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.

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.

Safety and efficacy of low-dose intracoronary thrombolysis during primary percutaneous coronary intervention in patients with ST elevation myocardial infarction: A meta-analysis of randomized trials.

BACKGROUND: In patients with ST elevation myocardial infarction (STEMI), intracoronary thrombolysis (ICT) may reduce thrombotic burden and microvascular obstruction in the infarct-related artery. We performed a meta-analysis to evaluate the role of adjunctive low-dose ICT during primary percutaneous coronary intervention (PPCI) in improving clinical outcomes and indices of microvascular function. METHODS: We searched electronic databases (Cochrane, EMBASE, Medline; inception to October 2023) for randomized controlled trials (RCTs) evaluating the effects of adjunctive ICT in STEMI patients undergoing PPCI, compared with placebo or usual care. Study-level data on efficacy and safety outcomes were pooled using a fixed-effect model. The primary outcome was major adverse cardiovascular events (MACE). RESULTS: A total of 8 RCTs were included, comprising a total of 1,208 patients. Compared with placebo or usual care, ICT was associated with a trend towards lower MACE (11.3% vs. 15.1%; odds ratio [OR] 0.73, 95% confidence interval [CI] 0.51 to 1.04). Infarct size (mean difference [MD] -1.98, 95% CI -3.68 to -0.27; p=0.02), ST-segment resolution (MD: 6.06, 95% CI: 0.69 to 11.43; p=0.03) and corrected TIMI frame count (MD: -2.26, 95% CI: -4.03 to -0.48; p=0.01; I2=78%). The odds for major (0.7% vs. 0.7%; OR 0.94, 95% CI 0.24 to 3.7; p=0.93) and minor bleeding (7.7% vs. 4.3%; OR 1.81, 95% CI 0.87 to 3.76; p=0.11) were similar between the two groups. CONCLUSION: Adjunctive low-dose ICT during PPCI is safe, associated with a trend towards lower MACE, and may improve surrogate markers of microvascular function. These hypothesis-generating findings warrant validation in larger, adequately powered randomized trials.

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.

Antisense Oligonucleotides for Rapid Translation of Gene Therapy in Glioblastoma.

PURPOSE: The limited efficacy of current treatments for malignant brain tumors necessitates novel therapeutic strategies. This study aimed to assess the potential of antisense oligonucleotides (ASOs) as adjuvant therapy for high-grade gliomas, focusing on their CNS penetration and clinical translation prospects. METHODS: A comprehensive review of the existing literature was conducted to evaluate the implications of ASOs in neuro-oncology. Studies that investigated ASO therapy's efficacy, CNS penetration, and safety profile were analyzed to assess its potential as a therapeutic intervention for high-grade gliomas. RESULTS: ASOs present a promising avenue for enhancing targeted gene therapies in malignant gliomas. Their potent CNS penetration, in vivo durability, and efficient transduction offer advantages over conventional treatments. Preliminary in vivo and in vitro studies suggest ASOs as a viable adjuvant therapy for high-grade gliomas, warranting further exploration in clinical trials. CONCLUSIONS: ASOs hold significant promise as adjuvant therapy for high-grade gliomas, offering improved CNS penetration and durability compared with existing treatments. While preliminary studies are encouraging, additional research is needed to establish the safety and efficacy of ASO therapy in clinical settings. Further investigation and clinical trials are warranted to validate ASOs as a transformative approach in neuro-oncology.

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.

Permanent Pacemaker-Mediated Exertional Hypoxemia in a Patient With Ebstein Anomaly.

Patients with Ebstein anomaly are known to have a higher incidence of interatrial communications and shunting of blood and its components through, mainly due to either streaming of tricuspid regurgitation or due to elevated right atrial pressure. Here we describe a case where permanent pacemaker lead kept a patent foramen ovale open leading to right-to-left shunting of blood and exertional hypoxemia. This is the first such case report in the published literature.

Minimally invasive keyhole approach for supramaximal frontal glioma resections: technical note.

OBJECTIVE: The authors aimed to review the frontal lobe's surgical anatomy, describe their keyhole frontal lobectomy technique, and analyze the surgical results. METHODS: Patients with newly diagnosed frontal gliomas treated using a keyhole approach with supramaximal resection (SMR) from 2016 to 2022 were retrospectively reviewed. Surgeries were performed on patients asleep and awake. A human donor head was dissected to demonstrate the surgical anatomy. Kaplan-Meier curves were used for survival analysis. RESULTS: Of the 790 craniotomies performed during the study period, those in 47 patients met our inclusion criteria. The minimally invasive approach involved four steps: 1) debulking the frontal pole; 2) subpial dissection identifying the sphenoid ridge, olfactory nerve, and optic nerve; 3) medial dissection to expose the falx cerebri and interhemispheric structures; and 4) posterior dissection guided by motor mapping, avoiding crossing the inferior plane defined by the corpus callosum. A fifth step could be added for nondominant lesions by resecting the inferior frontal gyrus. Perioperative complications were recorded in 5 cases (10.6%). The average hospital length of stay was 3.3 days. High-grade gliomas had a median progression-free survival of 14.8 months and overall survival of 23.9 months. CONCLUSIONS: Keyhole approaches enabled successful SMR of frontal gliomas without added risks. Robust anatomical knowledge and meticulous surgical technique are paramount for obtaining successful resections.

High output cardiac state: evaluating the incidence, plausible etiologies and outcomes.

INTRODUCTION: The high output cardiac state (HOCS) [cardiac index (CI) >4 L/min/m2 ], primarily driven by abnormally low systemic vascular resistance (SVR), is a relatively under-recognized condition. Although, majority of these patients meet criteria for heart failure (HF), their treatment should be aimed at the primary pathology, as the majority of guideline directed HF therapies can reduce SVR further. OBJECTIVES: To characterize patients with HOCS and provide valuable insight into the condition. METHODS: Patients investigated by right heart catheterization (RHC) at the St. Boniface Hospital, Winnipeg, Canada between January 2009 and November 2021 were reviewed. Two groups of patients were included: 1) HOCS [CI >4 L/min/m2], and 2) pre-HOCS [CI between 3.8-4.0 L/min/m2]. Their medical records were reviewed to identify plausible etiologies, relevant investigations, and outcomes. RESULTS: 177/2950 (6 %) patients met criteria for inclusion: 144/177 (81 %) with HOCS [mean age 51 years (range 19 - 82); 67/144 (47 %) female] and 33/177 (19 %) with pre-HOCS [mean age 55 years (range 30 - 83); 6/33 (18 %) female]. The most common plausible etiologies for the HOCS included anemia (36 %), obesity (34 %), cirrhosis (17 %), and lung disease (32 %). Trans-thoracic echocardiography and magnetic resonance imaging findings were non-specific and predominantly described preserved left ventricular ejection fraction, and pulmonary hypertension. The population experienced high rates of hospitalization, and significantly high mortality [36/144 (25 %) of HOCS at a median follow-up of 31.5 months, and 13/33 (39 %) of pre-HOCS at a median follow-up of 17 months]. CONCLUSIONS: HOCS is not an uncommon condition and is associated with high mortality. Current HF guideline should incorporate such evaluation into the diagnostic criteria.

1-Year Mortality Prediction through Artificial Intelligence Using Hemodynamic Trace Analysis among Patients with ST Elevation Myocardial Infarction.

Background and Objectives: Patients presenting with ST Elevation Myocardial Infarction (STEMI) due to occlusive coronary arteries remain at a higher risk of excess morbidity and mortality despite being treated with primary percutaneous coronary intervention (PPCI). Identifying high-risk patients is prudent so that close monitoring and timely interventions can improve outcomes. Materials and Methods: A cohort of 605 STEMI patients [64.2 ± 13.2 years, 432 (71.41%) males] treated with PPCI were recruited. Their arterial pressure (AP) wave recorded throughout the PPCI procedure was analyzed to extract features to predict 1-year mortality. After denoising and extracting features, we developed two distinct feature selection strategies. The first strategy uses linear discriminant analysis (LDA), and the second employs principal component analysis (PCA), with each method selecting the top five features. Then, three machine learning algorithms were employed: LDA, K-nearest neighbor (KNN), and support vector machine (SVM). Results: The performance of these algorithms, measured by the area under the curve (AUC), ranged from 0.73 to 0.77, with accuracy, specificity, and sensitivity ranging between 68% and 73%. Moreover, we extended the analysis by incorporating demographics, risk factors, and catheterization information. This significantly improved the overall accuracy and specificity to more than 76% while maintaining the same level of sensitivity. This resulted in an AUC greater than 0.80 for most models. Conclusions: Machine learning algorithms analyzing hemodynamic traces in STEMI patients identify high-risk patients at risk of mortality.

Comparative analysis of bevacizumab and LITT for treating radiation necrosis in previously radiated CNS neoplasms: a systematic review and meta-analysis.

PURPOSE: Radiation necrosis (RN) is a local inflammatory reaction that arises in response to radiation injury and may cause significant morbidity. This study aims to evaluate and compare the efficacy of bevacizumab and laser interstitial thermal therapy (LITT) in treating RN in patients with previously radiated central nervous system (CNS) neoplasms. METHODS: PubMed, Cochrane, Scopus, and EMBASE databases were screened. Studies of patients with radiation necrosis from primary or secondary brain tumors were included. Indirect meta-analysis with random-effect modeling was performed to compare clinical and radiological outcomes. RESULTS: Twenty-four studies were included with 210 patients in the bevacizumab group and 337 patients in the LITT group. Bevacizumab demonstrated symptomatic improvement/stability in 87.7% of cases, radiological improvement/stability in 86.2%, and steroid wean-off in 45%. LITT exhibited symptomatic improvement/stability in 71.2%, radiological improvement/stability in 64.7%, and steroid wean-off in 62.4%. Comparative analysis revealed statistically significant differences favoring bevacizumab in symptomatic improvement/stability (p = 0.02), while no significant differences were observed in radiological improvement/stability (p = 0.27) or steroid wean-off (p = 0.90). The rates of adverse reactions were 11.2% for bevacizumab and 14.9% for LITT (p = 0.66), with the majority being grade 2 or lower (72.2% for bevacizumab and 62.5% for LITT). CONCLUSION: Both bevacizumab and LITT exhibited favorable clinical and radiological outcomes in managing RN. Bevacizumab was found to be associated with better symptomatic control compared to LITT. Patient-, diagnosis- and lesion-related factors should be considered when choosing the ideal treatment modality for RN to enhance overall patient outcomes.

Cardiogenic Shock - Differences Between Males and Females and Sex Specific Risks.

Cardiogenic Shock (CS) remains a high-mortality condition despite technological and therapeutic advances. One key to potentially improving CS prognosis is understanding patient heterogeneity and which patients may benefit most from different treatment options, a key element of which is sex differences. While cardiovascular diseases have historically been thought of as a male-dominant conditions, the field is increasingly aware that females are also a substantial portion of the patient population. While estrogen has been implicated in protective roles against CVD and tissue hypoxia, it's role in CS remains unclear. Clinically, female CS patients tend to be older and have more severe comorbidities and are more likely to have non-acute myocardial infarction etiologies with preserved ejection fractions. Female CS patients are more likely to receive pharmacotherapy while less likely to receive mechanical circulatory support. There is increased short-term mortality in females, although long-term mortality is similar between the sexes. More sex-specific and age-stratified research needs to be done to fully understand the pathophysiological differences that are relevant in CS, to better recognize and manage CS patients and reduce its mortality.

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.

Impact of biological sex on valvular heart disease, interventions, and outcomes.

Valvular heart disease (VHD) is common, affecting >14% of individuals aged >75, and is associated with morbidity, including heart failure and arrhythmia, and risk of early mortality. Increasingly, important sex differences are being found between males and females with VHD. These sex differences can involve the epidemiology, pathophysiology, presentation, diagnosis, and outcomes of the disease. Females are often disadvantaged, and female sex has been shown to be associated with delayed diagnosis and inferior outcomes in various forms of VHD. In addition, the unique pathophysiologic state of pregnancy is associated with increased risk for maternal and fetal morbidity and mortality in many forms of VHD. Therefore, understanding and recognizing these sex differences, and familiarity with the attendant risks of pregnancy and management of pregnant females with VHD, is of great importance for any primary care or cardiovascular medicine practitioner caring for the female patient. This review will outline sex differences in aortic, mitral, pulmonic, and tricuspid VHD, with particular focus on differences in pathophysiology, clinical presentation, and outcomes. In addition, the pathophysiology and management implications of pregnancy will be discussed.

Chat-GPT on brain tumors: An examination of Artificial Intelligence/Machine Learning's ability to provide diagnoses and treatment plans for example neuro-oncology cases.

OBJECTIVE: Assess the capabilities of ChatGPT-3.5 and 4 to provide accurate diagnoses, treatment options, and treatment plans for brain tumors in example neuro-oncology cases. METHODS: ChatGPT-3.5 and 4 were provided with twenty example neuro-oncology cases of brain tumors, all selected from medical textbooks. The artificial intelligence programs were asked to give a diagnosis, treatment option, and treatment plan for each of these twenty example cases. Team members first determined in which cases ChatGPT-3.5 and 4 provided the correct diagnosis or treatment plan. Twenty neurosurgeons from the researchers' institution then independently rated the diagnoses, treatment options, and treatment plans provided by both artificial intelligence programs for each of the twenty example cases, on a scale of one to ten, with ten being the highest score. To determine whether the difference between the scores of ChatGPT-3.5 and 4 was statistically significant, a paired t-test was conducted for the average scores given to the programs for each example case. RESULTS: In the initial analysis of correct responses, ChatGPT-4 had an accuracy of 85% for its diagnoses of example brain tumors and an accuracy of 75% for its provided treatment plans, while ChatGPT-3.5 only had an accuracy of 65% and 10%, respectively. The average scores given by the twenty independent neurosurgeons to ChatGPT-4 for its accuracy of diagnosis, provided treatment options, and provided treatment plan were 8.3, 8.4, and 8.5 out of 10, respectively, while ChatGPT-3.5's average scores for these categories of assessment were 5.9, 5.7, and 5.7. These differences in average score are statistically significant on a paired t-test, with a p-value of less than 0.001 for each difference. CONCLUSIONS: ChatGPT-4 demonstrates great promise as a diagnostic tool for brain tumors in neuro-oncology, as attested to by the program's performance in this study and its assessment by surveyed neurosurgeon reviewers.

The use of advanced neuroimaging modalities in the evaluation of low-grade glioma in adults: a literature review.

Low-grade gliomas encompass a subgroup of cancerous glial cell growths within the central nervous system and are distinguished by their slow growth and relatively low malignant potential. Despite their less aggressive nature, these tumors can still cause significant neurological symptoms through the compression of surrounding neural and vascular structures and, in some instances, undergo malignant transformation. For these reasons, timely and appropriate evaluation and management of low-grade gliomas is critical. Medical imaging stands as a cornerstone for evaluating patients with low-grade gliomas because of its noninvasive nature and ability to provide a vast amount of information about the underlying lesion. With the growing number of neuroimaging techniques and their capabilities, there is a lack of clear guidance on which techniques to utilize for the assessment of low-grade gliomas and what their respective core use cases should be. In this literature review, the authors discuss in significant depth the available evidence pertaining to the use of advanced neuroimaging techniques in the evaluation and management of low-grade gliomas. Specifically, they review the specificity, sensitivity, accuracy, and use cases of magnetic resonance spectroscopy (MRS), perfusion MR imaging (perfusion MRI), diffusion tensor imaging (DTI), functional MRI (fMRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), as well as other emerging imaging techniques. They conclude that most of the advanced neuroimaging techniques are reliable in differentiating low- from high-grade gliomas, whereas MRS and DTI may further support molecular subclassification of the tumor. PET has been best employed for the purpose of tumor biopsy, whereas fMRI and DTI can be particularly valuable in preoperative surgical planning, as they delineate the functionally eloquent brain regions that need to be preserved during tumor resection. MRS, PET, SPECT, and perfusion MRI are best suited to monitor tumor progression, as their respective metrics closely correlate with the underlying metabolic activity of the tumor. Together, these techniques offer a vast amount of information and serve as tools for neurologists and neurosurgeons managing patients with low-grade gliomas.

The Learning Curve and Clinical Outcomes With 250 Laser Ablations for Brain Tumors: A Pathway to Experience.

BACKGROUND AND OBJECTIVES: Laser interstitial thermal therapy (LITT) has gained popularity as a minimally invasive technique for treating brain tumors. Despite its proven safety profile, LITT is not yet widely available, and there is a lack of data on the learning curve required to achieve proficiency. This study analyzes a 250-patient cohort of laser-ablated tumors to describe changes in patient selection and clinical outcomes over time and experience, with the aim of providing insight into the learning curve for incorporating LITT into a neuro-oncology program and identifying a cutoff point that distinguishes novice from expert performance. METHODS: We retrospectively reviewed 250 patients with brain tumor who underwent LITT between 2013 and 2022. Demographic and clinical data were analyzed. Kaplan Meier curves were used for survival analysis. Operative time was evaluated using exponential curve-fit regression analysis to identify when consistent improvement began. RESULTS: The patients were divided into quartiles (Q) based on their date of surgery. Mean tumor volume increased over time (Q1 = 5.7 and Q4 = 11.9 cm3, P = .004), and newly diagnosed lesions were more frequently ablated (P = .0001). Mean operative time (Q1 v Q4 = 322.3 v 204.6 min, P < .0001) and neurosurgical readmission rate (Q1 v Q4 = 7.8% v 0%, P = .03) were reduced over time. The exponential curve-fit analysis showed a sustained decay in operative time after case #74. The extent of ablation (P = .69), the recurrence (P = .11), and the postoperative complication rate (P = .78) did not vary over time. CONCLUSION: After treating 74 patients, a downward trend in the operative time is observed. Patient selection is broadened as experience increases.

Intrathecal chemotherapy for leptomeningeal disease in high-grade gliomas: a systematic review.

BACKGROUND: Leptomeningeal disease (LMD) secondary to high grade glioma (HGG), such as glioblastoma (GBM), are characterized by the spread of tumor cells to the leptomeninges which further complicates treatment approaches. Intrathecal (IT) chemotherapy has surfaced as a potential strategy to bypass the blood-brain barrier and address the challenges posed by disseminated disease. Here, we present a review of the safety and efficacy of IT chemotherapy in the treatment of LMD secondary to HGG. METHODS: A systematic review following PRISMA guidelines was conducted searching PubMed and Embase from January 1995 to September 2022 using specified terms related to IT chemotherapy for LMD. Included articles involved patients diagnosed with LMD from HGG, treated with intrathecal chemotherapy, and provided survival data. Data, including demographics, tumor characteristics, treatment, and survival information, were collected and independently extracted. RESULTS: A total of 68 patients across 10 clinical studies were diagnosed with LMD from HGG and included in the review. Among these patients, the average age at diagnosis was 44.2 years. GBM was the most common tumor type (n = 58, 85.3%). A majority of the patients presented with recurrent disease (n = 29, 60.4%). The review encompassed various IT chemotherapy regimens, including mafosfamide, thio-TEPA, 5-fluoro-2'-deoxyuridine (FdUrd), methotrexate (MTX), and cytarabine; however, dosages and frequencies were inconsistently reported. The mean progression-free survival (PFS) and overall survival (OS) for this cohort were 7.5 months and 11.7 months, respectively. Common side effects of IT chemotherapy included headaches, nausea, and vomiting, with more severe complications such as myelotoxicity, disseminated intravascular coagulopathy, meningitis, and gastrointestinal toxicity reported in some cases. CONCLUSION: LMD continues to be an uncommon complication associated with HGG with a poor prognosis. This article provides an overview of the presently available literature on IT chemotherapy for LMD secondary to HGG, and their respective treatment protocols with overall survival attributes. Additional research is warranted to ascertain how to maximize the potential efficacy of IT chemotherapy as a treatment option.