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Intraventricular hemorrhage (IVH) occurs in approximately 30–50% patients with spontaneous intracerebral hemorrhage (ICH), with a high 30-day mortality rate. Excess accumulation of parenchymal or ventricular blood associated with the development of acute hydrocephalus leads to poor outcomes. The prediction of shunt dependency is important to identify patients susceptible to requiring permanent shunt placement and benefit from the diversion. This retrospective analytical study aimed to establish a predictive model of shunt dependency in patients with IVH. This study included 179 patients with primary IVH with supratentorial origin or spontaneous ICH with extension into the ventricles between 2015 and 2021. Patients were grouped into “shunt required” and “shunt not required” groups. Variables, including age, sex, preexisting hypertension and diabetes, initial Glasgow Coma Scale scores, ICH location and volume, urokinase administration, modified Graeb score (mGraeb score), and bicaudate index, were analyzed. The shunt required group had significantly higher mGraeb scores (12.0 (6.5–15.0) vs. 7.0 (4.0–12.0), p = 0.001) and higher bicaudate index (0.20 (0.17–0.23) vs. 0.16 (0.13–0.18), P p = 0.533) nor urokinase dosage (p = 0.117) showed significant relevance in shunt dependency in patients who received external ventricular drainage. In logistic regression adjusted for the confounders, thalamic ICH (odds ratio (OR) 3.55; 95% confidence interval [(95%CI), 1.13–11.18], an mGraeb score greater than 8 (OR, 3.93; 95%CI, 1.84–8.38), and a bicaudate index greater than 0.16 (OR, 9.87; 95%CI, 3.79–25.73) were factors associated with a higher tendency for shunting. The findings of this study may help identify patients at risk for a permanent shunt after IVH.

Purpose Recurrent glioblastoma (GBM) is challenging, and effective treatment options after bevacizumab failure are limited. Re-irradiation combined with bevacizumab has emerged as a potential therapeutic option for recurrent GBM patients who have failed bevacizumab treatment. This study aims to evaluate the efficacy of re-irradiation in patients with progressive GBM refractory to bevacizumab monotherapy and explore the factors that may impact survival. Methods and materials This retrospective study enrolled 64 patients who developed a second progression after single-agent bevacizumab therapy. The patients were divided into two groups: 35 continued with bevacizumab alone (none-ReRT group), and 29 received bevacizumab and re-irradiation (ReRT group). The study measured overall survival time after bevacizumab failure (OST-BF) and after re-irradiation (OST-RT). Statistical tests were used to compare categorical variables, evaluate the difference in recurrence patterns between the two groups, and identify optimal cutoff points for re-irradiation volume. Results The Kaplan-Meier survival analysis revealed that the ReRT group had a significantly higher survival rate and longer median survival time than the none-ReRT group. The median OST-BF and OST-RT were 14.5 months and 8.8 months, respectively, for the ReRT group, while the OST-BF for the none-ReRT group was 3.9 months (p < 0.001). Cox univariate analysis for overall survival time after bevacizumab failure (OST-BF) identified KPS at bevacizumab failure, ORR, bevacizumab failure pattern, re-irradiation, and re-irradiation target volume as significant predictors of survival time after bevacizumab failure. The multivariable analysis found only the re-irradiation target volume to be significant for OST-RT. Conclusions The study suggests that re-irradiation combined with bevacizumab therapy may be a valuable treatment option for patients with recurrent GBM who have failed bevacizumab therapy. The re-irradiation target volume may be a valuable prognostic factor for these patients, with smaller target volumes associated with better survival outcomes. Further studies with larger sample sizes and prospective designs are necessary to confirm these results and determine the optimal treatment approach for these patients.

Trigeminal neuralgia (TN) is a disease characterized by recurring, short-lived, electric shock-like pain experienced on one side of the face. Microvascular decompression (MVD) is one of the most effective surgical interventions for resolving TN caused by neurovascular compression. This study aimed to determine the predictive and prognostic factors of surgical outcomes.This retrospective cohort study enrolled patients diagnosed with TN who underwent MVD at our hospital during 2013-2019. The demographic information, pain character, peri-operative Barrow Neurological Institute (BNI) scale, medication, operative finding were recorded. And the outcome was Outcomes were divided into drug-free and drug-dependent group. Predisposing factors for each outcome were analyzed by one-way analysis of variance, followed by a Mann-Whitney U test or Kruskal-Wallis test.A total of 104 consecutive patients received MVD to treat TN, and 88 patients were enrolled in this study. The overall postoperative drug-free outcome was 72.7%. A significant difference in drug-free outcomes was observed for patients with typical TN (80.8%) compared with patients with atypical TN (33.33%, p = 0001). When severe venous compression was encountered during MVD, the drug-free outcome fell to 50% (10/20, p = 0.009). The Mann-Whitney U test indicated typical TN as a positive predictive factor of a drug-free outcome, whereas severe venous compression was a negative predictive factor. The patients with preoperative BNI score of 4 had better improvement than others (p = 0.045). Age, onset duration, and arterial loop had no specific difference in this study.In our study, atypical TN and severe venous compression were associated with poor outcomes. Regrouping atypical TN into precise diagnosis represents an immediate priority according to our result. The preoperative BNI score could be used as an effective predictive tool for the outcome of MVD surgery.

Background Dendritic Cell Cytokine-induced killer cell (DC- CIK) coculture treatment in cancer immunotherapy has been shown to be effective. However, the cost of DC- CIK therapy is prohibitive for many patients, and the lack of standard manufacturing processes and treatment strategies are major limitations. Our study used tumor lysate as a tumor-associated antigen source and DCs and CIK cells in coculture. We developed an efficient method to obtain autologous DCs- and CIK cells from peripheral blood. We used flow cytometry to assess DC activation and the cytometric bead array assay to quantify cytokines secreted by CIK cells. Results We evaluated the antitumor activity of DC- CIK coculture in vitro with the K562 cell line. We demonstrated that a manufacturing process employing frozen immature DCs can yield the lowest loss with the highest economic benefits. DC-CIK coculture can effectively upgrade CIK cells’ immunological specificity to tumors in the presence of tumor-associated antigens. Conclusion In vitro experiments revealed that when the DC- CIK cell ratio was 1: 20 in the coculture, CIK cells secreted the highest number of cytokines on the 14th day and the antitumor immune effect showed the highest potency. CIK cells’ cytotoxicity to K562 cells was highest when the CIK: K562 cell ratio was 25: 1. We developed an efficient manufacturing process for DC- CIK coculture, while also establishing the optimal DC- CIK cell ratio for immunological activity and the best cytotoxic CIK: K562 cell ratio.

BACKGROUND Ossification of the posterior longitudinal ligament (OPLL) is a rare but potentially devastating cause of severe spinal cord compression and degenerative cervical myelopathy. Because OPLL is rarely accompanied by prominent syringomyelia, when both are observed, other causes of syringomyelia should be considered. Simultaneous presentation of OPLL and hemangioblastoma of the cervical spine is a rare encounter and has never been reported in the English-language literature. OBSERVATIONS The authors present a case of a 64-year-old man with muscle weakness of the right upper limb and worsening dysesthesia of the right thumb and index finger. Noncontrast magnetic resonance imaging (MRI) of the cervical spine from another institution revealed OPLL from the C2 to C6 levels with severe spinal cord compression and prominent syringomyelia. Repeated MRI with contrast showed an intramedullary tumor, about 11 mm in diameter, at the right posterior aspect of the C4 level. The authors performed laminectomies from C1 to C6 with posterolateral fusion and removed the C4 tumor. Pathohistological examination of the tumor demonstrated hemangioblastoma. LESSONS Careful evaluation of the preoperative imaging study is extremely important in surgical decision making. Although rare, concomitant cervical hemangioblastoma should be listed in the differential diagnosis when OPLL is accompanied with prominent syringomyelia.

Purpose Gamma knife radiosurgery (GK) is a commonly used approach for the treatment of intracranial lesions. Its radiation response is typically not immediate, but delayed. In this study, we analyzed cases from a prospectively collected database to assess the influence of COVID-19 pandemic on the decision making in patients treated by gamma knife radiosurgery. Methods From January 2019 to August 2021, 540 cases of intracranial lesions were treated by GK with 207 cases before COVID-19 pandemic as a control. During the COVID-19 pandemic, 333 cases were similarly treated on patients with or without the COVID-19 vaccination. All the GK treated parameters as well as time profile in the decision making were analyzed. The parameters included age, sex, characteristic of lesion, targeted volume, peripheral radiation dose, neurological status, Karnofsky Performance Status (KPS), time interval from MRI diagnosis to consultation, time interval from the approval to treatment, frequency of outpatient department (OPD) visit, and frequency of imaging follow-up. Results Longer time intervals from diagnosis to GK consultation and treatment were found in the pandemic group (36.8 ± 25.5/54.5 ± 27.6 days) compared with the pre-COVID control (17.1 ± 22.4/45.0 ± 28.0 days) or vaccination group (12.2 ± 7.1/29.6 ± 10.9 days) (p p p p Conclusions The decision making in patients requiring gamma knife treatment was most likely influenced by the status of the COVID-19 pandemic, while vaccination appeared to attenuate their hesitant behaviors. Patients with pre-treatment neurological deficits and high co-morbidity undergoing the gamma knife treatment were less affected by the COVID-19 pandemic.

Background Chitosan (Chi) is a natural material which has been widely used in neural applications due to possessing better biocompatibility. In this research study, a novel of nanocomposites film based on Chitosan (Chi) with Hyaluronic Acid (HA), combined with varying amounts of gold nanoparticles (AuNPs) was created resulting in pure Chi, Chi-HA, Chi-HA-AuNPs (25 ppm) and Chi-HA-AuNPs (50 ppm). Methods This study focused on evaluating their effects on Mesenchymal Stem Cell (MSC) viability, colony formation and biocompatibility. The surface morphology and chemical position was characterized through UV-Visible spectroscopy (UV-Vis), Fourier-transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM) and contact-angle assessment. Results When seeding MSCs on Chi-HA-AuNPs (50 ppm), the results showed high cell viability, biocompatibility, and the highest colony formation ability. Meanwhile, the evidence showed that Chi-HA-Au nano film was able to inhibit Nestin and β-Tubulin expression of MSCs, as well as inhibit the ability of neurogenic differentiation. Furthermore, the results of Matrix Metalloproteinase 2/9 (MMP2/9) expression in MSCs were also significantly higher in the Chi-HA-AuNP (50 ppm) group, guiding with angiogenesis and wound healing abilities. In addition, in our rat model, both capsule thickness and collagen deposition were the lowest in Chi-HA-AuNPs (50 ppm). Conclusion Thus, in view of the in vitro and in vivo results, Chi-HA-AuNPs (50 ppm) could not only maintain the greatest stemness properties and regulate the neurogenic differentiation ability of MSCs, but was able to also induce the least immune response. Herein, Chi-HA-Au 50 ppm nano film holds promise as a suitable material for nerve regeneration engineering.

Background Dopamine agonists such as bromocriptine and cabergoline have been found to be an effective treatment for hyperprolactinemia, not only inducing adenoma shrinkage but also lowering serum prolactin levels. Among known dopamine agonists, cabergoline is the drug of choice due to its enhanced tolerability compared with bromocriptine. This study aimed to evaluate cabergoline's effectiveness, along with transsphenoidal surgery, in the treatment of hyperprolactinemia. Methods We retrieved all patients with a diagnosis of prolactinoma who were treated in our hospital during 2000-2018. A total of 208 patients were enrolled in the analysis after applying exclusion criteria. Patients were divided into four groups according to the treatments received. The demographic data, dosage and duration of cabergoline, and serum prolactin levels at different time points were collected for analysis. Results Normalization was achieved in 59 patients (83.10%) within a short median duration of 2.80 months among those treated with cabergoline only. Although cabergoline alone was effective and well-tolerated, our data showed that long-term remission rates were more favorable when surgery was involved. The long-term remission rate of all patients enrolled was 53.8% (112 patients among 208 patients). The long-term remission rates for the different treatment groups were 17.8% (8 of 45 patients) in Group 1 (Operation→Drug), 83.3% (5 of 6 patients) in Group 2 (Drug→Operation), 79.0% (68 of 86 patients) in Group 3 (Operation only), and 43.7% (31 of 71 patients) in Group 4 (Drug only). Conclusion Cabergoline has been demonstrated to be effective and should be considered as a first-line treatment for hyperprolactinemia. In our study, transsphenoidal surgery was also demonstrated to achieve good results compared with medical treatment. Surgical intervention may resurface as an alternative first-line treatment. When used in combination with cabergoline, surgery offers a higher disease remission rate than either drug or operation alone.

BACKGROUND Pedicle screw loosening (PSL) is a postsurgical complication of spinal fusion surgery that can result in morbidity. The aim of this study was to evaluate the efficacy and safety of percutaneous parapedicle screw vertebroplasty (PPSV) for pain reduction and motility improvement in patients with PSL. METHODS The postsurgical solid inter-body fusion with inter-body bone mass formation of 32 patients who underwent lumbar-sacrum spinal fusion surgery was confirmed with plain films and CT scans. Each patient had one or two screws with symptomatic PSL and was treated with PPSV. All the patients were then followed up for 12 to 24 months. The visual analog scale (VAS) and Roland-Morris Disability Questionnaire (RMDQ) were used to evaluate each patient before the operation, after the operation, and during the follow-up period. RESULTS A total of 32 patients with a total of 47 screws with PSL were treated with PPSV and experienced different results in terms of pain reduction (with the mean VAS score dropping from 7.97 ± 0.74 to 2.34 ± 1.59, p < 0.001) and motility improvement (with the mean RMDQ score dropping from 16.75 ± 1.84 to 7.21 ± 4.08, p < 0.001). The motility improvement was significantly correlated with pain reduction (r = 0.42, p = 0.018), with the mean follow-up period being 19.3 ± 6.2 months (range: 8-36 months). However, five patients who experienced moderate improvements had eventually received a revision operation after undergoing PPSV. CONCLUSION The PPSV procedure is effective and safe for the reduction of pain and improvement of life quality in patients with PSL. It can thus be considered as a possible option for the revision of spinal fusion surgery.

Background Peripheral nerve injuries result in muscle denervation and apoptosis of the involved muscle, which subsequently reduces mitochondrial content and causes muscle atrophy. The local injection of mitochondria has been suggested as a useful tool for restoring the function of injured nerves or the brain. Objective To determine outcomes following the administration of isolated mitochondria into denervated muscle after nerve injury that have not been investigated. Methods Muscle denervation was conducted in a sciatic nerve crushed by a vessel clamp and the denervated gastrocnemius muscle was subjected to 195 μg hamster green fluorescent protein (GFP)-mitochondria intramuscular infusion for 10 min. Results The mitochondria were homogeneously distributed throughout the denervated muscle after intramuscular infusion. The increases in caspase 3, 8-oxo-dG, Bad, Bax, and ratio of Bax/Bcl-2 levels in the denervated muscle were attenuated by mitochondrial infusion, and the downregulation of Bcl-2 expression was prevented by mitochondrial infusion. In addition, the decrease in the expression of desmin and the acetylcholine receptor was counteracted by mitochondrial infusion; this effect paralleled the amount of distributed mitochondria. The restoration of the morphology of injured muscles and nerves was augmented by the local infusion of mitochondria. Mitochondrial infusion also led to improvements in sciatic functional indexes, compound muscle action potential amplitudes, and conduction latencies as well as the parameters of CatWalk (Noldus) gait analysis. Conclusion The local infusion of mitochondria can successfully prevent denervated muscle atrophy and augment nerve regeneration by reducing oxidative stress in denervated muscle.

BACKGROUND Flow diverter stenting is an effective treatment for large proximal internal carotid artery (ICA) aneurysms. Cranial neuropathy caused by the mass effect of the aneurysm usually subsides over time. However, a new onset of compressive optic neuropathy after successful flow diverter stenting of a large proximal ICA aneurysm is seldom reported. OBSERVATIONS A 57-year-old woman had a right supraclinoid ICA aneurysm (approximately 17 mm) on magnetic resonance angiography (MRA) in a health checkup. She received intervention with the Pipeline embolization device. Six months later, she started to experience progressive hemianopia in the left half of the visual field. Nine months after stenting, MRA showed that the aneurysm was growing and causing mass effect, but digital subtraction angiography confirmed that the aneurysm was completely excluded from the circulation. She received a craniotomy for microsurgical decompression of the optic nerve and coagulation shrinkage of the aneurysm. Clipping and thrombectomy were not attempted. Her visual fields recovered gradually. Follow-up MRA showed that the aneurysm also diminished in size. LESSONS Whether the coagulation technique of the flow-diverter-occluded aneurysm alone is enough to cause satisfactory shrinkage and interaction between the flow diverter and the aneurysmal vasa vasorum/neointima formation should be further examined.

Background and ObjectiveIn 2014, Taiwan’s National Health Insurance administration launched a post-acute care (PAC) program for patients to improve their functions after acute stroke. The present study was aimed to determine PAC assessment parameters, either alone or in combination, for predicting clinical outcomes.MethodsWe retrospectively enrolled stroke adult patients through one PAC network in central Taiwan between January 2014 and December 2020. We collected data on post-stroke patients’ functional ability at baseline and after PAC stay. The comprehensive assessment included the following: Modified Rankin Scale (MRS), Functional Oral Intake Scale (FOIS), Mini-Nutritional Assessment (MNA), Berg Balance Scale (BBS), Fugl-Meyer Assessment (FMA), Mini-Mental State Examination (MMSE), aphasia test, and quality of life. The above items were assessed first at baseline and again at discharge from PAC. Logistic regression was used to determine factors that were associated with PAC length of stay (LOS), 14-day hospital readmission, and 1-year mortality.ResultsA total of 267 adults (mean age 67.2 ± 14.7 years) with completed data were analyzed. MRS, activities of daily living (ADLs), instrumental activities of daily living (IADLs), BBS, and MMSE all had improved between disease onset and PAC discharge. Higher baseline and greater improvement of physical and cognitive functions between initial and final PAC assessments were significantly associated with less readmission, and lower mortality. Furthermore, the improved ADLs, FOIS, MNA, FMA-motor, and MMSE scores were related to LOS during PAC. Using logistic regression, we found that functional improvements ≥5 items [adjusted odds ratio (aOR) = 0.16; 95% confidence interval (CI) = 0.05–0.45] and improved MMSE (aOR = 0.19; 95% CI = 0.05–0.68) were significantly associated with reduced post-PAC mortality or readmission. Whereas, functional improvements ≥7 items, improved FOIS, and MNA significantly prolonged LOS during PAC.ConclusionPhysical performance parameters of patients with acute stroke improved after PAC. PAC assessment with multiple parameters better predicted clinical outcomes. These parameters could provide information on rehabilitation therapy for acute stroke patients receiving PAC.

BackgroundThe coexistence of Glioblastoma Multiforme (GBM) and Arteriovenous Malformation (AVM) is rarely reported in literature. Additionally, there is a paucity of data surrounding the simultaneous presentation of Glioblastoma Multiforme (GBM) with intracranial aneurysms. In the English literature, the concurrence of these three intracranial lesions has never been reported. Regarding our case, we present a case of an Internal Carotid Artery (ICA) aneurysm that occurred in a patient with coexisting GBM and AVM. In addition, we discuss the current literature relating to this unique combination of medical conditions.Case PresentationThe 44-year-old female was presented to our hospital experiencing intermittent headaches and dizziness. Magnetic Resonance Imaging (MRI) revealed a heterogeneously enhanced mass with peri-focal edema at the right temporal lobe. Upon additional computed tomographic angiography study, the presence of AVM nidus at the right temporal-parietal occipital region was noted. Moreover, the image study also demonstrated a right ICA aneurysm. After surgery, histopathological examination demonstrated GBM and AVM in the separately resected lesion specimen. Furthermore, we expected that the ICA aneurysm would reduce in size after removal of the ipsilateral AVM and glioblastoma. Unfortunately, the postoperative digital subtraction angiography revealed only sparse change in the right ICA aneurysm, resulting in the patient still needing to receive intervention involving flow diverter stent placement.ConclusionsIn this case, we discuss the current literature relating to this unique combination of medical conditions. The causality and correlation of this presentation remains uncertain. With regards to our case, the pre-surgical image survey provided us with much support towards making critical decisions. Surgery surrounding the removal of simultaneously coexisting AVM and GBM is always a challenging task due to the potential risk of massive intraoperative bleeding.

Vertebral osteomyelitis compromises approximately 1%–7% of all cases of osteomyelitis, whereas the cervical region is affected in 3%–10% of all cases. Not surprisingly, osteomyelitis at the craniocervical junction is a rare occurrence that poses certain challenge to surgeons. With the advancement of antibiotics, most patients with vertebral osteomyelitis can be successfully treated by conservative treatment. However, surgical intervention is indicated in cases presented with neurological deficits, spinal deformity, or instability. We present one case of retropharyngeal abscess involving the craniocervical junction that led to irreducible atlantoaxial rotatory dislocation and significant ventral cord compression. Staged procedures with endoscopic endonasal odontoidectomy assisted by nasoseptal flap reconstruction for decompression and posterior occipitocervical fusion were arranged in sequence. Nevertheless, postoperative magnetic resonance imaging revealed incomplete decompression at C2 level of the cervical spine. Prompt revision surgery with nasoseptal flap takedown and reuse performed uneventfully. The patient recovered well and was able to ambulate 5 weeks later. This case illustrated long-term radionecrosis complicated with osteomyelitis and craniocervical instability. An aggressive surgical decompression followed by staged spinal fusion would be beneficial in such complex osteomyelitis cases.

Gold nanoparticles (AuNPs) are well known to interact with cells, leading to different cell behaviors such as cell proliferation and differentiation capacity. Biocompatibility and biological functions enhanced by nanomedicine are the most concerning factors in clinical approaches. In the present research, AuNP solutions were prepared at concentrations of 1.25, 2.5, 5 and 10 ppm for biocompatibility investigations. Ultraviolet–visible spectroscopy was applied to identify the presence of AuNPs under the various concentrations. Dynamic Light Scattering assay was used for the characterization of the size of the AuNPs. The shape of the AuNPs was observed through a Scanning Electron Microscope. Afterward, the mesenchymal stem cells (MSCs) were treated with a differentiation concentration of AuNP solutions in order to measure the biocompatibility of the nanoparticles. Our results demonstrate that AuNPs at 1.25 and 2.5 ppm could significantly enhance MSC proliferation, decrease reactive oxygen species (ROS) generation and attenuate platelet/monocyte activation. Furthermore, the MSC morphology was observed in the presence of filopodia and lamellipodia while being incubated with 1.25 and 2.5 ppm AuNPs, indicating that the adhesion ability was enhanced by the nanoparticles. The expression of matrix metalloproteinase (MMP-2/9) in MSCs was found to be more highly expressed under 1.25 and 2.5 ppm AuNP treatment, relating to better cell migrating ability. Additionally, the cell apoptosis of MSCs investigated with Annexin-V/PI double staining assay and the Fluorescence Activated Cell Sorting (FACS) method demonstrated the lower population of apoptotic cells in 1.25 and 2.5 ppm AuNP treatments, as compared to high concentrations of AuNPs. Additionally, results from a Western blotting assay explored the possibility that the anti-apoptotic proteins Cyclin-D1 and Bcl-2 were remarkably expressed. Meanwhile, real-time PCR analysis demonstrated that the 1.25 and 2.5 ppm AuNP solutions induced a lower expression of inflammatory cytokines (TNF-α, IL-1β, IFN-γ, IL-6 and IL-8). According to the tests performed on an animal model, AuNP 1.25 and 2.5 ppm treatments exhibited the better biocompatibility performance, including anti-inflammation and endothelialization. In brief, 1.25 and 2.5 ppm of AuNP solution was verified to strengthen the biological functions of MSCs, and thus suggests that AuNPs become the biocompatibility nanomedicine for regeneration research.

A nanocomposite composed of polyethylene glycol (PEG) incorporated with various concentrations (~17.4, ~43.5, ~174 ppm) of gold nanoparticles (Au) was created to investigate its biocompatibility and biological performance in vitro and in vivo. First, surface topography and chemical composition was determined through UV-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), scanning electron microscopy (SEM), free radical scavenging ability, and water contact angle measurement. Additionally, the diameters of the PEG-Au nanocomposites were also evaluated through dynamic light scattering (DLS) assay. According to the results, PEG containing 43.5 ppm of Au demonstrated superior biocompatibility and biological properties for mesenchymal stem cells (MSCs), as well as superior osteogenic differentiation, adipocyte differentiation, and, particularly, neuronal differentiation. Indeed, PEG-Au 43.5 ppm induced better cell adhesion, proliferation and migration in MSCs. The higher expression of the SDF-1α/CXCR4 axis may be associated with MMPs activation and may have also promoted the differentiation capacity of MSCs. Moreover, it also prevented MSCs from apoptosis and inhibited macrophage and platelet activation, as well as reactive oxygen species (ROS) generation. Furthermore, the anti-inflammatory, biocompatibility, and endothelialization capacity of PEG-Au was measured in a rat model. After implanting the nanocomposites into rats subcutaneously for 4 weeks, PEG-Au 43.5 ppm was able to enhance the anti-immune response through inhibiting CD86 expression (M1 polarization), while also reducing leukocyte infiltration (CD45). Moreover, PEG-Au 43.5 ppm facilitated CD31 expression and anti-fibrosis ability. Above all, the PEG-Au nanocomposite was evidenced to strengthen the differentiation of MSCs into various cells, including fat, vessel, and bone tissue and, particularly, nerve cells. This research has elucidated that PEG combined with the appropriate amount of Au nanoparticles could become a potential biomaterial able to cooperate with MSCs for tissue regeneration engineering.

Glioma surgery near the functional area is still a dilemma. Intraoperative neurophysiologic monitoring (IONM) and functional mapping can play a role to maximize the extent of resection (EOR), while minimizing the risk of sequelae. We herein review the utility of tailored intraoperative mapping and monitoring in patients undergoing glioma surgery in our institute. Patients were divided into two groups on the basis of application tailored IONM (group A, 2013–2017, n = 53) or not (group B, 2008–2012, n = 49) between January 2008 and December 2017. The setup, tailored IONM protocols, surgery, and clinical results of all patients with eloquent glioma were analyzed with the EOR, functionality scores, overall survival (OS) and progression-free survival (PFS) retrospectively. The 102 patients were considered eligible for analysis. High grade and low grade gliomas accounted for 73 (72%) and 29 (28%) cases, respectively. There was a positive association between the application of neuromonitor and post-operative functional preservation, but no significant statistical differences over the EOR, OS and PFS between the two groups. In our experience, tailored intraoperative functional mapping provides an effective neurological function preservation. Routine implementation of neurophysiological monitoring with adequate pre-operative planning and intraoperative teamwork in eloquent glioma can get more satisfied functional preservation. Due to the maturation and experience of our IONM team may also be the variation factor, prospective studies with a more prominent sample and proper multivariate analysis will be expected to determine the real benefit.

Objective Long-term effects of endoscopic endonasal transsphenoidal intracapsular debulking and adjuvant somatostatin analogs (SSAs) were evaluated in patients with growth hormone- (GH) secreting pituitary macroadenomas. Methods We retrospectively reviewed the medical records of 45 patients with acromegalic macroadenoma who underwent endonasal endoscopic transsphenoidal intracapsular debulking and received adjuvant SSAs (octreotide) between 2006 and 2015 who had >1 year of follow-up. To evaluate the predictive factors for 1 year and long-term biochemical outcomes, univariate and multivariate analyses were performed. Results Biochemical remission was achieved in 1 year in 20 of the 45 (44.4%) patients, and in 31 of the 45 patients after long-term adjuvant SSA treatment. Tumor control was achieved in 43 of the 45 (93.3%) patients. The univariate analysis showed age (≥55 years), tumor size (diameter ≤1.5 cm), premedication GH levels (≤2.8 ng/mL), premedication insulin-like growth factor 1 levels (≤2-fold of upper limit of normal range), cavernous sinus invasion (Knops grades 2, 3, and 4), and near-total tumor resection were associated with long-term outcomes. The multivariate analysis showed near-total resection was a significant predictor for long-term outcomes (P = 0.019). There were no new pituitary dysfunctions. The observed complications included one case of cerebrospinal fluid leakage and one case of epistaxis requiring intervention. Conclusions Intracapsular debulking and adjuvant SSAs are a safe and viable treatment for patients with GH secreting pituitary macroadenoma to achieve biochemical remission and tumor control. Although adjuvant SSA treatment enhances residual tumor control, cavernous sinus invasion impedes the remission of endocrine tumors.

BACKGROUND In glioblastoma multiforme (GBM), bevacizumab increased progression-free survival but it has failed to improve overall survival (OS) in controlled trials. This study, therefore, aimed to retrospectively analyze the polymorphisms of p53 codon 72 and the clinical characteristics of GBM specimens from Taiwanese patients. METHODS The polymorphisms of p53 codon 72 in 99 patients with GBM treated at Taichung Veterans General Hospital in Taiwan from 2007 to 2017 were analyzed using direct DNA sequencing and PCR-RFLP analysis. RESULTS We found that among these GBM patients, the polymorphisms of p53 codon 72 were not directly associated with the overall survival of GBM, both the Arg/Arg and Arg/Pro genotypes were associated with significant benefits in terms of overall survival in patients treated with CCRT plus bevacizumab compared to patients treated with CCRT alone. CONCLUSIONS This pilot study suggests that both the Arg/Arg and Arg/Pro genotypes of p53 codon 72 polymorphism may have value as independent prognostic or predictive parameters for bevacizumab treatment response and failure. Relatedly, the results of the study further demonstrate the utility of stratifying GBM patientsaccording to bevacizumab sensitivity.

Glioblastoma (GBM) is a common, malignant brain tumor. While it rarely metastasizes to distant organs, the diffuse invasion of glioma cells within the brain makes it difficult to resect. P21 (Waf-1) is a cyclin-dependent kinase inhibitor that plays an essential role in cell growth arrest, terminal differentiation, and apoptosis. Thus, the existence of natural variants of p21 could be linked to specific cancer. The purpose of this study was to identify the polymorphism variants of p21 codon 31 (Ser31Arg) and to explore its role in the therapy of glioblastoma multiforme. A total of unrelated 99 GBM subjects, were enrolled in the study, and genomic DNA was obtained from each tumor sample for genotyping. Genotyping was performed by polymerase chain reaction (PCR) restriction fragment length polymorphism method (PCR-RFLP analysis. Odds ratios (Ors) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression analysis. We found that among these GBM patients, the distribution of codon 31 polymorphisms was 20.2% for Serine homozygotes (Ser/Ser), 32.3% for arginine homozygotes (Arg/Arg), and 47.5% for Serine/arginine heterozygotes (Ser/Arg). Although the polymorphisms of p21 codon 31 were not directly associated with the overall survival of GBM, both the Arg/Arg and Arg/Ser genotypes were associated with significant benefits in terms of overall survival in patients treated with CCRT plus bevacizumab compared to patients treated with CCRT alone. Our findings suggest that the p21 Ser31Arg polymorphism may play an important role in the pathogenesis and initiation of GBM. Moreover, the polymorphism seems to contribute to a significant prediction at early diagnosis for bevacizumab therapy.

Several meningioma cases arising through Meckel's cave (MC) at the middle and posterior fossa have been reported. However, few relevant meningiomas have been observed with a dumbbell shape.We report a rare case of a 36-year-old woman with a meningioma of MC with a typical dumbbell-shaped, schwannoma-like presentation on magnetic resonance imaging (MRI), resulting in a misleading differential diagnosis.In this case report, we discuss the characteristics of meningioma of MC observed on MRI and our surgical approach to this condition.This tumor was able to mimic a trigeminal schwannoma both clinically and radiographically. This case report has been reported in line with the SCARE 2020 criteria [1].

Heterochromatin, a type of condensed DNA in eukaryotic cells, has two main categories: Constitutive heterochromatin, which contains H3K9 methylation, and facultative heterochromatin, which contains H3K27 methylation. Methylated H3K9 and H3K27 serve as docking sites for chromodomain-containing proteins that compact chromatin. M33 (also known as CBX2) is a chromodomain-containing protein that binds H3K27me3 and compacts chromatin in vitro. However, whether M33 mediates chromatin compaction in cellulo remains unknown. Here we show that M33 compacts chromatin into DAPI-intense heterochromatin domains in cells. The formation of these heterochromatin domains requires H3K27me3, which recruits M33 to form nuclear bodies. G9a and SUV39H1 are sequentially recruited into M33 nuclear bodies to create H3K9 methylated chromatin in a process that is independent of HP1α. Finally, M33 decreases progerin-induced nuclear envelope disruption caused by loss of heterochromatin. Our findings demonstrate that M33 mediates the formation of condensed chromatin by forming nuclear bodies containing both H3K27me3 and H3K9me3. Our model of M33-dependent chromatin condensation suggests H3K27 methylation corroborates with H3K9 methylation during the formation of facultative heterochromatin and provides the theoretical basis for developing novel therapies to treat heterochromatin-related diseases.

Background It has previously been shown that bevacizumab, when added to chemotherapy, improved overall survival in several cancers. In glioblastoma multiforme (GBM), bevacizumab increased progression-free survival and it is widely used for tumor recurrence, though it has failed to improve overall survival (OS) in controlled trials. However, an effective biomarker for predicting the prognosis of bevacizumab treatment has yet to be identified. This study, therefore, aimed to retrospectively analyze the polymorphisms of p53 codon 72 and the clinical characteristics of GBM specimens from Taiwanese patients. Methods The polymorphisms of p53 codon 72 in 99 patients with GBM treated at Taichung Veterans General Hospital in Taiwan from 2007 to 2017 were analyzed using direct DNA sequencing and PCR-RFLP analysis. Results We found that among these GBM patients, the distribution of codon 72 polymorphisms was 28.3% for proline homozygotes (Pro/Pro), 38.4% for arginine homozygotes (Arg/Arg), and 33.3% for proline/arginine heterozygotes (Pro/Arg). Although the polymorphisms of p53 codon 72 were not directly associated with the overall survival of GBM, both the Arg/Arg and Arg/Pro genotypes were associated with significant benefits in terms of overall survival in patients treated with CCRT plus bevacizumab compared to patients treated with CCRT alone. Conclusions This pilot study suggests that both the Arg/Arg and Arg/Pro genotypes of p53 codon 72 polymorphism may have value as independent prognostic or predictive parameters for bevacizumab treatment response and failure. Relatedly, the results of the study further demonstrate the utility of stratifying GBM patients according to bevacizumab sensitivity.

Background A subgroup of patients with acute minor stroke (AMS) or transient ischemic attack (TIA) become disabled due to disease progression (DP) or recurrent stroke within 3 months. The aim of this article is to identify the risk factors for DP in AMS/TIA patients. In the literature, no studies focused on computed tomography perfusion (CTP) in AMS/TIA patients at the acute stage. Methods This retrospective study included patients with AMS or TIA (onset of symptoms ≤4.5 hours, baseline National Institutes of Health Stroke Scale [NIHSS] score of 0-4). DP was defined as a deterioration of NIHSS score of ≥2 points during hospitalization or modified Ranking Scale ≥2 at 3-month follow-up. Clinical data and imaging results were retrieved and measured for statistical analysis. Results From 2011 to 2017, total 135 patients were eligible for further analysis: 28 patients (20.7%, DP group) and 107 patients (79.3%, non-DP group). The DP group had significantly higher larger penumbra volumes (p = 0.028). In univariate model of the logistic regression, patients with the following risk factors tended to have unfavorable outcome: female gender, higher HbA1c, chronic kidney disease stage ≥3b, intracranial atherosclerosis, and penumbra volume were associated unfavorable outcome, but larger deadcore volume was not. In further multivariate analysis, only penumbra volume >5 cm (p = 0.049, odds ratio [OR] = 3.21, 95% CI: 1.00-10.27) had the statistical significance. The cut-point value of the penumbra volume for unfavorable outcome in AMS/TIA patients was 4.73 cm. Conclusion One fifth of the AMS/TIA patients had unfavorable outcome at 90 days. In CTP performed within 4.5 hours after the onset of AMS/TIA, the penumbra volume (>5 cm) was a significant risk factor for DP, and the cut-point value was 4.73 cm. Further studies could be designed to involve this subgroup of patients for more aggressive treatment.

Background: Dynamin-related protein 1 (DRP1) is a GTPase involved in mitochondrial fission, mitochondrial protein import, and drug sensitivity, suggesting an association with cancer progression. This study was conducted to evaluate the prognostic significance of DRP1 in glioblastoma multiforme (GBM). Methods: DRP1 expression was measured by immunohistochemistry and Western blotting. Correlations between DRP1 expression and clinicopathological parameters were determined by statistical analysis. Differences in survival were compared using the log-rank test. DRP1 expression was detected in 87.2% (41/47) of the investigated patients with GBM. Results: The patients with higher DRP1 levels had worse survival (p = 0.0398). In vitro, the silencing of DRP1 reduced cell proliferation, invasive potential, and radiation resistance. The addition of shikonin inhibited DRP1 expression and increased drug uptake. Moreover, shikonin reduced the nuclear entry of DNA repair-associated enzymes and increased radiation sensitivity, suggesting that reducing DRP1 expression could inhibit DNA repair and increase the radiation sensitivity of GBM cells. Conclusion: Our results indicate that DRP1 overexpression is a prospective radio-resistant phenotype in GBM. Therefore, DRP1 could be a potential target for improving the effectiveness of radiation therapy.

Cerebral venous sinus thrombosis (CVST) is a rare cause of cerebral infarction. Once patients survive the acute phase, long-term prognosis is generally satisfactory. CVST patients who harbored risk factors known for poor prognosis (e.g., deterioration of consciousness/neurological functions and seizures) were oftentimes unresponsive to systemic heparin treatment. The advantage of combined endovascular mechanical thrombectomy (EMT) and on-site chemical thrombolysis (OCT) plus systemic heparin for CVST over the heparin treatment alone has not been proved. A retrospective study was conducted to analyze consecutive patients with CVST from 2005 to 2015. Patients having clinical improvement or stable disease after heparin treatment were in I/S group; patients having continuous deterioration of consciousness/neurological functions and refractory seizures (despite the use of multiple anti-epileptic drugs) after heparin treatment were in D group. EMT and OCT were indicated for patients in D group. Imaging studies and medical records were reviewed for statistical analysis. Safety issues included new-onset/progression of symptomatic intracerebral hemorrhages (ICH) or procedure-related complications. Total thirty patients were included (I/S group = 16; D group = 14). In D group, the mean time frame from the start of heparin treatment to the endovascular treatment was 3.2 days. Compared with I/S group, all patients in D group had complete stenosis of the sinuses, with higher initial mRS, lower initial GCS, and more seizures (p = 0.006, 0.007, and 0.031, respectively), but no significant differences in the mRS at discharge (p = 0.504). Shorter length of thrombosis and lower initial mRS were associated with better outcomes (p = 0.009 and 0.003, respectively). Thrombosis involving the superior sagittal sinus (SSS) was associated with bad outcomes (p = 0.026). There were two patients (6.7%) with worsening symptomatic ICH, one in each group, managed surgically. The overall mortality of the study was 6.7% (2/30). Combined EMT and OCT after heparin treatment for severe CVST were reasonably safe, which might be considered as a salvage treatment in severe CVST patients who are unresponsive to heparin with heavy clot burden involving SSS in the acute phase. However, further studies are needed to confirm its efficacy and validity.