Cohesin SA1 and SA2 are RNA binding proteins that localize to RNA containing regions on DNA.

Cohesin SA1 (STAG1) and SA2 (STAG2) are key components of the cohesin complex. Previous studies have highlighted the unique contributions by SA1 and SA2 to 3D chromatin organization, DNA replication fork progression, and DNA double-strand break (DSB) repair. Recently, we discovered that cohesin SA1 and SA2 are DNA binding proteins. Given the recently discovered link between SA2 and RNA-mediated biological pathways, we investigated whether or not SA1 and SA2 directly bind to RNA using a combination of bulk biochemical assays and single-molecule techniques, including atomic force microscopy (AFM) and the DNA tightrope assay. We discovered that both SA1 and SA2 bind to various RNA containing substrates, including ssRNA, dsRNA, RNA:DNA hybrids, and R-loops. Importantly, both SA1 and SA2 localize to regions on dsDNA that contain RNA. We directly compared the SA1/SA2 binding and R-loops sites extracted from Chromatin Immunoprecipitation sequencing (ChIP-seq) and DNA-RNA Immunoprecipitation sequencing (DRIP-Seq) data sets, respectively. This analysis revealed that SA1 and SA2 binding sites overlap significantly with R-loops. The majority of R-loop-localized SA1 and SA2 are also sites where other subunits of the cohesin complex bind. These results provide a new direction for future investigation of the diverse biological functions of SA1 and SA2.

Surgical resection of glioblastoma in the very elderly: An analysis of survival outcomes using the surveillance, epidemiology, and end results database.

OBJECTIVE: Patients with glioblastoma (GBM) often undergo surgery to prolong survival. However, the use of surgery, and more specifically achieving gross total resection (GTR), in patients >80 years old has yet to be fully assessed. Using the Surveillance, Epidemiology, and End Results (SEER) database, we aim to assess the efficacy of surgical resection, radiotherapy (RT) and chemotherapy (CT) on overall survival (OS) in very elderly GBM patients compared to elderly counterparts (age 65-79 years). METHODS: The SEER database was queried for all patients >65 years old with GBM (2000-2020). Patients not undergoing surgery or biopsy were excluded. Patients were stratified by age, and demographic relationships were assessed with chi-squared testing for categorical variables. Bivariable models were created using Kaplan-Meier survival estimates. All significant variables from bivariable analysis were included on multivariable Cox survival regression models to determine independent associations between clinical variables and OS. RESULTS: A total of 27,090 operative GBM patients were identified; 1868 patients (15.92 %) were very elderly and 10,092 patients (84.38 %) were elderly. Very elderly patients were less likely to undergo GTR (28 % vs 35 %, p<0.001), RT (59 % vs 78 %, p<0.001) and CT (40 % vs 66 %, p<0.001). In multivariable Cox regression analysis, very elderly patients who achieved GTR (HR=.696, p<0.001), received RT (HR=0.583, p<0.001) and underwent CT (HR=0.4197, p<0.001) had significantly improved OS compared to very elderly patients that did not undergo these treatment options. CONCLUSION: Currently, very elderly GBM patients undergo lower rates of aggressive surgery, RT and CT. However, very elderly patients that undergo surgery, RT and CT may have a survival advantage. These treatments should be considered as potential options for this patient population.

A4 Thoracolumbar Fracture Class Is Associated With a Greater Degree of Vertebral Height Loss in Conservatively Managed Patients.

INTRODUCTION: Thoracolumbar (TL) junction fractures are common, often resulting from high-energy trauma or osteoporosis, and may lead to neurological deficits, deformities, or chronic pain. Treatment decisions for neurologically intact patients remain controversial, with nonsurgical management often favored. The AO classification system has been used to characterize thoracolumbar fractures using fracture morphology and clinical factors affecting clinical decision-making for fracture management. This study aims to assess the radiographic outcomes of utilizing a thoracolumbosacral orthosis (TLSO) brace in neurologically intact patients with TL fractures based on the AO classification system. METHODS: A retrospective analysis of 43 patients was conducted using data from the VCU Spine Database on patients with TL fractures managed conservatively with a TLSO brace from 2010 to 2019. Demographic variables and radiographic measurements of anterior height loss were analyzed and stratified by AO fracture class. RESULTS: Significant differences were observed in anterior height loss between AO fracture classes, with A4 fractures showing significantly greater anterior height loss at initial presentation (27.6 + 4.8%) compared to A1/A2 (16.1 + 2.2%; p=0.049). At follow up, A4 fractures had a significantly greater anterior height loss (40.2 + 6.6%) than both the A1/A2 (22.4 + 2.9%; p=0.029) and A3 fracture classes (20.5 + 3.6; p=0.020). CONCLUSIONS: The study highlights significant differences in anterior height loss among AO fracture classes, suggesting varying degrees of severity and potential implications for clinical management. While conservative treatment with TLSO braces may provide pain relief, surgical intervention may offer better structural recovery, especially in more severe fractures. Conservative management of TL fractures with TLSO braces may result in greater anterior height loss, particularly in A4 fractures, emphasizing the need for individualized treatment decisions. Further research, including prospective studies, is warranted to validate these findings and guide clinical practice effectively.

Mathematical modeling of meningioma volume change after radiation treatment.

OBJECTIVE: Meningiomas are the most common primary central nervous tumor and are often treated with radiation therapy. This study examines the long-term volumetric changes of intracranial meningiomas in response to radiation therapy. The objective is to analyze and model the volumetric changes following treatment. METHODS: Data from a retrospective single-institution database (2005-2015) were used, with inclusion criteria being patients with a diagnosis of meningiomas, along with additional inclusion criteria consisting of treatment with radiation, having at least three magnetic resonance imaging (MRI) scans with one or more before and after radiation treatment, and the patients following up for at least eighteen months. Exclusion criteria consisted of patients less than 18 years old, patients receiving surgery and/or adjuvant chemotherapy following radiation, and patients without any available details regarding radiation treatment parameters. Tumor volumes were measured via T1-weighted post-contrast MRI and calculated using the ABC/2 ellipsoidal approximation, a method allowing for the measurement of non-linear growth volume reduction. RESULTS: Of 48 meningioma patients considered, 10 % experienced post-radiation growth, while 75 % witnessed a ≥50 % decrease in volume over a follow-up period of 0.3-14.9 years. Median decay rate was 0.81, and within 1.17 years, 90 % achieved the predicted volume reduction. Predicted vs. actual volumes showed a mean difference of 0.009 ± 0.347 cc. Initial tumor volumes strongly correlated (Pearson's R=0.98, R-squared=0.96) with final asymptotic volumes, which had a median of 1.50 cc, with interquartile range (IQR) = [0.39, 3.67]. CONCLUSION: 90 % of patients achieved tumor-volume reduction at 1.17 years post-treatment, reaching a non-zero asymptote strongly correlated with initial tumor volume, and 75 % experienced at least a 50 % volume decrease. Individual volume changes for responsive meningiomas can be modeled and predicted using exponential decay curves.

Delayed Burr Hole Evacuation Compared With Acute Craniotomy for Acute Subdural Hematoma in Older Patients With Low-Energy Trauma.

Background Acute subdural hematomas commonly require emergent surgical decompression by craniotomy. There is currently limited research on alternative surgical strategies in the elderly population. This study investigates delayed surgical intervention for stable patients with low-energy trauma presenting with acute subdural hematomas. Methodology In this retrospective chart review, 45 patients over the age of 55 presenting with acute subdural hematomas with a Glasgow Coma Scale score greater than or equal to 13 in the setting of low-energy trauma were selected. Additionally, included patients had a maximal hematoma thickness of >10 mm and/or a midline shift size of >5 mm per the current Brain Trauma Foundations guidelines for surgical intervention of subdural hematomas. The study was performed at a large tertiary care center, with records being examined from 1995 to 2020. Comparison groups were immediate craniotomy (within 24 hours) or delayed burr hole (minimum of 48 hours passing since the initial presentation). Primary outcomes included minor complications, major complications, any complications, and any complications with mortality excluded. There was no significant difference in mortality between the two cohorts. Results The immediate craniotomy group consisted of 16 patients, while the delayed burr hole group consisted of 29 patients. The results demonstrated a statistically significant increase in the incidence of any complication including mortality (relative risk (RR) = 3.17, 95% confidence interval (CI) = 1.71-5.88, p < 0.0001), major complications (RR = 2.33, 95% CI = 1.07-5.07, p = 0.031), and minor complications (RR = 2.42, 95% CI = 1.02-5.74, p = 0.041) in the immediate craniotomy group compared to the delayed burr hole group. Conclusions Our study demonstrates the decreased risk of major and minor complications for delayed burr hole evacuation in stable patients >55 years old presenting with low-energy trauma and subdural hematoma. The results suggest that for this population of patients, it appears to be beneficial to delay surgery if the patient's clinical situation allows.

Hemimegalencephaly: A Systematic Comparison of Functional and Anatomic Hemispherectomy for Drug-Resistant Epilepsy.

BACKGROUND AND OBJECTIVES: Hemimegalencephaly (HME) is a rare diffuse malformation of cortical development characterized by unihemispheric hypertrophy, drug-resistant epilepsy (DRE), hemiparesis, and developmental delay. Definitive treatment for HME-related DRE is hemispheric surgery through either anatomic (AH) or functional hemispherectomy (FH). This individual patient data meta-analysis assessed seizure outcomes of AH and FH for HME with pharmacoresistant epilepsy, predictors of Engel I, and efficacy of different FH approaches. METHODS: PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature were searched from inception to Jan 13th, 2023, for primary literature reporting seizure outcomes in >3 patients with HME receiving AH or FH. Demographics, neurophysiology findings, and Engel outcome at the last follow-up were extracted. Postsurgical seizure outcomes were compared through 2-tailed t -test and Fisher exact test. Univariate and multivariate Cox regression analyses were performed to identify independent predictors of Engel I outcome. RESULTS: Data from 145 patients were extracted from 26 studies, of which 89 underwent FH (22 vertical, 33 lateral), 47 underwent AH, and 9 received an unspecified hemispherectomy with a median last follow-up of 44.0 months (FH cohort) and 45.0 months (AH cohort). Cohorts were similar in preoperative characteristics and at the last follow-up; 77% (n = 66) of the FH cohort and 81% (n = 38) and of the AH cohort were Engel I. On multivariate analysis, only the presence of bilateral ictal electroencephalography abnormalities (hazard ratio = 11.5; P = .002) was significantly associated with faster time-to-seizure recurrence. A number-needed-to-treat analysis to prevent 1 additional case of posthemispherectomy hydrocephalus reveals that FH, compared with AH, was 3. There was no statistical significance for any differences in time-to-seizure recurrence between lateral and vertical FH approaches (hazard ratio = 2.59; P = .101). CONCLUSION: We show that hemispheric surgery is a highly effective treatment for HME-related DRE. Unilateral ictal electroencephalography changes and using the FH approach as initial surgical management may result in better outcomes due to significantly lower posthemispherectomy hydrocephalus probability. However, larger HME registries are needed to further delineate the predictors of seizure outcomes.

Superficial siderosis: comparison of two cases indicates two distinct diagnostic entities. Illustrative cases.

BACKGROUND: Superficial siderosis is the deposition of hemosiderin in the superficial layers of the central nervous system. It has been described in patients with chronic leakage of blood into the cerebrospinal fluid or with amyloid angiopathy, often associated with Alzheimer's disease (AD). OBSERVATIONS: We present two cases of superficial siderosis with vastly different symptomatologies and treatment courses. The patient in case 1 had diffuse superficial siderosis demonstrated on T2-weighted magnetic resonance imaging (MRI), appearing mostly in the inferior cerebellum and extending throughout the neuraxis. He presented with hearing loss, spasticity, gait abnormalities, and urinary incontinence. Ultimately, surgical exploration of the thoracic spinal dura revealed an arteriovenous fistula, which was obliterated. His clinical course stabilized but with persistent deficits. The patient in case 2 had a family history of AD and underwent MRI to evaluate for memory impairment, which demonstrated superficial siderosis of the left occipital lobe. Lumbar puncture demonstrated only traumatic contamination by red blood cells, but tau protein analysis was consistent with the diagnosis of AD. LESSONS: Superficial siderosis is a diagnostic term prompted by findings on MRI that can arise due to two different pathological entities. The diagnosis in case 1 should be termed diffuse superficial siderosis and in case 2 should be termed lobar cortical siderosis.