Current chemotherapy strategies for adults with IDH-wildtype glioblastoma.

Introduction: Glioblastoma, despite advancements in molecular evolution, remains incurable and has low survival rates. Currently, two of the most commonly used chemotherapy regimens are temozolomide and CCNU. This review aims to provide a comprehensive analysis of the current status of chemotherapy strategies for GBM. Methods: We reviewed the published literature describing the chemotherapy regimen differences in system treatment of GBM reported in the last ten years and summarised the available information that may reveal the latest changes in chemotherapy. Results: In patients with adequate functioning, temozolomide and radiation are the primary treatments for newly diagnosed GBM. We recommend postoperative radiation therapy with concurrent and adjuvant temozolomide for patients with MGMT-methylated GBM who are less than 70 years old. Combining temozolomide and lomustine with radiation therapy may be an option for younger, fit patients, but efficacy data is inconclusive. For patients with unknown MGMT methylation status, radiation therapy combined with temozolomide remains the standard of care. We recommend hypofractionated radiation and concurrent temozolomide treatment for elderly patients over 70 years old who have satisfactory performance and no significant underlying health conditions. We should tailor treatment choices to each patient's personal preferences, previous treatments, function, quality of life, and overall care objectives. Conclusion: Radiation therapy, along with temozolomide, is still the standard of care for most people with MGMT-unmethylated GBMs because there aren't any better options, and it's generally safe and well-tolerated. These patients have a lower overall survival rate and less benefit from temozolomide, but there are no better alternatives. Clinical trial participation is encouraged.

UBE2D3 regulated by WTAP-mediated m6A modification inhibits temozolomide chemosensitivity in glioblastoma.

To explore how the ubiquitin-conjugating enzyme E2D3 (UBE2D3) influences temozolomide (TMZ) resistance in glioblastoma (GBM), and to clarify the association between UBE2D3 and WTAP. The UBE2D3 protein expression in GBM tissues were detected using immunohistochemistry (IHC) through tissue microarrays. The potential pathways of UBE2D3 in TCGA-GBM were predicted via Gene Set Enrichment Analysis (GSEA). To investigate UBE2D3's role in TMZ resistance, GBM cells were transduced with UBE2D3 shRNA or overexpression lentivirus, followed by assessments of CCK-8, flow cytometry, comet assay, and western blot analysis. Furthermore, a subcutaneous tumor model was established in nude mice using U87 cells transduced with interfering lentivirus to observe tumor growth and assess cell apoptosis using TUNEL staining. Mechanically, m6A content analysis, m6A methylated RNA immunoprecipitation quantitative PCR, reporter gene assay, mRNA stability measurements, RNA immunoprecipitation, quantitative Real-Time PCR, and Western blot assays were carried out to verify the role of WTAP/IGF2BP1 in regulating UBE2D3 expression. UBE2D3 exhibited elevated expression levels in GBM tissues compared with normal brain tissues and was associated with the DNA repair signaling pathway. In both in vitro and in vivo studies, it was demonstrated that TMZ treatment combined with reduced UBE2D3 expression further suppressed U87 cell viability and tumor growth, with a notable increase in apoptosis rate and DNA damage. Conversely, the overexpression of UBE2D3 had the opposite impact. Furthermore, our findings revealed that WTAP promotes the m6A modification of UBE2D3 via an IGF2BP1-dependent mechanism. The WTAP-IGF2BP1 axis regulates UBE2D3 stability in an m6A-dependent manner, influencing tumor malignancy and TMZ chemosensitivity in GBM via the DNA repair signaling pathway.

Initial Treatment of IDH-Wildtype Glioblastoma in Adults Older Than 70 Years.

The incidence of glioblastoma, the most common malignant primary brain tumour in adults, increases after the age of 40 and peaks in adults aged 75-84 years. Initial management involves maximising surgical resection while preserving neurologic function. IDH mutations and MGMT promoter methylation should be checked in tumour samples. Radiation and temozolomide constitute initial treatment for newly diagnosed glioblastoma patients with good functional status. It is suggested that patients who have received concurrent and adjuvant temozolomide treatment should undergo six cycles of adjuvant monthly temozolomide, as opposed to a more extended treatment regimen. Low-intensity alternating electric field therapy improved survival in a large randomised trial. We provide a detailed review, providing the latest treatment viewpoint for IDH-wildtype glioblastoma and including the current situation of immunotherapy. The treatment ideas and methods reviewed here would be of help to physicians when they encounter patients with this kind of IDH-wildtype glioblastoma in clinical practice.

Urokinase Salvage Therapy for Recurrent Chronic Subdural Hematoma Caused by Dual Antiplatelet Therapy.

Chronic subdural hematoma (cSDH) is one of the most common neurosurgical conditions among older adults. Here, we describe a case of recurrent cSDH resulting from seven days of dual antiplatelet therapy. A 76-year-old woman reported a headache resembling a chronic tension-type headache for the last 10 days. MRI revealed a right parietal cSDH and left frontoparietal cSDH. Single burr-hole aspiration and irrigation technique with continuous closed subdural drainage was performed bilaterally under general anesthesia. The patient experienced two bouts of transient ischemic attack and received seven days of dual antiplatelet therapy. On the 12th day after the initial surgery, the patient underwent another operation to re-evacuate the cSDH. Considering that the color of the output fluid persisted as oil-black and the average net output was 12.5 cc/day, we decided to use urokinase to restore the patency of the drainage catheter. In the early postoperative phase after the second surgery, a total of 20,000 units of urokinase was injected into the subdural space. On the 10th postoperative day, the patient was discharged home. In patients with cSDH presenting with obvious postoperative hematoma residue, the routine use of subdural injection of urokinase could be a new direction in cSDH management.

UBE2D3 Activates SHP-2 Ubiquitination to Promote Glycolysis and Proliferation of Glioma via Regulating STAT3 Signaling Pathway.

Glioma is a primary brain cancer with high malignancy and morbidity. Current management for glioma cannot reach optimal remission. Therefore, it is necessary to find novel targets for glioma treatment. Ubiquitin-conjugating enzyme E2 D3 (UBE2D3) is involved in the pathogenesis of various kinds of cancer. However, its role in glioma remains unclear. Our study aims to explore the function and underlying mechanism of UBE2D3 in the development of glioma. By analysis with The Cancer Genome Atlas-Glioblastoma multiforme (TCGA-GBM) dataset, we found that UBE2D3 was highly expressed in glioma and it is positive correlation with glycolysis, apoptosis, and STAT3 pathway. Then, we explore the effects of UBE2D3 knockdown in the biological functions of glioma cell lines. Cell proliferation and apoptosis were estimated by cell counting kit-8 assay and flow cytometry. Extracellular acidification rate and oxygen consumption rate were estimated to determine the level of cell glycolysis. Xenograft experiments were performed to identify in vivo function of UBE2D3. The results showed that the inhibition of UBE2D3 could suppress the proliferation, glycolysis, and STAT3 phosphorylation of GBM both in vitro and in vivo. UBE2D3 could interact with SHP-2 and promoted its ubiquitination, which elevated the activation of STAT3 pathway. Overexpressed SHP-2 could reverse the effect of UBE2D3 and they shared contrary expression patterns in glioma and normal brain tissues. In summary, our study revealed that UBE2D3 could promote the ubiquitination of SHP-2, which activated STAT3 pathway and promoted glioma proliferation as well as glycolysis. UBE2D3 could be a potential target for glioma treatment.

Efficacy of the Direct Aspiration-Irrigation Maneuver for the Treatment of Chronic Subdural Hematoma: A Single Hospital's Experience.

Objective The traditional methods for managing symptomatic chronic subdural hematoma (CSDH) at our hospital include evacuation via single burr-hole irrigation with continuous closed subdural drainage (SBID). The single burr-hole aspiration and irrigation technique with continuous closed subdural drainage (SBAID) is an attractive alternative method. The goal of this study was to evaluate the radiographic and clinical outcomes of SBAID compared with traditional SBID methods. Methods A database of 51 CSDH patients treated with the SBAID method and 35 CSDH patients treated with the SBID method was compiled, and a retrospective chart review was performed. Information regarding demographics, comorbidities, presenting symptoms, and outcomes were collected. Predictors of recurrence requiring reoperation and other outcomes were analyzed. Results Compared to the patients in the SBID group, the patients in the SBAID group had a shorter mean duration of surgery (56.6±5.6 minutes vs 59.5±4.8 minutes, respectively, P=0.02); a shorter mean interval from procedure to discharge (6.2±1.2 days vs 6.8±1.3 days, respectively, P=0.046); no significant difference in preoperative hematoma volume (106.4±21.7 cm3 vs 101.3±16.3 cm3, respectively, P=0.25); and a smaller subdural space volume 48 hours after the operation (43.6±7.4 cm3 vs 47.4±9.1 cm3, respectively, P=0.03). In addition, symptomatic hematoma recurrence developed in one patient in the SBAID group and five patients in the SBID group (P=0.03). The in-hospital mortality rates of the SBAID and SBID groups were 2% (1 of 51) and 6% (2 of 35), respectively; this difference was not statistically significant (P=0.35). Conclusions The SBAID method results in a remarkably low recurrence rate and good outcomes. This method should be considered for patients presenting with symptomatic CSDHs.

Iatrogenic Hypothalamus Injury After Resection of Subependymoma Within the Left Brain Ventricle.

Damage to the hypothalamus may result from direct surgical injury or from hemorrhage and ischemia caused by the procedure. Patients with hypothalamus damage can be comatose and exhibit hyperthermia. Here, we present a patient whose hypothalamus was directly damaged by a drainage catheter. His clinical manifestations included diabetes insipidus, hyperthermia and adrenocorticotropic hormone (ACTH) deficiency. The patient was a 48-year-old male and had a body weight of 95 kg. He was admitted to the hospital on August 31, 2019 for memory impairment and nonspecific dizziness that persisted for four months. A magnetic resonance image of the head showed an intraventricular mass attached to the anterior third of the septum pellucidum and Monro's foramen and enlargement of the left lateral ventricle. This intraventricular cystic tumor was 1.9 cm in diameter, without gadolinium enhancement. The tumor resection was performed without complications and with less bleeding than expected. The patient developed central diabetes insipidus within just two hours after the operation and presented with hyperthermia within six hours after the operation. ACTH deficiency was evident on day 1 after surgery. After we removed the catheter 19 hours after the operation, the patient never developed polyuria or high fever again. Two months later, his ACTH level was normal and never needed to take prednisone again. This unusual complication should be taken into account in patients who need external ventricular drains. Much attention should be paid to ensure that the length of the drainage catheter beneath the brain surface does not exceed 5 cm.

Massage of a Hematoma to Assist in Decreasing the Volume of an Intraparenchymal Hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) is one of the least treatable types of stroke, and its incidence and all-age mortality have increased over the last several decades in China. Surgical evacuation using standard craniectomy for supratentorial hematoma is always controversial. How to ensure effective decreasing of intracranial pressure (ICP) is crucial to the management of ICH. A 48-year-old right-handed woman was brought to our hospital by her family, who stated that the woman could not speak well and had developed sudden left-sided weakness three hours previously. The patients were diagnosed with supratentorial bilateral intraparenchymal hemorrhages, mainly in the putaminal area. After inserting a catheter into the hematoma, we began to perform the maneuver of massage through the catheter by frequently using multiple 2 mL quantities of normal saline and performing the injecting-aspiration maneuver. After performing this massage repeatedly for 15 min, we terminated the operation. After the patient was admitted to the ICU, urokinase (40,000 U) was administered through the catheter every 12 hours for three days. After the patient stayed for an additional 11 days, she was discharged home. Minimally invasive surgery with massage techniques followed by thrombolytic evacuation of clots will be a new method for treating ICH patients.

On the Dynamic RSS Feedbacks of Indoor Fingerprinting Databases for Localization Reliability Improvement.

Location data is one of the most widely used context data types in context-aware and ubiquitous computing applications. To support locating applications in indoor environments, numerous systems with different deployment costs and positioning accuracies have been developed over the past decade. One useful method, based on received signal strength (RSS), provides a set of signal transmission access points. However, compiling a remeasurement RSS database involves a high cost, which is impractical in dynamically changing environments, particularly in highly crowded areas. In this study, we propose a dynamic estimation resampling method for certain locations chosen from a set of remeasurement fingerprinting databases. Our proposed method adaptively applies different, newly updated and offline fingerprinting points according to the temporal and spatial strength of the location. To achieve accuracy within a simulated area, the proposed method requires approximately 3% of the feedback to attain a double correctness probability comparable to similar methods; in a real environment, our proposed method can obtain excellent 1 m accuracy errors in the positioning system.