Search

Glioma is the most prevalent primary brain tumor in adults among which glioblastoma is the most malignant and lethal subtype. Its common resistance to conventional chemotherapeutics calls for the development of alternative or concomitant treatment. Taking advantage of its endocrine function as a neurosteroid, vitamin D has become a target of interest to be used in conjunction with different chemotherapies. In this article, we review the mechanisms through which vitamin D and its analogs induce anti-tumor activity in glioblastoma, and the practical issues relevant to their potential application based on in vitro and in vivo studies. Vitamin D has largely been reported to promote cell cycle arrest and induce cell death to suppress tumor growth in glioblastoma. Glioblastoma cells treated with vitamin D have also shown reduced migratory and invasive phenotypes, and reduced stemness. It is worth noting that vitamin D analogs are able to produce similar inhibitory actions without causing adverse effects such as hypercalcemia in vivo. Upregulation of vitamin D receptors by vitamin D and its analogs may also play a role in enhancing its anti-tumor activity. Based on current findings and taking into consideration its potential cancer-protective effects, the clinical application of vitamin D in glioblastoma treatment and prevention will be discussed. With some study findings subject to controversy, further investigation is warranted to elucidate the mechanism of action of vitamin D and to evaluate relevant issues regarding its treatment efficacy and potential clinical application. Vitamin D has recently emerged as a neurosteroid and a regulator of various physiological functions. It has been widely reported to promote tumor-suppressive effects, however this proposal remains controversial. This article reviews the anti-tumoral mechanisms of vitamin D in glioblastoma, current evidence of its therapeutic application as a supplement to standard chemotherapy, and its potential applications for cancer prevention; it endeavors to offer insight into new means of overcoming chemoresistance and improving glioma patient survival.

With fast recovery time and effective in situ tumor tissue killing ability, thermal ablation has become a popular treatment for tumors compared with chemotherapy and radiation. The thermal dose measurement of current technology is usually accompanied by monitoring a large area impedance across two ablation catheters and the localized impedance measurement is difficult to achieve. In this work, thermal‐resistive sensor and impedance sensor are fabricated on the curved surface of a capillary tube with 1 mm outer diameter. The device is applied for real‐time in situ tissue impedance monitoring during thermal ablation. The calibrated thermal‐resistive sensors have an average temperature coefficient of resistance (TCR) of 0.00161 ± 5.9% °C‐1 with an accuracy of ±0.7 °C. By adding electro‐polymerized PEDOT:PSS (poly(3,4‐ethylenedioxythiophene)‐poly(styrenesulfonate)) on the 300 µm diameter gold electrodes, the interface impedance reduces two orders from 408 to 3.7 kΩ at 100 Hz. The Randles equivalent circuit model fittings show a two‐order improvement in the electrode capacitance from 7.29 to 753 nF. In the ex vivo porcine liver laser ablation test, the temperature of the porcine liver tissue can reach 70°C and the impedance would drop by 50% in less than 5 minutes. The integration of laser ablation fiber with the impedance and temperature sensors can further expand the laser ablation technique to smaller scale and for precise therapeutics.

Background The current treatment options for chronic subdural hematoma (CSDH) include burr hole drainage, twist drill drainage, and craniotomy with or without postoperative catheter drainage. Although generally effective, these treatments have continued to be complicated by recurrence, especially in partially hemolyzed or septated hematomas. Recently, interest in the use of fibrinolytic agents as an adjunct to surgical treatment to address this limitation has been increasing. We conducted a systematic review, focusing on the efficacy and safety profile of fibrinolytic agents and compared the different fibrinolytic agents. Methods The PubMed, EMBASE, CINAHL Plus, and Cochrane Library databases were searched for trials relevant to fibrinolytic administration in the treatment of CSDH. The findings are reported in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. The data from 1702 subjects from 6 retrospective observational studies were qualitatively analyzed. In addition, we included 11 case series and reports for discussion. Results For 1449 patients, the use of urokinase or tissue plasminogen activator improved hematoma drainage and shortened the hospital stay (7.04 days), with an overall hematoma recurrence rate of 1.59%. The incidence of infection, seizure, and intracranial bleeding was 3.18%, 0.80%, and 0.41%, respectively, which compared favorably with previously reported findings for surgical drainage without the use of fibrinolytic agents. Conclusions The routine use of intrathecal urokinase and tissue plasminogen activator could be a new direction in the management of CSDH. Conclusive clinical evidence is lacking, however, and further prospective controlled studies are warranted to confirm the benefit and safety of this treatment strategy and to identify the optimal agent and dosing regimen.

Background Gliosarcoma (GSM) is a distinct and aggressive variant of glioblastoma multiforme (GBM) with worse prognosis and few treatment options. It is often managed with the same treatment modalities with temozolomide (TMZ) as in GBM. However, the therapeutic benefits on GSM from such treatment regimen is largely unknown. Patient-derived xenograft (PDX) models have been used widely to model tumor progression, and subsequently to validate biomarkers and inform potential therapeutic regimens. Here, we report for the first time the successful development of a PDX model of secondary GSM. Methods Tissue obtained from a tumor resection revealed a secondary GSM arising from GBM. The clinical, radiological, and histopathological records of the patient were retrospectively reviewed. Samples obtained from surgery were cultured ex vivo and/or implanted subcutaneously in immunocompromised mice. Histopathological features between the primary GBM, secondary GSM, and GSM PDX are compared. Results In explant culture, the cells displayed a spindle-shaped morphology under phase contrast microscopy, consistent with the sarcomatous component. GSM samples were subcutaneously engrafted into immunocompromised mice after single-cell suspension. Xenografts of serial passages showed enhanced growth rate with increased in vivo passage. We did not observe any histopathological differences between the secondary GSM and its serial in vivo passages of PDX tumors. Conclusions Our PDX model for GSM retained the histopathological characteristics of the engrafted tumor from the patient. It may provide valuable information to facilitate molecular and histopathological modelling of GSM and be of significant implication in future research to establish precise cancer medicine for this highly malignant tumor.

Objective This study aimed to summarize the experience with the management of transorbital brain injury (TOBI) at our institution that may help inform surgical decision-making. Methods Four adults with TOBIs were admitted to our hospital and received surgical treatment. The patients’ clinical manifestations, physical findings, imaging data, surgical treatment, and postoperative outcome were prospectively collected and subject to retrospective analysis. Results All patients were male. In 2 patients, the entry point of the cranium was the superior orbital fissure, whereas in the other 2, the entry point was the orbital roof. Thorough physical examination and comprehensive diagnostic imaging were performed preoperatively in all patients for careful assessment of the foreign body and its surrounding important structures. In collaboration with our multidisciplinary trauma team, individualized surgeries were successfully designed and performed in the 4 patients to remove the foreign bodies along the path of their trajectories. Three patients had uneventful postoperative courses, whereas 1 patient died because of severe cerebral ischemia and refractory brain swelling after decompressive craniectomy. Conclusions A comprehensive understanding of the regional anatomy of the trajectory is the cornerstone for surgical management of TOBIs. Adequate preoperative imaging examinations are essential for the evaluation of surgical risks and for making a tailored management strategy. Early surgical exploration through multidisciplinary collaboration is highly recommended for achieving a favorable outcome.

Background: Vestibular schwannoma is an intracranial tumor which can lead to devastating neurological deficit and is prone to recurrence after surgery. Patients with inherited neurofibromatosis type 2 (NF2) syndrome are particularly susceptible to bilateral and aggressive schwannomas. However, the genome of vestibular schwannomas is not well known. There is an imminent need of developing effective chemotherapeutic agents either as a primary treatment modality or as adjuvant therapy for these patients. Methods: Here, we subjected both sporadic and NF2-related schwannomas to high-throughput DNA sequencing using a panel of therapeutically important cancer-related genes, in order to determine if targetable genetic changes are present in schwannomas. Results: A number of variants were detected in the genes NRAS, PDGFRA, KIT, and EGFR, in both sporadic and NF2-related cases. The results were confirmed by Sanger sequencing. Conclusion: Our study successfully detected some genetic variants in important cancer-related genes in schwannomas, and further elucidation of their relationship to drug-response will be pursued.

Background: International experiences have shown that trauma system development significantly reduces preventable deaths and disabilities. During the 8-year study, the aim was to find solutions for trauma system development in Shenzhen, China, so as to reduce trauma mortality and morbidity. Methods: Introducing the ATLS® program to mainland China was started in 2013. A geospatial analysis of traumatic incidents was conducted in 2014. A regional trauma center was illustrated as an example to be used as a reference. The trauma audit meeting was introduced as an approach to continuous trauma quality improvement. The Shenzhen Trauma Surgery Committee was established to finalize the plan for designation of trauma care hospitals. The American College of Surgeons Trauma System Development Guidelines were translated into Chinese. Results: ATLS® provider course was held in Shenzhen and totally 205 doctors received training. A regional trauma center where adopted ATLS® principles as the standard for trauma resuscitation and early trauma care, with results showing significant improvements in trauma team organization, trauma resuscitation, definitive trauma care and a significant reduction in mortality among major trauma patients. The trauma audit meeting was introduced to 8 hospitals. A new trauma system plan for Shenzhen was set up and a consensus was reached on trauma center designation. The American College of Surgeons' “Resources for Optimal Care of the Injured Patient” was translated into Chinese and published in November 2020. Conclusion: The critical steps in establishing the framework for the Shenzhen trauma system included: geospatial analysis of traumatic incidents, trauma care training for providers, trauma center development, regional trauma center designation and development of trauma quality improvement programs. This practical approach can be replicated in other countries seeking to establish a trauma system. We are now working toward extension of this approach to other regions of mainland China.

Introduction. Prolyl 4-hydroxylase, beta polypeptide (P4HB) has previously been identified by our group to play important roles in association with glioma malignancy and temozolomide (TMZ) resistance through the unfolded protein response (UPR). The present study focused on the prognostic value of P4HB in glioma. Methods. P4HB expression was assessed by immunohistochemical staining and semi-quantified by pathologist visual scoring in 73 WHO grade I-IV gliomas. Results were correlated with clinicopathological data. Results. Our results show that P4HB expression was significantly associated several clinicopathological parameters including age (p=0.035), tumour grade (p=0.002), and the number of TMZ treatment cycles received (p=0.043). Using Kaplan-Meier analysis, P4HB expression was positively correlated with mortality (p=0.014) and disease progression (p=0.026). In patients treated with TMZ, high P4HB expression level was significantly associated with poorer overall survival (OS) (p=0.014) and progression free survival (PFS) (p=0.027). The association between MGMT promoter methylation and P4HB expression was also interrogated. Patients with MGMTMethP4HBLow tumours had the most favourable progression free survival (48 months) than patients with other combination of MGMT methylation status and P4HB expression (log rank p=0.001). Multivariate analysis revealed that P4HB was an independent prognostic indicator for OS (p=0.048). Conclusions. P4HB could constitute an independent prognostic marker, especially for high grade glioma with the potential for informing a nuanced pathological stratification during clinical decision-making with respect to MGMT promoter methylation status and TMZ treatment.

Background Fall with head injury is a pervasive challenge, especially in the aging population. Contributing factors for mortality include the development of cerebral contusions and delayed traumatic intracerebral hematoma. Currently, there is no established specific treatment for these conditions. Object This study aimed to investigate the impact of independent factors on the mortality rate of traumatic brain injury with contusions or traumatic subarachnoid hemorrhage. Methods Data were collected from consecutive patients admitted for cerebral contusions or traumatic subarachnoid hemorrhage at an academic trauma center from 2010 to 2016. The primary outcome was the 30-day mortality rate. Independent factors for analysis included patient factors and treatment modalities. Univariate and multivariate analyses were conducted to identify independent factors related to mortality. Secondary outcomes included thromboembolic complication rates associated with the use of tranexamic acid. Results In total, 651 consecutive patients were identified. For the patient factors, low Glasgow Coma Scale on admission, history of renal impairment, and use of warfarin were identified as independent factors associated with higher mortality from univariate and multivariate analyses. For the treatment modalities, univariate analysis identified tranexamic acid as an independent factor associated with lower mortality (P = 0.021). Thromboembolic events were comparable in patients with or without tranexamic acid. Conclusion Tranexamic acid was identified by univariate analysis as an independent factor associated with lower mortality in cerebral contusions or traumatic subarachnoid hemorrhage. Further prospective studies are needed to validate this finding.

Introduction Normal skull base structures are destroyed either by the skull base pathology itself or during surgery that results in cerebrospinal fluid (CSF) leak. Skull base repair is usually performed transnasally by using a nasal septal flap. But when NSF is not available and failed repeated transnasal repair, a cranionasal repair with frontal pericranial flap (PF) can be attempted to achieve the highest successful chance. We performed a dual layer/split PF repair of a skull base defect using cranionasal approach and here we describe the technique. Case Description A 74-year-old man suffered from CSF leak and ventriculitis after multiple transnasal surgeries for pituitary macroadenoma despite multiple repairs with intranasal vascularized flaps. We performed repair by cranionasal approach and using frontal PF. The frontal PF was divided into left and right halves. The left half went intradural, through the chiasmatic window to reach the sella and cover the tubercular and sellar defect from above. The right half went through the nasion into the nose to cover the defect from below. So the defect was covered by two vascularized flap from a single frontal PF. The repair was successful with no CSF leak and infection successfully treated by antibiotics. Conclusion We introduced the cranionasal dual layer/split PF technique to repair anterior skull base and successfully stopped the CSF leak in a patient after multiple EEA surgeries. This technique should only be considered in specific difficult situation where usual repair by EEA is impossible.

BACKGROUND Surgery is the mainstay of meningioma treatment, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. DNA methylation profiling, copy number variants (CNVs), exome sequencing, and RNA sequencing have improved understanding of meningioma biology, but have not superseded histologic grading, or revealed biomarkers for radiotherapy responses. To address these unmet needs, we optimized and validated a targeted gene expression biomarker predicting meningioma outcomes and responses to radiotherapy. METHODS Targeted gene expression profiling was performed on a discovery cohort of 173 meningiomas (median follow-up 8.1 years) and a validation cohort of 331 meningiomas (median follow-up 6.1 years) treated with surgery (n=504) and postoperative radiotherapy (n=73) at independent, international institutions (70% WHO grade 1, 24% WHO grade 2, 6% WHO grade 3). Optimized targeted gene expression models predicting clinical outcomes (34 genes) or radiotherapy responses (12 genes) were developed from the discovery cohort, and compared to histologic and molecular classification systems by performing DNA methylation profiling, CNV analysis, exome sequencing, and RNA sequencing on the same meningiomas. RESULTS Targeted gene expression profiling achieved a concordance-index of 0.75 ± 0.03 (SEM) for local freedom from recurrence (LFFR) and 0.72 ± 0.03 for overall survival (OS) in the validation cohort, outperforming WHO grade (5-year LFFR delta-AUC 0.15, 95% CI 0.076-0.229, p=0.001) and DNA methylation grouping (delta-AUC 0.075, 95% CI 0.006-0.130, p=0.01) for LFFR, disease-specific survival, and OS. The biomarker was independently prognostic after accounting for WHO grade, extent of resection, primary versus recurrent presentation, CNV status, DNA methylation group, and Ki67 labeling index, and identified meningiomas benefiting from radiotherapy (interaction p-value=0.0008), suggesting postoperative radiotherapy could be refined in 30.2% of cases. CONCLUSIONS Targeted gene expression profiling of 504 meningiomas improves discrimination of meningioma local recurrence, disease-specific survival, and overall survival, and predicts radiotherapy responses.

Purpose/Objective(s) Indications for postoperative radiotherapy after meningioma resection are controversial. DNA methylation profiling identifies meningiomas at risk for recurrence, but logistic and technical barriers have encumbered clinical translation of this approach. The aim of this study was to optimize and validate a clinically-tractable targeted gene expression biomarker to predict meningioma outcomes and responses to postoperative radiotherapy. Materials/Methods Targeted gene expression and Illumina 850k DNA methylation profiling were performed on a discovery cohort of 173 meningiomas (median follow-up 7.8 years) and an external validation cohort of 331 meningiomas (median follow-up 5.8 years) from patients treated with surgery (n = 504) and postoperative radiotherapy (n = 73) at independent, international institutions (70% WHO grade 1, 24% WHO grade 2, 6% WHO grade 3). RNA sequencing was performed on the discovery cohort, and 125 genes were selected for targeted gene expression profiling based on associations with meningioma recurrence. Regularized Cox regression was used to develop continuous gene expression risk score for local freedom from recurrence (LFFR). The model (34 meningioma genes and 7 housekeeping genes) and risk quartiles (low, low-intermediate, high-intermediate, and high) were locked and validated on the external cohort. Multivariate regressions (MVR) incorporating WHO grade, DNA methylation grouping, extent of resection, primary versus recurrent presentation, and postoperative radiotherapy were used to assess the risk score across clinical contexts. Results The gene expression risk score (concordance-index 0.78 ± 0.03) outperformed DNA methylation grouping (0.71 ± 0.03) and WHO grade (0.65 ± 0.03) in stratifying meningioma LFFR in the validation cohort (n = 331). The risk score classified 43% of WHO grade 1 meningiomas as high-intermediate (n = 82) or high risk (n = 34), with 5-year LFFR and overall survival (OS) of 83% and 89% for high-intermediate risk WHO grade 1 meningiomas, and 41% and 73% for high risk WHO grade 1 meningiomas, respectively. Low risk WHO grade 1 meningiomas (n = 50) had 5-year LFFR and OS of 92% and 88%, respectively. High and high-intermediate risk scores were independently prognostic for LFFR (HR 2.9, 95% CI 1.2-4.4) and OS (HR 2.7, 95% CI 1.3-5.6) on MVR. An interaction term between postoperative radiotherapy and risk score was predictive for LFFR (P = 0.046) and OS (P = 0.001) on MVR in the validation cohort, suggesting meningiomas with higher risk scores derived greater benefit from postoperative radiotherapy. Conclusion Here we use targeted gene expression profiling to develop a risk score predicting meningioma outcomes and responses to postoperative radiotherapy. This cost-effective assay outperforms DNA methylation grouping and WHO grade in discriminating meningioma outcomes, and may be useful for guiding clinical trial design.

Trauma and Injury Severity Score (TRISS) has been the benchmark of mortality riskin trauma centers for over 30 years. TRISS utilizes the Injury Severity Score (ISS) as an index ofanatomical injury. This study investigated the efficacy of a new type of index of anatomical injury called the ICD-derived Injury Severity Score (ICISS) compared to the ISS using a logisticregression analysis and a global chi-square test of the areas under the Receiver OperatorCharacteristic (ROC) curves. We found that the empirically derived ICISS performed as well as the consensus derived ISS with no statistical differences between their respective area under the ROC curves.

The hyperdense middle cerebral artery sign (HMCAS) representing a thromboembolus has been declared as a vital CT finding for intravascular thrombus in the diagnosis of acute ischemia stroke. Early recognition of HMCAS can assist in patient triage and subsequent thrombolysis or thrombectomy treatment. A total of 624 annotated head non-contrast-enhanced CT (NCCT) image scans were retrospectively collected from multiple public hospitals in Hong Kong. In this study, we present a deep Dissimilar-Siamese-U-Net (DSU-Net) that is able to precisely segment the lesions by integrating Siamese and U-Net architectures. The proposed framework consists of twin sub-networks that allow inputs of left and right hemispheres in head NCCT images separately. The proposed Dissimilar block fully explores the feature representation of the differences between the bilateral hemispheres. Ablation studies were carried out to validate the performance of various components of the proposed DSU-Net. Our findings reveal that the proposed DSU-Net provides a novel approach for HMCAS automatic segmentation and it outperforms the baseline U-Net and many state-of-the-art models for clinical practice.

This was followed by an interactive discussion of investigation and management plan. Appropriate radiological imaging such as an MRI brain scan was shown to the group using the “share‐screen” function. Other clinical information such as laboratory results can likewise be displayed. The session was completed after thorough discussion on the appropriate treatment plan with respect to the patient’s scenario.

One of the treatment options for long segment common carotid artery (CCA) occlusion is bypass surgery with different combinations of donors and receipts. Using vertebral artery (VA) as the donor for CCA occlusion was uncommonly reported. The reported cases were using jump graft to connect V3 segment of VA to either CCA or ICA. We describe our patient using V2 segment as the donor for VA-CCA bypass as treatment for CCA occlusion. Our patient was a 51 years old gentleman with Marfan syndrome and had multiple operations that included total arch replacement. He presented with sudden onset of spontaneous right frontal subarachnoid haemorrhage and repeated episodes of TIA with left upper limb numbness. CTA showed occluded right CCA and anastomosis between branches from subclavian artery and occipital artery. CT perfusion showed hypoperfusion of right hemisphere. To avoid damaging the anastomosis at subclavian artery and occipital artery, we decided for V2-RAG (radial artery graft)-CCA bypass. It was done by exposing the V2 segment at C4/5 level, performing end-to-side anastomoses at V2-RAG and RAG-CCA junctions where the RAG was underneath the internal jugular vein. Patient had no new deficits after surgery and no more TIAs. CTA performed one week after surgery showed patent RAG. In conclusion, using V2 for VA-CCA bypass is technically feasible and may have theoretical advantages over using V3. V2-CCA bypass is an option for CCA occlusion in very selected patients.

Background The detection of large vessel occlusion (LVO) plays a critical role in the diagnosis and treatment of acute ischemic stroke (AIS). Identifying LVO in the pre-hospital setting or early stage of hospitalization would increase the patients' chance of receiving appropriate reperfusion therapy and thereby improve neurological recovery. Methods To enable rapid identification of LVO, we established an automated evaluation system based on all recorded AIS patients in Hong Kong Hospital Authority's hospitals in 2016. The 300 study samples were randomly selected based on a disproportionate sampling plan within the integrated electronic health record system, and then separated into a group of 200 patients for model training, and another group of 100 patients for model performance evaluation. The evaluation system contained three hierarchical models based on patients' demographic data, clinical data and non-contrast CT (NCCT) scans. The first two levels of modeling utilized structured demographic and clinical data, while the third level involved additional NCCT imaging features obtained from deep learning model. All three levels' modeling adopted multiple machine learning techniques, including logistic regression, random forest, support vector machine (SVM), and eXtreme Gradient Boosting (XGboost). The optimal cut-off for the likelihood of LVO was determined by the maximal Youden index based on 10-fold cross-validation. Comparisons of performance on the testing group were made between these techniques. Results Among the 300 patients, there were 160 women and 140 men aged from 27 to 104 years (mean 76.0 with standard deviation 13.4). LVO was present in 130 (43.3%) patients. Together with clinical and imaging features, the XGBoost model at the third level of evaluation achieved the best model performance on testing group. The Youden index, accuracy, sensitivity, specificity, F1 score, and area under the curve (AUC) were 0.638, 0.800, 0.953, 0.684, 0.804, and 0.847, respectively. Conclusion To the best of our knowledge, this is the first study combining both structured clinical data with non-structured NCCT imaging data for the diagnosis of LVO in the acute setting, with superior performance compared to previously reported approaches. Our system is capable of automatically providing preliminary evaluations at different pre-hospital stages for potential AIS patients.

Intracranial aneurysm can lead to hemorrhagic stroke upon rupture. Deployment of flow diverters can restrict the blood flow into aneurysm and mitigate the rupture risk. Computational fluid dynamics (CFD) and ultrasonography with pulse-wave and color Doppler ultrasound measurements were employed jointly to investigate the complex flow pattern in cerebral aneurysms, both before and after the deployment of flow diverters. Patient-specific configurations of both bifurcation and side-wall aneurysms were selected. The effect of downstream flow resistance was investigated by adjusting the volume flow rate and pressure at the outlet vessels computationally and experimentally. Velocity profiles in the aneurysm measured from ultrasonography showed good agreement with those from computer simulations. The discrepancy in velocity between the computational and experimental sets of data is less than 10%. The downstream resistance can alter the volume flux into a bifurcation aneurysm with a flow diverter deployed by 236%, while the corresponding value of a side-wall aneurysm is negligible. The vorticity of the aneurysmal flow was reduced by more than 80% in both cases after stenting. This study demonstrated that careful investigation of downstream flow resistance of a bifurcation aneurysm is essential to provide an accurate assessment of the aneurysmal flow dynamics after flow diverter deployment.

The rupture of intracranial aneurysms might lead to permanent disability or even death. One possible endovascular treatment is the deployment of flow diverters (FDs), which reduces flow into the sac and promotes thrombosis. Computational fluid dynamics simulations were used to assess the flow patterns and dynamics. The concept of energy loss, as a measure of necessary work done to overcome flow resistance, was utilized to correlate with clinical outcome. If a surgical operation is successful, the flow would be diverted to a shorter path and energy loss should be reduced. Conversely, persistent flow in the sac, associated with treatment failure, would display an increased energy loss as blood is then squeezed through the stent pores. Four illustrative clinical cases, involving both bifurcation and sidewall aneurysms, were selected. To reduce the numerical complexity, earlier works in the literature had used a porous medium approximation for the FDs. Here, the FD was simulated explicitly as a virtual (or computer-generated) stent, which would likely provide a more accurate description. Furthermore, quantitative comparisons between the approaches of virtual stenting and a porous medium with typical parameters were conducted by examining the effective flow influx into the aneurysm.

The city of Shenzhen, China, is planning to establish a trauma system. At present, there are few data on the geographical distribution of incidents, which is key to deciding on the location of trauma centres. The aim of this study was to perform a geographical analysis in order to inform the development of a trauma system in Shenzhen. Retrospective analysis of trauma incidents attended by Shenzhen Emergency Medical Services (EMS) in 2014. Data were obtained from Shenzhen EMS. Incident distribution was explored using dot and kernel density estimate maps. Clustering was determined using the nearest neighbour index. The type of healthcare facilities which patients were taken to was compared against patients’ needs, as assessed using the Field Triage Decision Scheme. There were 49,082 recorded incidents. A total of 3513 were classed as major trauma. Mapping demonstrates that incidents predominantly occurred in the western part of Shenzhen, with identifiable clusters. Nearest neighbour index was 0.048. Of patients deemed to have suffered major trauma, 8.5% were taken to a teaching hospital, 13.6% to a regional hospital, 42.6% to a community hospital, and 35.3% to a private hospital. The proportions of Step 1 or 2 negative patients were almost identical. The majority of trauma patients, including trauma patients who are at greater likelihood of severe injury, are taken to regional and community hospitals. There are areas with identifiable concentrations of volume, which should be considered for the siting of high-level trauma centres, although further modelling is required to make firm recommendations.

Objectives To compare surgical outcome both radiologically and clinically after interventions for patients with Moyamoya disease. Methods This retrospective observational study included 25 patients who were treated surgically for Moyamoya disease in the past 14 years. Clinical outcomes were analyzed by subgroups stratified by age, disease presentation, and surgical intervention. Serial postoperative brain computed tomography perfusion records were analyzed with respect to the cerebral blood flow and cerebrovascular reserve capacity (CVRC) of the middle cerebral artery territory. Changes in both the intervention ( n = 23) and nonintervtion ( n = 9) cerebral hemispheres were compared. Results All children treated by synangiosis ( n = 9), all adults receiving synangiosis ( n = 5), and 88.9% of adults undergoing bypass ( n = 9) had no neurologic deterioration, with a duration of at least 50.6 months, 85.7 months, and 27.7 months, respectively. Radiologically, CVRC improved more markedly after bypass surgery than synangiosis, particularly 12–24 months postoperatively (51.1% vs. −2.86%). The hemispheres that did not undergo intervention showed similar improvement in cerebral blood flow over time compared with the hemispheres that did undergo intervention, after surgery was performed. Conclusions Bypass surgery improved CVRC greater than synangiosis, which may correlate with decreased future stroke risks. The decision for bypass is to be balanced with a greater risk of postoperative neurologic deterioration in adults after this procedure. The hemisphere that did not undergo intervention also appeared to benefit from surgery performed on the contralateral brain.

BACKGROUND High-grade glioma is currently incurable. It was reported that glioma may be auxotrophic to arginine due to the lack of urea cycle genes expressions, suggesting arginase may be a potential agent for high grade glioma. AIM: We investigated the efficacy of pegylated arginase I (pegArg-I) or in combination with other anti-cancer drugs for high-grade glioma in vitro and in vivo. METHODS 4 high-grade glioma cell lines (U87, U373, U138, D54) were treated with pegArg-I in vitro. The molecular mechanism of pegArg-I-induced cytotoxicity was tested in U87. The ultra-morphological changes of pegArg-I-treated U87 was investigated by both scanning and transmission electron microscopy. Orthotopic glioma xenograft model with luciferase-transfected U87 cell line was tested for anti-cancer efficacy of peg-Arg I in vivo. RESULTS We showed that pegArg-I induced significant cell death in all 4 cell lines in vitro. Temozolomide, difluoromethyornithine and chloroquine (CQ) were then tested together with pegArg-I in U87 in vitro. We found that only CQ showed additive effect with pegArg-I against glioma in vitro. Such additive cytotoxic effect may be associated with enhanced autophagy and necrosis as shown in transmission electron microscopy and autophagy markers’ expression by Western blotting. PegArg-I prolonged the survival of glioma mice, suggesting its possible anti-glioma efficacy. However, CQ+pegArg-I didn’t show further significant anti-cancer efficacy in vivo. CONCLUSION PegArg-I may be useful in slowing the progression of glioma, but additional drug candidate which works synergistically with pegArg-I remains to be explored.

Background: Many medical schools and specialist accreditation bodies worldwide have cancelled or postponed professional examinations due to the COVID-19 pandemic. In Hong Kong, final-year medical students are not required to sit public examinations to qualify; rather rely on internal assessment. We therefore proceeded to administer all scheduled final-year statutory examinations during the months of April and May 2020. Methods: All 206 graduating medical students sat both written and objective structured clinical (OSCE) examinations under conditions of strict infection control, including self-reported health declaration forms (HDF), temperature screening and viral polymerase chain reaction (PCR) testing. Findings: Between 201 and 203 students who submitted a clean HDF were permitted to attend the examination venues. Fifteen (7·3%) students were found to have a tympanic temperature of ≥37·5°C on April 1, 2020, but their posterior oropharyngeal saliva samples taken on the same day were COVID-19 PCR-negative. Another 2 and 1 students were found to have a temperature ≥37·5°C on April 3, 2020 and April 9, 2020 respectively, but who were also tested COVID-19 PCR-negative. The tympanic temperatures of these 18 candidates were significantly higher than the rest throughout all examination days of the written (p≤0·0014) and OSCE (p≤0·039) examinations (except on April 15, 2020), suggestive of a higher basal body temperature. All staff members and participating patients with close contacts with the candidates/staff were free from COVID-19 before and after all examinations, up to 14 days post hoc. Interpretation: Rigorous clinical professional examinations could be safely conducted during the COVID-19 pandemic provided stringent infection control measures were followed. The choice of body temperature cutoff could significantly impact the assessment process for which we propose a number of mitigating measures for future reference. Funding Statement: None Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This cohort study was approved by HKUMed and designed by the investigators.

The burnout syndrome is characterized by emotional exhaustion, depersonalization, and reduced personal achievement. Uncertainty exists about the prevalence of burnout among medical and surgical residents. Associations between burnout and gender, age, specialty, and geographical location of training are unclear. In this meta-analysis, we aimed to quantitatively summarize the global prevalence rates of burnout among residents, by specialty and its contributing factors. We searched PubMed, PsycINFO, Embase, and Web of Science to identify studies that examined the prevalence of burnout among residents from various specialties and countries. The primary outcome assessed was the aggregate prevalence of burnout among all residents. The random effects model was used to calculate the aggregate prevalence, and heterogeneity was assessed by I2 statistic and Cochran’s Q statistic. We also performed meta-regression and subgroup analysis. The aggregate prevalence of burnout was 51.0% (95% CI: 45.0−57.0%, I2 = 97%) in 22,778 residents. Meta-regression found that the mean age (β = 0.34, 95% CI: 0.28−0.40, p < 0.001) and the proportion of males (β = 0.4, 95% CI = 0.10−0.69, p = 0.009) were significant moderators. Subgroup analysis by specialty showed that radiology (77.16%, 95% CI: 5.99−99.45), neurology (71.93%, 95% CI: 65.78−77.39), and general surgery (58.39%, 95% CI: 45.72−70.04) were the top three specialties with the highest prevalence of burnout. In contrast, psychiatry (42.05%, 95% CI: 33.09−51.58), oncology (38.36%, 95% CI: 32.69−44.37), and family medicine (35.97%, 95% CI: 13.89−66.18) had the lowest prevalence of burnout. Subgroup analysis also found that the prevalence of burnout in several Asian countries was 57.18% (95% CI: 45.8−67.85); in several European countries it was 27.72% (95% CI: 17.4−41.11) and in North America it was 51.64% (46.96−56.28). Our findings suggest a high prevalence of burnout among medical and surgical residents. Older and male residents suffered more than their respective counterparts.

Background Ischemic stroke due to large vessel occlusion can be effectively treated with thrombectomy but access to this treatment is limited in many parts of the world. Local incidence of large vessel occlusion is critical in determining the development of thrombectomy service, but reliable data from Asian countries are lacking. Aims We performed a population-based study to estimate the burden of large vessel occlusion and the service gap for thrombectomy in Hong Kong. Methods All acute ischemic stroke patients admitted in 2016 to the public healthcare system, which provided 90% of the emergency healthcare in the city, was identified from the Hong Kong Hospital Authority’s central electronic database. The diagnosis of large vessel occlusion was retrospectively verified by two independent cerebrovascular specialists in a randomly sampled cohort based on clinical and neuroimaging data. The incidence of large vessel occlusion in the population was estimated through weighting the sample results and compared with the thrombectomy data in the same period. Results There were 6859 acute ischemic stroke patients treated in the public health system in 2016. Amongst the 300 patients randomly sampled according to diagnosis coding, 130 suffered from anterior circulation large vessel occlusion. This translated to 918 patients (95% CI 653–1180) and 13.3% of all ischemic stroke patients. The estimated incidence of anterior circulation large vessel occlusion was 12.5 per 100,000 persons per year (95% CI 11.7–13.4). Large vessel occlusion stroke patients were more commonly female than male (67.4% vs. 31.6%, p = 0.003), and were older than non-large vessel occlusion stroke patients (mean of 80.5 years vs. 71.4 years, p = Conclusion The estimated incidence of anterior circulation large vessel occlusion in the Hong Kong Chinese population is lower than that in the West. There is however a substantial service gap for endovascular thrombectomy with less than 10% of large vessel occlusion patients receiving thrombectomy.

Background Neurogenic bladder refers to dysfunction of the urinary bladder secondary to diseases of the nervous system that result in problems with urine storage, micturition, or both. The most common causes are multiple sclerosis and spinal cord injury. Patients commonly present with recurrent UTIs, obstructive uropathies, and urinary retention. Without proper treatment, neurogenic bladder may result in nephropathy and renal failure, both of which have a significant negative impact on the health and life expectancy of patients. Restoration of lost neural function using artificial stimulators is a feasible therapeutic strategy. This article reviews the pathophysiology of neurogenic bladder and the 2 most commonly employed sacral nerve stimulation methods—the Brindley procedure and sacral neuromodulation.

Aim Spasticity gives rise to impairment in motor functions and activities of daily living. Botulinum toxin (BTX) can be injected to temporarily paralyze the affected muscles, which provides a window of opportunity for rehabilitation. We present our 2.5-year experience with BTX injection and a patient-specific rehabilitation program provided by a multidisciplinary team, which consists of neurosurgeons, nurses, physiotherapists, occupational therapists and prosthetic orthotists. Patients and Methods This is a retrospective study of prospectively collected data in a local hospital including 22 patients suffering from spasticity. Outcome measures include goal attainment, caregiver burden and biomechanical assessment by Modified Ashworth Scale and Modified Tardieu Scale (MTS). Results OnabotulinumtoxinA injection together with rehabilitation facilitates the attainment of patient-centred physical goals in daily activities. It reduces caregiver burden. Spasticity is reduced particularly for finger and wrist flexors as well as hip adductors. Responses of ankle plantarflexors are less satisfactory which may be due to inadequate dosages. Initial improvement in the R2 component of the MTS for ankle plantarflexors and hip adductors may be attributable to the application of ankle–foot orthosis and abduction pillow. Conclusions Multidisciplinary management for spasticity is feasible within our healthcare setting and our promising findings indicate its wider adoption in this locality.

A middle-aged lady in good health presented right abducens nerve palsy. Magnetic resonance imaging (MRI) of the brain showed bilateral cavernous ICA aneurysms. The left aneurysm measured 9 × 7 mm whereas the right aneurysm measured 22 × 15 mm, with mass effect on the cavernous sinus, explaining her symptoms (Fig. 1). Both were wide-neck aneurysms and were treated with PED alone sequentially, 3 months apart. She was loaded with Aspirin 300 mg and Clopidogrel 300 mg before treatment, with Aspirin continuing for 6 months and Clopidogrel for 3 months afterwards. There were no procedural complications. Digital subtraction angiogram at 1 year showed that the left aneurysm was completely occluded, whereas the right aneurysm had partially thrombosed but with a persistent filling. The right aneurysm persisted on CT angiogram at 2 years but with significant shrinkage and finally occluded at a 3-year follow-up (Fig. 2). The patient’s diplopia gradually improved after 3 years.

This operative video demonstrates an open surgical thrombectomy for a 61-yr-old woman with failed endovascular embolectomy in acute ischemic stroke. Good functional outcome can be achieved when this operation is timely performed within the therapeutic window. This patient has atrial fibrillation. She was admitted for sudden onset of left-sided hemiplegia and aphasia. National Institutes of Health Stroke Scale (NIHSS) was 20/42 before the operation. Computed tomography (CT) cerebral angiogram showed right internal cerebral artery (ICA) occlusion from the cervical portion. Urgent intra-arterial (IA) thrombectomy was started 2 h after symptom onset, but failed despite the use of a stentriver and a large-bore aspiration catheter together. Emergency rescue open thrombectomy was performed with right pterional craniotomy 6 h after symptom onset. Sylvian fissure was dissected to expose the supraclinoid ICA, ICA bifurcation, A1, and M1. A transverse arteriotomy was made at the ICA bifurcation and open surgical thrombectomy was performed. Reperfusion was established in 86 min after skin incision. Intraoperative indocyanine green video-angiography showed patent flow over ICA bifurcation to M1 and A1. She had a good recovery with the return of the left-sided power and was discharged home. At 2-mo postoperative assessment, she was able to walk unaided independently. The modified Barthel Index (BI) was 74/100. Her activity of daily living was independent. We must emphasize IA thrombectomy is the standard treatment, and the role of open surgery remains a potential rescue procedure. Good functional outcome can be achieved when emergency rescue open thrombectomy is performed within the therapeutic window.

Cerebral venous sinus thrombosis is an uncommon cause of stroke with high morbidity and mortality rates from venous infarction, intracranial hemorrhage, and extensive cerebral edema. Endovascular treatment with various devices has been proposed as a salvage treatment when standard medical treatment with systemic anticoagulation is ineffective, especially in long segment dural sinus thrombosis. We describe our technique of transvenous endovascular aspiration thrombectomy with large bore thrombectomy catheters, followed by placement of microcatheter for local thrombolytic infusion at the site of thrombosis. We report a retrospective study of angiographic and clinical outcome of six consecutive patients treated with this approach. Endovascular aspiration thrombectomy with large bore catheters followed by continuous local thrombolytic infusion appeared to be a safe and effective salvage treatment for selected patients with cerebral dural venous sinus thrombosis refractory to medical treatment.

Stenting and angioplasty of the vertebral artery (VA) is used to treat symptomatic stenosis but the long-term outcomes and complications are unclear. This study evaluated the long-term clinical outcomes and procedure-related complications in patients who underwent extracranial VA stenting and angioplasty, in particular the risks of in-stent restenosis (ISR) and stent fracture. This was a retrospective review of consecutive patients suffering from symptomatic extracranial VA stenosis who were treated with balloon-expandable bare metal stents. The clinical and angiographical outcomes were reviewed for procedural complications, recurrent stroke, ISR and stent fracture. In this study 22 patients (17 male, 5 female) with a mean age of 63.4 years (SD 9.1 years) were included. The median follow-up was 56 months (interquartile range IQR 51.8 months). There were no periprocedural complications. The cumulative ISR risk was 45% with 6 cases detected at 1 year and 3 cases detected at 3 years post operation. The cumulative stent fracture rate at 1 year, 3 years, 5 years and the entire follow-up period were 5%, 15%, 25%, and 30%, respectively. Posterior circulation stroke occurred in 1 patient (4.5%), and 3 patients died of non-cerebrovascular causes during follow-up. Of the patients 2 with ISR and stent fracture required additional treatment. The long-term ISR and stent fracture risks were high in extracranial VA stenosis treated with balloon-expandable bare metal stents. The risk of stent fracture increased over time during the follow-up period. Further studies should be conducted to clarify the long-term safety and efficacy of extracranial VA stenting.

Background An increasing number of patients with intracranial haemorrhages are aspirin-users. Neurosurgeons commonly attempt to minimize the risk of re-bleeding by withholding the medication and giving platelet transfusion. However, recent studies raised safety concerns and showed poorer outcome with platelet transfusion when the latter was not guided by changes in platelet function. Aim of study To study the temporal pattern and degree of changes in platelet activities following a fixed dose of platelet transfusion in aspirin-users with intracranial haemorrhages. Methods Aspirin-users with intracranial haemorrhages underwent baseline aspirin response units (ARU) using the VerifyNow® assay. Those who showed abnormal platelet activity received a single dose of 4 units of platelet concentrate. ARU were then repeated at 4 h, 24 h and 48 h post-transfusion. Patients were classified according to their responses to transfusion. Results Twenty patients were recruited. At 4 h after transfusion, 11 (55%) patients had normalised platelet activities while the rest may show delayed or absent of normalization. Overall, eight (40%) patients were ‘early and persistent transfusion responders’, five ‘delayed transfusion responders’, and five (25%) had persistently abnormal platelet function. Two (10%) patients who initially responded to transfusion failed to maintain normalized platelet activity. Conclusion Platelet activities in aspirin-users showed considerable heterogeneity up to 48 h following a blanket approach of platelet transfusion. The need for repeated transfusion or alternative therapy strongly argues for a guided practice for transfusion based on point-of-care platelet function assay. Future research should also adopt this approach to re-examine the safety and effectiveness of platelet transfusion in these patients.

RADA16-I is a synthetic type I self-assembling peptide nanofiber scaffold (SAPNS) which may serve as a novel biocompatible hemostatic agent. Its application in neurosurgical hemostasis, however, has not been explored. Although RADA16-I is nontoxic and nonimmunogenic, its intrinsic acidity may potentially provoke inflammation in the surgically injured brain. We conducted an animal study to compare RADA16-I with fibrin sealant, a commonly used agent, with the hypothesis that the former would be a comparable alternative. Using a standardized surgical brain injury model, 30 Sprague-Dawley rats were randomized into three treatment groups: RADA16-I, fibrin sealant or gelatin sponge (control). Animals were sacrificed on day 3 and 42. Astrocytic and microglial infiltrations within the cerebral parenchyma adjacent to the operative site were significantly lower in the RADA16-I and fibrin sealant groups than control. RADA16-I did not cause more cellular inflammatory response despite its acidity when compared with fibrin sealant. Immunohistochemical studies showed infiltration by astrocytes and microglia into the fibrin sealant and RADA16-I grafts, suggesting their potential uses as tissue scaffolds. RADA16-I is a promising candidate for further translational and clinical studies that focus on its applications as a safe and effective hemostat, proregenerative nanofiber scaffold as well as drug and cell carrier.

The aim of this study was to review all post-craniectomy cranioplasties performed in a single institution, with an emphasis on procedure-related complications and risk factor analysis. Post-craniectomy cranioplasty is known to be associated with significant complications. Previous studies on predictors of complications have yielded conflicting results. We conducted a retrospective study on prospectively collected data on all cranioplasties done between 1 January 2003 and 31 December 2012. Multivariate analysis was performed to interrogate potential risk factors predisposing to procedure-related complications. Of the 162 procedures, the overall complication rate was 16.7%. Infection and flap depression occurred in 13 (8%) and five patients (3.1%), respectively. These led to reoperations in 12 patients. The presence of a ventriculoperitoneal shunt during cranioplasty was the only significant factor associated with a higher rate of infection (28.6% versus 9.7%, p=0.001) and flap depression (14.3% versus 3.3%, p=0.03). Indications for the initial craniectomy, choice of graft materials and the time interval between craniectomy and cranioplasty had no significant association with complications. The presence of ventriculoperitoneal shunt at the time of cranioplasty is a significant risk factor for cranioplasty complications. Early cranioplasty is safe. Whether temporizing lumbar or external ventricular drainage is a better alternative to shunting in patients who are drainage-dependent at the time of cranioplasty remain to be determined.

OBJECTIVEHydrocephalus with a blocked ventriculoperitoneal (VP) shunt is a life-threatening condition. Emergency endoscopic third ventriculostomy (ETV) is a potential treatment option. The aim of the study was to identify independent risk factors associated with failure of ETV in treating patients with blocked shunts.METHODSThe authors retrospectively reviewed data from consecutive patients admitted for blocked shunt treated by ETV during the study period from 2000 to 2016. Univariate and multivariate analyses were performed to identify independent factors associated with failed ETV for blocked shunts, such as age, sex, history of CNS infection, number of previous shunt revisions, operations performed as an emergency or elective, number of specialists, and other factors.RESULTSIn total, 121 patients underwent ETV during the study period. Of these, 31 patients (25.6%) had ETV for treatment of a blocked shunt. In 25 (80.6%) of 31 ETV was performed as an emergency procedure. There was no significant difference in the success rate of ETV depending on whether it was performed as an emergency procedure (64% [16/25]) or an elective procedure (66.7% [4/6]; OR 0.062, 95% CI 0.001–2.708; p = 0.149). Univariate and multivariate analyses identified that history of a CNS infection was an independent risk factor for failure of ETV in treating patients with a blocked shunt (OR 0.030, 95% CI 0.001–0.888; p = 0.043).CONCLUSIONSEmergency ETV had a comparable success rate as elective ETV. A history of CNS infection is an independent predictor of ETV failure in treating patients with blocked shunts.

Glioblastoma multiforme (GBM) is the commonest primary brain tumour in adults characterized by relentless recurrence due to resistance towards the standard chemotherapeutic agent temozolomide (TMZ). Prolyl 4-hydroxylase, beta polypeptide (P4HB), an endoplasmic reticulum (ER) chaperone, is known to be upregulated in TMZ-resistant GBM cells. MicroRNAs (miRNAs) are non-protein-coding transcripts that may play important roles in GBM chemoresistance. We surmised that miRNA dysregulations may contribute to P4HB upregulation, hence chemoresistance. We found that miRNA-210 (miR-210) was P4HB-targeting and was highly downregulated in TMZ-resistant GBM cells. Forced overexpression of miR-210 led to P4HB downregulation and a reduction in TMZ-resistance. A reciprocal relationship between their expressions was also verified in clinical glioma specimens. Our study is the first to demonstrate a potential link between miR-210 and ER chaperone in determining chemosensitivity in GBM. The findings have important translational implications in suggesting new directions of future studies.

Background and Purpose—Little is known about the impact of quality of anticoagulation control, as reflected by time in therapeutic range (TTR), on the effectiveness and safety of warfarin therapy in Chinese patients with atrial fibrillation. We investigated the risks of ischemic stroke and intracranial hemorrhage (ICH) in relation to warfarin at various TTRs in a real-world cohort of Chinese patients with atrial fibrillation receiving warfarin and compared with those on dabigatran, aspirin, and no therapy.Methods—This is an observational study.Results—Of 8754 Chinese patients with atrial fibrillation and CHA2DS2-VASc ≥1 (79.5±9.2 years; CHA2DS2-VASc, 4.1±1.5; and Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile International Normalized Ratio, Elderly (>65 years), Drugs/Alcohol Concomitantly [HAS-BLED], 2.2±0.9), 16.3% received warfarin, 41.1% aspirin, 4.5% dabigatran, and 38.1% received no therapy. The incidence of ischemic stroke was highest in patients with no therapy (10.38%/y), followed by patients on aspirin (7.95%/y). The incidence of stroke decreased progressively with increasing TTR quartiles (56.2%) from 7.34%/y (first quartile) to 3.10%/y (fourth quartile). Patients on dabigatran had the lowest incidence of stroke among all groups (2.24%/y). The incidence of ICH was lowest in patients on dabigatran (0.32%/y) compared with those on warfarin (0.90%/y), aspirin (0.80%/y), and no therapy (0.53%/y). ICH incidence decreased with increasing TTR from 1.37%/y (first quartile) to 0.74%/y (fourth quartile).Conclusions—In Chinese patients with atrial fibrillation, the benefits of warfarin therapy for stroke prevention and ICH risk are closely dependent on the quality of anticoagulation, as reflected by TTR. Even at the top TTR quartile, warfarin was associated with a higher stroke and ICH risk than dabigatran.

Spinal cord injury (SCI) is a devastating condition to individuals, families, and society. Oligodendrocyte loss and demyelination contribute as major pathological processes of secondary damages after injury. Oligodendrocyte precursor cells (OPCs), a subpopulation that accounts for 5 to 8% of cells within the central nervous system, are potential sources of oligodendrocyte replacement after SCI. OPCs react rapidly to injuries, proliferate at a high rate, and can differentiate into myelinating oligodendrocytes. However, posttraumatic endogenous remyelination is rarely complete, and a better understanding of OPCs’ characteristics and their manipulations is critical to the development of novel therapies. In this review, we summarize known characteristics of OPCs and relevant regulative factors in both health and demyelinating disorders including SCI. More importantly, we highlight current evidence on post-SCI OPCs transplantation as a potential treatment option as well as the impediments against regeneration. Our aim is to shed lights on important knowledge gaps and to provoke thoughts for further researches and the development of therapeutic strategies.

// Stella Sun 1 , Karrie M.Y. Kiang 1 , Amy S.W. Ho 1 , Derek Lee 1 , Ming-Wai Poon 1 , Fei-Fan Xu 1 , Jenny K.S. Pu 1 , Amanda N.C. Kan 2 , Nikki P.Y. Lee 1 , Xiao-Bing Liu 1 , Kwan Man 1 , Philip J.R. Day 3 , Wai-Man Lui 1 , Ching-Fai Fung 1 and Gilberto K.K. Leung 1 1 Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong 2 Department of Pathology and Clinical Biochemistry, Queen Mary Hospital, Pokfulam, Hong Kong 3 The Manchester Institute of Biotechnology, Faculty of Biology, Medicine and Health Sciences, University of Manchester, Manchester, United Kingdom Correspondence to: Gilberto K.K. Leung, email: gilberto@hku.hk Keywords: P4HB, angiogenesis, glioma, invasion, MAPK signaling Received: April 19, 2017 Accepted: May 08, 2017 Published: May 19, 2017 ABSTRACT Endoplasmic reticulum (ER) chaperone Prolyl 4-hydroxylase, beta polypeptide (P4HB) has previously been identified as a novel target for chemoresistance in glioblastoma multiforme (GBM). Yet its functional roles in glioma carcinogenesis remain elusive. In clinical analysis using human glioma specimens and Gene Expression Omnibus (GEO) profiles, we found that aberrant expression of P4HB was correlated with high-grade malignancy and an angiogenic phenotype in glioma. Furthermore, P4HB upregulation conferred malignant characteristics including proliferation, invasion, migration and angiogenesis in vitro , and increased tumor growth in vivo via the mitogen-activated protein kinase (MAPK) signaling pathway. Pathway analysis suggested genetic and pharmacologic inhibition of P4HB suppressed MAPK expression and its downstream targets were involved in angiogenesis and invasion. This is the first study that demonstrates the oncogenic roles of P4HB and its underlying mechanism in glioma. Since tumor invasion and Vascularisation are typical hallmarks in malignant glioma, our findings uncover a promising anti-glioma mechanism through P4HB-mediated retardation of MAPK signal transduction.

Background Iatrogenic cerebral venous sinus injury and occlusion may occur during resection of parasagittal meningioma and lateral skull base surgery. The former involves the superior sagittal sinus, and direct surgical repair is associated with good results. Outcome of direct repair of transverse–sigmoid sinus injury is less clear. We present a patient with iatrogenic sigmoid sinus injury in whom direct repair was complicated by subsequent thrombosis that was successfully salvaged by combined endovascular mechanical and chemical thrombolysis. Case Description A 60-year-old man with left tentorial atypical meningioma had disease recurrence after 3 excisions. Angiography revealed that the straight sinus and torcular and bilateral transverse sinuses were occluded. He underwent a fourth craniotomy with inadvertent occlusion of the transverse–sigmoid sinus junction. Direct surgical repair was done but was complicated by thrombosis. Mechanical endovenous thrombectomy was done followed by continuous urokinase infusion for 1 week. Digital subtraction angiography performed 7 days after endovascular treatment showed improved venous drainage through the left transverse–sigmoid sinus junction. The patient was ambulatory and fully independent, with no new neurologic deficit. Conclusions This case emphasizes the need to preserve every vein, especially when major venous sinuses have been obliterated. Detailed study of high-quality preoperative digital subtraction angiography is extremely important. Venous injury should be repaired immediately whenever possible. Postrepair venous sinus thrombosis may be effectively salvaged by endovascular thrombectomy for rapid recannulation, with or without combined use of continuous in situ thrombolytic therapy.

Background Antiplatelet resumption in patients who developed intracerebral hemorrhage (ICH) while on antiplatelet therapy (antiplatelet-related ICH) represents an important medical dilemma. We aimed to study the long-term cardiovascular outcomes of antiplatelet-related ICH survivors, and the risk of recurrent ICH with antiplatelet resumption. Methods This was an observational study of 109 antiplatelet-related ICH survivors. The clinical end points were recurrent ICH, ischemic vascular events, and vascular death (fatal ICH or ischemic vascular events). Predictors of recurrent ICH and vascular death were derived using a multivariable Cox regression model. Results The median duration of follow-up was 3.5 years (interquartile range, 1.6–5.8 years). Ischemic vascular events were more common than recurrent ICHs (6.8 per 100 patient-years vs. 2.6 per 100 patient-years; P = 0.028). Antiplatelet use was not associated with an elevated risk of recurrent ICH (hazard ratio [HR], 1.11, 95% confidence interval [CI], 0.27–4.62). A mean follow-up systolic blood pressure of >140 mmHg increased the risk of both recurrent ICH (HR, 4.28; 95% CI, 1.01–18.11) and vascular death (HR, 11.14; 95% CI, 2.72–45.62). Cerebral amyloid angiopathy (CAA) was an independent predictor for recurrent ICH (HR, 24.34; 95% CI, 2.80–211.47). Conclusions Antiplatelet resumption after antiplatelet-related ICH did not appear to carry a clinically significant risk of recurrent ICH, whereas inadequate blood pressure control and CAA contributed to a more robust risk. Antiplatelet resumption should be considered, especially in survivors with adequate blood pressure control and without CAA.

In two experiments we investigated factors that undermine conclusions about implicit motor learning in the continuous tracking paradigm. In Experiment 1, we constructed a practice phase in which all three segments of the waveform pattern were random, in order to examine whether tracking performance decreased as a consequence of time spent on task. Tracking error was lower in the first segment than in the middle segment and lower in the middle segment than in the final segment, indicating that tracking performance decreased as a function of increasing time-on-task. In Experiment 2, the waveform pattern presented in the middle segment was identical in each trial of practice. In a retention test, tracking performance on the repeated segment was superior to tracking performance on the random segments of the waveform. Furthermore, substitution of the repeated pattern with a random pattern (in a transfer test) resulted in a significantly increased tracking error. These findings imply that characteristics of the repeated pattern were learned. Crucially, tests of pattern recognition implied that participants were not explicitly aware of the presence of a recurring segment of waveform. Recommendations for refining the continuous tracking paradigm for implicit learning research are proposed.

Background: Dexamethasone (DEXA) is commonly used to reduce brain swelling during neurosurgical procedures. DEXA, however, has many side-effects that can increase the risks of post-operative complications. In contrast, progesterone (PRO) has fewer side-effects and has been found to be neuroprotective on traumatic brain injury (TBI). Whether PRO may be used as an alternative to DEXA during routine procedures has not been fully explored. Object: To compare the effects of DEXA and PRO on surgical brain injury (SBI). Methods: Seventy-five adult male Sprague Dawley rats were randomized into five groups: (1) SBI + drug vehicle (peanut oil, 1 ml kg � 1 ); (2) SBI + DEXA (1 mg kg � 1 ); (3) SBI + low-dose PRO (10 mg kg � 1 ); (4) SBI + high-dose PRO (20 mg kg � 1 ); and (5) sham SBI + drug vehicle. Magnetic resonance imaging study and assessments of brain water content (BWC), blood–brain barrier (BBB) permeability, cellular inflammatory responses and matrix metalloproteinase 9 (MMP-9) expression were conducted. Results: This model consistently resulted in increased BWC and BBB disruption. PRO reduced astrocyte and microglia responses and attenuated brain oedema with preservation of BBB. A significant down-regulation of MMP-9 expression occurred in the PRO 20 group. Conclusions: PRO is as effective as DEXA in reducing brain oedema and inflammation following SBI; 10 mg kg � 1 of PRO was demonstrated to be more effective in relieving acute cellular

Background A post-irradiated carotid pseudoaneurysm at the skull base can cause life-threatening blowout syndrome. Conventional treatments include parent vessel occlusion, endovascular coiling or covered stenting. Use of the Pipeline embolization device (PED) for pseudoaneurysm exclusion at the skull base is not well described. Objective To report the clinical and angiographic outcome after using multiple PEDs to treat recently ruptured radiation-induced carotid pseudoaneurysms at the skull base. Methods Retrospective review of the clinical and angiographic records of patients who received PEDs as primary treatment for skull base carotid pseudoaneurysm between April 1, 2011 to March 31, 2013. Results Seven patients (five men, two women) with a mean age of 58 years (range 47–65) were treated in the study period. Primary treatment with the PED alone, with adjunct coil embolization in two patients, achieved immediate hemostasis in all patients, with no pseudoaneurysm rebleeding after a mean follow-up of 15.3 months (range 4–24 months). One patient had periprocedural cerebral infarction. Delayed internal carotid artery occlusion secondary to in-stent thrombosis occurred in three patients, one of whom had lacunar infarct and two remained asymptomatic. Conclusions Endovascular treatment with the PED was effective in excluding skull base post-irradiated carotid pseudoaneurysms and preventing recurrent blowout. However, the risk of ischemic complications in this group of patients was high and our experience did not support the use of flow diverters as a first-line treatment for this condition.