THOC1 complexes with SIN3A to regulate R-loops and promote glioblastoma progression.

Glioblastoma (GBM), the most common and aggressive malignant brain tumor in adults, has a median survival of 21 months. To identify drivers of GBM proliferation, we conducted a CRISPR-knockout screen, which revealed THO Complex 1 (THOC1) as a key driver. Knocking down THOC1 significantly reduced GBM cell viability across patient-derived xenograft (PDX) lines, enhancing survival (p<0.01) in primary PDX models. Conversely, overexpressing THOC1 in non-cancerous cells bolstered viability, decreasing survival and causing tumor engraftment in vivo (p<0.01). Further investigation revealed THOC1's robust interaction with SIN3A, a histone deacetylase complex. Histone deacetylation has been previously shown to prevent the buildup of R-loops, structures that form normally during transcription but can be lethal in excess. We found that THOC1-knockdown leads to elevated R-loop levels and reduced histone deacetylation levels. Next, to understand the networks specifically regulated by THOC1-mediated R-loop prevention, we conducted unbiased RNA-sequencing on control and THOC1-knockdown GBM cells. We found that THOC1's role in R-loop prevention primarily affects telomeres, critical regions for cell replication. We further show that THOC1-knockdown results in significantly increased telomeric R-loop levels and shortened telomeres. Ultimately, this study suggests that targeting THOC1 shows promise as a therapeutic strategy to disrupt the delicate R-loop landscape and undermine GBM's replicative potential.

Cellular senescence in glioma.

INTRODUCTION: Glioma is the most common primary brain tumor and is often associated with treatment resistance and poor prognosis. Standard treatment typically involves radiotherapy and temozolomide-based chemotherapy, both of which induce cellular senescence-a tumor suppression mechanism. DISCUSSION: Gliomas employ various mechanisms to bypass or escape senescence and remain in a proliferative state. Importantly, senescent cells remain viable and secrete a large number of factors collectively known as the senescence-associated secretory phenotype (SASP) that, paradoxically, also have pro-tumorigenic effects. Furthermore, senescent cells may represent one form of tumor dormancy and play a role in glioma recurrence and progression. CONCLUSION: In this article, we delineate an overview of senescence in the context of gliomas, including the mechanisms that lead to senescence induction, bypass, and escape. Furthermore, we examine the role of senescent cells in the tumor microenvironment and their role in tumor progression and recurrence. Additionally, we highlight potential therapeutic opportunities for targeting senescence in glioma.

Meningitis after elective intracranial surgery: a systematic review and meta-analysis of prevalence.

Meningitis is a potential complication of elective intracranial surgery (EIS). The prevalence of meningitis after EIS varies greatly in the literature. The objective of this study was to estimate the overall pooled prevalence of meningitis following EIS. Four databases (PubMed, Scopus, Web of Science, and Embase) were searched to identify relevant studies. Meta-analyses of proportions were used to combine data. Cochran's Q and I2 statistics were used to assess and quantify heterogeneity. Additionally, several subgroup analyses were conducted to investigate the source of heterogeneity and examine differences in the prevalence based on variables such as geographical regions, income level, and meningitis type. The meta-analysis included 83 studies (30 959 patients) from 26 countries. The overall pooled prevalence of meningitis after EIS was 1.6% (95% CI 1.1-2.1), with high heterogeneity present (I2 = 88%). The pooled prevalence in low- to middle-income countries and high-income countries was 2.7% (95% CI 1.6-4.1) and 1.2% (95% CI 0.8-1.7), respectively. Studies that reported only aseptic meningitis had a pooled prevalence of 3.2% (95% CI 1.3-5.8). The pooled prevalence was 2.8% (95% CI 1.5-4.5) in studies that reported only bacterial meningitis. Similar prevalence rates of meningitis were observed in the subgroups of tumor resection, microvascular decompression, and aneurysm clipping. Meningitis is a rare but not exceptional complication following EIS, with an estimated prevalence of 1.6%.

Surgical resection versus biopsy in the treatment of primary central nervous system lymphoma: a systematic review and meta-analysis.

PURPOSE: Despite the improvement in treatment and prognosis of primary central nervous system lymphoma (PCNSL) over the last decades, the 5-year survival rate is approximately 30%; thus, new therapeutic approaches are needed to improve patient survival. The study's aim was to evaluate the role of surgical resection of PCNSL. METHODS: Primary outcomes were the overall survival (OS) and progression-free survival (PFS) of patients with PCNSL who underwent surgical resection versus biopsy alone. The meta-analysis was conducted to calculate pooled hazard ratios (HRs) under a random-effects model for the time-to-event variables. The odds ratios (ORs) were calculated for binary, secondary outcome parameters. RESULTS: Seven studies (n = 1046) were included. We found that surgical resection was associated with significantly better OS (HR 0.63 [95% CI 0.51-0.77]) when compared with biopsy. PFS was also significantly improved (HR 0.64 [95% CI 0.49-0.85]) in patients who underwent resection compared with those who underwent biopsy. The heterogeneity for OS and PFS was low (I2 = 7% and 24%, respectively). We also found that patients who underwent biopsy more often had multiple (OR 0.38 [95% CI 0.19-0.79]) or deep-seated (OR 0.20 [95% CI 0.12-0.34]) lesions compared with those who underwent surgical resection. There were no significant differences in chemotherapy or radiotherapy use or the occurrence of postoperative complications between the two groups. CONCLUSION: In selected patients, surgical resection of PCNSL is associated with significantly better overall survival and progression-free survival compared with biopsy alone.

Deterioration After Mild Traumatic Brain Injury: A Single-Center Experience With Cost Analysis.

Background: Most traumatic brain injuries (TBIs) are mild (GCS score of 13-15). Patients with mild TBI (mTBI) are generally in good condition. In some cases, a neurological deterioration (manifested by a drop of ≥1 point in GCS score) can occur and neurosurgical intervention (NI) may be needed. Because of that, these patients are frequently admitted to a hospital for observation. The aim of our study was to determine the number of patients with mTBI that deteriorate or need NI. We also considered an economic aspect of hospital admissions of these patients. Methods: The study group consisted of 186 adult patients admitted to the neurosurgical department due to mTBI. Patients were divided into three groups according to an initial GCS score. The occurrence of deterioration, need for NI, length of stay (LOS), cost of stay and occurrence of death were analyzed. Results: The deterioration was observed in 7 (3.76%) out of all cases. In 3 (1.61%) of them, the NI was needed. The average LOS was 7.96 days and it was closely linked with an initial GCS score (p < 0.001). The total cost of stay of all patients included in this study was about 1,188,668 PLN (306,357 USD). Conclusion: The deterioration occurred in a small number of patients with mTBI, the need for NI was even less common. Hospitalization of these patients is expensive. Further studies with prognostic model helping decide on admission/discharge are necessary.

Impact of surgical resection of butterfly glioblastoma on survival: a meta-analysis based on comparative studies.

Butterfly glioblastoma (bGBM) is a rare brain tumor that invades both hemispheres by crossing the corpus callosum. bGBM is associated with a dismal prognosis with a median survival time of a few months. Surgical resection is a rare treatment option due to the unfavorable location and assumed poor risk-to-benefit ratio. Therefore, a biopsy-alone approach is considered the main treatment option. This meta-analysis aimed to systematically evaluate whether resection of bGBM is associated with improved overall survival compared with biopsy alone. We searched three databases to find studies that compare resection with biopsy in 6-, 12- and 18-months overall survival in patients with bGBM. We calculated the pooled relative risk (RR) of mortality using a random-effects model. Five studies with 194 patients were included in the meta-analysis. Mortality was decreased for resection compared with biopsy at 6-months (RR 0.63 [95% CI 0.44-0.91]). No significant differences in overall survival were found at 12 (RR 0.76 [95% CI 0.50-1.14]) and 18-months (RR 0.84 [95% CI 0.56-1.26]). Surgical resection of bGBM is associated with an improved 6-months overall survival compared with biopsy alone. We have not found strong evidence supporting the superiority of resection over biopsy alone in overall survival at 12 and 18-months.