Naoxueshu Oral Liquid Accelerates Post-Craniotomy Hematoma Absorption in Patients: An Open-Label, Multicenter, and Randomized Controlled Trial.

OBJECTIVE: To investigate whether Naoxueshu Oral Liquid (NXS) could promote hematoma absorption in post-craniotomy hematoma (PCH) patients. METHODS: This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18-80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS (10 mL thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage (ICH). RESULTS: A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients (60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set (FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median (Q1, Q3): 85% (71%, 97%) vs. 76% (53%, 93%), P<0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set (P>0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH (all P<0.05). CONCLUSIONS: The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics. (Registration No. ChiCTR1800017981).

Exploring the Causal Role of Immune Cells in Cerebral Aneurysm Through Single-Cell Transcriptomics and Mendelian Randomization Analysis.

Cerebral aneurysm (CA) represent a significant clinical challenge, characterized by pathological dilation of cerebral arteries. Recent evidence underscores the crucial involvement of immune cells in CA pathogenesis. This study aims to explore the complex interplay between immune cells and CA formation. We analyzed single-cell RNA sequencing data from the GSE193533 dataset, focusing on unruptured CA and their controls. Comprehensive cell-type identification and pseudotime trajectory analyses were conducted to delineate the dynamic shifts in immune cell populations. Additionally, a two-sample Mendelian Randomization (MR) approach was employed to investigate the causal influence of various immunophenotypes on CA susceptibility and the reciprocal effect of CA formation on immune phenotypes. Single-cell transcriptomic analysis revealed a progressive loss of vascular smooth muscle cells (VSMCs) and an increase in monocytes/macrophages (Mo/MΦ) and other immune cells, signifying a shift from a structural to an inflammatory milieu in CA evolution. MR analysis identified some vital immunophenotypes, such as CD64 on CD14+ CD16+ monocytes (OR: 1.236, 95% CI: 1.064 to 1.435, p=0.006), as potential risk factors for CA development, while others, like CD28- CD8br %CD8br (OR: 0.883, 95% CI: 0.789 to 0.988, p=0.030), appeared protective. Reverse MR analysis demonstrated that CA formation could modulate specific immunophenotypic expressions, highlighting a complex bidirectional interaction between CA pathology and immune response. This study underscores the pivotal role of immune cells in this process through the integration of single-cell transcriptomics with MR analysis, offering a comprehensive perspective on CA pathogenesis, potentially guiding future therapeutic strategies targeting specific immune pathways.

Establishment and validation of a CT-based prediction model for the good dissolution of mild chronic subdural hematoma with atorvastatin treatment.

PURPOSE: To develop and validate a prediction model based on imaging data for the prognosis of mild chronic subdural hematoma undergoing atorvastatin treatment. METHODS: We developed the prediction model utilizing data from patients diagnosed with CSDH between February 2019 and November 2021. Demographic characteristics, medical history, and hematoma characteristics in non-contrast computed tomography (NCCT) were extracted upon admission to the hospital. To reduce data dimensionality, a backward stepwise regression model was implemented to build a prognostic prediction model. We calculated the area under the receiver operating characteristic curve (AUC) of the prognostic prediction model by a tenfold cross-validation procedure. RESULTS: Maximum thickness, volume, mean density, morphology, and kurtosis of the hematoma were identified as the most significant predictors of good hematoma dissolution in mild CSDH patients undergoing atorvastatin treatment. The prediction model exhibited good discrimination, with an area under the curve (AUC) of 0.82 (95% confidence interval [CI], 0.74-0.90) and good calibration (p = 0.613). The validation analysis showed the AUC of the final prognostic prediction model is 0.80 (95% CI 0.71-0.86) and it has good prediction performance. CONCLUSION: The imaging data-based prediction model has demonstrated great prediction accuracy for good hematoma dissolution in mild CSDH patients undergoing atorvastatin treatment. The study results emphasize the importance of imaging data evaluation in the management of CSDH patients.

Cognitive impairment in Chinese traumatic brain injury patients: from challenge to future perspectives.

Traumatic Brain Injury (TBI) is a prevalent form of neurological damage that may induce varying degrees of cognitive dysfunction in patients, consequently impacting their quality of life and social functioning. This article provides a mini review of the epidemiology in Chinese TBI patients and etiology of cognitive impairment. It analyzes the risk factors of cognitive impairment, discusses current management strategies for cognitive dysfunction in Chinese TBI patients, and summarizes the strengths and limitations of primary testing tools for TBI-related cognitive functions. Furthermore, the article offers a prospective analysis of future challenges and opportunities. Its objective is to contribute as a reference for the prevention and management of cognitive dysfunction in Chinese TBI patients.

Cannabidiol alleviates neurological deficits after traumatic brain injury by improving intracranial lymphatic drainage.

Traumatic brain injury (TBI)-a severe clinical problem-is compounded by a lack of effective treatments and impeded intracranial metabolic waste clearance. The glymphatic system and meningeal lymphatic vessels are instrumental in TBI pathophysiology and crucial for clearing harmful substances. Cannabidiol (CBD) has the potential to address metabolic imbalances and improve cognitive functions in neurodegenerative diseases, but its specific effect on TBI remains unclear. Using a fluid percussion injury model, we adopted a comprehensive approach that included behavioral testing, various imaging techniques, and deep cervical lymph node (dCLN) ligation to evaluate CBD's effects on neurological outcomes and lymphatic clearance in a TBI mouse model. Our results demonstrated that CBD markedly enhanced motor, memory, and cognitive functions, correlating with reduced levels of detrimental neural proteins. CBD also expedited the removal of intracranial tracers, increased cerebral blood flow, and improved tracer migration from lymphatic vessels to dCLNs. Intriguingly, CBD treatment modified aquaporin-4 polarization and diminished neuroinflammatory indicators. A key observation was that disrupting efferent lymphatic channels nullified CBD's positive effects on waste removal and cognitive enhancements, whereas its anti-inflammatory benefits continued. This finding suggests that CBD's ability to improve waste clearance may operate via the lymphatic system, thereby improving neurological outcomes in TBI patients. Therefore, our study underscores CBD's potential therapeutic role in TBI management.

CD4+ CD11b+ T cells infiltrate and aggravate the traumatic brain injury depending on brain-to-cervical lymph node signaling.

AIM: We aim to identify the specific CD4+ T-cell subtype influenced by brain-to-CLN signaling and explore their role during the acute phase of traumatic brain injury (TBI). METHOD: Cervical lymphadenectomy or cervical afferent lymphatic ligation was performed before TBI. Cytokine array and western blot were used to detect cytokines, while the motor function was assessed using mNss and rotarod test. CD4+ T-cell subtypes in blood, brain, and CLNs were analyzed with Cytometry by time-of-flight analysis (CyTOF) or fluorescence-activated cell sorting (FACS). Brain edema and volume changes were measured by 9.4T MRI. Neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. RESULTS: Cervical lymphadenectomy and ligation of cervical lymphatic vessels resulted in a decreased infiltration of CD4+ T cells, specifically CD11b-positive CD4+ T cells, within the affected region. The population of CD4+ CD11b+ T cells increased in ligated CLNs, accompanied by a decrease in the average fluorescence intensity of sphingosine-1-phosphate receptor-1 (S1PR1) on these cells. Administration of CD4+ CD11b+ T cells sorted from CLNs into the lateral ventricle reversed the attenuated neurologic deficits, brain edema, and lesion volume following cervical lymphadenectomy. CONCLUSION: The infiltration of CD4+ CD11b+ T cells exacerbates secondary brain damage in TBI, and this process is modulated by brain-to-CLN signaling.

Fingolimod improves diffuse brain injury by promoting AQP4 polarization and functional recovery of the glymphatic system.

BACKGROUND: Diffuse brain injury (DBI) models are characterized by intense global brain inflammation and edema, which characterize the most severe form of TBI. In a previous experiment, we found that fingolimod promoted recovery after controlled cortical impact injury (CCI) by modulating inflammation around brain lesions. However, it remains unclear whether fingolimod can also attenuate DBI because of its different injury mechanisms. Furthermore, whether fingolimod has additional underlying effects on repairing DBI is unknown. METHODS: The impact acceleration model of DBI was established in adult Sprague-Dawley rats. Fingolimod (0.5 mg/kg) was administered 0.5, 24, and 48 h after injury for 3 consecutive days. Immunohistochemistry, immunofluorescence analysis, cytokine array, and western blotting were used to evaluate inflammatory cells, inflammatory factors, AQP4 polarization, apoptosis in brain cells, and the accumulation of APP after DBI in rats. To evaluate the function of the glymphatic system (GS), a fluorescent tracer was injected into the cistern. The neural function of rats with DBI was evaluated using various tests, including the modified neurological severity score (mNSS), horizontal ladder-crossing test, beam walking test, and tape sensing and removal test. Brain water content was also measured. RESULTS: Fingolimod administration for 3 consecutive days could reduce the levels of inflammatory cytokines, neutrophil recruitment, microglia, and astrocyte activation in the brain following DBI. Moreover, fingolimod reduced apoptotic protein expression, brain cell apoptosis, brain edema, and APP accumulation. Additionally, fingolimod inhibited the loss of AQP4 polarization, improved lymphatic system function, and reduced damage to nervous system function. Notably, inhibiting the GS weakened the therapeutic effect of fingolimod on the neurological function of rats with DBI and increased the accumulation of APP in the brain. CONCLUSIONS: In brief, these findings suggest that fingolimod alleviates whole-brain inflammation and GS system damage after DBI and that inhibiting the GS could weaken the positive effect of fingolimod on nerve function in rats with DBI. Thus, inhibiting inflammation and regulating the GS may be critical for the therapeutic effect of fingolimod on DBI.

The value of computed tomography texture analysis in identifying chronic subdural hematoma patients with a good response to polytherapy.

This study aimed to investigate the predictive factors of therapeutic efficacy for chronic subdural hematoma (CSDH) patients receiving atorvastatin combined with dexamethasone therapy by using clinical imaging characteristics in conjunction with computed tomography (CT) texture analysis (CTTA). Clinical imaging characteristics and CT texture parameters at admission were retrospectively investigated in 141 CSDH patients who received atorvastatin combined with dexamethasone therapy from June 2019 to December 2022. The patients were divided into a training set (n = 81) and a validation set (n = 60). Patients in the training data were divided into two groups based on the effectiveness of the treatment. Univariate and multivariate analyses were performed to assess the potential factors that could indicate the prognosis of CSDH patients in the training set. The receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of the significant factors in predicting the prognosis of CSDH patients and was validated using a validation set. The multivariate analysis showed that the hematoma density to brain parenchyma density ratio, singal min (minimum) and singal standard deviation of the pixel distribution histogram, and inhomogeneity were independent predictors for the prognosis of CSDH patients based on atorvastatin and dexamethasone therapy. The area under the ROC curve between the two groups was between 0.716 and 0.806. As determined by significant factors, the validation's accuracy range was 0.816 to 0.952. Clinical imaging characteristics in conjunction with CTTA could aid in distinguishing patients with CSDH who responded well to atorvastatin combined with dexamethasone.

Delayed Administration of an Angiotensin II Type 2 Receptor Agonist Promotes Functional Recovery of the Brain and Heart After Traumatic Brain Injury.

Cardiac injury is a common complication following traumatic brain injury (TBI) that can lead to poor clinical outcomes. Angiotensin II type 2 receptor (AT2R) activation exerts protective roles in the brain and heart, yet its potential impact on TBI or TBI-induced cardiac deficits remains elusive. The goal of this study was to investigate the influence of AT2R activation on recovery after TBI-induced cognitive and cardiac injury using the selective nonpeptide AT2R agonist compound 21 (C21). TBI was induced by cortical impact injury in male adult C57BL/6J mice, and the mice received C21 (0.03 mg/kg, intraperitoneally) starting from 24 h after TBI and continuing once daily. C21 facilitated cognitive function recovery until 1 month after TBI. C21 alleviated blood-brain barrier leakage and brain edema and inhibited the expression of proinflammatory cytokines in the brain after 3 consecutive days of treatment. C21 improved cerebral blood flow after 1 month, although the lesion volume was not affected. C21 also reduced the expression of proinflammatory cytokines in the heart after a 3-day consecutive treatment. Meanwhile, C21 benefited cardiac function, as identified by increased left ventricular ejection fraction 1 month after TBI. In addition, C21 alleviated TBI-induced cardiac hypertrophy and fibrosis; however, blood pressure was not affected. Our results demonstrate that AT2R activation ameliorates TBI-induced neurological and cardiac deficits.

Inactivation of ERK1/2 signaling mediates dysfunction of basal meningeal lymphatic vessels in experimental subdural hematoma.

Rationale: Meningeal lymphatic vessels (MLVs) are essential for the clearance of subdural hematoma (SDH). However, SDH impairs their drainage function, and the pathogenesis remains unclear. Herein, we aimed to understand the pathological mechanisms of MLV dysfunction following SDH and to test whether atorvastatin, an effective drug for SDH clearance, improves meningeal lymphatic drainage (MLD). Methods: We induced SDH models in rats by injecting autologous blood into the subdural space and evaluated MLD using Gadopentetate D, Evans blue, and CFSE-labeled erythrocytes. Whole-mount immunofluorescence and transmission electron microscopy were utilized to detect the morphology of MLVs. Phosphoproteomics, western blot, flow cytometry, and in vitro experiments were performed to investigate the molecular mechanisms underlying dysfunctional MLVs. Results: The basal MLVs were detected to have abundant valves and play an important role in draining subdural substances. Following SDH, these basal MLVs exhibited disrupted endothelial junctions and dilated lumen, leading to impaired MLD. Subsequent proteomics analysis of the meninges detected numerous dephosphorylated proteins, primarily enriched in the adherens junction, including significant dephosphorylation of ERK1/2 within the meningeal lymphatic endothelial cells (LECs). Subdural injection of the ERK1/2 kinase inhibitor PD98059 resulted in dilated basal MLVs and impaired MLD, resembling the dysfunctional MLVs observed in SDH. Moreover, inhibiting ERK1/2 signaling severely disrupted intercellular junctions between cultured LECs. Finally, atorvastatin was revealed to protect the structure of basal MLVs and accelerate MLD following SDH. However, these beneficial effects of atorvastatin were abolished when combined with PD98059. Conclusion: Our findings demonstrate that SDH induces ERK1/2 dephosphorylation in meningeal LECs, leading to disrupted basal MLVs and impaired MLD. Additionally, we reveal a beneficial effect of atorvastatin in improving MLD.

Multimodality management for chronic subdural hematoma in China: protocol and characteristics of an ambidirectional, nationwide, multicenter registry study.

BACKGROUND: Despite its prevalence, there is ongoing debate regarding the optimal management strategy for chronic subdural hematoma (CSDH), reflecting the variability in clinical presentation and treatment outcomes. This ambidirectional, nationwide, multicenter registry study aims to assess the efficacy and safety of multimodality treatment approaches for CSDH in the Chinese population. METHODS/DESIGN: A multicenter cohort of CSDH patients from 59 participating hospitals in mainland China was enrolled in this study. The treatment modalities encompassed a range of options and baseline demographics, clinical characteristics, radiographic findings, and surgical techniques were documented. Clinical outcomes, including hematoma resolution, recurrence rates, neurological status, and complications, were assessed at regular intervals during treatment, 3 months, 6 months, 1 year, and 2 years follow-up. RESULT: Between March 2022 and August 2023, a comprehensive cohort comprising 2173 individuals who met the criterion was assembled across 59 participating clinical sites. Of those patients, 81.1% were male, exhibiting an average age of 70.12 ± 14.53 years. A historical record of trauma was documented in 48.0% of cases, while headache constituted the predominant clinical presentation in 58.1% of patients. The foremost surgical modality employed was the burr hole (61.3%), with conservative management accounting for 25.6% of cases. Notably, a favorable clinical prognosis was observed in 88.9% of CSDH patients at 3 months, and the recurrence rate was found to be 2.4%. CONCLUSION: This registry study provides critical insights into the multimodality treatment of CSDH in China, offering a foundation for advancing clinical practices, optimizing patient management, and ultimately, improving the quality of life for individuals suffering from this challenging neurosurgical condition. TRIAL REGISTRATION: ChiCTR2200057179.

Vitamin D accelerates the subdural hematoma clearance through improving the meningeal lymphatic vessel function.

Subdural hematoma (SDH) drains into the extracranial lymphatic system through the meningeal lymphatic vessels (mLVs) but the formation of SDH impairs mLVs. Because vitamin D (Vit D) can protect the endothelial cells, we hypothesized that Vit D may enhance the SDH clearance. SDH was induced in Sprague-Dawley rats and treated with Vit D or vehicle. Hematoma volume in each group was measured by H&E staining and hemoglobin quantification. Evans blue (EB) quantification and red blood cells injection were used to evaluated the drainage of mLVs. Western blot analysis and immunofluorescence were conducted to assess the expression of lymphatic protein markers. We also examined the inflammatory factors levels in subdural space by ELISA. Vit D treatment significantly reduced SDH volume and improved the drainage of SDH to cervical lymph nodes. The structure of mLVs in SDH rats were protected by Vit D, and the expressions of LYVE1, PROX1, FOXC2, and VE-cadherin were increased after Vit D treatment. The TNF-α, IL-6, and IL-8 levels were reduced in Vit D group. In vitro, Vit D also increased the VE-cadherin expression levels under inflammation. Vit D protects the structure of mLVs and enhances the absorption of SDH, partly by the anti-inflammatory effect of Vit D.

Chinese Neurosurgical Randomized Controlled Trials: Dynamics in Trial Implementation and Completion.

BACKGROUND AND OBJECTIVES: The focus on evidence-based neurosurgery has led to a considerable amount of neurosurgical evidence based on randomized controlled trials (RCTs) being published. Nevertheless, there has been no systematic appraisal of China's contribution to RCTs. Information about the changes in characteristics of Chinese neurosurgical RCTs before and during the COVID-19 pandemic is limited. This study aims to perform a detailed examination and comprehensive analysis of the characteristics of Chinese neurosurgical RCTs and to examine the differences before and during the COVID-19 pandemic. METHODS: We conducted a comprehensive database search including PubMed, Web of Science, Embase, and Cochrane Library up to March 2023, with a criterion of inclusion based on an impact factor above 0. We subsequently examined the design and quality parameters of the included RCTs and assessed the differences before and during the COVID-19 pandemic (based on follow-up ending before or after January 2020). Moreover, we investigated potential factors that may affect the quality and developmental trends of neurosurgical RCTs in China. RESULTS: The main focus of the 91 neurosurgical RCTs was vascular disease (47.3%) and trauma (18.7%). Over half of the trials used Consolidated Standards of Reporting Trial diagrams (69.2%), and the majority compared nonsurgical treatments (63.7%). Larger trials tended to have better quality scores, but those with significant efficacy were less likely to have power calculations. Over time, there was an increase in the use of Consolidated Standards of Reporting Trial diagrams and well-specified outcomes. The COVID-19 pandemic may have hindered the completion of neurosurgical RCTs in China, but it has had little impact on the design and quality so far. CONCLUSION: Chinese neurosurgeons have made significant progress in advancing neurosurgical RCTs despite challenges. However, shortcomings in sample size and power calculation need attention. Improving the rigor, rationality, and completeness of neurosurgical RCT design is crucial.

Age-adjusted D-Dimer Thresholds Combined with the Modified Wells Score as a Predictor of Lower Extremity Deep Venous Thrombosis.

BACKGROUND: Neurosurgical patients are at an increased risk of deep venous thrombosis (DVT), which, if not properly managed, can lead to pulmonary embolism. This study aimed to investigate the accuracy of age-adjusted D-dimer thresholds combined with the modified Wells score as a predictor for lower extremity DVT diagnosis. METHODS: We conducted a study among patients aged >50 years with suspected lower extremity DVT in the neurosurgery intensive care unit between December 2019 and December 2020. Receiver operating characteristic curve analysis was performed to examine the diagnostic capacity of age-adjusted D-dimer combined with the modified Wells score. RESULTS: A total of 233 participants, with an average age of 71.81 ± 12.59 years, were enrolled in the study. The mean D-dimer levels were 0.73 ± 0.39 mg/L. Among the participants, 57 (57.9%, 33 males) were diagnosed with DVT. The age-adjusted D-dimer combined with the modified Wells score had the highest area under the curve for diagnosing lower extremity DVT compared to D-dimer and age-adjusted D-dimer alone, with an AUC of 0.858. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the age-adjusted D-dimer combined with the modified Wells score for DVT diagnosis were 78.95%, 80.68%, 57%, 92.2%, and 80.26%, respectively. When analyzing subgroups, the accuracy was 79.55% for participants with cerebral hemorrhage, 81.69% for those with craniocerebral injury, 74.99% for participants with intracranial infection, and 88.89% for those with craniocerebral tumor. CONCLUSION: The combination of the age-adjusted D-dimer thresholds with the modified Wells score might effectively predict lower extremity DVT.

Three-dimensional laser combined with C-arm computed tomography-assisted puncture of intracerebral hemorrhage.

Background: Intracerebral hemorrhage (ICH) is the deadliest subtype of stroke, with a 30-day case fatality rate of approximately 40%. Timely and accurate treatment is essential to facilitate recovery. The introduction of stereotactic instruments and navigation systems has greatly improved the accuracy of surgical treatment. In this study, we explored the application and effects of a three-dimensional (3D) laser combined with C-arm computed tomography (CT) on ICH puncture. Materials and methods: According to the principle of randomness, 118 patients with ICH were divided into control and experimental groups. The control group was treated with CT-guided puncture, and the experimental group was treated with 3D laser combined with C-arm CT puncture. The hematoma clearance rates at 3, 5, and 7 days after surgery and the prognosis at 1, 3, and 6 months after surgery were compared between the two groups. Results: The hematoma clearance rates of the group using 3D laser combined with C-arm CT at 3, 5, and 7 days after surgery were significantly higher than those of the control group, and the difference was statistically significant (p < 0.05). One month postoperatively, the daily living ability (ADL) grading and recovery of the patients in the test group was significantly better than those of the control group (p < 0.05), but there was no statistically significant difference in ADL 3 and 6 months after surgery (p > 0.05). Conclusion: 3D laser combined with C-arm CT puncture has the advantages of real-time guidance, accurate positioning, and simple operation. It is an effective minimally invasive surgical method that is easy to master.

Improvements of the Tada formula in estimating the intracerebral hemorrhage volume based on computed tomography.

Background: The Tada formula has been used widely for assessing intracerebral hemorrhage (ICH) volume. However, it is only suitable for calculating regular and small volume hematomas. Therefore, we attempted to improve the formula to increase its accuracy and maintain its efficiency. Methods: Computed tomography (CT) data of 15 balls of different shapes filled with predetermined volumes of water were collected to verify the high accuracy of FireVoxel in measuring the volume. CT data from 329 patients with ICH from two different hospitals grouped by hematoma shape and volume were retrospectively reviewed. The distinctly shaped ICH volumes of 245 patients from one of the hospitals were estimated using FireVoxel and the Tada formula grouped by the hematoma shape and volume. Taking the hematoma volumes measured by FireVoxel as the reference standard, the accuracy and reliability of the Tada formula were evaluated. Polynomial fitting was employed to determine the associations of the values calculated between the Tada formula and FireVoxel. Then, a corrected Tada formula (C-Tada formula) was produced, and the limits of agreement between the C-Tada formula and Tada formula were analyzed with Bland-Altman analysis. The C-Tada formula was validated by the CT data of 84 patients from another hospital. Results: The volume measured by FireVoxel can be set as the reference standard. The ICH volume calculated by the Tada formula was significantly greater than that calculated by FireVoxel for different shapes and volumes. The percentage deviation between the volumes calculated by FireVoxel and the Tada formula was also statistically significant and influenced by ICH shape and volume. The limits of agreement between the C-Tada formula and FireVoxel were tighter than those between the Tada formula and FireVoxel. The percentage deviation of the C-Tada formula calculation from the FireVoxel estimate was greatly reduced relative to that for the Tada formula for each group. Conclusions: The C-Tada formula is more clinically valuable than the Tada formula, given its sufficient efficiency and greater accuracy and reliability in ICH volume calculation.

Susceptibility to Hepatotoxic Drug-induced Liver Injury Increased after Traumatic Brain Injury in Mice.

The early stages of brain injury can induce acute liver injury, which can be recovered in the short term. Continued medication treatment during hospitalization for brain injury alleviates the prognosis and contributes to a high incidence of drug-induced liver injury (DILI). We hypothesize that there is an interaction between changes in the hepatic environment after brain injury and liver injury produced by intensive drug administration, leading to an upregulation of the organism's sensitivity to DILI. In this study, mice models of TBI were established by controlled cortical impact and models of DILI were constructed by acetaminophen (APAP). All mice were divided into four groups: Sham, TBI, APAP, and TBI+APAP, and related liver injury indicators in liver and serum were detected by Western blot, RT-PCR, and immunohistochemical staining. The results suggested that liver injury induced in the early stages of brain injury recovered in three days, but this state could still significantly aggravate DILI, represented by higher liver enzymes (AST and ALT), oxidative stress (increase in malondialdehyde concentration and deregulation of glutathione and superoxide dismutase activities), inflammatory response (activation of HMGB1/TLR4/NF-κB signaling pathway, and increased mRNA and protein levels of pro-inflammatory cytokines including TNF-α, IL-6, and IL-1ß), and apoptosis (TUNEL assay, upregulation of Bax protein and deregulation of Bcl-2 protein). In summary, our results suggested that traumatic brain injury is a potential susceptibility factor for DILI and exacerbates DILI.

Factors influencing wait-and-watch management in mild primary chronic subdural hematoma: a retrospective case-control study.

PURPOSE: To identify prognostic factors in patients with primary chronic subdural hematoma (CSDH) undergoing wait-and-watch management. METHODS: A case-control study was conducted in a single center from February 2019 to November 2021 to identify independent influencing factors of wait-and-watch management in mild CSDH patients using wait-and-watch as monotherapy. A total of 39 patients who responded to wait-and-watch management (cases) and 24 nonresponders (controls) matched for age, sex, height, weight, MGS-GCS (Markwalder grading scale and Glasgow Coma Scale), and bilateral hematoma were included. Demographics, blood cell counts, serum biochemical levels, imaging data, and relevant clinical features at baseline were collected. RESULTS: Univariate analysis revealed significant differences between cases and controls in hematoma volume, ability to urinate, maximal thickness of the hematoma, and hypodensity of the hematoma. Hypodense hematoma and hematoma volume were independently associated with the outcome in multivariate analysis. Combining these independently influencing factors revealed an area under the receiver operator characteristic curve of 0.741 (95% CI 0.609-0.874, sensitivity = 0.783, specificity = 0.667). CONCLUSIONS: The results of this study may aid in identifying patients with mild primary CSDH who could benefit from conservative management. While wait-and-watch management may be an option in some cases, clinicians need to suggest medical interventions, such as pharmacotherapy, when appropriate.

Cerebral glucagon-like peptide-1 receptor activation alleviates traumatic brain injury by glymphatic system regulation in mice.

AIM: We aimed to assess the effects of cerebral glucagon-like peptide-1 receptor (GLP-1R) activation on the glymphatic system and whether this effect was therapeutic for traumatic brain injury (TBI). METHODS: Immunofluorescence was employed to evaluate glymphatic system function. The blood-brain barrier (BBB) permeability, microvascular basement membrane, and tight junction expression were assessed using Evans blue extravasation, immunofluorescence, and western blot. Immunohistochemistry was performed to assess axonal damage. Neuronal apoptosis was evaluated using Nissl staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and western blot. Cognitive function was assessed using behavioral tests. RESULTS: Cerebral GLP-1R activation restored glymphatic transport following TBI, alleviating BBB disruption and neuronal apoptosis, thereby improving cognitive function following TBI. Glymphatic function suppression by treatment using aquaporin 4 inhibitor TGN-020 abolished the protective effect of the GLP-1R agonist against cognitive impairment. CONCLUSION: Cerebral GLP-1R activation can effectively ameliorate neuropathological changes and cognitive impairment following TBI; the underlying mechanism could involve the repair of the glymphatic system damaged by TBI.