Targeting ZNF638 activates antiviral immune responses and potentiates immune checkpoint inhibition in glioblastoma.

Viral mimicry refers to the activation of innate anti-viral immune responses due to the induction of endogenous retroelement (RE) expression. Viral mimicry has been previously described to augment anti-tumor immune responses and sensitize solid tumors to immunotherapy including colorectal cancer, melanoma, and clear renal cell carcinoma. Here, we found that targeting a novel, master epigenetic regulator, Zinc Finger Protein 638 (ZNF638), induces viral mimicry in glioblastoma (GBM) preclinical models and potentiates immune checkpoint inhibition (ICI). ZNF638 recruits the HUSH complex, which precipitates repressive H3K9me3 marks on endogenous REs. In GBM, ZNF638 is associated with marked locoregional immunosuppressive transcriptional signatures, reduced endogenous RE expression and poor immune cell infiltration (CD8 + T-cells, dendritic cells). ZNF638 knockdown decreased H3K9-trimethylation, increased cytosolic dsRNA and activated intracellular dsRNA-signaling cascades (RIG-I, MDA5 and IRF3). Furthermore, ZNF638 knockdown upregulated antiviral immune programs and significantly increased PD-L1 immune checkpoint expression in patient-derived GBM neurospheres and diverse murine models. Importantly, targeting ZNF638 sensitized mice to ICI in syngeneic murine orthotopic models through innate interferon signaling. This response was recapitulated in recurrent GBM (rGBM) samples with radiographic responses to checkpoint inhibition with widely increased expression of dsRNA, PD-L1 and perivascular CD8 cell infiltration, suggesting dsRNA-signaling may mediate response to immunotherapy. Finally, we showed that low ZNF638 expression was a biomarker of clinical response to ICI and improved survival in rGBM patients and melanoma patients. Our findings suggest that ZNF638 could serve as a target to potentiate immunotherapy in gliomas.

A novel leucine zipper-like transcriptional regulator 1 variant identified in a pair of siblings with familial schwannomatosis.

Background: Schwannomatosis is a rare genetic disorder marked by the emergence or predisposition to developing multiple schwannomas. Patients typically present with chronic pain or a mass in the second or third decade of life. Schwannomatosis is characterized by its associated gene, or if the specific gene is not known, then a descriptor is used. Here, we report a new Leucine zipper-like transcriptional regulator 1 (LZTR1) pathogenic variant identified in a pair of siblings with familial LZTR1-related schwannomatosis. Case Descriptions: A 35-year-old male presented for evaluation of the left lower extremity pain. Magnetic resonance imaging (MRI) demonstrated multiple lesions throughout his body, highly likely for schwannomatosis. He underwent surgical resection of two of these lesions, located in the left femoral nerve and distal shin. Pathology confirmed that the resected lesions were schwannomas. Six months later, his 34-year-old sister was referred and evaluated for a right ankle mass, previously diagnosed as a ganglion cyst. MRI of her right ankle demonstrated a one-centimeter subcutaneous tumor. She underwent surgical resection, and pathology confirmed that the tumor was a schwannoma. Both siblings elected to undergo genetic analysis for pathogenic variants associated with schwannomatosis. Both results were positive for the c.263del pathogenic variant of the LZTR1 gene associated with LZTR1-related schwannomatosis. Additionally, genetic analysis also determined the mother of the siblings also carried the same c.263del pathogenic variant. Conclusion: There are still schwannomatosis cases with novel switch/sucrose non-fermentable-related matrix-associated actin-dependent regulators of chromatin subfamily B member 1 or LZTR1 mutations to be reported. We report the first three cases of the c.263+1del LZTR1 pathogenic variant causing LZTR1-related schwannomatosis initially found in the two siblings. Identifying further LZTR1 pathogenic variants can give more insight into the pathogenicity of each variant.

Predicting telomerase reverse transcriptase promoter mutation in glioma: A systematic review and diagnostic meta-analysis on machine learning algorithms.

BACKGROUND: Glioma is one of the most common primary brain tumors. The presence of the telomerase reverse transcriptase promoter (pTERT) mutation is associated with a better prognosis. This study aims to investigate the TERT mutation in patients with glioma using machine learning (ML) algorithms on radiographic imaging. METHOD: This study was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The electronic databases of PubMed, Embase, Scopus, and Web of Science were searched from inception to August 1, 2023. The statistical analysis was performed using the MIDAS package of STATA v.17. RESULTS: A total of 22 studies involving 5371 patients were included for data extraction, with data synthesis based on 11 reports. The analysis revealed a pooled sensitivity of 0.86 (95% CI: 0.78-0.92) and a specificity of 0.80 (95% CI 0.72-0.86). The positive and negative likelihood ratios were 4.23 (95% CI: 2.99-5.99) and 0.18 (95% CI: 0.11-0.29), respectively. The pooled diagnostic score was 3.18 (95% CI: 2.45-3.91), with a diagnostic odds ratio 24.08 (95% CI: 11.63-49.87). The Summary Receiver Operating Characteristic (SROC) curve had an area under the curve (AUC) of 0.89 (95% CI: 0.86-0.91). CONCLUSION: The study suggests that ML can predict TERT mutation status in glioma patients. ML models showed high sensitivity (0.86) and moderate specificity (0.80), aiding disease prognosis and treatment planning. However, further development and improvement of ML models are necessary for better performance metrics and increased reliability in clinical practice.

Optimizing outpatient neurosurgery: evaluating ambulatory surgery and same-day discharge following intracranial tumor surgery and endoscopic third ventriculostomy.

OBJECTIVE: Outpatient surgery and same-day discharge are developing fields that align with the evolving needs of modern healthcare, presenting a notable advantage by reducing patient susceptibility to nosocomial infections, thromboembolic complications, and medical errors. When paired with enhanced recovery after surgery protocols, they hold promise in safely transitioning certain patients undergoing cranial surgery to outpatient care. This study aimed to evaluate discharge on the same day of surgery after intracranial tumor resection and endoscopic third ventriculostomy (ETV) and to investigate potential associations with anesthesia methods, complications, and readmission rates. METHODS: A retrospective analysis of patients scheduled for planned discharge on the same day of surgery between August 2020 and October 2023 was conducted. Data included patient demographic characteristics, preoperative clinical deficits, diagnosis, findings on preoperative and postoperative MRI, lesion characteristics, complications, and readmission rates. RESULTS: A total of 202 patients were included in the study. The mean age was 56.8 years and 117 (57.9%) patients were female. Patients were admitted the evening before surgery to obtain preoperative clearance and undergo MRI. The most common diagnoses were metastasis (23.3%), meningioma (20.8%), glioblastoma (12.4%), and low-grade glioma (10.4%). Craniotomy (46.5%), stereotactic needle biopsy (35.1), and ETV (6.9%) were the most common procedures performed. Thirteen (6.4%) patients underwent awake craniotomy, and 189 (93.6%) surgical procedures were conducted under general anesthesia. Complications occurred in 1.5% of patients, with no permanent complications observed during a mean follow-up of 9.3 months. In total, 179 (88.6%) patients were successfully discharged on the same day of surgery. The median length of hospitalization was 26.8 hours, with the median length of postoperative stay being 7 hours. Twenty-three (11.4%) patients were deemed ineligible for discharge on postoperative day 0 and instead discharged on postoperative day 1. The reasons for these delays included further clinical monitoring (n = 12), social factors (n = 4), and patient preference (n = 7). Age was positively correlated with length of hospitalization (p = 0.006). In total, 6.4% of patients were readmitted within 1-30 days after discharge, with 2.5% readmitted to the department of neurosurgery. CONCLUSIONS: This study demonstrates the safety and feasibility of discharge on the same day of surgery, with a high success rate and low complication rates. Early discharge did not increase morbidity or readmission rates. Implementation of clear discharge protocols and thorough patient education are crucial for successful same-day discharge programs in neurosurgery.

Pediatric shunt failure in a resource limited Lower-Middle Income Country (LMIC) institution in La Paz, Bolivia.

BACKGROUND: Shunt failure is an undesirable but common occurrence following neurosurgical shunting for pediatric hydrocephalus. Little is known about the occurrence of failure in lower-middle income country (LMIC) settings in South America. The objective of this study was to evaluate shunt failure in the sole publicly funded pediatric hospital in La Paz, Bolivia, with limited resources. METHODS: A retrospective review of all patients at the Children's Hospital of La Paz, Bolivia (Hospital del Niño "Dr. Ovidio Aliaga Uria"), was conducted to identify all patients whose index surgical shunting for hydrocephalus was performed between 2019 and 2023. Categorical, continuous, and shunt failure data were statistically summarized. RESULTS: A total of 147 unique pediatric patients underwent index ventriculoperitoneal shunting for hydrocephalus in the study period. There were 90 (61%) male and 57 (39%) female patients, with a median age of 2.2 months at index shunting procedure. The most common surgical indications were congenital hydrocephalus (n = 95, 65%), followed by hydrocephalus secondary to congenital defect (n = 25, 17%) and tumor (n = 18, 12%). A total of 18 (12%) of patients experienced inpatient failure during index admission requiring surgical revision at a median time of 12.5 days after index shunting. Postoperative imaging (OR 2.97, P = 0.037) and postoperative infection (OR 3.26, P = 0.032) during index admission both independently and statistically predicted inpatient failure. Of the 96 patients (65%) with postoperative follow-up, 16 (n = 16/96, 17%) patients experienced outpatient failure requiring readmission to hospital and surgical revision at a median time of 3.7 months after discharge. Kaplan-Meier estimations of overall inpatient and outpatient failure in this cohort were 23% (95% CI 14-37) and 28% (95% CI 15-49), respectively. CONCLUSIONS: Both inpatient and outpatient shunt failures are significant complications in the management of pediatric hydrocephalus in La Paz, Bolivia. We identify multiple avenues to improve these outcomes which are institution-specific based on the review of these failures. Lessons learnt may be applicable to other similarly resourced institutions across South American LMICs.

Infant Hydrocephalus.

Hydrocephalus is a neurosurgical condition that is highly prevalent in pediatric medicine. In the infant population, there is a distinct set of features that all primary pediatricians would benefit from understanding. Infant hydrocephalus can present prenatally on imaging and postnatally with symptomatic enlargement of the head and associated skull features and raised intracranial pressures. The 2 major pathophysiology models of infant hydrocephalus are the bulk flow and the intracranial pulsatility models. The most common acquired forms of hydrocephalus include posthemorrhagic hydrocephalus, postinfectious hydrocephalus, and brain tumor. The most common congenital forms of hydrocephalus include those due to myelomeningocele, aqueductal stenosis, and posterior fossa malformations. There are various evaluation and treatment algorithms for these different types of hydrocephalus, including cerebrospinal fluid shunting and endoscopic third ventriculostomy. The aim of this review was to elaborate on those features of hydrocephalus to best equip primary pediatricians to diagnose and manage hydrocephalus in infants.

The Feasibility of Robot-assisted Laser Interstitial Thermal Therapy (LITT) for Brain Tumors in Octogenarians.

BACKGROUND: The use of robot-assisted laser interstitial thermal therapy (LITT) is emerging as a viable treatment option for brain tumors in patients aged 80-90 years (octogenarians). Correspondingly, the aim of this study was to describe the clinical feasibility of octogenarians undergoing LITT procedure for brain tumors at our institution. METHODS: A retrospective review was conducted of all robot-assisted LITT procedures performed at our institution between 2013 and 2023 for octogenarians. Comparison of continuous variables was by Student t tests, and Kaplan-Meier estimates were used to estimate survival outcomes. RESULTS: A total of 20 of 311 (6%) LITT patients in the search cohort were octogenarians. Mean age was 82.6 years (range, 80.1-88.0 years) with 13 (65%) female patients. Brain tumor lesions most commonly were located on the left side (65%), and, for ablation, all were single trajectories with mean number of 2.3 ablations. No operative complications were seen during hospitalization, with mean length of stay of 1.6 days and most common disposition destination being home (95%). There were no 30- or 90-day readmissions or emergency department presentations. Mean follow-up was 12.4 months without any complications in that time. The most common pathology in our cohort was glioblastoma (55%). CONCLUSIONS: Robot-assisted LITT is a safe and effective treatment option for brain tumors in octogenarians with a very low morbidity risk. Therefore, further investigation is required to understand how LITT can translate to therapeutic benefit in patients aged over 80 years old with brain tumors.

Recurrence of atypical and anaplastic intracranial Meningiomas: A meta-analysis of risk factors.

BACKGROUND: The predictive role of multiple risk factors for intracranial atypical and anaplastic meningioma recurrence is convoluted. This meta-analysis assessed the predictive value of selected factors for recurrence in these Meningiomas. METHODS: Studies encompassing risk factor data including gross total resection (GTR), subtotal resection (STR), post-op radiotherapy, Ki-67 % index >3 %, and location were searched for in PubMed, Embase, and Web of Science, and thereafter analyzed using robust Bayesian meta-analysis. RESULTS: Eighteen observational studies involving 1589 patients met inclusion criteria for analysis. GTR was identified as a good prognostic factor for recurrence (OR = 0.212; 95 % CI (-1.972, -1.002); heterogeneity BF=0.702), and STR had a significantly higher risk of recurrence (OR = 4.43; 95 % CI 0.658-2.011; heterogeneity BF=0.724). Post-operative radiotherapy did not statistically significantly affect the recurrence process (OR = 1.02; 95 % CI (-1.848, 0.626); heterogeneity (BF=1.034)). Ki67 % index >3 % had an augmented chance of recurrence (OR = 2.38; 95 % CI (-0.220, 2.355); heterogeneity (BF=1.162)). A meta-regression analysis showed that WHO grade III Meningiomas had a higher chance of recurring than grade II Meningiomas. CONCLUSION: Among the selected factors, STR and Ki67 % index > 3 % were associated with a higher risk of recurrence, with post-operative radiotherapy making no difference. GTR appeared to inversely impact recurrence. Compared to grade II, grade III Meningiomas had higher odds of recurring.

Utilizing tubular retractors in colloid cyst resection: A single surgeon experience.

Background: Colloid cysts are intracranial lesions originating from abnormalities in the primitive neuroepithelium folding of the third ventricle. Various surgical approaches have been explored for the management of colloid cysts, each carrying its own set of advantages and limitations. Tubular retractors developed recently alleviate retraction pressure through radial distribution, potentially offering benefits for colloid cyst resection. This study aims to introduce and assess a modified microsurgical method utilizing the tubular retractor for addressing colloid cysts. Methods: The study included a retrospective assessment of patients who had colloid cysts and who were treated between 2015 and 2023 by one experienced surgeon. The demographic, clinical, radiological, histological, and surgical data regarding these patients were evaluated. The patients were assessed using the colloid cyst risk score, indicating a risk for obstructive hydrocephalus. Results: The minimally invasive microsurgical approach was successfully applied to all 22 identified patients. No postoperative surgical complications were reported. Gross total resection was achieved in 21 (95.5%) patients. The early complication rate was 22.7% (n = 5). There were no postoperative seizures, permanent neurological deficits, or venous injuries. The average hospital stay was 3 days. There was no evidence of recurrence at an average follow-up length of 25.9 months. Conclusion: The transtubular approach is an effective, safe method for treating colloid cysts. It achieves complete cyst removal with minimal complications, offering the benefits of less invasiveness, improved visualization, and reduced tissue disruption, strengthening its role in colloid cyst surgery.

Intramedullary pediatric low-grade glioma of the spine.

PURPOSE: Pediatric intramedullary spinal cord low-grade gliomas (pLGGs) are rare diagnoses among central nervous system (CNS) tumors in the pediatric population. The classic presentation of the patients includes some degree of neurologic deficit, although many times the symptoms are vague which leads to delayed diagnosis. MATERIAL AND METHODS: The first step in the diagnosis includes special parameters in spinal imaging, particularly magnetic resonance imaging (MRI), and surgical resection remains the cornerstone for both diagnosis and treatment. Yet, recent years advancement in molecular and genetic understanding of CNS tumors allows for better adjustment of the treatment and follow-up regimens. Based on postoperative status, adjuvant therapy may provide additional therapeutic advantage for some types of tumors. CONCLUSION: Ultimately, patients have a very promising prognosis when treated appropriately in most of the cases of pediatric spinal cord LGG with continued advances arising. This manuscript summarizes the most contemporary evidence regarding clinical and treatment features of intramedullary pLGGs.

Surgical Management of Brain Metastasis from Esophageal Cancer: A Systematic Review and Single-Center Experience.

BACKGROUND: Brain metastases from esophageal cancer (BMEC) are rare and aggressive, with limited literature on optimal treatment modalities and a standard of care yet to be established. The objective of this study was to systematically review existing literature and perform a retrospective analysis of our institution's patients to evaluate the influence of different treatment modalities on patient outcomes. METHODS: A systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines and a retrospective review of our institutional experience with BMEC were both conducted. Data based on mean survival,histology, metastasis location, and treatment modality were abstracted. RESULTS: A total of 48 studies representing 136 patients with BMEC were identified, in addition to the 11 patients treated at our institution. There were a total of 100 males (12 unreported), with a median age of 62.2 at diagnosis in our systematic review, along with 8 males with a median age of 62 in our institutional review. Collectively, survival rates observed based on histology were not similar (squamous cell carcinoma: 9.2 months, adenocarcinoma: 13.4 months), however, based on treatment modalities (surgery: 11.6 months, radiation: 10.4 months, chemotherapy: 12.3 months), and metastasis location (supratentorial: 10.5 months, infratentorial: 9.9 months), the survival times were comparable. CONCLUSIONS: Our review suggests that causes of death were often independent of brain metastases highlighting the need for further studies on early detection and prevention of primary esophageal cancer, as well as improved treatment modalities for BMECs.

Laser interstitial thermal therapy in neurosurgery: a single-surgeon experience of 313 patients.

OBJECTIVE: Real-time MRI-guided focused laser interstitial thermal therapy (LITT) is a minimally invasive surgical treatment choice for challenging intracranial lesions that are either resistant to conventional therapies or located in deep or critical areas of the brain. However, existing studies on LITT within surgical neuro-oncology are relatively small and have limited follow-up periods. The authors aimed to present a comprehensive analysis of their experiences with LITT in surgical neuro-oncology, with the intent to provide a clearer understanding of the safety and efficacy of this procedure. METHODS: This study was an exploratory cohort analysis encompassing all patients who underwent LITT for brain tumors at a single center between 2013 and 2023. The primary focus was extent of ablation (EOA), time to recurrence (TTR), and overall survival (OS). Secondary outcomes, including the rate of complications, were also evaluated. Comparative analyses were conducted based on lesion subtypes, and factors predicting outcomes were identified. RESULTS: Three hundred thirteen patients underwent LITT procedures. During a mean follow-up of 10.4 months, 66.8% of patients remained alive and 26.2% of the ablated lesions recurred. The mean age of the cohort was 60.4 ± 13.3 years (58.5% female). The lesion subtypes that were treated comprised metastases (30%), glioblastoma (GBM; 41.6%), low-grade glioma (9.1%), radiation necrosis (11.4%), and meningioma (2.2%). The permanent neurological deficit rate was 14% (n = 44), with 25 (8%) of them new-onset deficits and 19 deficits (6.1%) that were present preoperatively and did not resolve after LITT. The mean TTR and OS were 12.2 and 38.1 months, respectively. TTR and OS varied significantly by lesion subtype (p < 0.001, log-rank analysis). A high-grade lesion was identified as the single factor linked to tumor recurrence. Age, high-grade lesion, preoperative lesion volume, and readmission within 30 days were identified as factors significantly associated with OS in the multivariable Cox regression analysis. EOA > 100% predicted longer OS in metastases and GBM by log-rank analysis. CONCLUSIONS: LITT stands as a secure and feasible ablative treatment choice for intracranial lesions, potentially suitable for specific patient cases otherwise not amenable to surgical intervention. These findings further corroborate the safety of the procedure and its favorable outcomes, underscoring its potential significance in clinical practice.

Minimally invasive resection of intracranial lesions using tubular retractors: A single surgeon series.

OBJECTIVE: Tubular retractors are increasingly used due to their low complication rates, providing easier access to lesions while minimizing trauma from brain retraction. Our study presents the most extensive series of cases performed by a single surgeon aiming to assess the effectiveness and safety of a transcortical-transtubular approach for removing intracranial lesions. METHODS: We performed a retrospective review of patients who underwent resection of an intracranial lesion with the use of tubular retractors. Electronic medical records were reviewed for patient demographics, preoperative clinical deficits, diagnosis, preoperative and postoperative magnetic resonance imaging (MRI) scans, lesion characteristics including location, volume, extent of resection (EOR), postoperative complications, and postoperative deficits. RESULTS: 112 transtubular resections for intracranial lesions were performed. Patients presented with a diverse number of pathologies including metastasis (31.3 %), GBM (21.4 %), and colloid cysts (19.6 %) The mean pre-op lesion volume was 14.45 cm3. A gross total resection was achieved in 81 (71.7 %) cases. Seventeen (15.2 %) patients experienced early complications which included confusion, short-term memory difficulties, seizures, meningitis and motor and visual deficits. Four (3.6 %) patients had permanent complications, including one with aphasia and difficulty finding words, another with memory loss, a third with left-sided weakness, and one patient who developed new-onset long-term seizures. Mean post-operative hospitalization length was 3.8 days. CONCLUSION: Tubular retractors provide a minimally invasive approach for the extraction of intracranial lesions. They serve as an efficient tool in neurosurgery, facilitating the safe resection of deep-seated lesions with minimal complications.

Assessing pediatric neurosurgery capacity in La Paz, Bolivia: an illustrative institutional experience of a lower-middle-income country in South America.

OBJECTIVE: The current pediatric neurosurgery capacity in lower-middle-income countries (LMICs) in South America is poorly understood. Correspondingly, the authors sought to interrogate the neurosurgical inpatient experience of the sole publicly funded pediatric hospital in one of the largest regional departments of Bolivia to better understand this capacity. METHODS: A retrospective review of all neurosurgical procedures performed at the Children's Hospital of La Paz, Bolivia (Hospital del Niño "Dr. Ovidio Aliaga Uria") between 2019 and 2023 was conducted after institutional approval using a recently implemented national electronic medical record system. RESULTS: A total of 475 neurosurgical admissions satisfied inclusion for analysis over the 5-year span. The majority of admissions were from within the La Paz Department (87%) via the emergency department (77%), without private insurance (83%). The most common indications for neurosurgical intervention were trauma (35%), followed by hydrocephalus (28%), congenital disease (12%), infection (5%), and craniosynostosis (3%). Overall, the median age at time of surgery was 2.0 years, and the median operating time was 1.5 hours with a minority of intraoperative complications (2%). The most common inpatient complication was unplanned return to the operating room (19%), most commonly seen in congenital indications. At final discharge, the median postoperative length of stay was 10 days. Twenty-seven (6%) of the 475 patients died during hospitalization, most commonly seen in tumor indications. Of the 448 patients who were discharged, 299 (67%) returned for at least one follow-up appointment. CONCLUSIONS: There is restricted breadth in neurosurgical indications and outcomes achievable at the Children's Hospital of La Paz, Bolivia. As such, the capacity of pediatric neurosurgery at institutions in LMICs in South America such as this one is very limited. Identifying and prioritizing actionable interventions to improve this capacity is institution- and LMIC-dependent, and as such, future efforts will need to be tailored appropriately.

Antiretroviral Drug Repositioning for Glioblastoma.

Outcomes for glioblastoma (GBM) remain poor despite standard-of-care treatments including surgical resection, radiation, and chemotherapy. Intratumoral heterogeneity contributes to treatment resistance and poor prognosis, thus demanding novel therapeutic approaches. Drug repositioning studies on antiretroviral therapy (ART) have shown promising potent antineoplastic effects in multiple cancers; however, its efficacy in GBM remains unclear. To better understand the pleiotropic anticancer effects of ART on GBM, we conducted a comprehensive drug repurposing analysis of ART in GBM to highlight its utility in translational neuro-oncology. To uncover the anticancer role of ART in GBM, we conducted a comprehensive bioinformatic and in vitro screen of antiretrovirals against glioblastoma. Using the DepMap repository and reversal of gene expression score, we conducted an unbiased screen of 16 antiretrovirals in 40 glioma cell lines to identify promising candidates for GBM drug repositioning. We utilized patient-derived neurospheres and glioma cell lines to assess neurosphere viability, proliferation, and stemness. Our in silico screen revealed that several ART drugs including reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs) demonstrated marked anti-glioma activity with the capability of reversing the GBM disease signature. RTIs effectively decreased cell viability, GBM stem cell markers, and proliferation. Our study provides mechanistic and functional insight into the utility of ART repurposing for malignant gliomas, which supports the current literature. Given their safety profile, preclinical efficacy, and neuropenetrance, ARTs may be a promising adjuvant treatment for GBM.

The Potential of Liquorpheresis to Treat Leptomeningeal Disease.

Leptomeningeal disease (LMD) is a devastating sequela of many cancers, with an extremely poor prognosis. Barriers to improving outcomes are related to the inability of many traditional therapies to effectively reach the cerebrospinal fluid (CSF) space within the central nervous system. Liquorpheresis is an emerging treatment modality specific to CSF diseases, the primary mechanism of action of which is direct targeted filtration of CSF content by neurosurgical access. In this review, we highlight the principles of liquorpheresis and detail how LMD can be amenable to this treatment. Further, we summarize the current in vitro and in vivo evidence supporting liquorpheresis as a feasible method to treat LMD and other central nervous system diseases as well as describe its conceivable limitations.

Characteristics and Outcomes of Patients Treated with Cervical Spine Fusion at High Volume Hospitals.

BACKGROUND: High volume (HV) has been associated with improved outcomes in various neurosurgical procedures. The objective of this study was to explore the regional distribution of HV spine centers for cervical spine fusion and compare characteristics and outcomes for patients treated at HV centers versus lower volume centers. METHODS: The National Inpatient Sample database 2016-2020 was queried for patients undergoing cervical spine fusion for degenerative pathology. HV was defined as case-loads greater than 2 standard deviations above the mean. Patient characteristics, procedures, and outcomes were compared. RESULTS: Of 3895 hospitals performing cervical spine fusion for degenerative pathology, 28 (0.76%) were HV. The Mid-Atlantic and West South Central regions had the highest number of HV hospitals. HV hospitals were more likely to perform open anterior fusion surgeries (P < 0.01). Patients treated at HV hospitals were less likely to have severe symptomatology or comorbidities (P < 0.01 for all). When controlling for severity and demographics on multivariate analysis, HV centers had higher odds of length of stay ≤1 day, favorable discharge, and decreased total charges. CONCLUSIONS: Patients who underwent cervical spine fusion surgery at HV hospitals were less complex and had increased odds of length of stay ≤1, favorable discharge, and total charges in the lower 25th percentile than patients treated at non-HV hospitals. Physician comfort, patient selection, institutional infrastructure, and geographic characteristics likely play a role.

The Effect of the Coronavirus Disease 2019 Pandemic on Pituitary Surgery.

OBJECTIVE: As the coronavirus disease 2019 (COVID-19) pandemic spread to the United States in 2020, there was an impetus toward postponing or ceasing nonurgent transsphenoidal pituitary surgeries to prevent the spread of the virus. Some centers encouraged transcranial approaches for patients with declining neurologic function. However, no large-scale data exist evaluating the effects that this situation had on national pituitary practice patterns. METHODS: Pituitary surgeries in the National Inpatient Sample were identified from 2017 to 2020. Surgeries in 2020 were compared with the 3 years previously to determine any differences in demographics, surgical trends/approaches, and perioperative outcomes. RESULTS: In 2020, there was a decline in overall pituitary surgeries (34.2 vs. 36.3%; odds ratio (OR), 0.88; P < 0.001) yet transsphenoidal approaches represented a higher proportion of interventions (69.0 vs. 64.9%; P < 0.001). Neurosurgical complications were higher (51.9 vs. 47.4%; OR, 1.13; P < 0.001) and patients were less likely to be discharged home (86.4 vs. 88.5%; OR, 0.84; P < 0.001). This finding was especially true in April 2020 during the first peak in COVID-19 cases, when transcranial approaches and odds of mortality/complications were highest. CONCLUSIONS: In 2020, transsphenoidal surgery remained the preferred approach for pituitary tumor resection despite initial recommendations against the approach to prevent COVID-19 spread. Pituitary surgeries had a higher risk of periprocedural complications despite accounting for preoperative comorbidities, COVID-19 infection status, and surgical approach, suggesting that an overwhelmed hospital system can negatively influence surgical outcomes in noninfected patients.

Impact of Previous Surgery on Success of Magnetic Resonance-guided Laser Interstitial Thermal Therapy (MRgLITT) to Treat Pediatric Epilepsy: An Institutional Experience.

BACKGROUND: There is an emerging role for minimally invasive magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) in the treatment of pediatric epilepsy refractory to medication. To date, predictors of MRgLITT success have not been established in a sizeable singular experience. Correspondingly, the aim of this study was to elucidate if previous surgical history predicts MRgLITT success in this setting. METHODS: A retrospective review was conducted of our MRgLITT procedures for pediatric (patient age <19 years) epilepsy from 2011 to 2020 with documented seizure outcomes at 1 and 2 years after procedure. Categorical and continuous data were compared using χ2 and Student's t test, respectively. RESULTS: A total of 41 patients satisfied all criteria with 16 (39%) female and 25 (61%) male patients. Following MRgLITT, seizure-freedom at 1-year was achieved in 15 (37%) patients. In the cohort, there were 14 (34%) patients who had undergone previous open surgery for epilepsy at mean age of 9.4 ± 5.5 years. Patients with a previous open surgery history were found to statistically experience longer length of hospitalization after MRgLITT (P = 0.04) with a statistically lower proportion of seizure-freedom at 1-year after MRgLITT (14% vs. 48%, P = 0.03). However, there was no difference in the rate of seizure-freedom at 2 years (29% vs. 41%, P = 0.44), as well as no difference in subsequent surgical interventions for seizure management between groups. CONCLUSIONS: Based on our institutional experience, patients with previous open surgery history may experience longer length of hospitalization after MRgLITT for pediatric epilepsy and lesser response in seizure-freedom within the first year but with non-inferior seizure freedom by the second year.

Pediatric neurosurgical medulloblastoma outcomes in La Paz, Bolivia: How a Lower Middle-Income Country (LMIC) institution in South America compares to the United States.

BACKGROUND: How pediatric medulloblastoma patients fare in Lower Middle-Income Country (LMICs) in South America is not well understood. Correspondingly, the aim of this study was to summarize the pediatric neurosurgical experience of an institution in La Paz, and compare outcomes to that of a generalized High Income Country (HIC) United States (US) experience. METHODS: A retrospective review of all pediatric neurosurgical medulloblastoma patients at the Children's Hospital of La Paz, Bolivia (Hospital del Niño "Dr. Ovidio Aliaga Uria") between 2014 and 2023 was conducted and compared to a generalized US experience abstracted from the US National Cancer Database (NCDB) and National Inpatient Sample (NIS) databases. Categorical, continuous and survival data were statistically summarized and compared. RESULTS: A total of 24 pediatric medulloblastoma patients underwent neurosurgical treatment at the Hospital del Niño. In this La Paz cohort, there were 15 (63%) males and 9 (38%) females, with a mean age of 5.6 years old at diagnosis. The majority of patients underwent subtotal resection (STR, 79%), while the remaining patients underwent biopsy only. Ten (42%) patients expired during their hospitalization, and mean length of stay overall was 39 days. Only 8 (33%) patients received adjuvant treatment after surgery. Median overall survival from diagnosis in the La Paz cohort was 1.9 months. Compared to the US databases, the La Paz cohort experienced significantly more emergency room admissions for surgery, less gross total resection, more STR, more return to operating room for ventriculoperitoneal shunting, more bacteremia, more tracheostomy procedures, more percutaneous gastrostomy placements, longer lengths of stay, less adjuvant chemotherapy, less radiation therapy, shorter follow-up, and ultimately, significantly shorter overall survival (all P < 0.050). CONCLUSIONS: Pediatric neurosurgical medulloblastoma outcomes at the Children's Hospital of La Paz, Bolivia are significantly inferior to that of a generalized US experience. Future research is required to identify institution- and country-specific initiatives to improve discrepancies between institutions in LMICs in South America compared to HICs.