Overloaded transnidal pressure gradient as the hemodynamic mechanism leading to arteriovenous malformation rupture: a quantitative analysis using intravascular pressure monitoring and color-coded digital subtraction angiography.

BACKGROUND: The hemodynamics of brain arteriovenous malformations (AVMs) may have implications for hemorrhage. This study aimed to explore the hemodynamics of ruptured AVMs by direct microcatheter intravascular pressure monitoring (MIPM) and indirect quantitative digital subtraction angiography (QDSA). METHODS: We recruited patients with AVMs at a tertiary neurosurgery center from October 2020 to March 2023. In terms of MIPM, we preoperatively super-selected a predominant feeding artery and main draining vein through angiography to measure intravascular pressure before embolization. In processing of QDSA, we adopted previously standardized procedure for quantitative hemodynamics analysis of pre-embolization digital subtraction angiography (DSA), encompassing main feeding artery, nidus, and the main draining vein. Subsequently, we investigated the correlation between AVM rupture and intravascular pressure from MIPM, as well as hemodynamic parameters derived from QDSA. Additionally, we explored the interrelationships between hemodynamic indicators in both dimensions. RESULTS: After strict screening of patients, our study included 10 AVMs (six ruptured and four unruptured). We found that higher transnidal pressure gradient (TPG) (53.00±6.36 vs 39.25±8.96 mmHg, p=0.042), higher feeding artery pressure (FAP) (72.83±5.46 vs 65.00±6.48 mmHg, p=0.031) and higher stasis index of nidus (3.54±0.73 vs 2.43±0.70, p=0.043) were significantly correlated with AVM rupture. In analysis of interrelationships between hemodynamic indicators in both dimensions, a strongly positive correlation (r=0.681, p=0.030) existed between TPG and stasis index of nidus. CONCLUSIONS: TPG and FAP from MIPM platform and nidus stasis index from QDSA platform were correlated with AVM rupture, and both were positively correlated, suggesting that higher pressure load within nidus may be the central mechanism leading to AVM rupture.

Risk factors for delayed postoperative hemorrhage in patients with brain arteriovenous malformations: an analysis of the nationwide multicenter prospective registry MATCH study.

OBJECTIVE: Reducing the incidence of delayed postoperative hemorrhage (DPH) is one of the challenges in the surgical treatment of patients with brain arteriovenous malformations (bAVMs). This study aimed to identify several risk factors for DPH after bAVM resection and evaluate the impact of these risk factors in patients with bAVMs. METHODS: The authors retrospectively reviewed consecutive patients with bAVMs who underwent microsurgical resection between August 2011 and September 2021. Patients were divided into either the DPH group or non-DPH group based on whether they experienced a postoperative intracerebral hemorrhage into the bAVM bed within 14 days after bAVM resection. Factors associated with DPH were assessed using multivariate logistic regression analyses. RESULTS: A total of 1284 consecutive patients with bAVMs were evaluated; DPH events occurred in 18 patients (1.4%). There were several differences in vascular architecture between the two cohorts. A giant nidus, a nidus involved in the eloquent area, a periventricular nidus, and a nidus accompanied by venous ectasia were more likely to be associated with DPH events. The multivariate analysis identified two independent factors associated with DPH: maximum diameter (OR 1.44 per 1-cm increase, 95% CI 1.13-1.83) and periventricular lesion (OR 4.10, 95% CI 1.33-12.59). The area under the receiver operating characteristic curve for the maximum lesion diameter and development of DPH was 0.71 (95% CI 0.58-0.84). The cutoff value for the maximum bAVM diameter was 4.15 cm. Furthermore, patients with a giant bAVM, of which the maximum diameter was ≥ 4.15 cm, had a higher DPH risk after surgery (HR 5.79, 95% CI 2.01-16.67; p < 0.01). The incidence rates of DPH for patients with periventricular lesions were higher than those for patients without periventricular lesions (HR 4.50, 95% CI 1.77-11.40; p < 0.01). CONCLUSIONS: Patients with giant bAVMs or periventricular lesions are at higher risk for DPH after surgery. Strategies such as blood pressure control, preoperative embolization, intraoperative monitoring, and careful patient selection should be considered to reduce the risk of DPH in high-risk patients.

A retrospective study on the relationship between serum electrolyte disorder and delayed cerebral infarction after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Delayed cerebral ischemia (DCI)-induced cerebral infarction is a major cause of adverse neurological outcomes following aneurysmal subarachnoid hemorrhage (aSAH). This study aimed to investigate the relationship between postoperative serum electrolyte levels and DCI in patients with aSAH. MATERIALS AND METHODS: We analyzed the data of patients with aSAH between 2015 and 2022. The patients were classified into two groups according to whether they experienced DCI. Electrolyte levels were categorized into three groups based on the normal ranges for electrolytes. Logistic regression models were used to study the relationship between electrolyte levels and DCI. Another logistic regression analysis was conducted to explore the relationship between the different severity levels of statistically significant indicators and DCI. A restrictive cubic spline model was adopted to assess the potential linear relationship between electrolytes and DCI. Subsequently, sensitivity analysis was performed to assess the impact of collinearity among ions. Finally, subgroup analysis was performed. RESULTS: This study included 1,099 patients. Patients with hyperchloremia were more prone to DCI than those with normal chloride levels. Subsequently, excluding the population with hypochloremia, both mild and severe hyperchloremia were found to be associated with an increased risk of DCI compared with normal chloride levels. Within the framework of a restrictive cubic spline, our findings revealed an increased incidence of DCI (P for nonlinear = 0.735) as chloride levels increased. Sensitivity analysis revealed that patients with severe hyperchloremia were more susceptible to DCI. CONCLUSIONS: This study found that patients with aSAH and postoperative hyperchloremia are more prone to developing DCI.

Comparative Analysis of Personality Traits in Major Depressive Disorder and Bipolar Disorder: Impact, Differences, and Associations with Symptoms.

Purpose: This cross-sectional study aimed to compare the personality traits of patients with major depressive disorder (MDD) and bipolar disorder (BD) with those of healthy individuals. The goal was to gain insight into the potential impact of personality traits on the development and manifestation of mood disorders. Methods: One hundred seventy-eight patients with mood disorders were analyzed as either MDD or BD, with each group containing euthymic and depressive members: e-MDD, d-MDD, e-BD, and d-BD. Mood status was assessed using the Young Mania Rating Scale (YMRS), and the 17-item Hamilton Depression Rating Scale (HAMD-17). Ninety-five healthy individuals served as controls. Personality traits were assessed with the Eysenck Personality Questionnaire. Results: The scores for neuroticism in the patient groups were comparable, but each group had higher scores compared to the control group (P < 0.001). Each patient group exhibited significantly lower scores for extraversion compared to the control group, with e-MDD, d-MDD, and d-BD showing particularly notable differences (P < 0.001); these groups scored significantly lower than the e-BD (P = 0.041, 0.009, 0.038). In patients with BD, there was an inverted association between extraversion score and HAMD total score (P = 0.010, r = -0.27), and a positive association with the YMRS total score (P = 0.022, r = 0.24). In the MDD group, there was a positive association between the neuroticism score and HAMD total score (P = 0.021, r = 0.25). Conclusion: Patients with mood disorders are characterized by lower extraversion and higher neuroticism. Level of neuroticism associated with depression severity in MDD. Patients with BD may be more extraverted, but their extraversion can be affected by depressive episodes. Extraversion may be a feature of BD, and may differentiate BD from MDD. Personality traits are related to disease diathesis and state, and shaped by symptom manifestations.

Timing of microsurgical resection for ruptured brain arteriovenous malformations: a propensity score-matched analysis using prospective single-center registry data.

OBJECTIVE: The optimal microsurgical timing in ruptured brain arteriovenous malformations (AVMs) is not well understood and is surrounded by controversy. This study aimed to elucidate the impacts of microsurgical resection timing on clinical outcomes. METHODS: The authors retrieved and reviewed the records on all ruptured AVMs treated at their institution and registered in a nationwide multicenter prospective collaboration registry between August 2011 and August 2021. Patients were dichotomized into an early resection group (≤ 30 days from the last hemorrhagic stroke) and a delayed resection group (> 30 days after the last hemorrhagic stroke). Propensity score-matched analysis was used to compare long-term outcomes. The primary outcome was neurological status as assessed using the modified Rankin Scale (mRS). The secondary outcomes were complete obliteration rate, postoperative seizure, and postoperative hemorrhage. RESULTS: Of the 3649 consecutive AVMs treated at the authors' institution, a total of 558 ruptured AVMs were microsurgically resected and had long-term follow-up. After propensity score matching, 390 ruptured AVMs (195 pairs) were included in the comparison of outcomes. The mean (± standard deviation) clinical follow-up duration was 4.93 ± 2.94 years in the early resection group and 5.61 ± 2.56 years in the delayed resection group. Finally, as regards the distribution of mRS scores, short-term neurological outcomes were better in the delayed resection group (risk difference [RD] 0.3%, 95% CI -0.1% to 0.6%, p = 0.010), whereas long-term neurological outcomes were similar between the two groups (RD 0.0%, 95% CI -0.2% to 0.2%, p = 0.906). Long-term favorable neurological outcomes (early vs delayed: 90.8% vs 90.3%, p > 0.999; RD 0.5%, 95% CI -5.8% to 6.9%; RR 1.01, 95% CI 0.94-1.07) and long-term disability (9.2% vs 9.7%, p > 0.999; RD -0.5%, 95% CI -6.9% to 5.8%; RR 0.95, 95% CI 0.51-1.75) were also similar between these groups. In terms of secondary outcomes, postoperative seizure (early vs delayed: 8.7% vs 5.6%, p = 0.239; RD 3.1%, 95% CI -2.6% to 8.8%; RR 1.55, 95% CI 0.74-3.22), postoperative hemorrhage (1.0% vs 1.0%, p > 0.999; RD 0.0%, 95% CI -3.1% to 3.1%; RR 1.00, 95% CI 0.14-7.04), and hospitalization time (16.4 ± 8.5 vs 19.1 ± 7.9 days, p = 0.793) were similar between the two groups, whereas early resection had a lower complete obliteration rate (91.3% vs 99.0%, p = 0.001; RD -7.7%, 95% CI -12.9% to 3.1%; RR 0.92, 95% CI 0.88-0.97). CONCLUSIONS: Early and delayed resection of ruptured AVMs had similar long-term neurological outcomes. Delayed resection can lead to a higher complete obliteration rate, although the risk of rerupture during the resection waiting period should be vigilantly monitored.

ITGA2 as a prognostic factor of glioma promotes GSCs invasion and EMT by activating STAT3 phosphorylation.

Glioma is the most common malignant brain tumor in adults with a high mortality and recurrence rate. Integrin alpha 2 (ITGA2) is involved in cell adhesion, stem cell regulation, angiogenesis and immune cell function. The role of ITGA2 in glioma malignant invasion remains unknown. The function and clinical relevance of ITGA2 were analysed by bioinformatics databases. The expression of ITGA2 in parent cells and GSCs was detected by flow cytometry and immunofluorescence double staining. The role of ITGA2 on the malignant phenotype of GSCs and epithelial-mesenchymal transition (EMT) was identified by stem cell function assays and Western blot. The effect of ITGA2 on glioma progression in vivo was determined by the intracranial orthotopic xenograft model. Immunohistochemistry, Spearman correlation and Kaplan-Meier were used to analyse the relationship of ITGA2 with clinical features and glioma prognosis. Biological analysis showed that ITGA2 might be related to cell invasion and migration. ITGA2, enriched in GSCs and co-expressed with SOX2, promoted the invasion and migration of GSCs by activating STAT3 phosphorylation and enhancing EMT. ITGA2 knockout suppressed the intracranial orthotopic xenograft growth and prolonged the survival of xenograft mice. In addition, the expression level of ITGA2 was significantly correlated to the grade of malignancy, N-cadherin and Ki67. High expression of ITGA2 indicated a worse prognosis of glioma patients. As a biomarker for the prediction of prognosis, ITGA2 promotes the malignant invasion of GSCs by activating STAT3 phosphorylation and enhancing EMT, leading to tumor recurrence and poor prognosis.

Comparison of conservative management, microsurgery only, and microsurgery with preoperative embolization for unruptured arteriovenous malformations: A propensity score weighted prospective cohort study.

AIMS: To compare the efficacy and deficiency of conservative management (CM), microsurgery (MS) only, and microsurgery with preoperative embolization (E + MS) for unruptured arteriovenous malformations (AVMs). METHODS: We prospectively included unruptured AVMs undergoing CM, MS, and E + MS from our institution between August 2011 and August 2021. The primary outcomes were long-term neurofunctional outcomes and hemorrhagic stroke and death. In addition to the comparisons among CM, MS, and E + MS, E + MS was divided into single-staged hybrid and multi-staged E + MS for further analysis. Stabilized inverse probability of treatment weighting using propensity scores was applied to control for confounders by treatment indication across the three groups. RESULTS: Of 3758 consecutive AVMs admitted, 718 patients were included finally (266 CM, 364 MS, and 88 E + MS). The median follow-up duration was 5.4 years. Compared with CM, interventions (MS and E + MS) were associated with neurological deterioration. MS could lower the risk of hemorrhagic stroke and death. Multi-staged E + MS was associated with neurological deterioration and higher hemorrhagic risks compared with MS, but the hybrid E + MS operation significantly reduced the hemorrhage risk. CONCLUSION: In this study, unruptured AVMs receiving CM would expect better neurofunctional outcomes but bear higher risks of hemorrhage than MS or E + MS. The single-staged hybrid E + MS might be promising in reducing inter-procedural and subsequent hemorrhage.

Recurrence of Cerebral Arteriovenous Malformation Following Complete Obliteration Through Endovascular Embolization.

Arteriovenous malformation (AVM) recurrence after embolization was rarely reported. This study aimed to explore the potential risk factors of recurrence in angiographically obliterated AVMs treated with endovascular embolization. This study reviewed AVMs treated with embolization only in a prospective multicenter registry from August 2011 to December 2021, and ultimately included 92 AVMs who had achieved angiographic obliteration. Recurrence was assessed by follow-up digital subtraction angiography (DSA) or magnetic resonance imaging (MRI). Hazard ratios (HRs) with 95% confidence intervals were calculated using Cox proportional hazards regression models. Nineteen AVMs exhibited recurrence on follow-up imaging. The recurrence rates after complete obliteration at 6 months, 1 year, and 2 years were 4.35%, 9.78%, and 13.0%, respectively. Multivariate Cox regression analysis identified diffuse nidus (HR 3.208, 95% CI 1.030-9.997, p=0.044) as an independent risk factor for recurrence. Kaplan-Meier analysis confirmed a higher cumulative risk of recurrence with diffuse nidus (log-rank, p=0.016). Further, in the exploratory analysis of the effect of embolization timing after AVM rupture on recurrence after the complete obliteration, embolization within 7 days of the hemorrhage was found as an independent risk factor (HR 4.797, 95% CI 1.379-16.689, p=0.014). Kaplan-Meier analysis confirmed that embolization within 7 days of the hemorrhage was associated with a higher cumulative risk of recurrence in ruptured AVMs (log-rank, p<0.0001). This study highlights the significance of diffuse nidus as an independent risk factor for recurrence after complete embolization of AVMs. In addition, we identified a potential recurrent risk associated with early embolization in ruptured AVMs.

Prediction of stress-related gastrointestinal bleeding in patients with aneurysmal subarachnoid hemorrhage using caudate Hounsfield unit value in ASPECT score.

Background: Stress-related gastrointestinal bleeding (SRGB) is one of the major complications after aneurysmal subarachnoid hemorrhage (aSAH), and it can present challenges in patient care and treatment. The aim of this study was to explore the clinical significance of the caudate Hounsfield unit (HU) value in the Alberta Stroke Program Early CT (ASPECT) score for predicting SRGB in patients with aSAH. Methods: We retrospectively analyzed the data of 531 aSAH patients admitted to our institution between 2019 and 2022. Potential predictors of SRGB were identified using multivariate Cox regression analysis. We used a restricted cubic spline (RCS) to evaluate whether there is a nonlinear relationship between the right caudate HU value and SRGB. MaxStat analysis (titled as maximally selected rank statistics) was performed to identify the optimal cutoff point for the right caudate HU value. Another Kaplan-Meier method with the log-rank test was used to analyze the right caudate HU value in predicting the occurrence of SRGB. Results: The incidence rate of SRGB was 17.9%. In the multivariate Cox regression analysis, the right caudate HU value was an independent predictor of SRGB [Hazard ratio (HR) = 0.913; 95% confidence interval (CI): 0.847-0.983, and p = 0.016]. The RCS indicated that the incidence of developing SRGB reduces with increasing right caudate HU values (nonlinear p = 0.78). The optimal cut-off value of the right caudate HU was 25.1. Conclusion: Among aSAH patients, lower right caudate HU values indicated a higher risk of developing SRGB. Our findings provide further evidence for the relationship between the gastrointestinal system and the brain.

Re-rupture in ruptured brain arteriovenous malformations: a retrospective cohort study based on a nationwide multicenter prospective registry.

BACKGROUND: This study aimed to investigate the natural history of re-rupture in ruptured brain arteriovenous malformations (AVMs) and to provide comprehensive insights into its associated factors and prevention. METHODS: This study included 1712 eligible ruptured AVMs from a nationwide multicenter prospective collaboration registry between August 2011 and September 2021. The natural rupture risk before intervention and the annual rupture risk after intervention were both assessed. Cox proportional hazard regression models and Kaplan-Meier survival curves were used to explore independent factors associated with AVM re-rupture. The correlation between these factors and AVM re-rupture was verified in multiple independent cohorts, and the prevention effect of intervention timing and intervention strategies on AVM re-rupture was further analyzed. RESULTS: The annual re-rupture risk in ruptured AVMs was 7.6%, and the cumulative re-rupture risk in the first 1, 3, 5, and 10 years following the initial rupture were 10%, 25%, 37.5%, and 50%, respectively. Cox proportional hazard regression analysis confirmed adult patients, ventricular system involvement, and any deep venous drainage as independent factors associated with AVM re-rupture. The intervention was found to significantly reduce the risk of AVM re-rupture (annual rupture risk 11.34% vs 1.70%, p<0.001), especially in those who underwent surgical resection (annual rupture risk 0.13%). CONCLUSIONS: The risk of re-rupture in ruptured AVMs is high. Adult patients, ventricular system involvement, and any deep venous drainage are independent risk factors for re-rupture. Applying the results universally to all ruptured AVM cases may be biased. Intervention could effectively reduce the risk of re-rupture.

Long-term outcomes of microsurgery and stereotactic radiosurgery as the first-line treatment for arteriovenous malformations: a propensity score-matched analysis using nationwide multicenter prospective registry data.

BACKGROUND: This study aimed to compare the risk and benefit profile of microsurgery (MS) and stereotactic radiosurgery (SRS) as the first-line treatment for unruptured and ruptured arteriovenous malformations (AVMs). MATERIALS AND METHODS: The authors included AVMs underwent MS or SRS as the first-line treatment from a nationwide prospective multicenter registry in mainland China. The authors used propensity score-matched methods to balance baseline characteristics between the MS and SRS groups. The primary outcomes were long-term hemorrhagic stroke or death, and the secondary outcomes were long-term obliteration and neurological outcomes. Subgroup analyses and sensitivity analyses with different study designs were performed to confirm the stability of our findings. RESULTS: Of the 4286 consecutive AVMs in the registry from August 2011 to December 2021; 1604 patients were eligible. After matching, 244 unruptured and 442 ruptured AVMs remained for the final analysis. The mean follow-up duration was 7.0 years in the unruptured group and 6.1 years in the ruptured group. In the comparison of primary outcomes, SRS was associated with a higher risk of hemorrhagic stroke or death both in the unruptured and ruptured AVMs (unruptured: hazard ratio 4.06, 95% CI: 1.15-14.41; ruptured: hazard ratio 4.19, 95% CI: 1.58-11.15). In terms of the secondary outcomes, SRS was also observed to have a significant disadvantage in long-term obliteration [unruptured: odds ratio (OR) 0.01, 95% CI: 0.00-0.04; ruptured: OR 0.09, 95% CI: 0.05-0.15]. However, it should be noted that SRS may have advantages in preventing neurofunctional decline (unruptured: OR 0.56, 95% CI: 0.27-1.14; ruptured: OR 0.41, 95% CI: 0.23-0.76). The results of subgroup analyses and sensitivity analyses were consistent in trend but with slightly varied powers. CONCLUSIONS: This clinical practice-based real-world study comprehensively compared MS and SRS for AVMs with long-term outcomes. MS is more effective in preventing future hemorrhage or death and achieving obliteration, while the risk of neurofunctional decline should not be ignored.

Inflammatory Burden Index: Association Between Novel Systemic Inflammatory Biomarkers and Prognosis as Well as in-Hospital Complications of Patients with Aneurysmal Subarachnoid Hemorrhage.

Purpose: Systemic inflammation plays an important role in the pathophysiology and progression of aneurysmal subarachnoid hemorrhage (aSAH). In this study, we aimed to investigate the association between a new biomarker, the inflammatory burden index (IBI) and the prognosis as well as in-hospital complications of aSAH patients. Patients and Methods: We analyzed data from patients with aSAH between January 2019 and September 2022 who were included in the LongTEAM (Long-term Prognosis of Emergency Aneurysmal Subarachnoid Hemorrhage) registry study. The IBI was formulated as C-reactive protein × neutrophils/lymphocytes. The unfavorable functional prognosis was assessed by the modified Rankin Scale (mRS). Receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal cut-off values for IBI to distinguish the unfavorable functional prognosis. Multivariate logistic regression was applied to investigate the association between IBI and in-hospital complications. Propensity score matching was adjusted for imbalances in baseline characteristics to assess the effect of IBI on prognosis. Results: A total of 408 consecutive patients with aSAH enrolled in the study, of which 235 (57.6%) were female patients and the mean age was 55.28 years old. An IBI equal to 138.03 was identified as the best cut-off threshold to distinguish the unfavorable prognosis at 3 months (area under the curve [AUC] [95% CI] 0.637 [0.568-0.706]). ln IBI was independently associated with 3-month functional prognosis (OR [95% CI] 1.362 [1.148-1.615]; P<0.001), pneumonia (OR [95% CI] 1.427 [1.227-1.659]; P<0.001) and deep venous thrombosis (DVT). (OR [95% CI] 1.326 [1.124-1.564]; P=0.001). After propensity score matching (57:57), an increased proportion of patients with IBI ≥138.03 had a poor functional prognosis at 3 months and in-hospital complications including developed pneumonia and DVT. Conclusion: In patients with aSAH, high IBI level at admission was associated with unfavorable functional prognosis as well as pneumonia and deep vein thrombosis.

Comparison of Long-Term Outcomes in Ruptured Diffuse Brain Arteriovenous Malformations Between Interventional Therapy and Conservative Management.

Brain arteriovenous malformations (AVMs) with a diffuse nidus structure present a therapeutic challenge due to their complexity and elevated risk of hemorrhagic events. This study examines the long-term effectiveness of interventional therapy versus conservative management in reducing hemorrhagic stroke or death in patients with ruptured diffuse AVMs. The analysis was conducted based on a multi-institutional database in China. Patients were divided into two groups: conservative management and interventional therapy. Using propensity score matching, patients were compared for the primary outcome of hemorrhagic stroke or death and the secondary outcomes of disability and neurofunctional decline. Out of 4286 consecutive AVMs in the registry, 901 patients were eligible. After matching, 70 pairs of patients remained with a median follow-up of 4.0 years. The conservative management group showed a trend toward higher rates of the primary outcome compared to the interventional group (4.15 vs. 1.87 per 100 patient-years, P = 0.090). While not statistically significant, intervention reduced the risk of hemorrhagic stroke or death by 55% (HR, 0.45 [95% CI 0.18-1.14], P = 0.094). No significant differences were observed in secondary outcomes of disability (OR, 0.89 [95% CI 0.35-2.26], P = 0.813) and neurofunctional decline (OR, 0.65 [95% CI 0.26 -1.63], P = 0.355). Subgroup analysis revealed particular benefits in interventional therapy for AVMs with a supplemented S-M grade of II-VI (HR, 0.10 [95% CI 0.01-0.79], P = 0.029). This study suggests a trend toward lower long-term hemorrhagic risks with intervention when compared to conservative management in ruptured diffuse AVMs, especially within supplemented S-M grade II-VI subgroups. No evidence indicated that interventional approaches worsen neurofunctional outcomes.

Association of nidus size and rupture in brain arteriovenous malformations: Insight from angioarchitecture and hemodynamics.

This study aims to investigate the correlation between AVM size and rupture by examining natural history, angioarchitecture characteristics, and quantitative hemodynamics. A retrospective review of 90 consecutive AVMs from the MATCH registry was conducted. Patients were categorized into small nidus (< 3 cm) and large nidus (≥ 3 cm) groups based on the Spetzler-Martin grading system. Natural history analysis used prospective cohort survival data, while imaging analysis examined angioarchitecture characteristics and quantitative hemodynamic parameters measured with QDSA. The small-nidus group had a significantly higher annualized rupture risk (2.3% vs. 1.0%; p = 0.011). Cross-sectional imaging revealed independent hemorrhagic risk factors, including small nidus (OR, 4.801; 95%CI, 1.280-18.008; p = 0.020) and draining vein stenosis (OR, 6.773; 95%CI, 1.179-38.911; p = 0.032). Hemodynamic analysis identified higher stasis index in the feeding artery (OR, 2.442; 95%CI, 1.074-5.550; p = 0.033), higher stasis index in the draining vein (OR, 11.812; 95%CI, 1.907-73.170; p = 0.008), and lower outflow gradient in the draining vein (OR, 1.658; 95%CI, 1.068-2.574; p = 0.024) as independent predictors of AVM rupture. The small nidus group also showed a higher likelihood of being associated with hemorrhagic risk factors. Small AVM nidus has a higher risk of rupture based on natural history, angioarchitecture, and hemodynamics. Clinical Trial Registration-URL: http://www.clinicaltrials.gov . Unique identifier: NCT04572568.

Association of the combined stereotactic radiosurgery and embolization strategy and long-term outcomes in brain arteriovenous malformations with a volume ≤10 mL: a nationwide multicenter observational prospective cohort study.

BACKGROUND: To compare the long-term outcomes of stereotactic radiosurgery (SRS) with or without prior embolization in brain arteriovenous malformations (AVMs) (volume ≤10 mL) for which SRS is indicated. METHODS: Patients were recruited from a nationwide multicenter prospective collaboration registry (the MATCH study) between August 2011 and August 2021, and categorized into combined embolization and SRS (E+SRS) and SRS alone cohorts. We performed propensity score-matched survival analysis to compare the long-term risk of non-fatal hemorrhagic stroke and death (primary outcomes). The long-term obliteration rate, favorable neurological outcomes, seizure, worsened mRS score, radiation-induced changes, and embolization complications were also evaluated (secondary outcomes). Hazard ratios (HRs) were calculated using Cox proportional hazards models. RESULTS: After study exclusions and propensity score matching, 486 patients (243 pairs) were included. The median (IQR) follow-up duration for the primary outcomes was 5.7 (3.1-8.2) years. Overall, E+SRS and SRS alone were similar in preventing long-term non-fatal hemorrhagic stroke and death (0.68 vs 0.45 per 100 patient-years; HR=1.46 (95% CI 0.56 to 3.84)), as well as in facilitating AVM obliteration (10.02 vs 9.48 per 100 patient-years; HR=1.10 (95% CI 0.87 to 1.38)). However, the E+SRS strategy was significantly inferior to the SRS alone strategy in terms of neurological deterioration (worsened mRS score: 16.0% vs 9.1%; HR=2.00 (95% CI 1.18 to 3.38)). CONCLUSIONS: In this observational prospective cohort study, the combined strategy of E+SRS does not show substantial advantages over SRS alone. The findings do not support pre-SRS embolization for AVMs with a volume ≤10 mL.

Association of embolization with long-term outcomes in brain arteriovenous malformations: a propensity score-matched analysis using nationwide multicenter prospective registry data.

BACKGROUND: Brain arteriovenous malformations (AVMs) account for 25% of hemorrhagic strokes in young adults. Although embolization has been widely performed as a stand-alone procedure to cure brain AVM, it is undermined whether patients benefit from this treatment. This study aimed to compare the long-term outcome of hemorrhagic stroke or death in patients with either conservative management or stand-alone embolization for AVM. METHODS: The study population was derived from a nationwide multicenter prospective collaboration registry (the MATCH registry) between August 2011 and August 2021. The propensity score-matched survival analysis was performed in the overall and stratified AVM cases (unruptured and ruptured), respectively, to compare the long-term outcome of hemorrhagic stroke or death, and neurological status. The efficacy of distinct embolization strategies was also evaluated. Hazard ratios (HRs) with 95% CI were calculated using Fine-Gray competing risk models. RESULTS: Of the 3682 consecutive AVMs, 906 underwent either conservative management or embolization as the stand-alone management strategy. After propensity score matching, a total of 622 (311 pairs) patients constituted an overall cohort. The unruptured and ruptured subgroups were composed of 288 cases (144 pairs) and 252 cases (126 pairs), respectively. In the overall cohort, embolization did not prevent long-term hemorrhagic stroke or death compared with conservative management [2.07 vs. 1.57 per 100 patient-years; HR, 1.28 (95% CI, 0.81-2.04)]. Similar results were maintained in both unruptured AVMs [1.97 vs. 0.93 per 100 patient-years; HR, 2.09 (95% CI, 0.99-4.41)] and ruptured AVMs [2.36 vs. 2.57 per 100 patient-years; HR, 0.76 (95% CI, 0.39-1.48)]. Stratified analysis showed that the target embolization might be beneficial for unruptured AVMs [HR, 0.42 (95% CI, 0.08-2.29)], while the curative embolization improved the outcome of ruptured AVMs [HR, 0.29 (95% CI, 0.10-0.87)]. The long-term neurological status was similar between these two strategies. CONCLUSIONS: This prospective cohort study did not support a substantial superiority of embolization over conservative management for AVMs in preventing long-term hemorrhagic stroke or death.

Application of Quantitative Computed Tomographic Perfusion in the Prognostic Assessment of Patients with Aneurysmal Subarachnoid Hemorrhage Coexistent Intracranial Atherosclerotic Stenosis.

The comorbidity of aneurysmal subarachnoid hemorrhage (aSAH) with intracranial atherosclerotic stenosis (ICAS) has been suggested to increase the risk of postoperative ischemic stroke. Logistic regression models were established to explore the association between computed tomography perfusion (CTP) parameters and 3-month neurological outcomes and delayed cerebral ischemia (DCI). Prognostic-related perfusion parameters were added to the existing prognostic prediction models to evaluate model performance improvement. Tmax > 4.0 s volume > 0 mL was significantly associated with 3-month unfavorable neurological outcomes after adjusting for potential confounders (OR 3.90, 95% CI 1.11-13.73), whereas the stenosis degree of ICAS was not. Although the cross-validated area under the curve (AUC) was similar after the addition of the Tmax > 4.0 s volume > 0 mL (SAHIT: p = 0.591; TAPS: p = 0.379), the continuous net reclassification index (cNRI) and integrated discrimination index (IDI) showed that the perfusion parameters significantly improved the performance of the two models (p < 0.001 for all comparisons). Patients with coexistent aSAH and ICAS, Tmax > 4.0 s volume > 0 mL is an independent factor of 3-month neurological outcomes. A quantitative assessment of cerebral perfusion may help accurately screen patients with poor outcomes due to the coexistence of aSAH and ICAS.

Development and Validation of a Scoring System for Hemorrhage Risk in Brain Arteriovenous Malformations.

Importance: The dilemma between natural rupture risk and adverse outcomes of intervention is of major concern for patients with unruptured arteriovenous malformations (AVMs). The existing risk score for AVM rupture includes factors that are controversial and lacks prospective validation. Objective: To develop and robustly validate a reliable scoring system to predict the rupture risk of AVMs. Design, Setting, and Participants: This prognostic study developed a prediction model derived from a single-center cohort (derivation cohort) and validated in a multicenter external cohort (multicenter external validation cohort) and a cohort of patients receiving conservative treatment management (conservative treatment validation cohort). Patients were recruited from a nationwide multicenter prospective collaboration registry in China. A total of 4135 patients were enrolled in the registry between August 1, 2011, and September 1, 2021. Of those, 3962 patients were included in the study (3585 in the derivation cohort and 377 in the multicenter external validation cohort); 1028 patients from the derivation cohort who had time-to-event data and prerupture imaging results were included in the conservative treatment validation cohort. Data were analyzed from March 10 to June 21, 2022. Main Outcomes and Measures: A scoring system was developed based on risk factors identified from a literature review and a robust selection process. Patients were stratified into different risk groups based on scores to calculate hemorrhage-free probability in future years, and Kaplan-Meier curves were plotted to visualize risk stratification. Receiver operating characteristic curves were used to assess the discrimination of models. Univariable analyses (logistic regression analysis for descriptive data and Cox regression analysis for survival data) were used to compare baseline information and assess bias. Results: Among 3962 patients (2311 men [58.3%]; median [IQR] age, 26.1 [14.6-35.5] years), 3585 patients (2100 men [58.6%]; median [IQR] age, 25.9 [14.6-35.0] years) were included in the derivation cohort, and 377 patients (211 men [56.0%]; median [IQR] age, 26.4 [14.5-39.2] years) were included in the multicenter external validation cohort. Thirty-six hemorrhages occurred over a median (IQR) follow-up of 4.2 (0.3-6.0) years among 1028 patients in the conservative treatment validation cohort. Four risk factors were used to develop the scoring system: ventricular system involvement, venous aneurysm, deep location, and exclusively deep drainage (VALE). The VALE scoring system performed well in all 3 cohorts, with areas under the receiver operating characteristic curve of 0.77 (95% CI, 0.75-0.78) in the derivation cohort, 0.85 (95% CI, 0.81-0.89) in the multicenter external validation cohort, and 0.73 (95% CI, 0.65-0.81) in the conservative treatment validation cohort. The 10-year hemorrhage-free rate was 95.5% (95% CI, 87.1%-100%) in the low-risk group, 92.8% (95% CI, 88.8%-97.0%) in the moderate-risk group, and 75.8% (95% CI, 65.1%-88.3%) in the high-risk group; the model discrimination was significant when comparing these rates between the high-risk group and the low- and moderate-risk groups (P < .001 for both comparisons). Conclusions and Relevance: In this prognostic study, the VALE scoring system was developed to distinguish rupture risk among patients with AVMs. The stratification of unruptured AVMs may enable patients with low risk of rupture to avoid unnecessary interventions. These findings suggest that the scoring system is a reliable and applicable tool that can be used to facilitate patient and physician decision-making and reduce unnecessary interventions or unexpected AVM ruptures.

Efficacy and acceptability of supervised group exercise for mild to moderate major depressive disorder: A feasibility study.

BACKGROUND: Exercise can efficiently reduce the symptoms of major depression disorder (MDD). This study aims to examine the efficacy and acceptability of supervised group exercise intervention among patients in an acute phase of mild to moderate MDD. METHODS: We enrolled patients in the psychiatric clinic of Beijing Anding Hospital affiliated to Capital Medical University in a prospective, single-arm objective performance criteria (OPC) trial. A total of 40 adults aged 18-50 who had a diagnosis of an episode of depression and the 17-item Hamilton Rating Scale for Depression (HRSD-17) score of 7-20 were recruited. Supervised exercise group intervention was applied on participants with a new episode of mild to moderate depression 3 times a week for 8 weeks without any other treatment. Every exercise session should meet the standard of moderate intensity, defined as approximately equal to 50 %-80 % of the maximal heart rate for 150 min every week. The primary end point was the clinical response at week 8, defined as a 50 % reduction in the baseline HRSD-17 score. Meanwhile, the secondary end points included the acceptability of the supervised group exercise intervention for both patients and investigators, remission rate (defined as an HRSD-17 score of 7 or less), the change of Patient Health Questionnaire (PHQ-9) and the Quality of Life, Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF). RESULTS: Among the 46 screened patients, 40 were enrolled. Of them, 4 people dropped out, while 36 received all the planned sessions of the supervised group exercise therapy and completed the week-8 assessment. At week 8, the response rate was 89 % (95 % confidence interval [CI] 74 % to 97 %) and the remission rate was 83 % (95%CI 67 % to 94 %). The overall acceptance of the supervised group exercise based on the VAS score (range 0-10) was 9.19 ± 1.27 for patients and 9.67 ± 0.62 for investigators. The least-squares mean (±SE) change from baseline at week 8 was-9.99 in the PHQ-9 score and 25.15 in the Q-LES-Q-SF score. No serious adverse events were reported during this trial. The percentage of any adverse event was 5 %. CONCLUSION: Supervised group exercise intervention is effective in patients with acute mild to moderate MDD and has good acceptance rate among both patients and investigators.