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.

An Audio-Visual Speech Separation Model Inspired by Cortico-Thalamo-Cortical Circuits.

Audio-visual approaches involving visual inputs have laid the foundation for recent progress in speech separation. However, the optimization of the concurrent usage of auditory and visual inputs is still an active research area. Inspired by the cortico-thalamo-cortical circuit, in which the sensory processing mechanisms of different modalities modulate one another via the non-lemniscal sensory thalamus, we propose a novel cortico-thalamo-cortical neural network (CTCNet) for audio-visual speech separation (AVSS). First, the CTCNet learns hierarchical auditory and visual representations in a bottom-up manner in separate auditory and visual subnetworks, mimicking the functions of the auditory and visual cortical areas. Then, inspired by the large number of connections between cortical regions and the thalamus, the model fuses the auditory and visual information in a thalamic subnetwork through top-down connections. Finally, the model transmits this fused information back to the auditory and visual subnetworks, and the above process is repeated several times. The results of experiments on three speech separation benchmark datasets show that CTCNet remarkably outperforms existing AVSS methods with considerably fewer parameters. These results suggest that mimicking the anatomical connectome of the mammalian brain has great potential for advancing the development of deep neural networks.

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.

Parvalbumin and Somatostatin: Biomarkers for Two Parallel Tectothalamic Pathways in the Auditory Midbrain.

The inferior colliculus (IC) represents a crucial relay station in the auditory pathway, located in the midbrain's tectum and primarily projecting to the thalamus. Despite the identification of distinct cell classes based on various biomarkers in the IC, their specific contributions to the organization of auditory tectothalamic pathways have remained poorly understood. In this study, we demonstrate that IC neurons expressing parvalbumin (ICPV+) or somatostatin (ICSOM+) represent two minimally overlapping cell classes throughout the three IC subdivisions in mice of both sexes. Strikingly, regardless of their location within the IC, these neurons predominantly project to the primary and secondary auditory thalamic nuclei, respectively. Cell class-specific input tracing suggested that ICPV+ neurons primarily receive auditory inputs, whereas ICSOM+ neurons receive significantly more inputs from the periaqueductal gray and the superior colliculus (SC), which are sensorimotor regions critically involved in innate behaviors. Furthermore, ICPV+ neurons exhibit significant heterogeneity in both intrinsic electrophysiological properties and presynaptic terminal size compared with ICSOM+ neurons. Notably, approximately one-quarter of ICPV+ neurons are inhibitory neurons, whereas all ICSOM+ neurons are excitatory neurons. Collectively, our findings suggest that parvalbumin and somatostatin expression in the IC can serve as biomarkers for two functionally distinct, parallel tectothalamic pathways. This discovery suggests an alternative way to define tectothalamic pathways and highlights the potential usefulness of Cre mice in understanding the multifaceted roles of the IC at the circuit level.

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.

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.

Molecular characterization and antimicrobial activity of cecropin family in Hermetia illucens.

Antimicrobial peptides are potential alternatives to traditional antibiotics in the face of increasing bacterial resistance. Insects possess many antimicrobial peptides and have become a valuable source of novel and highly effective antimicrobial peptides. Hermetia illucens as a resource insect, for example, has the highest number of antimicrobial peptides of any dipteran. However, most antimicrobial peptides, especially cecropin, have not been comprehensively identified and have not been evaluated for their antimicrobial ability. In this study, we analyzed the localization and gene structure of 33 cecropin molecules in the H. illucens genome and evaluated their activity against common human pathogens. The results showed that 32 cecropin molecules were concentrated on 1 chromosome, most with 2 exons. More importantly, most of the cecropins had a good antibacterial effect against Gram-negative bacteria, and were not hemolytic. The minimum inhibitory concentration (MIC) of the cecropin designated H3 against E. coli was 4 µg/mL. The toxicity, killing time kinetics, and anti-biofilm activity of H3 were further investigated and confirmed its antimicrobial ability. Overall, H3 is a potential candidate for the development of new antimicrobials to treat severe infections caused by Gram-negative pathogens such as E. coli.

The "spillover effect" of long-term care insurance in China on spouses' health and well-being.

This study examined the spillover effect of long-term care insurance (LTCI) on the health outcomes and well-being of spouses for Chinese middle and old-aged adults with expected LTC demand or actual care burdens. Using panel data from the China Health and Retirement Longitudinal Study between 2011 and 2018, we investigated the impact of the introduction of LTCI pilots across several cities on old individuals by using the difference-in-differences (DID) approach. We found a spillover effect of LTCI on the health and well-being outcomes of spouses of middle and old-aged individuals with functional limitations. It might due to the fact that LTCI could relieve economic burden by reducing out-of-pocket medical expenditures, which further affects health and well-being of spouses. The spillover effect on health and well-being was found to be stronger for male spouses and low-educated spouses. Spouses of the individuals aged below 80 years old and those live without adult children were more likely to benefit from the introduction of LTCI. Moreover, providing combination benefits seems to make spouses better off than offering direct services. Therefore, the results implied that the expansion of LTCI not only helped the care recipients themselves but could also improve the health and well-being of the spouses of functionally impaired older adults.

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.

Insular cortex Hounsfield units predict postoperative neurocardiogenic injury in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Our study aims to investigate the association between the Hounsfield unit (Hu) value of the insular cortex (IC) during emergency admission and the subsequent occurrence of post-operative neurocardiogenic injury (NCI) among patients afflicted with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Patients baseline characteristics were juxtaposed between those with and without NCI. The significant variables were incorporated into a multivariable stepwise logistic regression model. Receiver operating characteristic (ROC) curves were drafted for each significant variable, yielding cutoff values and the area under the curve (AUC). Subgroup and sensitivity analyses were performed to assess the predictive performance across various cohorts and ascertain result stability. Propensity score matching (PSM) was ultimately employed to redress any baseline characteristic disparities. RESULTS: Patients displaying a right IC Hu value surpassing 28.65 exhibited an escalated risk of postoperative NCI upon confounder adjustment (p < 0.001). The ROC curve eloquently manifested the predictive capacity of right IC Hu in relation to NCI (AUC = 0.650, 95%CI, 0.591-0.709, p < 0.001). Further subgroup analysis revealed significant interactions between right IC Hu and factors such as age, history of heart disease, and Graeb 5-12 score. Sensitivity analysis further upheld the results' significant (p = 0.002). The discrepancy in NCI incidence between the two groups, both prior (p < 0.002) and post (p = 0.039) PSM, exhibited statistical significance. After PSM implementation, the likelihood of NCI displayed an ascending trend with increasing right IC Hu values, from the Hu1 cohort onward, receding post the Hu4 cohort. CONCLUSION: This study definitively establishes an elevated right IC Hu value in the early stages of emergency admission as an autonomous predictor for ensuing NCI subsequent to aSAH.

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.

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.

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.

A common thalamic hub for general and defensive arousal control.

The expression of defensive responses to alerting sensory cues requires both general arousal and a specific arousal state associated with defensive emotions. However, it remains unclear whether these two forms of arousal can be regulated by common brain regions. We discovered that the medial sector of the auditory thalamus (ATm) in mice is a thalamic hub controlling both general and defensive arousal. The spontaneous activity of VGluT2-expressing ATm (ATmVGluT2+) neurons was correlated with and causally contributed to wakefulness. In sleeping mice, sustained ATmVGluT2+ population responses were predictive of sensory-induced arousal, the likelihood of which was markedly decreased by inhibiting ATmVGluT2+ neurons or multiple downstream pathways. In awake mice, ATmVGluT2+ activation led to heightened arousal accompanied by excessive anxiety and avoidance behavior. Notably, blocking their neurotransmission abolished alerting stimuli-induced defensive behaviors. These findings may shed light on the comorbidity of sleep disturbances and abnormal sensory sensitivity in specific brain disorders.

Transcriptome-wide profiling of A-to-I RNA editing by Slic-seq.

Adenosine-to-inosine (A-to-I) RNA editing is a post-transcriptional processing event involved in diversifying the transcriptome and is responsible for various biological processes. In this context, we developed a new method based on the highly selective cleavage activity of Endonuclease V against Inosine and the universal activity of sodium periodate against all RNAs to enrich the inosine-containing RNA and accurately identify the editing sites. We validated the reliability of our method in human brain in both Alu and non-Alu elements. The conserved sites of A-to-I editing in human cells (HEK293T, HeLa, HepG2, K562 and MCF-7) primarily occurs in the 3'UTR of the RNA, which are highly correlated with RNA binding and protein binding. Analysis of the editing sites between the human brain and mouse brain revealed that the editing of exons is more conserved than that in other regions. This method was applied to three neurological diseases (Alzheimer's, epilepsy and ageing) of mouse brain, reflecting that A-to-I editing sites significantly decreased in neuronal activity genes.