A Novel Rat Model of Venous Hypertensive Myelopathy Produced by Arteriovenous Bypass Plus Venous Stenosis.

BACKGROUND AND OBJECTIVES: Venous hypertensive myelopathy (VHM), mainly induced by the spinal dural arteriovenous fistula, is a congestive spinal cord injury that currently has no appropriate animal model available in preclinical research. METHODS: Sprague Dawley rats (280-320 g) were used. The rats were divided into 3 groups: (1) Group 1, which underwent renal artery-dorsal spinal venous bypass (AVB group); (2) Group 2, which underwent renal artery-dorsal spinal venous bypass and drainage vein stenosis (AVB/VS group); and (3) Control group, with T13 dorsal vein ligation. The success of the model was assessed using Doppler ultrasound and 7.0-T magnetic resonance imaging. Transmission electron microscopy, histochemistry, proteomics, and western blot analysis were used to evaluate ultrastructural, pathological, and molecular features in the spinal cord and cerebrospinal fluid (CSF). RESULTS: The success rate of the arteriovenous bypass was 100% at 5 days and 83% at 2 weeks. The locomotor assessment showed decreased lower extremity strength in the AVB/VS group (P = .0067), whereas unremarkable changes were found in the AVB and Control groups. Histochemical staining suggested a 2-fold expansion of the dorsal spinal vein in the AVB/VS group, which was lower than that in the AVB group (P < .05); however, the former displayed greater myelin and neuronal damage (P < .05) and slight dilatation of the central canal (P > .05). Proteomics analysis revealed that the complement and coagulation cascade pathways were upregulated in the CSF of AVB/VS rats, whereas the C3 level was elevated both in the CSF and bilateral spinal cord. Furthermore, overexpression of C3, ITGB2, and CD9 in the spinal cord was confirmed by immunoblotting. CONCLUSION: These findings suggest that the AVB/VS model can effectively mimic the clinical and molecular characteristics of VHM. Furthermore, they suggest that impaired deep intramedullary venous drainage is the key reason for the VHM.

Gas migration characteristics in vehicle tank under different ventilation conditions.

In recent years, due to the frequent occurrence of accidents in confined space operations, horizontal ammonia tank trucks with higher accident frequencies were selected for numerical simulation research through comparative analysis. The ammonia concentration variation characteristics of horizontal ammonia tank cars were simulated under four conditions: natural ventilation with 0° incoming air, natural ventilation with 45° incoming air, mechanical ventilation with extraction, and mechanical ventilation with compression. The results indicate that natural ventilation requires 48 h to reduce the ammonia concentration to a safe range for operation, while mechanical ventilation reduces the ammonia concentration to infinity and approaches zero within 30 min according to regulations, making the working environment safer; Set up monitoring points inside the tank to monitor the gas disturbance inside the tank at different wind speeds. Based on the ammonia concentration cloud map and the monitoring point wind speed, it can be concluded that local ammonia accumulation is more likely to occur on both sides of the tank due to poor ventilation. Comparing and analyzing the simulated values with theoretical calculations and experiments, it was found that there are differences in the degree of gas change but the overall trend is the same. This indicates that ventilation simulation and the determination of ammonia migration characteristics have practical significance for guiding on-site operations.

Clinical features, treatment strategies and outcomes of craniocervical junction arteriovenous fistulas: a cohort study of 193 patients.

BACKGROUND: Craniocervical junction (CCJ) arteriovenous fistulas (AVFs) are rare. The current treatment strategies for AVFs with different angioarchitecture need to be clarified. The present study aimed to analyse the correlation between angioarchitecture and clinical characteristics, share our experience in treating this disease and identify risk factors associated with subarachnoid haemorrhage (SAH) and poor outcomes. METHODS: A total of 198 consecutive patients with CCJ AVFs from our neurosurgical centre were retrospectively reviewed. The patients were grouped according to their clinical manifestations, and their baseline clinical characteristics, angioarchitecture, treatment strategies and outcomes were summarised. RESULTS: The patients' median age was 56 years (IQR 47-62 years). The majority of patients were men with 166 (83.8%) patients. The most common clinical manifestation was SAH (52.0%), followed by venous hypertensive myelopathy (VHM) (45.5%). The most common CCJ AVFs type was dural AVF, with 132 (63.5%) fistulas. The most frequent fistula location was C-1 (68.7%) and dural branch of vertebral artery (70.2%) was the most involved arterial feeders for fistulas. The most common direction of venous drainage was descending intradural drainage (40.9%), followed by ascending intradural drainage (36.5%). Microsurgery was the most common treatment strategy applied for 151 (76.3%) patients, 15 (7.6%) patients were treated with interventional embolisation only, and 27 (13.6%) received both interventional embolisation and microsurgical treatment. The learning curve for microsurgery only was analysed by cumulative summation method, and the turning point was the 70th case, and blood loss in post-group was lower than that in pre-group (p=0.034). At the last follow-up, there were 155 (78.3%) patients with favourable outcomes (modified Rankin Scale(mRS)<3). Age≥56 (OR 2.038, 95% CI 1.039 to 3.998, p=0.038), VHM as the clinical manifestation (OR 4.102, 95% CI 2.108 to 7.982, p<0.001) and pretreatment mRS≥3 (OR 3.127, 95% CI 1.617 to 6.047, p<0.001) were significantly associated with poor outcomes. CONCLUSION: The arterial feeders and direction of the venous drainage were important factors in the clinical presentations. The location of fistula and drainage vein was essential for choosing different treatment strategies. Older age, VHM onset and poor pretreatment functional status predicted poor outcomes.

Clinical and prognostic features of venous hypertensive myelopathy from craniocervical arteriovenous fistulas: a retrospective cohort study.

OBJECTIVE: Current knowledge about venous hypertensive myelopathy (VHM) is incomplete. This study was performed with the aim of clarifying the clinical features and outcomes of craniocervical VHM. METHODS: This retrospective, single-center cohort study included 65 patients with craniocervical junction arteriovenous fistulas resulting in VHM treated in Xuanwu Hospital from January 1, 2002, to December 30, 2020. All patients underwent microsurgery or endovascular treatment. The primary outcome was neurological function assessment using the Japanese Orthopaedic Association (JOA) scale, modified Aminoff-Logue Scale (mALS), and Venous Hypertensive Myelopathy Scale (VHMS). The secondary outcomes were recurrences and postoperative adverse events. Pearson linear regression and receiver operating characteristic curves were used to evaluate the relationships among the three scales. Kaplan-Meier and multivariate logistic regression analyses were performed to predict outcomes. RESULTS: The mean patient age was 57.4 ± 11.4 years, and 88% of patients were male. The 1-year follow-up rate was 83.1%, and the 5-year follow-up rate was 50.8%. The VHMS was correlated with the JOA (R2 = 0.6722) and mALS (R2 = 0.7399) and increased the assessment accuracy by approximately 20% when compared with the other two scales. Overall, 25.9% of patients experienced delayed neurological decline beyond the 1-year follow-up. Further logistic regression suggested that age > 65 years was an independent predictor (OR 7.831, 95% CI 1.090-56.266; p = 0.041). Embolic recanalization and new bilateral symmetry feeders were the major reasons for recurrence. Recurrence increased the risk of adverse events after the second surgery (OR 20.455, 95% CI 1.170-357.320; p = 0.039). CONCLUSIONS: CCJ AVFs resulting in VHM are a rare but deadly complication, and providers should be cautious of age-related delayed neurological decline and strive for a one-time anatomical cure.

Diagnosis and Treatment of a Dural Arteriovenous Fistula Involving the Superior Petrosal Vein.

OBJECTIVE: A dural arteriovenous fistula involving the superior petrosal vein (SPV DAVF) is an extremely rare condition. Therefore, its clinical presentation, imaging characteristics, treatment methods, and risk factors remain unclear. In this study, we discuss and analyze the aforementioned features of an SPV DAVF. METHODS: We retrospectively reviewed 30 patients with SPV DAVFs, with a 1-year follow-up rate of 96.67% (29 of 30). The neurological function of the patients was assessed using the modified Aminoff-Logue scale and the modified Rankin Scale score. The risk factors before and after treatment were established using univariate and multivariate logistic regression analyses. Additionally, treatments involving 3 distinct SPV DAVF drainage patterns were presented. RESULTS: Of the 30 patients, 24 were men (80.0%). Besides, the angiography images were reexamined 12 months after surgery. Univariate analyses indicated that the extent of edema (odds ratio 1.889, 95% confidence interval 1.132-3.154) and the number of draining veins (≤2) (odds ratio 10.833, 95% confidence interval 1.961-59.834) were risk factors for pretreatment modified Rankin Scale score ≥3. However, multivariate analyses revealed no statistically significant differences (P = 0.051, P = 0.055). Following the multivariate analyses, steroid pulse (odds ratio 12.153 95% confidence interval 1.080-136.772) was found to be the only significant risk factor for post-treatment difference between pretreatment and 1-year follow-up modified Rankin Scale score ≥2. CONCLUSIONS: A DAVF with SPV drainage is an uncommon type of intracranial vascular malformation. Most lesions involve the brain stem or high cervical spinal cord, thereby posing a higher risk of disability or death. Moreover, neuronal damage from persistent venous hypertension is permanent. Therefore, precise diagnosis and timely treatment are key to a good patient prognosis.

Potential biomarkers of spinal dural arteriovenous fistula: C4BPA and C1QA.

BACKGROUND AND PURPOSE: A major challenge in spinal dural arteriovenous fistula (SDAVF) is timely diagnosis, but no specific predictive biomarkers are known. METHODS: In the discovery cohort (case, n = 8 vs. control, n = 8), we used cerebrospinal fluid (CSF) and paired plasma samples to identify differentially expressed proteins by label-free quantitative proteomics. Further bioinformatics enrichment analyses were performed to screen target proteins. Finally, it was validated by ELISA in two of the new cohorts (case, n = 17 vs. control, n = 9), and univariate analysis, simple linear regression, and receiver operator characteristic (ROC) curve analysis were performed to evaluate the diagnostic potential. RESULTS: In the discovery cohort, the most overexpressed proteins were APOB and C4BPA in CSF samples of patients. The GO/KEGG enrichment analysis indicated that the upregulated proteins were mainly involved in the acute inflammatory response and complement activation. Hub-gene analysis revealed that APP might be the key protein in the molecular interaction network. In the validation cohort, C4BPA and C1QA were significantly overexpressed in the CSF of patients, averaging 3046.9 ng/ml and 2167.2 ng/ml, respectively. Simple linear regression demonstrated that levels of C1QA and C4 were positively correlated with total protein in CSF (R2 = 0.8021, p = 0.0005; R2 = 0.7447, p = 0.0013). The areas under the ROC curves of C4BPA and C1QA were 0.86 and 1.00, respectively. CONCLUSIONS: This study was the first to identify C4BPA and C1QA as potential biomarkers for the diagnosis of SDAVF and revealed that complement pathway activation might be one of the molecular mechanisms for venous hypertension myelopathy.

Arteriovenous fistulas in the craniocervical junction region: With vs. without spinal arterial feeders.

Objective: Arteriovenous fistulas (AVFs) in the craniocervical junction (CCJ) region are a rare occurrence with special clinical manifestations. This study retrospectively reviewed patients with CCJ AVFs treated at our neurosurgical center, aiming to enhance the understanding of CCJ AVFs. Methods: A total of 113 patients with CCJ AVFs treated at our neurosurgical center between January 2013 and December 2020 were enrolled. They were grouped as patients with CCJ AVFs with spinal arterial feeders (n = 20) and patients with CCJ AVF without spinal arterial feeders (n = 93). Clinical presentation, angiographic characteristics, intraoperative findings, and treatment outcomes were analyzed. Results: The patients' median age was 55 years (IQR 47.5-62 years). The proportion of males in the group without spinal arterial feeders was significantly higher (p = 0.001). Subarachnoid hemorrhage (SAH) was the most common clinical presentation, especially in the group with spinal arterial feeders (p < 0.001). There were significant differences in AVF type, fistula location, and direction of the venous drainage between the two groups (p < 0.001). Intervention embolization combined with microsurgery was more common in treating AVFs with spinal arterial feeders (p = 0.006). Spinal arterial feeders did not affect the outcome (p = 0.275). Conclusions: SAH was the most common presentation of CCJ AVFs in this study. Microsurgery and interventional embolization were optional treatment strategies. The angioarchitecture of CCJ AVFs was essential for selecting treatment strategies.

Comparative Clinical Effectiveness and Safety of Bone Morphogenetic Protein Versus Autologous Iliac Crest Bone Graft in Lumbar Fusion: A Meta-analysis and Systematic Review.

STUDY DESIGN: This is a systematic literature review and meta-analysis. OBJECTIVE: We aimed to evaluate the efficacy and safety of recombinant human bone morphogenetic protein (RhBMP) and autologous iliac crest bone graft (ICBG) in lumbar fusion. SUMMARY OF BACKGROUND DATA: RhBMP has been emphasized in lumbar fusion due to high fusion success rate. However, ICBG remains the criterion standard graft approach for lumbar fusion. The safety and effectiveness of rhBMP are controversial. METHODS: Prospective randomized controlled trials were searched from PubMed, EMBASE, and Cochrane Central Register of Controlled Trails by using Medical Subject Headings terms "bone morphogenetic protein,' "bone transplantation,' and "spinal fusion.' Two independent investigators screened eligible studies, assessed the bias of original articles, extracted data including fusion success, Oswestry disability index improvement, improved short form 36 questionnaire scores, adverse events and re-operation, and a subgroup analysis. The GRADE approach was used to grade quality of evidence. RESULTS: Twenty randomized controlled trials (2185 patients) met the inclusion criteria. There were higher fusion success rate (odds ratio [OR] 3.79, 95% confidence interval [CI] 1.88-7.63, P = 0.0002), better improvement of Oswestry Disability Index (mean difference 1.54, 95% CI 0.18-2.89, P = 0.03), and lower re-operation rate (OR 0.59, 95% CI 0.43-0.80, P = 0.0007) in rhBMP group. Heterogeneity was obvious in fusion success rate (I = 58%); hence, a subgroup analysis, based on protein type (rhBMP-2 or rhBMP-7), was performed, which suggested that only rhBMP-2 was better than ICBG for lumbar fusion. There was no difference in the incidence of adverse events between rhBMP and ICBG (OR 0.91, 95% CI 0.70-1.18, P = 0.47). CONCLUSION: In lumbar fusion, rhBMP-2 exhibited a higher fusion success rate and reduced the risk of re-operation. No difference in complication rate is between rhBMP (rhBMP-2 and rhBMP-7) and ICBG. We suggest rhBMP especially rhBMP-2 as an effective substitute for ICBG for lumbar fusion. LEVEL OF EVIDENCE: 1.

Comparative Clinical Effectiveness of Tubular Microdiscectomy and Conventional Microdiscectomy for Lumbar Disc Herniation: A Systematic Review and Network Meta-Analysis.

STUDY DESIGN: This study is a systematic literature review and meta-analysis. OBJECTIVE: To evaluate the efficacy of tubular microdiscectomy (TMD) compared with conventional microdiscectomy (CMD) for lumbar disc herniation (LDH). SUMMARY OF BACKGROUND DATA: TMD has developed rapidly due to reduced tissue trauma by minimization of the required access to spine and disc herniation; however, CMD remains the standard of care for this patient group. To date, it remains debatable whether TMD is superior to CMD for LDH. METHODS: We performed a comprehensive database search of PubMed, EMBASE, and Cochrane Central Register of Controlled Trails for prospective randomized controlled trials (RCTs), through using Medical Subject Headings (MeSH) terms "microdiscectomy," "tubular microdiscectomy," "minimally invasive surgery," and "spinal disease." The retrieved results were last updated on March 15, 2018. Two independent investigators selected qualified studies, extracted indispensable data, assessed risk of bias of original papers. The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used to grade quality of evidence. If I >50, the heterogeneity is considerable. RESULTS: Four RCT studies (total n = 605), involving 610 individuals with a follow-up period of no less than 12 months, were selected for further review. We assessed these studies as low overall risk of bias. There was low-quality evidence that TMD was superior to CMD considering postoperative Oswestry Disability Index scores (SMD, -3.43, 95% CI, -4.64 to -2.21, P < 0.00001). Compared with CMD, the TMD group exhibited significantly worse Short Form-36 physical function scores (SMD, -4.83, 95% CI, -8.94 to -0.72, P = 0.02). There were no significant differences in the visual analogue scale (P = 0.30), operative time (P = 0.68), dural tear (P = 0.52), and reoperation (P = 0.98). CONCLUSION: The benefits 1 year after TMD were similar to that of CMD. There was no significant difference in the incidence of reoperation and dural tear. LEVEL OF EVIDENCE: 1.

Outcome predictors in the management of intramedullary classic ependymoma: An integrative survival analysis.

This is a retrospective study.The aim of this study was to illustrate the survival outcomes of patients with classic ependymoma (CE) and identify potential prognostic factors.CE is the most common category of spinal ependymomas, but few published studies have discussed predictors of the survival outcome.A Boolean search of the PubMed, Embase, and OVID databases was conducted by 2 investigators independently. The objects were intramedullary grade II ependymoma according to 2007 WHO classification. Univariate Kaplan-Meier analysis and Log-Rank tests were performed to identify variables associated with progression-free survival (PFS) or overall survival (OS). Multivariate Cox regression was performed to assess hazard ratios (HRs) with 95% confidence intervals (95% CIs). Statistical analysis was performed by SPSS version 23.0 (IBM Corp.) with statistical significance defined as P < .05.A total of 35 studies were identified, including 169 cases of CE. The mean follow-up time across cases was 64.2 ±â€Š51.5 months. Univariate analysis showed that patients who had undergone total resection (TR) had better PFS and OS than those with subtotal resection (STR) and biopsy (P = .002, P = .004, respectively). Within either univariate or multivariate analysis (P = .000, P = .07, respectively), histological type was an independent prognostic factor for PFS of CE [papillary type: HR 0.002, 95% CI (0.000-0.073), P = .001, tanycytic type: HR 0.010, 95% CI (0.000-0.218), P = .003].It was the first integrative analysis of CE to elucidate the correlation between kinds of factors and prognostic outcomes. Definite histological type and safely TR were foundation of CE's management. LEVEL OF EVIDENCE: 4.

Microscope-assisted anterior cervical discectomy and fusion combined with posterior minimally invasive surgery through tubular retractors for multisegmental cervical spondylotic myelopathy: A retrospective study.

This study aimed to investigate the clinical efficacy and outcome of combined microscope-assisted anterior cervical discectomy and fusion (ACDF) with posterior minimally invasive surgery through tubular retractors for patients with multisegmental cervical spondylotic myelopathy (MCSM).This retrospective study included 28 patients (19 males and 9 females) with multisegmental cervical spondylotic myelopathy, who underwent combined microscope-assisted ACDF with posterior minimally invasive surgery through tubular retractors in our single center between January 2012 and December 2016. The evaluated postoperative clinical outcomes were operation time, length of hospitalization, blood loss, levels of creatine phosphokinase isoenzyme MM (CPK-MM), Japanese Orthopedic Association (JOA) scores, visual analogue scale (VAS) scores, Cobb angle of C2-C7, and radiological assessments (included X-rays, computed tomography scans, and magnetic resonanceimaging images).The mean surgery time was 198.42 ±â€Š17.53 minutes, the average hospitalization length of hospital was 7.59 ±â€Š1.38 days, and the mean follow-up time was 13 ±â€Š2.45 months. On average, about 36.42 ±â€Š10.15 mL of blood was lost and CPK-MM increased to 331.75 ±â€Š23.15 IU/mL postoperatively (P < .001). The mean modified JOA scores increased from 8.21 ±â€Š0.69 preoperatively to 13.96 ±â€Š1.57 postoperatively (P < .001), whereas the mean VAS scores decreased from 6.64 ±â€Š1.28 preoperatively to 0.39 ±â€Š0.50 postoperatively (P < .001). Cobb angle of C2-C7 increased from 13.86°â€Š±â€Š5.69° preoperatively to 14.10°â€Š±â€Š5.56° postoperatively (P = .16).In conclusion, combined microscope-assisted ACDF with posterior minimally invasive surgery through tubular retractors appears to be a safe and effective treatment for patients with MCSM.

Association between CYP3A5 polymorphisms and the risk of adverse events in patients undergoing clopidogrel therapy: Meta-analysis.

INTRODUCTION: We wished to explore the relationship between CYP3A5 polymorphisms and adverse events in patients undergoing clopidogrel therapy. METHODS: A Boolean search of the PubMed, EMbase, OVID and Cochrane Library databases was conducted in April 2016. The primary outcome was major adverse cardiovascular events (MACE). The secondary outcome was bleeding events and resistance to the effects of clopidogrel. The CYP3A5 polymorphism was classified into three types: wild-type (AA), heterozygote (AG) and homozygous mutant (GG). We estimated pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) using the Mantel-Haenszel model. RESULTS: Twelve studies involving 8284 patients were eligible for our meta-analysis. CYP3A5 polymorphisms had no obvious influence on MACE (AA+AG vs. GG: OR=1.032, 95% CI=0.583-1.824, p=0.915; AA vs. AG+GG: 1.415, 0.393-5.094, 0.595). There was no significant relationship between CYP3A5 polymorphisms and bleeding (GG vs. AA+AG: OR=0.798, 95% CI=0.370-1.721, p=0.565) or clopidogrel resistance (AA+AG vs. GG: 1.009, 0.685-1.488, 0.963; AA vs. AG+GG, 0.618, 0.368-1.039, 0.069). CONCLUSION: No significant correlation was found between CYP3A5 polymorphisms and adverse events due to clopidogrel therapy.