed if small or ...misinterpreted when they are near the internal cerebral artery bifurcation or Anterior Communicating Artery region. The association with congenital vascular anomalies and multiplicity makes them unique. Methods Seventeen A1 aneurysms were diagnosed in sixteen patients between January 2000 and October 2014 in our institution. A retrospective review of the clinical, radiological, and management (microsurgical and endovascular) details of these patients was conducted. Results The incidence of A1 aneurysm was 1.71% of all patients harboring aneurysms and 1.19% of all aneurysms. Half of these patients exhibited subarachnoid hemorrhage. Fourteen aneurysms underwent microsurgical or endovascular intervention. All patients recovered well, except for one patient who died in the postoperative period. Conclusions A1 aneurysms are rare, with wide anatomic variations. In this article, we discuss those variations in detail with illustrative cases and pictures. We also discussed the microsurgical and endovascular strategies to encounter them highlighting the technical challenges.
Background
Patient's age is an important factor in determining the risk of aneurysm rupture. However, there is limited data on how aneurysm morphology differs among age groups. We studied ...morphological characteristics of brain aneurysms among age groups in a large cohort.
Methods
Aneurysms from the Stroke Thrombectomy and Aneurysm Registry (STAR) were analyzed. The following parameters were included: location, size, neck, width, height, aspect ratio, and regular versus irregular morphology. The risk of rupture presentation was estimated using logistic regression.
Results
A total of 1407 unruptured and 607 ruptured saccular aneurysms were included. The most common locations of ruptured aneurysms in patients younger than 70 years-old were the middle cerebral artery (MCA) and the anterior communicating artery (ACOM). The most common location of ruptured aneurysms in patients older than 70 years-old were the posterior communicating artery (PCOM) and ACOM. The size of unruptured aneurysms increased with age (p < .001). Conversely, the size of ruptured aneurysms was similar among age groups (p = .142). Unruptured and ruptured aneurysms became more irregular at presentation with older age (p < .001 and p .025, respectively). Irregular morphology and location were associated with rupture status across all age groups in multivariate regression.
Conclusions
Younger patients have small unruptured and ruptured aneurysms, and ruptured aneurysms are mostly located in the MCA and ACOM. Older patients have larger and more irregular unruptured aneurysms, and ruptured aneurysms are mostly located in the PCOM and ACOM. An irregular morphology increases the risk of rupture in all age groups.
The Woven EndoBridge (WEB) device has been widely used to treat intracranial wide neck bifurcation aneurysms. Initial studies have demonstrated that approximately 90% of patients have same or ...improved long-term aneurysm occlusion after the initial 6-month follow up. The aim of this study is to assess the long-term follow-up in aneurysms that have achieved complete occlusion at 6 months. We also compared the predictive value of different imaging modalities used. This is an analysis of a prospectively maintained database across 13 academic institutions. We included patients with previously untreated cerebral aneurysms embolized using the WEB device who achieved complete occlusion at first follow-up and had available long-term follow-up. A total of 95 patients with a mean age of 61.6 ± 11.9 years were studied. The mean neck diameter and height were 3.9 ± 1.3 mm and 6.0 ± 1.8 mm, respectively. The mean time to first and last follow-up was 5.4 ± 1.8 and 14.1 ± 12.9 months, respectively. Out of all the aneurysms that were completely occluded at 6 months, 84 (90.3%) showed complete occlusion at the final follow-up, and 11(11.5%) patients did not achieve complete occlusion. The positive predictive value (PPV) of complete occlusion at first follow was 88.4%. Importantly, this did not differ between digital subtraction angiography (DSA), magnetic resonance angiography (MRA), or computed tomography angiography (CTA). This study underlines the importance of repeat imaging in patients treated with the WEB device even if complete occlusion is achieved short term. Follow-up can be performed using DSA, MRA or CTA with no difference in positive predictive value.
Several studies have shown promising outcomes of the Woven EndoBridge (WEB) device for the treatment of wide-necked intracranial bifurcation aneurysms. This is a multicenter study attempts to explore ...the changes in trends and treatment outcomes over time for WEB embolization of intracranial aneurysms. The WorldWideWEB consortium is a retrospective multicenter collaboration of data from international centers spanning from January 2011 and June 2021, with no limitations on aneurysm location or rupture status. Both bifurcation and sidewall aneurysms were included. These patients were stratified based on treatment year into five treatment intervals: 2011–2015 (
N
= 66), 2016–2017 (
N
= 77), 2018 (
N
= 66), 2019 (
N
= 300), and 2020–2021 (
N
= 173). Patient characteristics and angiographic and clinical outcomes were compared between these time intervals. This study comprised 671 patients (median age 61.4 years; 71.2% female) with 682 intracranial aneurysms. Over time, we observed an increasing tendency to treat patients presenting with ruptured aneurysms and aneurysms with smaller neck, diameter, and dome widths. Furthermore, we observed a trend towards more off-label use of the WEB for sidewall aneurysms and increased adoption of transradial access for WEB deployment. Moreover, the proportion of patients with adequate WEB occlusion immediately and at last follow-up was significantly higher in more recent year cohorts, as well as lower rates of compaction and retreatment. Mortality and complications did not differ over time. This learning curve study suggests improved experience using the WEB for the treatment of intracranial aneurysms and has yielded higher rates of adequate occlusion over time.
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