Net water uptake as a predictive neuroimaging marker for acute ischemic stroke outcomes: a meta-analysis.

OBJECTIVE: To assess the role of net water uptake (NWU) in predicting outcomes in acute ischemic stroke (AIS) patients. METHODS: A systematic review and meta-analysis were performed, adhering to established guidelines. The search covered PubMed, Scopus, Web of Science, and Embase databases until July 1, 2023. Eligible studies reporting quantitative ischemic lesion NWU in admission CT scans of AIS patients, stratified based on outcomes, were included. Data analysis was performed using R software version 4.2.1. RESULTS: Incorporating 17 original studies with 2217 AIS patients, NWU was significantly higher in patients with poor outcomes compared to those with good outcomes (difference of medians: 5.06, 95% CI: 3.00-7.13, p < 0.001). Despite excluding one outlier study, considerable heterogeneity persisted among the included studies (I2 = 90.8%). The meta-regression and subgroup meta-analyses demonstrated significantly higher NWU in patients with poor functional outcome, as assessed by modified Rankin Scale (difference of medians: 3.83, 95% CI: 1.98-5.68, p < 0.001, I2 = 72.9%), malignant edema/infarct (difference of medians: 8.30, 95% CI: 4.01-12.58, p < 0.001, I2 = 95.6%), and intracranial hemorrhage (difference of medians: 5.43, 95% CI: 0.44-10.43, p = 0.03, I2 = 91.1%). CONCLUSION: NWU on admission CT scans shows promise as a predictive marker for outcomes in AIS patients. Prospective, multicenter trials with standardized, automated NWU measurement are crucial for robustly predicting diverse clinical outcomes. CLINICAL RELEVANCE STATEMENT: The potential of net water uptake as a biomarker for predicting outcomes in acute ischemic stroke patients holds significant promise. Further validation through additional research could lead to its integration into clinical practice, potentially improving the accuracy of clinical decision-making and allowing for the development of more precise patient care strategies. KEY POINTS: • Net water uptake, a CT-based biomarker, quantifies early brain edema after acute ischemic stroke. • Net water uptake is significantly higher in poor outcome acute ischemic stroke patients. • Net water uptake on CT scans holds promise in predicting diverse acute ischemic stroke outcomes.

Common Design and Data Elements Reported on Idiopathic Intracranial Hypertension Trials: A Systematic Review.

BACKGROUND: There are an increasing number of controlled clinical trials and prospective studies, ongoing and recently completed, regarding management options for idiopathic intracranial hypertension (IIH). We present a Common Design and Data Element (CDDE) analysis of controlled and prospective IIH studies with the aim of aligning essential design and recommending data elements in future trials and enhancing data synthesis potential in IIH trials. METHODS: We used PubMed and ClinicalTrials.gov to screen for ongoing and published trials assessing treatment modalities in people with IIH. After our search, we used the Nested Knowledge AutoLit platform to extract pertinent information regarding each study. We examined outputs from each study and synthesized the data elements to determine the degree of homogeneity between studies. RESULTS: The most CDDE for inclusion criteria was the modified Dandy criteria for diagnosis of IIH, used in 9/14 studies (64%). The most CDDE for outcomes was change in visual function, reported in 12/14 studies (86%). Evaluation of surgical procedures (venous sinus stenting, cerebrospinal fluid shunt placement, and others) was more common, seen in 9/14 studies (64%) as compared with interventions with medical therapy 6/14 (43%). CONCLUSIONS: Although all studies have similar focus to improve patient care, there was a high degree of inconsistency among studies regarding inclusion criteria, exclusion criteria, and outcomes measures. Furthermore, studies used different time frames to assess outcome data elements. This heterogeneity will make it difficult to achieve a consistent standard, and thus, making secondary analyses and meta-analyses less effective in the future. Consensus on design of trials is an unmet research need for IIH.

Safety and efficacy profile of off-label use of the Pipeline Embolization Device: A systematic review and meta-analysis.

OBJECTIVE: The off-label utilization of the Pipeline Embolization Device (PED) is a common practice in numerous medical centers globally. Therefore, we conducted a systematic review and meta-analysis to evaluate the overall outcomes of this off-label usage of PEDs. METHODS: PubMed, Web of Science, Ovid Medline, Ovid Embase, and Scopus were searched up to February 2023 using the Nested Knowledge platform to identify studies assessing the off-label use of PEDs. Any use of PED outside of the FDA-approved indication granted in 2018 is considered off-label use. Overall angiographic occlusion rates, ischemic and hemorrhagic complications, mortality, retreatment rates, and favorable clinic outcomes were included. Statistical analyses were performed to compare the overall outcome rates of anterior cerebral artery(ACA) vs. middle cerebral artery(MCA) and anterior vs posterior circulation subgroups. RESULTS: We included 26 studies involving a total of 1,408 patients. The overall rate of complete occlusion was 80.3 % (95 % CI= 76.0-84.1). Subgroup analysis demonstrated a statistically significant difference in the rate of complete occlusion between anterior circulation (78.9 %) and posterior circulation (69.2 %) (p value=0.02). The rate of good clinical outcomes was 92.8 % (95 % CI= 88.8-95.4). The mortality rate was 1.4 % (95 % CI= 0.5-2.7). The overall rate of ischemic complications was 9.5 % (95 % CI= 7.7-11.6), with a comparable difference between anterior circulation (7.7 %) and posterior circulation (12.8 %) (p value=0.07). There was no statistically significant difference in MCA vs ACA subgroups in all parameters. CONCLUSIONS: Off-label use of PEDs can be a safe and effective treatment option for intracranial aneurysms. However, there is a need for more prospective, high-quality, non-industry-funded registry studies and randomized trials to test the efficacy and safety of off-label usage of PEDs and to expand its indications.

Endovascular outcomes for anterior choroidal artery aneurysms: systematic review and meta-analysis.

BACKGROUND: Anterior choroidal artery (AchoA) aneurysms are relatively rare compared to other types of aneurysms. However, the occurrence of transient or permanent occlusion of the choroidal artery during endovascular or surgical treatment is an uncommon but potentially serious complication. In this study, we aim to investigate the safety and efficacy profile of endovascular treatment (EVT) for AchoA aneurysms. METHODS: The primary outcome of interest was angiographic and clinical outcomes. Secondary outcome variables transient and permanent ischemic complications, symptomatic choroidal artery occlusion and retreatment rates. A random-effects model was used to calculate prevalence rates and their corresponding 95 % confidence intervals (CI), and subgroup analyses were performed to assess the complication rates for Type 1(arterial type, directly arising from ICA) and Type 2(neck type, arising from AchoA branch)) AchoA aneurysms, ruptured vs non-ruptured and for flow diverter (FD) treatment versus coiling. RESULTS: Our study included 10 studies with 416 patients with 430 AchoA aneurysms. The overall good clinical outcome rate (mRS score 0-2) is 94.5 % with a retreatment rate of 2.0 %. A subgroup analysis showed no statistical difference between coiling(75.3 %) and flow diverter(80.9 %) treatment in terms of complete occlusion(p-value:0.62). Overall permanent complication rate is 1.4 % (p-value:0.54) and transient ischemic complications rate is 4.2 %(p-value:0.61). Symptomatic choroidal artery occlusion rate is 0.8 %(p-value:0.51)Type 2 AchoA aneurysms had a significantly higher complication rate of 9.8 % (p-value<0.05) compared to Type 1 aneurysms. Unruptured aneurysms have significantly better clinical outcomes than ruptured aneurysms(OR: 0.11; [0.02;0.5], p-value:<0.05) CONCLUSION: Endovascular treatment of AchoA aneurysms demonstrated positive clinical results, with low rates of retreatment and complications. Coiling and flow diverters proved similar outcomes in achieving aneurysm occlusion. Ruptured aneurysms have lower good clinical outcomes comparing to unruptured aneurysms. Type 2 AchoA aneurysms had a higher risk of complications compared to Type 1.

The impact of pre-stroke metformin use on clinical outcomes after acute ischemic stroke: A systematic review and meta-analysis.

OBJECTIVES: Stroke is a leading cause of mortality and disability globally, with limited treatment options available for acute ischemic stroke (AIS) patients. Type 2 diabetes mellitus (T2DM) is not only widespread but also a known risk factor for stroke. Our meta-analysis aims to assess the influence of pre-stroke metformin use on the clinical outcomes in AIS patients with T2DM. MATERIALS AND METHODS: We conducted this study following PRISMA guidelines, searching the following databases: Medline, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials up to February 29, 2024. All studies providing separate data on AIS patients using metformin were included, and statistical analysis was conducted using R software to pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI). RESULTS: Out of 1051 studies, 7 met the inclusion criteria for our meta-analysis with a total of 11589 diabetic patients, including 5445 patients taking metformin and 6144 diabetic patients in the non-metformin group. Compared to the non-metformin group, the metformin group had a significantly higher rate of mRS 0-2 score at discharge (OR 1.56; 95% CI 1.25:1.95; p=< 0.01) and a lower rate of 90-day mortality (OR 0.51; 95% CI 0.42:0.61; p=< 0.01), with no significant difference in sICH (OR 0.88; 95% CI 0.47:1.64; p= 0.68) between the two groups. CONCLUSIONS: Our meta-analysis demonstrated that pre-stroke metformin use is associated with higher functional independence and lower mortality in AIS patients with T2DM.

Off-Label Use of the 8-F Angio-Seal for Closure of Greater than 8-F Common Femoral Arterial Access: A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the safety of >8-F access closures using 8-F Angio-Seal. MATERIALS AND METHODS: An electronic search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines using Web of Science, Embase, Scopus, and PubMed databases from inception until January 17, 2022. Actionable and nonactionable bleeding events were defined in conjugation with the Bleeding Academic Research Consortium definition. Prevalence rates with corresponding 95% CIs were calculated using R software version 4.2.2. Eight articles, with 422 patients, were included in the analysis. RESULTS: The overall groin adverse event rate was 5.92% (95% CI, 3.01-11.34). The most commonly reported adverse events were any bleeding (5.74%; 95% CI, 3.23-10.00) (nonactionable bleeding, 0.96% [95% CI, 0.10-8.30]; actionable bleeding, 2.30% [95% CI, 0.89-5.84]), pseudoaneurysm (1.18%; 95% CI, 0.49-2.81), and groin hematoma (1.28%; 95% CI, 0.23-6.79). The least commonly reported adverse events were device failure and vessel occlusion/stenosis, with rates 0.29% (95% CI, 0.01-7.41) and 0.45% (95% CI, 0.02-7.74), respectively. No studies recorded events regarding the following adverse events: mortality, infection, deep venous thrombosis, and retroperitoneal hematoma. Moreover, the results showed significant differences, based on the sheath size used, in actionable bleeding (P = .04) and the rate of need for surgical repair (P < .01). CONCLUSIONS: Common femoral artery access of >8-F can be effectively closed with the Angio-Seal with comparable outcomes to those of <8 F; however, larger access approaching 14 F is associated with a significant increase in morbidity. Further safety is needed, especially for the larger access sizes.

Metabolite signature in acute ischemic stroke thrombi: a systematic review.

Metabolites are reliable biomarkers for many diseases. However, their role in acute ischemic stroke (AIS) pathogenesis is not well understood. In this systematic review we aim to evaluate the current literature on the presence of metabolites in thrombi retrieved by mechanical thrombectomy from AIS patients. Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 guidelines, we searched OVID Medline, PubMed, OVID Embase, Scopus, and Web of Science until July 13, 2022. Metabolites lists were extracted, and pathway analysis was performed in MetaboAnalyst database. Four articles listing metabolites were included in this systematic review. D-Glucose, diacylglycerol, phytosphingosine, galabiosylceramide, glucosylceramide and 4-hydroxynonenal were reported to be associated with clots. Metabolomics data analysis showed that glycolysis, lactose, and sphingolipid metabolism pathways were enriched. In conclusion, results of the present study show that the thrombi niche has a glycolytic phenotype. Future studies should work to better understand the metabolic properties of AIS thrombi.

First-pass effect in posterior acute ischemic stroke undergoing endovascular thrombectomy: A systematic review and meta-analysis.

OBJECTIVES: First-pass effect (FPE) has been shown to be a predictor of favorable clinical outcomes following endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) in the anterior circulation. Literature regarding FPE for posterior circulation AIS is sparse; we conducted a systematic review and meta-analysis to explore FPE in posterior circulation stroke undergoing EVT. MATERIALS AND METHODS: We conducted a systematic review of the English literature in PubMed, Embase, Scopus, and Web of Science. FPE was defined as thrombolysis in cerebral infarction (TICI) 2c-3 and modified FPE (mFPE) was defined as TICI 2b-3 in one pass. Definitions of non-FPE and non-mFPE varied among studies. The primary outcome of interest was modified Rankin Scale (mRS) 0-2. Secondary outcomes of interest were mRS 0-3, symptomatic intracranial hemorrhage (sICH), and mortality. We calculated odds ratios (OR) and corresponding 95% confidence intervals (CI). Heterogeneity was assessed with Q statistic and I2 test. RESULTS: Seven studies with 417 patients in the mFPE group, 942 in the non-mFPE group, 545 in the FPE group, and 1023 in the non-FPE group were included. Overall, FPE was associated with greater rates of 90-day mRS 0-2 (OR= 2.78, 95% CI= 2.11-3.65; P-value< 0.001) and mRS 0-3 (OR= 2.67, 95% CI= 1.98-3.60; P-value< 0.001); however, there was significant heterogeneity among studies for both mRS 0-2 (I2= 69%; P-value< 0.001) and mRS 0-3 (I2= 69%; P-value< 0.001). FPE and non-FPE were associated with similar rates of sICH (OR= 0.65, 95% CI= 0.40-1.07; P-value= 0.09), and no heterogeneity was observed (I2= 0%; P-value= 0.95). FPE was associated with lower rates of mortality (OR= 0.44, 95% CI= 0.33-0.58; P-value< 0.001), although heterogeneity was observed (I2= 58%; P-value= 0.01). CONCLUSIONS: FPE is associated with favorable clinical outcomes in patients undergoing EVT for posterior circulation AIS. Future studies should work to further quantify the impact of FPE on outcomes in the posterior circulation.

Differences between males and females following endovascular therapy for stroke: A systematic review and meta-analysis.

BACKGROUND: Endovascular therapy (EVT) represents the standard of care for eligible patients with acute ischemic stroke (AIS) and large vessel occlusion. To better understand differences in baseline characteristics and outcomes between males and females following EVT, we conducted a systematic review and meta-analysis. METHODS: We identified, using the Nested Knowledge AutoLit platform, prospective studies that reported 90-day outcomes in males and females treated with EVT for AIS. The primary outcome of interest was 90-day modified Rankin Scale (mRS) 0-2. Secondary outcome variables included mRS 0-1, symptomatic intracranial hemorrhage (sICH), thrombolysis in cerebral infarction (TICI) score 2b-3, and mortality. Using R software version 4.1.2, we calculated pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI). RESULTS: We included 10 studies with 10,209 patients. There was no difference between males and females in rate of mRS 0-2 (OR= 1.16; 95% CI= 0.87-1.56; P-value= 0.316); however, after removing outliers, males had higher rates of mRS 0-2 (OR= 1.40; 95% CI= 1.19-1.66; P-value< 0.001). Similar results were reported for mRS 0-1 (OR= 1.21; 95% CI= 0.93-1.56; P-value= 0.15), after removing outliers (OR= 1.32; 95% CI= 1.17-1.50; P-value< 0.001). There was no difference between males and females in rate of sICH (OR= 0.89; 95% CI= 0.74-1.08; P-value= 0.246), mortality (OR= 0.88; 95% CI= 0.74-1.05; P-value= 0.15), or TICI 2b-3 (OR= 1.19; 95% CI= 0.85-1.67; P-value= 0.309). CONCLUSIONS: Males tend to experience better outcomes following EVT for AIS, even in the setting of similar reperfusion. The mechanisms underlying this phenomenon remain unclear, and further research is warranted. EVT remains a safe and effective option for both males and females with AIS.

The diagnostic performance of artificial intelligence algorithms for identifying M2 segment middle cerebral artery occlusions: A systematic review and meta-analysis.

BACKGROUND: Artificial intelligence (AI)-based algorithms have been developed to facilitate rapid and accurate computed tomography angiography (CTA) assessment in proximal large vessel occlusion (LVO) acute ischemic stroke, including internal carotid artery and M1 occlusions. In clinical practice, however, the detection of medium vessel occlusion (MeVO) represents an ongoing diagnostic challenge in which the added value of AI remains unclear. PURPOSE: To assess the diagnostic performance of AI platforms for detecting M2 occlusions. METHODS: Studies that report the diagnostic performance of AI-based detection of M2 occlusions were screened, and sensitivity and specificity data were extracted using the semi-automated AutoLit software (Nested Knowledge, MN) platform. STATA (version 16 IC; Stata Corporation, College Station, Texas, USA) was used to conduct all analyses. RESULTS: Eight studies with a low risk of bias and significant heterogeneity were included in the quantitative and qualitative synthesis. The pooled estimates of sensitivity and specificity of AI platforms for M2 occlusion detection were 64% (95% CI, 53 to 74%) and 97% (95% CI, 84 to 100%), respectively. The area under the curve (AUC) in the SROC curve was 0.79 (95% CI, 0.74 to 0.83). CONCLUSION: The current performance of the AI-based algorithm makes it more suitable as an adjunctive confirmatory tool rather than as an independent one for M2 occlusions. With the rapid development of such algorithms, it is anticipated that newer generations will likely perform much better.

Histological composition of retrieved emboli in acute ischemic stroke is independent of pre-thrombectomy alteplase use.

BACKGROUND AND PURPOSE: Given recent evidence suggesting the clot composition may be associated with revascularization outcomes and stroke etiology, clot composition research has been a topic of growing interest. It is currently unclear what effect, if any, pre-thrombectomy thrombolysis has on clot composition. Understanding this association is important as it is a potential confounding variable in clot composition research. We retrospectively evaluated the composition of retrieved clots from ischemic stroke patients who did and did not receive pre-treatment tPA to study the effect of tPA on clot composition. MATERIALS AND METHODS: Consecutive patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using Martius Scarlett Blue (MSB) staining and area of the clot was also measured on the gross photos. Student's t test was used for continuous variables and chi-squared test for categorical variables. RESULTS: A total of 1430 patients were included in this study. Mean age was 68.4±13.5 years. Overall rate of TICI 2c/3 was 67%. A total of 517 patients received tPA (36%) and 913 patients did not (64%). Mean RBC density for the tPA group was 42.97±22.62% compared to 42.80±23.18% for the non-tPA group (P=0.89). Mean WBC density for the tPA group was 3.74±2.60% compared to 3.42±2.21% for the non-tPA group (P=0.012). Mean fibrin density for the tPA group was 26.52±15.81% compared to 26.53±15.34% for the non-tPA group (P=0.98). Mean platelet density for the tPA group was 26.22±18.60% compared to 26.55±19.47% for the non-tPA group (P=0.75). tPA group also had significantly smaller clot area compared to non-tPA group. CONCLUSIONS: Our study 1430 retrieved emboli and ischemic stroke patients shows no interaction between tPA administration and clot composition. These findings suggest that tPA does not result in any histological changes in clot composition.

Selective brain hypothermia: feasibility and safety study of a novel method in five patients.

BACKGROUND/OBJECTIVE: Reduction of brain temperature remains the most common method of neuroprotection against ischemic injury employed during cardiac surgery. However, cooling delivered via the cardiopulmonary bypass circuit is brief and cooling the body core along with the brain has been associated with a variety of unwanted effects. This study investigated the feasibility and safety of a novel selective brain cooling approach to induce rapid, brain-targeted hypothermia independent of the cardiopulmonary bypass circuit. METHODS: This first-in-human feasibility study enrolled five adults undergoing aortic valve replacement with cardiopulmonary bypass support. During surgery, the NeuroSave system circulated chilled saline within the pharynx and upper esophagus. Brain and body core temperature were continuously monitored. Adverse effects, cardiopulmonary function, and device function were noted. RESULTS: Patient 1 received cooling fluid for an insignificant period, and Patients 2-5 successfully underwent the cooling procedure using the NeuroSave system for 56-89 minutes. Cooling fluid was 12°C for Patients 1-3, 6°C for Patient 4, and 2°C for Patient 5. There were no NeuroSave-related adverse events and no alterations in cardiopulmonary function during NeuroSave use. Brain temperature decreased by 3°C within 15 minutes and remained at least 3.5°C colder than the body core. During a brief episode of hypotension in one patient, the brain cooled an additional 4°C in 2 minutes, briefly reaching 27.4°C. CONCLUSION: The NeuroSave system can induce rapid brain-targeted hypothermia and simultaneously maintain a favorable body-brain temperature gradient, even during hypotension. Further studies are required to evaluate the function of the system during longer periods of use.

Platelet-Rich Emboli in Cerebral Large Vessel Occlusion Are Associated With a Large Artery Atherosclerosis Source.

Background and Purpose- Nearly 30% of large vessel occlusion acute ischemic stroke clots are from an unknown source. We assessed histological clot composition in a series of patients with large vessel occlusion and investigated correlations between clot composition and stroke pathogenesis. Methods- As part of the multi-institutional STRIP registry (Stroke Thromboembolism Registry of Imaging and Pathology), consecutive emboli retrieved during mechanical thrombectomy were stained using Martius Scarlett Blue and analyzed using machine learning software. We assessed proportions of red blood cells, fibrin, platelets, and white blood cells. Correlations between clot components and stroke pathogenesis (large artery atherosclerosis, cardioembolism, and stroke of undetermined pathogenesis) were assessed using SPSS22. Results- One hundred five patients were included. The proportion of platelet-rich clots (55.0% versus 21.2%; P=0.005) and percentage of platelet content (22.1±4.2% versus 13.9±14.2%; P=0.03) was significantly higher in the large artery atherosclerosis group compared with the cardioembolic group. The proportion of platelet-rich clots (50.0% versus 21.2%; P=0.024) was also significantly higher in the cryptogenic group compared with cardioembolic cases. Large artery atherosclerosis and cryptogenic cases had a similar proportion of platelet-rich clots (55.0% versus 50.0%; P=0.636). There was no significant difference between stroke pathogenesis and the other major clot components. Conclusions- High platelet content of emboli is associated with a large artery atherosclerosis etiology of large vessel occlusion.

Comparison of Gadolinium Concentrations within Multiple Rat Organs after Intravenous Administration of Linear versus Macrocyclic Gadolinium Chelates.

Purpose To compare gadolinium tissue concentrations of multiple linear and macrocyclic chelates in a rat model to better understand the scope and extent of tissue deposition following multiple intravenous doses of gadolinium-based contrast agent (GBCA). Materials and Methods In this Institutional Animal Care and Use Committee-approved study, healthy rats received 20 intravenous injections of 2.5 mmol gadolinium per kilogram (gadolinium-exposed group) or saline (control group) over a 26-day period. Unenhanced T1 signal intensities of the dentate nucleus were measured from magnetic resonance (MR) images obtained prior to GBCA injection and 3 days after final injection. Rat brain and renal, hepatic, and splenic tissues were harvested 7 days after final injection and subjected to inductively coupled plasma mass spectrometry and transmission electron microscopy for quantification and characterization of gadolinium deposits. Results Gadolinium deposition in brain tissue significantly varied with GBCA type (F = 31.2; P < .0001), with median concentrations of 0 µg gadolinium per gram of tissue (95% confidence interval [CI]: 0, 0.2) in gadoteridol-injected rats, 1.6 µg gadolinium per gram of tissue (95% CI: 0.9, 4.7) in gadobutrol-injected rats, 4.7 µg gadolinium per gram of tissue (95% CI: 3.5, 6.1) in gadobenate dimeglumine-injected rats, and 6.9 µg gadolinium per gram of tissue (95% CI: 6.2, 7.0) in gadodiamide-injected rats; a significant positive dose-signal intensity correlation was identified (ρ = 0.93; P < .0001). No detectable neural tissue deposition or MR imaging signal was observed in control rats (n = 6). Similar relative differences in gadolinium deposition were observed in renal, hepatic, and splenic tissues at much higher tissue concentrations (P < .0001). Gadolinium deposits were visualized directly in the endothelial capillary walls and neural interstitium in GBCA-injected rats, but not in control rats. Conclusion Tissue deposition of gadolinium was two- to fourfold higher following administration of the linear agents gadodiamide and gadobenate dimeglumine compared with the macrocyclic agents gadobutrol and gadoteridol. These findings suggest that organ tissue deposition is reduced but not eliminated following administration of macrocyclic GBCA chelates in lieu of linear chelates. © RSNA, 2017 Online supplemental material is available for this article.

Imaging Characteristics of Growing and Ruptured Vertebrobasilar Non-Saccular and Dolichoectatic Aneurysms.

BACKGROUND AND PURPOSE: Vertebrobasilar, nonsaccular, and dolichoectatic aneurysms generally have a poor natural history. We performed a study examining the natural history of vertebrobasilar, nonsaccular, and dolichoectatic aneurysms receiving serial imaging and studied imaging characteristics associated with growth and rupture. METHODS: We included all vertebrobasilar dolichoectatic, fusiform, and transitional aneurysms with serial imaging follow-up seen at our institution over a 15-year period. Two radiologists and a neurologist evaluated aneurysms for size, type, mural T1 signal, mural thrombus, daughter sac, mass effect, and tortuosity. Primary outcomes were aneurysm growth or rupture. Univariate analysis was performed with chi-squared tests for categorical variables and Student's t test or analysis of variance for continuous variables. Multivariate logistic regression analysis was performed to identify variables independently associated with aneurysm growth or rupture. RESULTS: One hundred and fifty-two patients with 542 patient-years (mean 3.6±3.5 years) of imaging follow-up were included. Aneurysms were fusiform in 45 cases (29.6%), dolichoectatic in 75 cases (49.3%), and transitional in 32 cases (21.1%). Thirty-five aneurysms (23.0%) grew (growth rate=6.5%/year). Eight aneurysms (5.3%) ruptured (rupture rate=1.5%/year). Variables associated with growth and rupture on univariate analysis were size >10 mm (57.6% versus 16.0%, P<0.0001), mural T1 signal (39.7% versus 16.3%, P=0.001), daughter sac (56.3% versus 21.3%), and mural thrombus (45.5% versus 13.4%, P<0.0001). 26.7% of fusiform aneurysms, 9.3% of dolichoectatic aneurysms, and 59.4% of transitional aneurysms grew or ruptured (P<0.0001). The only variable independently associated with rupture was transitional morphology (P=0.003). CONCLUSIONS: Vertebrobasilar, nonsaccular, and dolichoectatic aneurysms are associated with a poor natural history with high growth and rupture rates. Further research is needed to determine the best treatments for this disease.

Delayed hemorrhagic complications after flow diversion for intracranial aneurysms: a literature overview.

INTRODUCTION: Delayed aneurysm rupture and delayed intraparenchymal hemorrhages (DIPH) are poorly understood and often fatal complications of flow diversion (FD) for intracranial aneurysms. The purpose of this study was to identify risk factors for these complications. METHODS: We performed a systematic review on post-FD delayed aneurysm rupture and DIPH. For each reported case, we collected the following information: aneurysm location, size and rupture status, type of flow diverter used, timing of the hemorrhage, and neurological outcome. We reported descriptive statistics of patients suffering DIPH and delayed aneurysm rupture to determine if there were any characteristics consistently present among patients with these complications. RESULTS: We identified 81 delayed aneurysm ruptures and 101 DIPH. Of the delayed ruptures, 76.6% (45/58) occurred within 1 month. The prognosis of delayed ruptures was poor, with 81.3% (61/75) experiencing death or poor neurological outcome. Giant aneurysms accounted for 46.3% of ruptures (31/67). Of these aneurysms, 80.9% (55/68) were initially unruptured. Of the delayed ruptured aneurysms, 17.8% (13/73) had prior or concomitant coiling. DIPHs were ipsilateral to the treated aneurysm in 82.2% (60/73) of cases. Of the DIPH, 86.0% (43/50) occurred within 1 month after FDS. Combined morbidity/mortality rate was 68.5% (50/73) following DIPH. Of DIPHs, 23.0% (14/61) occurred in patients with giant aneurysms. CONCLUSIONS: Our study demonstrates that giant aneurysms represent almost 50% of delayed aneurysm ruptures in the flow diverter literature. About 2% of delayed ruptures occurred despite associated coiling. A substantial proportion of DIPHs occur early following FDS treatment of giant aneurysms.

Cellular mechanisms of aneurysm occlusion after treatment with a flow diverter.

PURPOSE: To characterize the progression of healing across aneurysm necks following treatment with a flow diverter in a rabbit aneurysm model. MATERIALS AND METHODS: With institutional animal care and use committee approval, saccular aneurysms were created in 20 rabbits and treated with flow diverters. On days 1, 3, and 7 and weeks 4 and 8 after implantation, the aneurysm and the device-implanted vessel were harvested. En face staining of the gross specimen was performed for endothelial cells, endothelial progenitor cells, smooth muscle cells, and inflammatory cells. RESULTS: The parent artery segments covered by the flow diverters were completely devoid of endothelial cells at 1 and 3 days but had completely reendothelialized by 7 days. At all time points, the struts along the patent portions of the aneurysm necks harbored scattered tissue islands composed exclusively of inflammatory cells. At 4 and 8 weeks, all samples contiguous with the tissue along the parent arteries had translucent tissue present along the occluded segments of the aneurysm neck. The vast majority of endothelial cells were contiguous with the parent artery and had smooth muscle cells underlying them. Endothelial progenitor cells were not observed along the neck of any aneurysm. Aneurysm closure was noted only when complete or nearly complete endothelialization over the device struts was present. CONCLUSION: The initial event following flow diversion treatment is adherence of clusters of inflammatory cells across the aneurysm neck. Endothelialization is relatively delayed and derived exclusively from cells in the adjacent parent artery.

Common Design, Data Elements and Core Outcome Measures Reported on Clinical Trials of Genicular Artery Embolization for Knee Osteoarthritis: An Interactive Systematic Review.

RATIONALE AND OBJECTIVES: Genicular artery embolization (GAE) is an emerging, potentially effective treatment option in patients with knee osteoarthritis (OA). This study aimed to describe the current state of common design data elements (CDDEs) and core outcome measures (COMs) in recent trials of GAE for knee OA. MATERIALS AND METHODS: A comprehensive search of seven online databases were searched within the Nested Knowledge AutoLit living review platform, followed by categorization of primary and secondary outcomes. Studies were tagged with the relevant outcomes of interest in each article. Results were synthesized and examined for the CDDEs. RESULTS: Pain is the most frequent reported outcome, present in 23 of the 24 studies (95.8%). However, there is considerable variability in the description of in the study designs, procedural techniques, embolic materials, time points, and MRI parameters. Greater consistency is observed in eligibility criteria, and adverse events reporting. Although findings thus far have been favorable, current data is still constrained by the heterogeneity of the study design, embolization area nomenclature, limited follow-up, and in many cases, the absence of control group. CONCLUSION: To enhance the potential for future meta-analyses and robust, evidence-based evaluations of GAE as a treatment for knee OA, further research is required to address the identified shortcomings. By establishing more standardized protocols, the efficacy and safety of GAE can be more accurately assessed and understood.

Effect of Treatment Choice on Short-Term and Long-Term Outcomes for Carotid Near-Occlusion: A Meta-Analysis.

OBJECTIVE: Current guidelines recommend best medical treatment (BMT) over revascularization for carotid near-occlusion (CNO); however, it remains unclear whether BMT, carotid artery stenting (CAS), or carotid endarterectomy (CEA) is the optimal treatment strategy. The present meta-analysis aimed to compare outcomes among patients with CNO receiving BMT, CAS, or CEA. METHODS: PubMed, Web of Science, Scopus, and Embase were searched. English studies with ≥1 month follow-up, that used established CNO diagnostic guidelines, that provided outcomes by treatment, and in which 95% confidence intervals (CIs) were calculable were included. Studies on acute ischemic stroke (AIS) requiring emergent reperfusion therapy, nonatherosclerotic lesions, nonprimary research articles, non-English, and nonhuman studies were excluded. Outcomes were mortality, AIS, transient ischemic attack, myocardial infarction within and beyond 30 days, and restenosis. A generalized linear mixed model, subgroup analysis, and meta-regression were used to compare outcomes. RESULTS: Thirty-eight studies were included. Pooled rates for AIS beyond 30 days were 9.90% (95% CI, 4.31%-21.16%), 0.79% (95% CI, 0.24%-2.53%), and 0.80% (95% CI, 0.15%-4.07%) for BMT, CAS, and CEA, respectively. Subgroup analysis was statistically significant (P < 0.001). Meta-regression showed lower incidence favoring procedural intervention (CAS vs. BMT, P = 0.001; CEA vs. BMT, P = 0.003). Subgroup analysis for mortality beyond 30 days was also significant (P = 0.016) but meta-regression did not favor one treatment over another. Other outcomes were not statistically significant. CONCLUSIONS: Revascularization for CNO may decrease long-term stroke rates. Given that current guidelines are based on randomized controlled trials from the 1990s, updated randomized trials are warranted to determine the optimal treatment for CNO.

Efficacy and safety of flow diverters in retreatment of recurrent intracranial aneurysms-A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Treatment of recurrent intracranial aneurysms after their initial therapy has been a significant challenge in the field of neurointervention. Recently flow diverters stents are widely used for treating intracranial aneurysms. In this systematic review and meta-analysis, we assessed the safety and efficacy of flow diverter in treating recurrent or recanalized intracranial aneurysms. METHODS: This meta-analysis is reported following the PRISMA 2020 guidelines. We conducted a systematic review of literature in the PubMed, Embase, Web of Sciences, and Scopus databases. Pooled prevalence and the corresponding 95% are calculated from extracted data using a random-effect model. RESULTS: The systematic literature search included 21 studies involving 411 patients, with 135 (32.8%) being male and 276 (67.2%) being females with a total number of 447 aneurysms. The overall rate of adequate occlusion was 90.67% (95% CI: 84.23%-94.65%), and the rates were comparable between the surgery (93.48%), coiling (91.78%), and stenting (85.77%) groups. The overall pooled rate of complete occlusion was 81.80 (95% CI: 71.14%-89.13%). On doing a subgroup analysis, the complete occlusion rates were 89.68%, 84.39%, and 73.47% for the surgery, coiling, and stenting groups, respectively. The overall mortality rate and achieving modified Rankin scale score of 0-2 was 1.28% (95% CI: 0.45%-3.64%) and (95% CI: 89.92%-97.84%), respectively. No significant heterogeneity is noted in the included studies. CONCLUSION: Flow diverter stents are an effective and safe method for retreating recurrent or residual intracranial aneurysms with a high rate of complete and adequate occlusion. The rate of mortality, intracerebral hemorrhage, and overall and procedural complications following using flow diverters for intracranial aneurysms is low.