The latest medical research on Neurosurgery

With the previous experiences in performing laparoscopic for over a period of 15 years and da Vinci colorectal surgeries from 2010 to 2013, we star...

Cerebral autoregulation refers to the physiological mechanism that aims to maintain blood flow to the brain approximately constant when blood press...

Enhanced recovery after surgery programs reduce postoperative complications and length of stay after laparoscopic colorectal surgery, but are still...

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<5% of medulloblastoma patients survive following failure of contemporary radiation-based therapies. Understanding the molecular drivers of medulloblastoma relapse (rMB) will be essential to improve outcomes. Initial genome-wide investigations suggested significant genetic divergence of the relapsed disease.

We undertook large-scale integrated characterization of the molecular features of rMB - molecular subgroup, novel subtypes, copy number variation (CNV) and driver gene mutation. 119 rMBs were assessed in comparison with their paired diagnostic samples (n=107), alongside an independent reference cohort sampled at diagnosis (n=282). rMB events were investigated for association with outcome post-relapse in clinically-annotated patients (n=54).

Significant genetic evolution occurred over disease-course; 40% of putative rMB drivers emerged at relapse and differed significantly between molecular subgroups. MBSHH Non-infant displayed significantly more chromosomal CNVs at relapse (TP53 mutation-associated). Relapsed MBGroup4 demonstrated the greatest genetic divergence, enriched for targetable (e.g. CDK amplifications) and novel (e.g. USH2A mutations) events. Importantly, many hallmark features of medulloblastoma were stable over time; novel subtypes (>90% of tumors) and established genetic drivers (e.g. SHH/WNT/P53 mutations; 60% of rMB events) were maintained from diagnosis. Critically, acquired and maintained rMB events converged on targetable pathways which were significantly enriched at relapse (e.g. DNA damage-signaling) and specific events (e.g. 3p loss) predicted survival post-relapse.

rMB is defined by the emergence of novel events and pathways, in concert with selective maintenance of established genetic drivers. Together, these define the actionable genetic landscape of rMB and provide a basis for improved clinical management and development of stratified therapeutics, across disease-course.

Surgical education courses and certification tests require human evaluators to assess performance. Deep neural network (DNN) methods include techni...

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In patients with locally recurrent brain metastases (LRBMs), the role of (repeat) craniotomy is controversial. This study aimed to analyze long-term oncological outcomes in this heterogeneous population.

Craniotomies for LRBM were identified from a tertiary neuro-oncological institution. First, we assessed overall survival (OS) and intracranial control (ICC) stratified by molecular profile, prognostic indices, and multimodality treatment. Second, we compared LRBMs to propensity score-matched patients who underwent craniotomy for newly diagnosed brain metastases (NDBM).

Across 180 patients, median survival after LRBM resection was 13.8 months and varied by molecular profile, with >24 months survival in ALK/EGFR+ lung adenocarcinoma and HER2+ breast cancer. Furthermore, 102 patients (56.7%) experienced intracranial recurrence; median time to recurrence was 5.6 months. Compared to NDBMs (n = 898), LRBM patients were younger, more likely to harbor a targetable mutation and less likely to receive adjuvant radiation (p < 0.05). After 1:3 propensity matching stratified by molecular profile, LRBM patients generally experienced shorter OS (hazard ratio 1.67 and 1.36 for patients with or without a mutation, p < 0.05) but similar ICC (hazard ratio 1.11 in both groups, p > 0.20) compared to NDBM patients with similar baseline. Results across specific molecular subgroups suggested comparable effect directions of varying sizes.

In our data, patients with LRBMs undergoing craniotomy comprised a subgroup of brain metastasis patients with relatively favorable clinical characteristics and good survival outcomes. Recurrent status predicted shorter OS but did not impact ICC. Craniotomy could be considered in selected, prognostically favorable patients.

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While EEG is frequently reported as abnormal after CAR T cell therapy, its clinical significance remains unclear. We aim to systematically describe EEG features in a large single-center cohort and correlate them with clinical and radiological findings.

We retrospectively identified patients undergoing CAR T cell therapy who had continuous EEG. Neurotoxicity grades, detailed neurological symptoms, and brain MRI or FDG-PET were obtained. Correlation between clinical and radiological findings and EEG features was assessed.

In 81 patients with median neurotoxicity grade 3 (IQR 2-3), diffuse EEG background slowing was the most common finding and correlated with neurotoxicity severity (p <0.001). A total of 42 patients had rhythmic or periodic patterns, 16 of them within the ictal-interictal-continuum (IIC), 5 with clinical seizures, and 3 with only electrographic seizures. Focal EEG abnormalities, consisting of lateralized periodic discharges (LPD, n=1), lateralized rhythmic delta activity (LRDA, n=6), or focal slowing (n=19), were found in 22 patients. All patients with LRDA, LPD, and 10/19 patients with focal slowing had focal clinical symptoms concordant with these EEG abnormalities. In addition, these focal EEG changes often correlated with PET hypometabolism or MRI hypoperfusion, in absence of a structural lesion.

In adult patients experiencing neurotoxicity after CAR T cell infusion, EEG degree of background disorganization correlated with neurotoxicity severity. IIC patterns and focal EEG abnormalities are frequent and often correlate with focal clinical symptoms and with PET-hypometabolism/MRI-hypoperfusion, without structural lesion. The etiology of these findings remains to be elucidated.

Optimizing cerebral perfusion is key to rescuing salvageable ischemic brain tissue. Despite being an important determinant of cerebral perfusion, t...

Postoperative pediatric cerebellar mutism syndrome (pCMS), characterized mainly by delayed onset transient mutism is a poorly understood complicati...

While laser ablation has become an increasingly important tool in the neurosurgical oncologist's armamentarium, deep seated lesions, and those loca...

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Tumor-specific metabolic processes essential for cell survival are promising targets to potentially circumvent intratumoral heterogeneity, a major resistance factor in gliomas. Tumor cells preferentially using nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the salvage pathway for synthesis of NAD, a critical cofactor for diverse biological processes including cellular redox reactions, energy metabolism and biosynthesis. NAMPT is overexpressed in most malignancies, including gliomas, and can serve as a tumor-specific target.

Effects of pharmacological inhibition of NAMPT on cellular oxygen consumption rate, extracellular acidification, mitochondrial respiration, cell proliferation, invasion and survival were assessed through in vitro and ex vivo studies on genetically heterogeneous glioma cell lines, glioma stem-like cells (GSCs) and mouse and human ex vivo organotypic glioma slice culture models.

Pharmacological inhibition of the NAD salvage biosynthesis pathway using a highly specific inhibitor, KPT-9274, resulted in reduction of NAD levels and related downstream metabolites, inhibited proliferation, and induced apoptosis in vitro in cell lines and ex vivo in human glioma tissue. These effects were mediated by mitochondrial dysfunction, DNA damage and increased oxidative stress leading to apoptosis in GSCs independent of genotype, IDH status or MGMT promoter methylation status. Conversely, NAMPT inhibition had minimal in vitro effects on normal human astrocytes (NHA) and no apparent in vivo toxicity in non-tumor-bearing mice.

Pharmacological NAMPT inhibition by KPT9274 potently targeted genetically heterogeneous gliomas by activating mitochondrial dysfunction. Our preclinical results provide a rationale for targeting the NAMPT-dependent alternative NAD biosynthesis pathway as a novel clinical strategy against gliomas.

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Gliomas are the most common primary brain tumors and are universally fatal. Mutations in the isocitrate dehydrogenase genes (IDH1 and IDH2) define a distinct glioma subtype associated with an immunosuppressive tumor microenvironment. Mechanisms underlying systemic immunosuppression in IDH mutant (mutIDH) gliomas are largely unknown. Here, we define genotype-specific local and systemic tumor immunomodulatory functions of tumor-derived glioma exosomes (TEX).

TEX produced by human and murine wildtype and mutant IDH glioma cells (wtIDH and mutIDH, respectively) were isolated by size exclusion chromatography (SEC). TEX morphology, size, quantity, molecular profiles and biodistribution were characterized. TEX were injected into naive and tumor-bearing mice, and the local and systemic immune microenvironment composition was characterized.

Using in vitro and in vivo glioma models, we show that mutIDH TEX are more numerous, possess distinct morphological features and are more immunosuppressive than wtIDH TEX. mutIDH TEX cargo mimics their parental cells, and induces systemic immune suppression in naive and tumor-bearing mice. TEX derived from mutIDH gliomas and injected into wtIDH tumor-bearing mice reduce tumor-infiltrating effector lymphocytes, dendritic cells and macrophages, and increase circulating monocytes. Astonishingly, mutIDH TEX injected into brain tumor-bearing syngeneic mice accelerate tumor growth and increase mortality compared with wtIDH TEX.

Targeting of mutIDH TEX represents a novel therapeutic approach in gliomas.

The latest medical research on Neurosurgery

Colorectal cancer surgery: by Cambridge Medical Robotics Versius Surgical Robot System-a single-institution study. Our experience.

The INfoMATAS project: Methods for assessing cerebral autoregulation in stroke.

Implementation of an enhanced recovery after surgery program with robotic surgery in high-risk patients obtains optimal results after colorectal resections.

Emergence and maintenance of actionable genetic drivers at medulloblastoma relapse.

Deep neural networks are effective tools for assessing performance during surgical training.

Neurosurgical resection for locally recurrent brain metastasis.

EEG findings in CART T associated neurotoxicity: clinical and radiological correlations.

Integrative cerebral blood flow regulation in ischemic stroke.

A CBF decrease in the left supplementary motor areas: New insight into postoperative pediatric cerebellar mutism syndrome using arterial spin labeling perfusion MRI.

Robotic guidance platform for laser interstitial thermal ablation and stereotactic needle biopsies: a single center experience.

Inhibition of nicotinamide phosphoribosyltransferase, the rate-limiting enzyme of the nicotinamide adenine dinucleotide salvage pathway, to target glioma heterogeneity through mitochondrial oxidative stress.

Characterization of systemic immunosuppression by IDH mutant glioma small extracellular vesicles.

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