Chimeric Antigen Receptor T Cells Targeting CD19 and GCC in Metastatic Colorectal Cancer: A Nonrandomized Clinical Trial.

Importance: Chimeric antigen receptor (CAR) T-cell therapy (CART) has transformed the treatment landscape of hematologic cancer, but has negligible effects for adult solid cancers. In this trial, an autologous CAR T-cell product demonstrated antitumor activity in heavily pretreated patients with metastatic colorectal cancer (mCRC). Objective: To evaluate the safety and efficacy of guanylate cyclase-C (GCC19) CART in participants with metastatic colorectal cancer (mCRC). Design, Setting, and Participants: This single-arm, nonrandomized, phase 1 trial was conducted at the First Hospital of Jilin University from December 3, 2020, to April 13, 2022. Data analysis was conducted from May 2022 to April 2024. Adults with relapsed and refractory mCRC expressing GCC were treated with GCC19CART, a mixture of autologous CAR T cells transduced with lentiviral vectors expressing genes that encode either CD-19 CAR or GCC CAR. Main Outcomes and Measures: Safety and tolerability of CAR T-cell therapy targeting GCC in patients with mCRC without therapeutic options is capable of conferring a reasonable likeliness of clinical benefit. Other outcomes included objective response rate, progression-free survival, overall survival, and immune activation. Results: Of 15 patients 9 (60%) were women, and the median (range) age was 44 (33-61) years. Treatment with GCC19CART was associated with the development of cytokine release syndrome and diarrhea in most patients, all of which were self-limited and manageable. The objective response rate was 40%, with a partial response in 2 of 8 and 4 of 7 patients treated with either 1 × 106 cells/kg or 2 × 106 cells/kg. Median overall survival was 22.8 months (95% CI, 13.4-26.1) at data cutoff; the median progress-free survival was 6.0 months in the high dose level group (95% CI, 3.0 to not available). Conclusions and Relevance: The results of this nonrandomized clinical trial suggest that GCC19CART was safe and tolerable in heavily pretreated patients with mCRC and is the first CAR T-cell therapy known to produce objective clinical activity in refractory cancer. Given the paucity of effective therapeutics developed for colorectal cancer in recent decades, the observation that CD-19 CART target engagement can robustly induce GCC19CART target engagement sufficient to produce objective activity may serve as a foundation to develop effective cellular therapy in mCRC and other solid cancers. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000040645.

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.

RSTN COVID-19 Hand Recovery: Two years on, where are we now?

Hand surgery services were required to rapidly adapt to the coronavirus disease 2019 (COVID-19). Two years following the initial wave, hand surgery units continue to adapt and recover from the pandemic. The aim of the RSTN COVID-19 Hand Recovery survey was to evaluate what adaptions made to hand surgery services during COVID-19 have been maintained in the COVID recovery phase. A survey was distributed to hand surgery units, across the UK and Ireland. The survey was completed by consultant hand surgeons across 39 hospitals. Most practices returned to pre-pandemic standards. The main changes that endured were the increase in consultant-led triaging for referrals and utilisation of video conferencing platforms for teaching and meetings. Changes made during the pandemic, such as increased use of WALANT, out of theatre operating and use of telemedicine were not sustained during the recovery period. The COVID-19 pandemic allowed the opportunity for hand surgery services to adapt their services. Several changes that were implemented have since been proven to be more efficient and equally effective for patients. However, these changes have not been sustained and the barriers preventing permanent implementation should be scrutinised. We call on hand surgery units to evaluate their current practice to ensure that patients are provided a streamlined and sustainable service.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Do reconstructive techniques for osteochondritis dissecans of the skeletally mature knee work? A systematic review and meta-analysis.

PURPOSE: Osteochondritis dissecans (OCD) is a common cause of knee pain. Management for adult-onset OCD (AOCD) usually involves surgery. Surgical treatments include palliative, reparative and reconstructive techniques. The aim of this systematic review and meta-analysis is to evaluate the efficacy of reconstructive techniques for the treatment of OCD in skeletally mature knees. METHODS: A systematic search was carried out on four databases up to November 2023 (Medline, Embase, Cochrane Library, Web of Science). The study was registered on international prospective register of systematic reviews and performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Clinical studies on skeletally mature patients were included, which utilised reconstructive techniques such as autologous chondrocyte implantation (ACI), matrix-induced autologous chondrocyte implantation, osteochondral allograft transplantation surgery or bone marrow-derived cellular transplantation. Demographical data, patient-reported outcome measures and postoperative complications were recorded. Quantitative outcome measures that were comparable across studies were pooled for meta-analysis. A random effects model was used. Heterogeneity was assessed using the I2 statistic and Cochran's Q test. Statistical significance was set at p < 0.05. Risk of bias was assessed using the risk of bias in non-randomised studies - of interventions tool for nonrandomised studies. RESULTS: Sixteen studies were included with 458 OCD lesions in 432 patients. The average age was 24.9, and 62.6% were male. The mean follow-up time was 61.5 months. At 36 months follow-up, International Knee Documentation Committee (IKDC) subjective, Tegner and EuroQol-visual analogue scale (EQ-VAS) scores improved from 42.4 to 78.6 (standard mean difference [SMD]: 2.47; p < 0.001), 2.27-4.99 (SMD: 2.363; p = 0.002) and 30.4-57.5 (SMD: 2.390; p < 0.001), respectively. Overall complication rate was 8.9%. Smaller OCD lesion sizes resulted in a greater improvement in IKDC subjective (SMD: 2.64 vs. 2.01; p = 0.038), EQ-VAS (SMD: 3.16 vs. 0.95; p = 0.046) and Tegner scores (SMD: 3.13 vs. 1.05; p = 0.007) and had a lower complication rate (p = 0.008). Males showed a larger improvement in IKDC subjective scores than females (SMD: 2.56 vs. 1.56; p = 0.029), while younger patients had a larger improvement in IKDC subjective scores (SMD: 2.71 vs. 2.12; p = 0.045) and fewer complications than older patients (p = 0.003). There were no significant differences between cohorts treated with ACI and those treated with non-ACI reconstructive techniques. Publication bias was not detected (n.s.). CONCLUSION: Reconstructive techniques used to treat OCD in the skeletally mature knee resulted in significant improvements in clinical and functional outcomes, with a low overall complication rate. Since a younger age leads to a greater improvement in IKDC subjective score and a lower complication rate, surgical intervention should not be delayed, especially in AOCD lesions which are more likely to follow a progressive and unremitting clinical course. LEVEL OF EVIDENCE: Level III.

Risk factors for vascular injuries in anterior lumbar interbody fusion: a single-institution retrospective study.

OBJECTIVE: Vascular injuries in anterior lumbar interbody fusion (ALIF) occur due to the vascular manipulation needed to achieve optimal disc space exposure. In this study, the authors aimed to evaluate intraoperative vascular injuries in patients undergoing single- and multilevel ALIF at a large tertiary academic center. METHODS: Prospectively collected data specifically addressing postoperative complications in patients who underwent ALIF by neurosurgery spine faculty working with a specialized vascular surgeon were retrospectively reviewed. Demographic characteristics and intraoperative data were collected. Patients were split into vascular injury and non-vascular injury groups. Outcome comparisons were conducted using the chi-square exact and Wilcoxon rank-sum tests for categorical and continuous data, respectively. Logistic regression was used to investigate associations with vascular injury, with univariate analysis first conducted to identify candidate associations. Based on these results, variables demonstrating a between-groups test statistic of p < 0.10 were included in the multivariate analysis to determine the independent predictors of vascular injuries. RESULTS: In total, 323 patients who underwent ALIF procedures were identified: 51% were male (n = 166) and 49% were female (n = 157). The mean age was 57.1 years, with 56% (n = 182) having undergone prior lumbar surgery. Vascular injuries were encountered intraoperatively in 7.1% (n = 23) of patients, and the majority (91% [n = 21]) involved the left common iliac vein. Patients with vascular injuries were statistically older (mean 63.6 vs 56.6 years), had greater incidence rates of coronary artery disease, opioid use, multilevel ALIF surgery involving the L2-3 level, and surgery involving multiple disc spaces, had more multilevel anterior instrumentation, and experienced greater blood loss during surgery and longer length of stay (all p < 0.05). Overall, there was 1 death (0.3%) secondary to aortic artery injury. Multivariate analysis identified opioid use, multilevel ALIF involving L2-3, and multiple interbodies as statistically independent predictors of vascular injury (all p < 0.05). CONCLUSIONS: Identifying patient risk factors can reduce the risk of vascular injuries in ALIF. Opioid use, multilevel ALIF involving L2-3, and multiple interbodies were independent predictors of vascular injuries in ALIF.

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.