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.

Altered effective connectivity among face-processing systems in major depressive disorder.

BACKGROUND: Neuroimaging studies have revealed abnormal functional interaction during the processing of emotional faces in patients with major depressive disorder (MDD), thereby enhancing our comprehension of the pathophysiology of MDD. However, it is unclear whether there is abnormal directional interaction among face-processing systems in patients with MDD. METHODS: A group of patients with MDD and a healthy control group underwent a face-matching task during functional magnetic resonance imaging. Dynamic causal modelling (DCM) analysis was used to investigate effective connectivity between 7 regions in the face-processing systems. We used a Parametric Empirical Bayes model to compare effective connectivity between patients with MDD and controls. RESULTS: We included 48 patients and 44 healthy controls in our analyses. Both groups showed higher accuracy and faster reaction time in the shape-matching condition than in the face-matching condition. However, no significant behavioural or brain activation differences were found between the groups. Using DCM, we found that, compared with controls, patients with MDD showed decreased self-connection in the right dorsolateral prefrontal cortex (DLPFC), amygdala, and fusiform face area (FFA) across task conditions; increased intrinsic connectivity from the right amygdala to the bilateral DLPFC, right FFA, and left amygdala, suggesting an increased intrinsic connectivity centred in the amygdala in the right side of the face-processing systems; both increased and decreased positive intrinsic connectivity in the left side of the face-processing systems; and comparable task modulation effect on connectivity. LIMITATIONS: Our study did not include longitudinal neuroimaging data, and there was limited region of interest selection in the DCM analysis. CONCLUSION: Our findings provide evidence for a complex pattern of alterations in the face-processing systems in patients with MDD, potentially involving the right amygdala to a greater extent. The results confirm some previous findings and highlight the crucial role of the regions on both sides of face-processing systems in the pathophysiology of MDD.

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.

A comprehensive analysis of patients with cerebral arteriovenous malformation with headache: assessment of risk factors and treatment effectiveness.

BACKGROUND: Due to the high mortality and disability rate of intracranial hemorrhage, headache is not the main focus of research on cerebral arteriovenous malformation (AVM), so research on headaches in AVM is still scarce, and the clinical understanding is shallow. This study aims to delineate the risk factors associated with headaches in AVM and to compare the effectiveness of various intervention treatments versus conservative treatment in alleviating headache symptoms. METHODS: This study conducted a retrospective analysis of AVMs who were treated in our institution from August 2011 to December 2021. Multivariable logistic regression analysis was employed to assess the risk factors for headaches in AVMs with unruptured, non-epileptic. Additionally, the effectiveness of different intervention treatments compared to conservative management in alleviating headaches was evaluated through propensity score matching (PSM). RESULTS: A total of 946 patients were included in the analysis of risk factors for headaches. Multivariate logistic regression analysis identified that female (OR 1.532, 95% CI 1.173-2.001, p = 0.002), supply artery dilatation (OR 1.423, 95% CI 1.082-1.872, p = 0.012), and occipital lobe (OR 1.785, 95% CI 1.307-2.439, p < 0.001) as independent risk factors for the occurrence of headaches. There were 443 AVMs with headache symptoms. After propensity score matching, the microsurgery group (OR 7.27, 95% CI 2.82-18.7 p < 0.001), stereotactic radiosurgery group(OR 9.46, 95% CI 2.26-39.6, p = 0.002), and multimodality treatment group (OR 8.34 95% CI 2.87-24.3, p < 0.001) demonstrate significant headache relief compared to the conservative group. However, there was no significant difference between the embolization group (OR 2.24 95% CI 0.88-5.69, p = 0.091) and the conservative group. CONCLUSIONS: This study identified potential risk factors for headaches in AVMs and found that microsurgery, stereotactic radiosurgery, and multimodal therapy had significant benefits in headache relief compared to conservative treatment. These findings provide important guidance for clinicians when developing treatment options that can help improve overall treatment outcomes and quality of life for patients.

The micro-pathological characteristics in cerebral arteriovenous malformations(cAVMs).

BACKGROUND: Rupture and hemorrhage is the most serious complication of cerebral arteriovenous malformation(cAVMs), and have a significant impact on quality of life. OBJECTIVES: We investigated the hematoxylin and eosin staining and ultrastructural features of cAVMs and characterized the abnormal vascular structure of cAVMs. METHODS: Light and electron microscopy were performed on a series of pathological specimens obtained from 12 patients with cAVMs who underwent surgical resection for the first time without radiosurgery or embolization therapy. RESULTS: In tunica intima, we found that the vascular endothelial cells of cAVMs were damaged, and the lysis of the cell body occurred in multiple regions. In tunica media, the arrangement of the elastic layer was disordered, and the thickness was uneven. Part of the structure of the elastic lamina was missing. The part of tunica adventitia was fractured and discontinuous. In addition, we also observed the phenomenon that different blood vessels share the same vascular wall. Macrophage phagocytosis and lymphocyte infiltration in the adventitial region of ruptured cAVMs. Abnormal lipid deposition in vascular endothelial cells and smooth muscle cells. CONCLUSIONS: The structural incompleteness of cAVMs may be an important cause of hemorrhage.

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.

Elevated blood hemoglobin on admission as an independent predictor of unfavorable outcomes in patients with aneurysmal subarachnoid hemorrhage.

Hemoglobin (HGB), a potent spasmogen, may cause irreversible damage to the brain after aneurysm rupture. However, there is no clinical evidence to reveal the relationship between blood HGB concentrations on admission and the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH). We retrospectively reviewed all aSAH patients admitted to our institution between January 2015 and December 2020. Functional outcome was assessed at 90 days after discharge using the modified Rankin scale (mRS). Independent risk factors associated with 90-day unfavorable outcomes were derived from a forward stepwise multivariate analysis. Receiver operating characteristic curve analysis was conducted to identify the best cutoff value of HGB to discriminate 90-day unfavorable outcomes. Then, patients were divided into two groups according to the cutoff value of HGB, and to account for imbalances in baseline characteristics, propensity score matching (PSM) was carried out to assess the impact of HGB on in-hospital complications. A total of 800 aSAH patients without anemia on admission were retrospectively enrolled in this study. Elevated blood HGB (OR = 1.02, 95% CI = 1.00-1.03, p = 0.018) on admission was identified as an independent risk factor associated with 90-day unfavorable outcomes, and the cutoff value was 149.5 g/L. After PSM, patients with an HGB > 149.5 g/L had a higher incidence of in-hospital delayed cerebral ischemia (DCI) (33.9% vs. 22.0%, p = 0.013) and deep vein thrombosis (DVT) (11.9% vs. 4.0%, p = 0.006). Patients with a blood HGB > 149.5 g/L on admission might develop more DCI and DVT during hospitalization, leading to 90-day unfavorable outcomes in aSAH patients. ClinicalTrials.gov Identifier: NCT04785976. 2021/03/05, retrospectively registered.

The effect of sex differences on complications and 90-day outcomes after aneurysmal subarachnoid hemorrhage: a propensity score-matched analysis.

Aneurysmal subarachnoid hemorrhage (aSAH) is the most devastating form of stroke. Up to now, little is known about the effect of sex differences on complications and outcomes. We retrospectively reviewed aSAH patients admitted to our institution between January 2015 and December 2020. The functional outcomes at discharge and 90 days after discharge were assessed using the modified Rankin Scale (mRS). Baseline characteristics, in-hospital complications, and outcomes were compared after 1:1 propensity score matching (PSM). The area under the curve (AUC) in the receiver operating characteristic curve (ROC) analysis was calculated to measure each independent risk factor's prediction ability. A total of 833 patients were included. After PSM, 109 male patients were compared with 109 female patients. Female patients had a higher incidence of anemia (47/109 [43.1%] vs. 30/109 [27.5%], p = 0.016) than male patients, while male patients had a higher incidence of pneumonia (36/109 [33.0%] vs. 19/109 [17.4%], p = 0.008) than female patients. No significant differences were found in the rate of unfavorable outcomes at discharge and 90-day outcomes (40/109 [36.7%] vs. 50/109 [45.9%], p = 0.169; 15/109 [13.8%] vs. 19/107 [17.8%], p = 0.420) between female and male patients. Pneumonia (AUC = 0.749, 95% confidence interval [CI] = 0.623-0.875, p < 0.001) and anemia (AUC = 0.753, 95% CI = 0.632-0.873, p = 0.002) showed good ability to predict 90-day unfavorable outcomes in male and female patients, respectively. Female patients had a higher incidence of anemia but a lower incidence of pneumonia during hospitalization. However, differences in in-hospital complications did not result in differences in outcomes between women and men. Clinical Trial Registration: NCT04785976. 2021/03/05, retrospectively registered.

Long-term outcomes of Spetzler-Martin grade IV and V arteriovenous malformations: a single-center experience.

OBJECTIVE: This study aimed to explore whether intervention can benefit Spetzler-Martin (SM) grade IV-V arteriovenous malformations (AVMs). METHODS: Eighty-two patients with SM grade IV-V AVMs were retrospectively reviewed from 2015 to 2018. Patients were divided into two groups: those who received conservative management (22 cases [26.8%]) and intervention (60 cases [73.2%], including 21 cases of microsurgery, 19 embolization, and 20 hybrid surgery). Neurofunctional outcomes were assessed with the modified Rankin Scale (mRS). The primary outcome was long-term neurofunctional status, and the secondary outcomes were short-term neurofunctional status, long-term obliteration rate, seizure control, and risk of subsequent hemorrhage. RESULTS: Regarding the primary outcome, after an average of 4.7 years of clinical follow-up, long-term neurofunctional outcomes were similar after conservative management or intervention (absolute difference -0.4 [95% CI -1.5 to 0.7], OR 0.709 [95% CI 0.461-1.090], p = 0.106), whereas intervention had an advantage over conservative management for avoidance of severe disability (defined as mRS score > 3) (1.7% vs 18.2%, absolute difference 16.5% [95% CI -23.6% to 56.6%], OR 0.076 [95% CI 0.008-0.727], p = 0.025). Regarding the secondary outcomes, intervention was conducive to better seizure control (Engel class I-II) (70.0% vs 0.0%, absolute difference 70.0% [95% CI 8.6%-131.4%], p = 0.010) and avoidance of subsequent hemorrhage (1.4% vs 6.0%, absolute difference 4.6% [95% CI -0.4% to 9.6%], p = 0.030). In the subgroup analysis based on different intervention modalities, microsurgery and hybrid surgery achieved higher complete obliteration rates than embolization (p < 0.001), and hybrid surgery resulted in significantly less intraoperative blood loss than microsurgery (p = 0.041). CONCLUSIONS: Intervention is reasonable for properly indicated SM grade IV-V AVMs because it provides satisfactory seizure control with decreased risks of severe disability and subsequent hemorrhage than conservative management. Clinical trial registration no.: NCT04572568 (ClinicalTrials.gov).

Long-term outcomes and prognostic predictors of 111 pediatric hemorrhagic cerebral arteriovenous malformations after microsurgical resection: a single-center experience.

Comparison in pediatric hemorrhagic arteriovenous malformations (AVMs) to clarify the long-term neurological outcomes and prognostic predictors after surgical intervention was relatively rare, especially in the selection of surgical timing. The objective of this study was to elucidate these points. The authors retrospectively reviewed the pediatric hemorrhagic AVMs resected in their neurosurgical department between March 2010 and June 2017. The natural history was represented by rupture risk. Neurological outcome was assessed with the modified Rankin Scale (mRS) for children. Multivariate logistic regression analyses were used to assess the risk factors for disability (mRS > 2). The hemorrhagic early phase was defined as less than 30 days after bleeding. The corresponding prognosis of different surgical timing (early intervention or delayed intervention) was compared after propensity-score matching (PSM). A total of 111 pediatric hemorrhagic AVM patients were evaluated. The average patient age was 11.1 ± 4.0 years, with a mean follow-up of 4.3 ± 2.1 years. The annualized rupture risk was 9.3% for the pediatric hemorrhagic AVMs, and the annualized re-rupture risk was 9.8%. 7.2% of the patients had disabilities (mRS > 2) and 82.0% achieved neurological deficit-free (mRS < 2) at the last follow-up. Pre-treatment mRS (P = 0.042) and flow-related aneurysms (P = 0.039) were independent factors for long-term disability. In terms of short-term outcomes, early intervention was better than delayed intervention (P = 0.033), but the long-term outcomes were similar between the two groups (P = 0.367). Surgical intervention for pediatric hemorrhagic AVMs is recommended, most of the patients can achieve good neurological outcomes. Moreover, early surgical intervention is preferred after the initial hemorrhage.

Effect of heating palladium-silver alloys on ceramic bond strength.

STATEMENT OF PROBLEM: The effects of different heat treatments on the internal oxidation and metal-ceramic bond in Pd-Ag alloys with different trace elements require further documentation. PURPOSE: The purpose of this in vitro study was to determine whether heat treatment affects the metal-ceramic bond strength of 2 Pd-Ag alloys containing different trace elements. MATERIAL AND METHODS: Thirteen cast specimens (25×3×0.5 mm) from each of 2 Pd-Ag alloy groups (W-1 and Argelite 61+3) were allocated to heat treatments before porcelain application: heating under reduced atmospheric pressure of 0.0014 MPa and 0.0026 MPa and heating under normal atmospheric pressure. Bond strengths were evaluated using a 3-point bending test according to ISO9693. Results were analyzed using 2-way ANOVA and Tukey HSD test (α=.05). Visual observation was used to determine the failure types of the fractured specimens. Scanning electron microscopy and energy dispersive spectroscopy were used to study morphologies, elemental compositions, and distributions in the specimens. RESULTS: The W-1 group had a mean bond strength significantly higher than that of Argelite 61+3 (P<.001). Heating under reduced atmospheric pressures of 0.0014 MPa and 0.0026 MPa resulted in similar bond strengths (P=.331), and both pressures had significantly higher bond strengths than that of heating under normal atmospheric pressure (P=.002, P<.001). Heating under different air pressures resulted in Pd-Ag alloys that contained either Sn or In and Ga, with various degrees of internal oxidation and different quantities of metallic nodules. CONCLUSIONS: Heating under reduced atmospheric pressure effectively improved the bond strength of the ceramic-to-Pd-Ag alloys.

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.

Lesion-Filling Index from Quantitative DSA Correlates with Hemorrhage of Cerebral AVM.

BACKGROUND AND PURPOSE: Rupture is the most life-threatening manifestation of cerebral AVMs. This study aimed to explore the hemodynamic mechanism of AVM rupture. We introduced a new quantitative DSA parameter that can reflect the degree of intranidal blood stasis, called the lesion-filling index. MATERIALS AND METHODS: This study examined patients with AVMs who had undergone both DSA and MR imaging between 2013 and 2014. Clinical presentations, angioarchitecture, and hemodynamic parameters generated from quantitative DSA were analyzed using univariate and multivariable logistic regression. The lesion-filling index was defined as the arterial diagnostic window divided by the volume of the AVM. To assess the correlation between the lesion-filling index and rupture, we incorporated the lesion-filling index into 2 published prediction models widely recognized for predicting AVM rupture risk, R2eD and VALE. The DeLong test was used to examine whether the addition of the lesion-filling index improved predictive efficacy. RESULTS: A total of 180 patients with AVMs were included. The mean lesion-filling index values in the ruptured group were higher compared with the unruptured group (390.27 [SD, 919.81] versus 49.40 [SD, 98.25]), P < .001). A higher lesion-filling index was significantly correlated with AVM rupture in 3 different multivariable logistic models, adjusting for angioarchitecture factors (OR = 1.004, P = .02); hemodynamic factors (OR = 1.005, P = .009); and combined factors (OR = 1.004, P = .03). Both R2eD (area under the curve, 0.601 versus 0.624; P = .15) and VALE (area under the curve, 0.603 versus 0.706; P < .001) predictive models showed improved predictive performance after incorporating the lesion-filling index and conducting 10-fold cross-validation. CONCLUSIONS: The lesion-filling index showed a strong correlation with AVM rupture, suggesting that overperfusion is the hemodynamic mechanism leading to AVM rupture.

Modulation of brain function and antidepressant effects by transcranial alternating current stimulation in patients with major depressive disorder: Evidence from ERP.

Transcranial alternating current stimulation (tACS) is an emerging non-invasive neuromodulation treatment for major depressive disorder (MDD), but its mechanism remains unclear. Therefore, we evaluated the effects of tACS on event-related potentials (ERP) based on a randomized controlled study. All patients were divided into two groups to receive either 20 sessions 77.5Hz-tACS or 20 sessions of sham stimulation during 4 weeks. The Hamilton Depression Rating Scale for Depression -17 item (HAMD-17) and ERP during face-word Stroop task were recorded before and after the treatment (the fourth weekend). Our findings indicate a significant alleviation of depressive symptoms after tACS. For the behavioral performance, sham group showed a significant decrease in reaction time to the sad incongruent condition and an increase in accuracy to the happy condition. The active group showed an increase in accuracy to the incongruent condition. ERP analysis revealed that tACS significantly shortened the latency of P2 to incongruent condition, decreased the amplitude and prolonged the latency of N2 to negative condition. These ERP alterations suggest a potential rectification of negative bias and enhancement of cognitive functioning in patients with MDD, offering insights into the antidepressant mechanisms of tACS.

Effect of add-on transcranial alternating current stimulation (tACS) in major depressive disorder: A randomized controlled trial.

BACKGROUND: The effect of transcranial alternating current stimulation (tACS) on major depressive disorder (MDD) was not confirmed. OBJECTIVE: To evaluate the feasibility, safety, and efficacy of tACS as an add-on treatment for the symptoms of depression and to understand how tACS affects brain activity. METHODS: The 4-week, double-blind, randomized, sham-controlled trial was performed from January 29, 2023 to December 22, 2023. Sixty-six participants were recruited and randomly assigned to receive 20 40-min sessions of either active (77.5Hz, 15 mA) or sham stimulation, with one electrode on the forehead and two on the mastoid, each day (n = 33 for each group) for four weeks (till Week 4). The participants were followed for 4 more weeks (till Week 8) without stimulation for efficacy/safety assessment. During the 4-week trial, all participants were required to take 10-20 mg of escitalopram daily. The primary efficacy endpoint was the change in HAMD-17 scores from baseline to Week 4 (with 20 treatment sessions completed). Resting-state electroencephalography (EEG) was collected with a 64-channel EEG system (Brain Products, Germany) at baseline and the Week 4 follow-up. The chi-square test, Fisher's exact test, independent-sample t-test, or Wilcoxon rank-sum test were used, as appropriate, to compare the differences in variables between groups. The effect of the intervention on the HAMD-17 score was also evaluated with linear mixed modeling (LMM) as sensitivity analysis. The correlation between the mean reduction in EEG and the mean reduction in the HAMD-17 total score was evaluated using Spearman correlation analysis. RESULTS: A total of 66 patients (mean [SD] age, 28.4 [8.18] years; 52 [78.8 %] female) were randomized, and 57 patients completed the study. Significant differences were found in the reductions in the HAMD-17 scores at Week 4 (t = 3.44, P = 0.001). Response rates at Week 4 were significantly higher in the active tACS group than in the sham tACS group (22 out of 33 patients [66.7 %] versus 11 out of 33 [33.3 %], P = 0.007). In the active tACS group, a correlation between the mean change in alpha power and HAMD-17 scores at Week 4 was found (r = 2.38, P = 0.024), and the mean change in alpha power was significantly bigger for responders (Z = 2.46, P = 0.014). No serious adverse events were observed in this trial. CONCLUSION: The additional antidepressant effect of tACS is significant, and the combination of tACS with antidepressants is a feasible and effective approach for the treatment of MDD. The antidepressant mechanism of tACS may be the reduction in alpha power in the left frontal lobe. Future research directions may include exploring more appropriate treatment parameters of tACS.

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.

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.

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.

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.

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.