Predictors of extubation failure and prolonged mechanical ventilation among patients with intracerebral hemorrhage after surgery.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is a condition associated with high mortality and morbidity. Survivors may require prolonged intubation with mechanical ventilation (MV). The aim of this study was to analyze the predictors of extubation failure and prolonged MV in patients who undergo surgical evacuation. METHODS: This retrospective study was conducted on adult patients with ICH who underwent MV for at least 48 h and survived > 14 days after surgery. The demographics, clinical characteristics, laboratory tests, and Glasgow Coma Scale score were analyzed. RESULTS: A total of 134 patients with ICH were included in the study. The average age of the patients was 60.34 ± 15.59 years, and 79.9% (n = 107) were extubated after satisfying the weaning parameters. Extubation failure occurred in 11.2% (n = 12) and prolonged MV in 48.5% (n = 65) patients. Multivariable regression analysis revealed that a white blood cell count > 10,000/mm3 at the time of extubation was an independent predictor of reintubation. Meanwhile, age and initial Glasgow Coma Scale scores were predictors of prolonged MV. CONCLUSIONS: This study provided the first comprehensive characterization and analysis of the predictors of extubation failure and prolonged MV in patients with ICH after surgery. Knowledge of potential predictors is essential to improve the strategies for early initiation of adequate treatment and prognosis assessment in the early stages of the disease.

Minimally invasive endoscopic evacuation with the novel, portable Axonpen neuroendoscopic system for spontaneous intracerebral hemorrhage.

Minimally invasive surgeries have shown potential to improve mortality and clinical outcomes of spontaneous intracerebral hemorrhage (ICH). The present study assessed the first-in-human outcomes of a novel, portable neuroendoscopic system for ICH evacuation at our single center. This neuroendoscopic system integrates real-time visualization into a handpiece which has controllable suction, irrigation, and coagulation to allow a neurosurgeon to conduct minimally invasive ICH evacuation independently with bimanual dexterity. Pre- and postoperative data of ten patients who had spontaneous basal ganglia hemorrhage (mean: 46.5 ± 12.2 mL) and underwent evacuation with the specified neuroendoscopic system were collected prospectively. The mean time to receive surgery was 12.1 ± 7.6 h. Mean operative time was 3.4 ± 0.9 h. The mean hematoma volume decreased to 6.0 ± 3.9 mL at postoperative 6 h, resulting in a mean volume reduction of 86.0 ± 11.2% (P = 0.005). The median length of intensive care unit stay was 3 days (IQR, 3-4 days). At discharge, the median Glasgow Coma Scale (GCS) score significantly improved to 11.5 (IQR, 11-15; P = 0.016), and the median modified Rankin Scale (mRS) score was 4 (IQR, 4-5). Six patients (60%) showed a favorable mRS score of ≤ 3 on their last return visit. Neither death nor rebleeding occurred during the follow-up periods. Integrated design of the innovative device is valuable to optimize minimally invasive endoscopic ICH evacuation procedure. Further studies are needed to clarify long-term benefits from such type of the innovative device to early intervention of ICH.

Gelatin-Based Hydrogel for Three-Dimensional Neuron Culture Application.

Gelatin is a biocompatible biomaterial composed of a variety of amino acids that provides a possibility to regulate the interaction between cationic amino acids and neural cells. Based on our first finding that the neuron viability was improved as the lysine on the gelatin was converted into a guanidine structure, a three-dimensional (3D) gelatin hydrogel composed of gelatin and poly(allylguanidine) (PAG) was prepared to investigate neural cell behaviors. As expected, improved neuron viability, neurite outgrowth, synaptogenesis, and inhibited glial cell growth were simultaneously observed in the gelatin cross-linked with the PAG hydrogel (G-PAG) but not in the gelatin hydrogel cross-linked with poly-d-lysine (PDL) or polyethylenimine (PEI). In addition, in vivo tests also illustrated that G-PAG could provide an environment for neural culture, with improving neuron viability and neurite outgrowth. Several hydrogel characteristics-including the swelling ratio, mechanical strength, and electric property-that theoretically can influence neural cell response showed no significant difference among them. Therefore, the guanidine structure of PAG was proposed to determine the behaviors of neural cells within the gelatin-polycation hydrogels, and we proposed that the neural cell behavior is regulated by a specific gelatin-neuron relationship. The information found in this study provides a concept to design and modify gelatin-based hydrogels for neural tissue engineering applications.

Brain-derived neurotrophic factor contributes to neurogenesis after intracerebral hemorrhage: a rodent model and human study.

Background and purpose: Intracerebral hemorrhage (ICH) enhances neurogenesis in the subventricular zone (SVZ); however, the mechanism is not fully understood. We investigated the role of brain-derived neurotrophic factor (BDNF) in post-ICH neurogenesis in a rodent model and in patients with ICH using cerebrospinal fluid (CSF). Methods: A rat model of ICH was constructed via stereotaxic injection of collagenase into the left striatum. Patients with ICH receiving an external ventricular drain were prospectively enrolled. CSF was collected from rats and patients at different post-ICH times. Primary cultured rat neural stem cells (NSCs) were treated with CSF with or without BDNF-neutralized antibody. Immunohistochemistry and immunocytochemistry were used to detect NSC proliferation and differentiation. The BDNF concentration in CSF was quantified using enzyme-linked immunosorbent assays (ELISA). Results: In the rat model of ICH, the percentage of proliferating NSCs and neuroblasts in SVZ was elevated in bilateral hemispheres. The cultured rat NSCs treated with CSF from both rats and patients showed an increased capacity for proliferation and differentiation toward neuroblasts. BDNF concentration was higher in CSF collected from rats and patients with ICH than in controls. Blocking BDNF decreased the above-noted promotion of proliferation and differentiation of cultured NSCs by CSF treatment. In patients with ICH, the BDNF concentration in CSF and the neurogenesis-promoting capacity of post-ICH CSF correlated positively with ICH volume. Conclusion: BDNF in CSF contributes to post-ICH neurogenesis, including NSC proliferation and differentiation toward neuroblasts in a rat model and patients with ICH.

Current Indications for Spinal Endoscopic Surgery and Potential for Future Expansion.

Endoscopic spine surgery (ESS) has evolved as a safe, effective, and efficient alternative for minimally invasive spine surgery (MISS). The innovation of full-endoscopic systems makes definitive decompression surgery through different approaches feasible. The approach can be determined according to the location of the target lesion or the surgeon's preference. During the past 2 decades, ESS has expanded its indications from lumbar to cervical spines. Except for decompression, endoscopy-assisted fusion surgery is also developing. However, ESS is still evolving and has a steep learning curve. The revolution of technologies and ESS techniques will enable surgeons to treat various spinal diseases more practically. In recent years, the application of the computer-assisted navigation system and augmented reality have reformed imaging quality and interpretation. The endoscopic rhizotomy techniques have opened a new way for MISS of chronic low back pain. This review introduces the current indications of ESS and its potential future expansion.

Ultrasound-Guided Perineural Vitamin B12 Injection for Brachial Plexus Injury: A Preliminary Study.

Individuals with brachial plexus injury (BPI) require upper limb function restoration, but the treatment remains controversial. Vitamin B12 may aid in pain control and nerve regeneration. We present the technical aspects of ultrasound-guided perineural vitamin B12 injection for BPI. The demonstrative case is a 50-year-old man with BPI resulting from a traffic accident. Under ultrasound guidance, vitamin B12 was injected precisely into the brachial plexus compartment around the swollen neuroma of the C6 root. Motor and sensory functions of the left upper extremity improved over 6 months. Ultrasound-guided perineural vitamin B12 injection may be an efficient and personalized intervention in cases of post-ganglionic BPI that failed to improve in the first 3 months.

Robot-Assisted Kyphoplasty versus Fluoroscopy-Assisted Kyphoplasty: A Meta-Analysis of Postoperative Outcomes.

Osteoporotic vertebral compression fractures are the most common manifestation of osteoporosis. Percutaneous kyphoplasty (PKP) can lead to both pain improvement and correction of kyphosis secondary to collapsed vertebral bodies. Robot-assisted (RA) PKP has been reported to provide better vertebral body fracture correction than conventional fluoroscopy-assisted (FA) PKP. The aim of this meta-analysis is to compare clinical outcomes of RA PKP versus FA PKP. The Pubmed, Embase, and MEDLINE electronic databases were searched from January 1900 to December 2022, with no language restrictions for relevant articles. We extracted the preoperative and postoperative mean pain score and standard deviation from the included studies and pooled them using an inverse variance method. Statistical analyses were performed using functions available in the metafor package in R software. The results of this meta-analysis were summarized with weighted mean differences (WMDs). Our search strategy identified 181 references from the Pubmed, Embase, and MEDLINE electronic databases. We excluded duplicates and irrelevant references, after screening titles and abstracts. The remaining 12 studies were retrieved for full-text review, and, finally, we included five retrospective cohort studies from 2015 to 2021, comprising 223 patients undergoing RA PKP and 246 patients undergoing FA PKP. No difference was found in subgroup analysis based on the timing of postoperative pain assessment, despite the overall estimate of postoperative pain indicating a significant difference between the RA PKP and FA PKP groups (WMD, -0.22; 95% CI, -0.39 to -0.05). The long-term pain assessment revealed a significantly lower VAS in the RA PKP group than the FA PKP group at six months postoperatively (WMD, -0.15; 95% CI, -0.30 to -0.01), but no difference between the subgroups at three (WMD, 0.06; 95% CI, -0.41 to -0.54) and twelve months (WMD, -0.10; 95% CI, -0.50 to 0.30) postoperatively. Our meta-analysis revealed no significant difference in postoperative pain between RA PKP and FA PKP. Patients undergoing RA PKP had better pain improvement compared to FA PKP at 6 months postoperatively. However, further studies focusing on long-term outcomes in patients undergoing RA PKP are warranted to clarify its benefit, given the small number of included studies.

Association between systemic rheumatic diseases and dementia risk: A meta-analysis.

Background and aims: Epidemiological studies have been conducted on the relationship between systemic rheumatic diseases (SRDs) and dementia. Therefore, we focused on determining the extent of alliances bounded by SRDs, along with the risk of dementia. Materials and methods: Two independent reviewers assessed all studies retrieved from the PubMed, EMBASE, Scopus, and Web of Science databases between January 1, 2000 and November 30, 2021. Only observational studies that estimated the possibility of dementia in participants with SRD were considered. The random-effects model was applied to forecast pooled risk ratios (RRs) and 95% confidence intervals (CI). Heterogeneity among the studies was evaluated using the Q and I2 statistics. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Funnel plots were used to calculate the risk of bias. Results: Seventeen observational studies with 17,717,473 participants were recruited. Our findings showed that among the participants with SRDs, those with osteoarthritis, systemic lupus erythematosus, and Sjogren's syndrome were highly related to an elevated risk of dementia (pooled RR: 1.31; 95% CI: 1.15-1.49, p<0.001; pooled RR: 1.43; 95% CI: 1.19-1.73, p<0.001; and pooled RR: 1.26; 95% CI: 1.14-1.39, p<0.001, respectively). However, participants with rheumatoid arthritis (RA) were not associated with an increased risk of dementia (pooled RR: 0.98; 95% CI: 0.90-1.07, p<0.001). Conclusion: This systematic review and meta-analysis demonstrated an increased dementia risk among SRDs participants, except for RA.

Cervical cerebrospinal fluid venous fistula with syringomyelia treated with suboccipital decompression: illustrative case.

BACKGROUND: Cerebrospinal fluid (CSF) venous fistulas are a recently discovered and underdiagnosed cause of spontaneous spinal CSF leak, which may lead to spontaneous intracranial hypotension. Most cases occur in the thoracic spine, and only 2 cases were reported in the cervical spine. Treatments include the epidural blood patch, fibrin glue injection, and surgical ligation of the fistula. OBSERVATIONS: The authors report the treatment of a C6-7 CSF venous fistula, for which direct ligation was not feasible, with suboccipital decompression, leading to the complete resolution of the symptoms. Based on the clinical course and outcome in our patient, the authors summarize the previous theory and propose a hypothesis for the pathophysiology of headache and other symptoms in patients with CSF venous fistulas. LESSONS: The symptoms of CSF venous fistulas may be linked not only to intracranial hypotension but also to the altered CSF dynamics induced by tonsillar herniation. Suboccipital decompression should be considered as a potential treatment option, especially in patients with Valsalva-induced headache who show a poor response to surgical ligation, patients in whom surgical ligation is not feasible, and patients with foramen magnum obstruction. Further investigation of the pathophysiology of CSF venous fistulas is warranted and should be performed in the future.

Multidisciplinary management of patients with non-small cell lung cancer with leptomeningeal metastasis in the tyrosine kinase inhibitor era.

OBJECTIVE: Leptomeningeal metastasis (LM) is a challenging scenario in non-small cell lung cancer (NSCLC). Considering that outcomes of treatment modalities stratified by LM chronological patterns related to brain metastasis (BM) are lacking, the aim of this study was to evaluate outcomes and explore prognostic factors. METHODS: The authors retrospectively collected data of patients with NSCLC undergoing Ommaya reservoir implantation, ventriculoperitoneal shunt implantation, or lumboperitoneal shunt implantation. Based on radiographic findings and time from diagnosis of NSCLC to LM, the authors divided them into subtypes of LM as follows: LM without BM; LM concurrent with BM; or LM after BM. The Kaplan-Meier method was applied to analyze overall survival (OS) and multivariate Cox regression for prognostic factors. RESULTS: Sixty-one patients with LM were included, with a median OS of 8.1 (range 0.2-70.0) months. Forty-three (70.5%) patients had EGFR-mutant disease. Forty-two (68.9%) patients had 19-del or L858R mutation, and one (1.6%) patient had G719A mutation. Fifty-seven (93.4%) patients had hydrocephalus. Twenty-one (34.4%) patients received whole-brain radiotherapy before LM diagnosis, 3 (4.9%) patients underwent operation for BMs before LM diagnosis, and 42 (68.9%) patients received EGFR tyrosine kinase inhibitor (TKI) therapy before LM diagnosis. Eleven patients were treated with chemotherapy, 10 patients were treated with TKIs, and 32 patients were treated with chemotherapy combined with TKIs before LM diagnosis. Patients with LM after BM had lower Karnofsky Performance Status (KPS) scores (KPS score 50) than did those with LM without BM (KPS score 80) or LM concurrent with BM (KPS score 70; p = 0.003). More patients with LM after BM received intrathecal methotrexate than in the other subgroups (p < 0.001). The median OS was significantly shorter in the LM after BM than in the concurrent LM and BM and the LM without BM subgroups (5.4 vs 5.5 vs 11.6 months; p = 0.019). Cox regression revealed that a KPS score ≥ 70 (HR 0.51; p = 0.027) and shunt implantation (HR 0.41; p = 0.032) were favorable prognostic factors. CONCLUSIONS: Patients with NSCLC who had LM without BM had better survival outcomes (11.6 months) compared with those who had LM after BM or concurrent LM and BM. Aggressive shunt implantation may be favored for LM.

Gross Total Resection Promotes Subsequent Recovery and Further Enhancement of Impaired Natural Killer Cell Activity in Glioblastoma Patients.

Glioblastoma is the most common primary malignant brain tumor, and median survival is relatively short despite aggressive standard treatment. Natural killer (NK) cell dysfunction is strongly associated with tumor recurrence and metastasis but is unclear in glioblastoma. NK activity (NKA) represents NK cell-secreted interferon-γ (IFN-γ), which modulates immunity and inhibits cancer progression. This study aimed to analyze NKA in glioblastoma patients to obtain a clearer overview of immunity surveillance. From 2020 to 2021, a total of 20 patients and six healthy controls were recruited. Peripheral blood samples were collected preoperatively and on postoperative days (POD) 3 and 30. Then, NKA was measured using the NK VUE kit. Although NKA decreased on POD3, it recovered and further significantly enhanced on POD30, with a nearly five-fold increase compared to baseline (p = 0.004). Furthermore, the percentage of CD56brightCD16- NK cells decreased significantly on POD3 (p = 0.022) and further recovered on PO30. Subgroup analysis of extent surgical resection further revealed that the recovery of impaired NKA was attributable to gross total resection (GTR) rather than subtotal resection (STR). In conclusion, NKA is significantly impaired in glioblastoma, and GTR has demonstrated superior benefit in improving the suppressed NKA and increased CD56brightCD16- NK subset in glioblastoma patients, which may be associated with subsequent patients' prognosis. Therefore, the goal of performing GTR for glioblastoma should be achieved when possible since it appears to increase NKA cell immunity.

Minimally Invasive Neurosurgery for Spontaneous Intracerebral Hemorrhage-10 Years of Working Progress at National Taiwan University Hospital.

Intracerebral hemorrhage (ICH) is a life-threatening disease with a global health burden. Traditional craniotomy has neither improved functional outcomes nor reduced mortality. Minimally invasive neurosurgery (MIN) holds promise for reducing mortality and improving functional outcomes. To evaluate the feasibility of MIN for ICH, a retrospective analysis of patients with ICH undergoing endoscopic-assisted evacuation was performed. From 2012 to 2018, a total of 391 patients who underwent ICH evacuation and 76 patients who received early (<8 h) MIN were included. The rebleeding, mortality, and morbidity rates were 3.9, 7.9, and 3.9%, respectively, 1 month after surgery. At 6 months, the median [interquartile range (IQR)] Glasgow Coma Scale score was 12 (4.75) [preoperative: 10 (4)], the median (IQR) Extended Glasgow Outcome Scale score was 3 (1), and the median (IQR) Modified Rankin Scale score was 4 (1). The results suggested that early (<8 h) endoscope-assisted ICH evacuation is safe and effective for selected patients with ICH. The rebleeding, morbidity, and mortality rates of MIN in this study are lower than those of traditional craniotomy reported in previous studies. However, the management of intraoperative bleeding and hard clots is critical for performing endoscopic evacuation. With this retrospective analysis of MIN cases, we hope to promote the specialization of ICH surgery in the field of MIN.

Feasibility of Nonintubated Anesthesia for Lumboperitoneal Shunt Implantation.

Lumboperitoneal shunt (LPS) implantation is a cerebrospinal fluid diversion therapy for the communicating type of normal-pressure hydrocephalus (NPH); NPH mainly affects older adults. However, endotracheal intubation for mechanical ventilation with muscle relaxant increases perioperative and postoperative risks for this population. Based on knowledge from nonintubated thoracoscopic surgery, which has been widely performed in recent years, we describe a novel application of nonintubated anesthesia for LPS implantation in five patients. Anesthesia without muscle relaxants, with a laryngeal mask in one patient and a high-flow nasal cannula in four patients, was used to maintain spontaneous breathing during the surgery. The mean anesthesia time was 103.8 min, and the mean operative duration was 55.8 min. All patients recovered from anesthesia uneventfully. In our experience, nonintubated LPS surgery appears to be a promising and safe surgical technique for appropriately selected patients with NPH.

Combination of Acupoints for Alzheimer's Disease: An Association Rule Analysis.

Background: Alzheimer's disease (AD) is an ongoing neurological degeneration characterized by amnesia and a decline in cognitive abilities. Hippocampal neurogenesis is the leading cause of AD. Mild cognitive impairment (MCI), a prodromal state of AD, is mainly due to the degradation of neuropsychiatric manifestations. Previous systematic reviews demonstrated that treatment with acupuncture with Chinese herbs is tolerable and effective in improving cognitive function in patients with AD. Our investigation aimed to discover the main acupoint combination for AD management based on a preceding systematic review and meta-analysis of randomized control trials (RCTs). Materials and Methods: Our investigation was executed using association rule analysis, which is a common data mining technique accessible within R. Our study elucidated acupoint locations as binary data from 15 of the included studies using the Apriori algorithm. Results: Thirty-two acupoints were selected from 15 RCTs. The 10 most frequent acupoints were selected. We inspected 503 association rules using the interpreted acupuncture data. The obtained results showed that {SP6, BI10} ≥ {HT7} and {HT7, BI10} ≥ {SP6} were the most associated rules in 15 RCTs. Conclusion: The combination of acupoints ({SP6, BI10} ≥ {HT7} and {HT7, BI10} ≥ {SP6}) can be acknowledged as a core combination for future acupuncture regimens of AD.

Predictors of Prolonged Mechanical Ventilation Among Patients with Aneurysmal Subarachnoid Hemorrhage After Microsurgical Clipping.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) is a fatal event with high mortality and morbidity rates. Survivors may require prolonged intubation with mechanical ventilation (MV). However, the risk factors for prolonged intubation in these patients remain unclear. The aim of this study was to determine the predictors of prolonged MV in aSAH patients who underwent surgical clipping. METHODS: In total, 108 adult patients with a primary diagnosis of aSAH who were on MV > 48 h and survived > 14 days after surgery were included. Clinicodemographic and radiological characteristics, laboratory tests on admission, and initial Glasgow Coma Scale (GCS) and its components were analyzed. RESULTS: The average age of the patients included in the analysis was 59.1 ± 12.5 years. Overall, 32 patients (29.6%) had prolonged MV. The group with prolonged MV showed a higher prevalence of diabetes mellitus and hypertension, lower initial GCS and its components, higher World Federation of Neurosurgeons (WFNS) and Hunt and Hess grades, and higher initial white cell counts. The independent factors associated with prolonged MV were a history of diabetes mellitus (odds ratio [OR] 5.799, 95% confidence interval [CI] 1.109-30.334; P = 0.037) and Hunt and Hess grade 3-5 (OR 7.217, 95% CI 1.090-47.770; P = 0.040). CONCLUSION: A history of diabetes mellitus and Hunt and Hess grade 3-5 independently predict prolonged MV after microsurgical clipping in patients with aSAH. Thus, knowledge of potential predictors for prolonged MV is essential to improve the early initiation of adequate treatment in the early stages of treatment and provide useful information for communication between caregivers and families.

Posterior Reversible Encephalopathy Syndrome after Lenvatinib Therapy in a Patient with Olfactory Neuroblastoma.

Posterior reversible encephalopathy syndrome (PRES) is a rare but severe neurological syndrome that may stem from the use of some medications. Although its mechanism is not well-known, hypertension and endothelial dysfunction have been mentioned in previous literature as being related. Lenvatinib serves as a neoplastic agent that inhibits the tyrosine kinase of vascular endothelial growth factor receptors (VEGFR). VEGFR inhibitors result in endothelial dysfunction and consequent hypertension by nitric oxide pathway suppression and endothelin (ET)-1 stimulation. We hypothesized that VEGFR inhibitors would cause PRES. Herein, we report the case of a 40-year-old man with olfactory neuroblastoma who developed PRES while undergoing treatment with lenvatinib, 7 months after initiation. The symptoms included loss of consciousness and seizures. Fortunately, the symptoms and presence of PRES in imaging resolved, 7 days and 1 month, respectively, after cessation of lenvatinib.

Surgical application of endoscopic-assisted minimally-invasive neurosurgery to traumatic brain injury: Case series and review of literature.

BACKGROUND/PURPOSE: Adequate decompression is the primary goal during surgical management of patients with traumatic brain injury (TBI). Therefore, it may seem counterintuitive to use minimally-invasive strategies to treat these patients. However, recent studies show that endoscopic-assisted minimally-invasive neurosurgery (MIN) can provide both adequate decompression (which is critical for preserving viable brain tissue) and maximize neurological recovery for patients with TBI. Hence, we reviewed the pertinent literature and shared our experiences on the use of MIN. METHODS: This was a retrospective multi-center study. We collected data of 22 TBI patients receiving endoscopic-assisted MIN within 72 hours after the onset, with Glasgow Coma Scale (GCS) scores of 6-14 and whose hemorrhage volume ranging from 30 to 70 mL. RESULTS: We have applied MIN techniques to a group of 22 patients with traumatic ICH (TICH), epidural hematoma (EDH), and subdural hematoma (SDH). The mean pre-operative GCS score was 7.5 (median 7), and mean hemorrhage volume was 57.14 cm3 Surgery time was shortened with MIN approaches to a mean of 59.6 min. At 6-month follow-up, the mean GCS score had improved to 12.3 (median 15). By preserving more normal brain tissue, MIN for patients with TBI can result in beneficial effects on recoveries and neurological outcomes. CONCLUSION: Endoscopic-assisted MIN in TBI is safe and effective in a carefully selected group of patients.

Poly(allylguanidine)-Coated Surfaces Regulate TGF-ß in Glioblastoma Cells to Induce Apoptosis via NF-κB Pathway Activation.

Polycationic biomaterials are currently widely applied in neuronal cell cultures to promote cell adhesion and viability. However, polycations generally have cytotoxic properties that limit their application in the field of biomaterials. In this study, we examined the use of a novel polycation poly(allylguanidine) (PAG), which contains a guanidine group in the side chain and a structure similar to poly(allylamine hydrochloride) (PAH), an example of another commonly used polycation. Our findings showed that exposure to PAG induced apoptosis in glioblastoma (GBM) cells, while exposure to PAH induced necrosis. Compared to control groups, the PAG coating significantly limited the proliferation of GBM8901 in vitro and in vivo. Furthermore, GBM8901 cells exposed to the PAG coating exhibited increased levels of phospho-p65 and phosphor-IκB, implying that GBM8901 cells underwent apoptotic cell death via the NF-κB pathway by the regulation of TGF-ß. This result was further confirmed to be consistent with the experimental results from western blot protein analysis and apoptosis/necrosis assays. These findings indicate that the polycation PAG has the potential to not only suppress the proliferation of GBM8901 cancer cells but also improve the neural viability and promote the differentiation of neural stem/precursor cells into mature neurons. In conclusion, biomaterials such as PAG act as extremely potent options for applications in the treatment of pathological conditions such as brain cancer.

Prognostic Value of Circadian Brain Temperature Rhythm in Basal Ganglia Hemorrhage After Surgery.

INTRODUCTION: Intracerebral hemorrhage (ICH) is associated with high mortality and morbidity rates. However, both the rhythmic variation and prognostic value of brain temperature after ICH remain unknown. In this study, we investigated brain temperature rhythm and its prognostic value for post-operative mortality and long-term functional outcomes in patients with ICH. METHODS: Post-operative diurnal brain temperature patterns at the basal ganglion are described. Following surgery for ICH, 78 patients were enrolled, and intracranial pressure and brain temperature were monitored using a fiber optic device. Brain temperature mesor, amplitude, and acrophase were estimated from the recorded temperature measurements, using cosinor analysis, and the association between these patterns and clinical parameters, mortality, and functional outcomes at the 12-month follow-up were examined. RESULTS: According to cosinor analysis, brain temperature in 55.1% of patients showed a circadian rhythm within 72 h post-surgery. The rhythm-adjusted mesor of brain temperature (± standard deviation) was 37.6 (± 0.7) °C, with a diminished mean amplitude. A temperature acrophase shift was also observed. Multivariate logistic regression analysis revealed that initial age and circadian rhythm of brain temperature appeared to be predictive and prognostic of functional outcomes. Further, patients with higher brain temperature mesor were more likely to survive than those with a lower mesor. CONCLUSION: For patients with ICH, brain temperature rhythm analysis is an improved prognostic tool for mortality and functional outcome predictions.

Investigation of the Therapeutic Effect of Doxorubicin Combined With Focused Shockwave on Glioblastoma.

BACKGROUND: Glioblastoma multiforme (GBM) is currently the most devastating brain tumor globally and produces a high mortality rate. GBM is also challenging to eradicate using surgery due to its invasive characteristics. Moreover, the blood-brain barrier (BBB) increases the difficulty of transporting most therapeutic drugs to tumor sites. The use of transcranial focused ultrasound (FUS) has recently been investigated for opening the BBB to facilitate drug delivery. A special form of FUS, the shockwave (SW), has also been shown to open BBB efficiently. SW has several advantages including no heating effect, less reactive oxygen species production, good transcranial ability, and no need to supply microbubbles. METHODS: We employed a commercial SW device, which is a common tool used for musculoskeletal disorders, to improve doxorubicin delivery across the BBB and evaluated its therapeutic efficacy on GBM rat models. SW emits relatively short but stronger mechanical pulses comparing with FUS. RESULTS: The results demonstrated that doxorubicin combined with SW treatment substantially inhibited tumor growth and prolonged overall survival. CONCLUSIONS: The present study shows the non-invasive transcranial SW may have potential for the treatment of GBM in future clinical setting.