Chaichana, Kaisorn L.

Abstract Background Glioblastoma (GBM) remains a devastating cancer with limited treatment options, largely due to its heterogeneity. While supramaximal resection has recently provided survival benefits, therapeutic profiling of different tumor compartments, particularly its infiltrative edge remains largely unexplored. Methods Here, we leveraged magnetic resonance imaging (MRI)-guided multi-sampling, collecting 2 cores and 2 margins per case, to query GBM heterogeneity. Whole-exome and RNA-seq with drug testing in two patient-derived 3D models were used to reveal similarities and differences in genomic and transcriptomic makeups, cellular compositions, and drug responses across cores and margins. Bioinformatics interrogations further identified response biomarkers. Results Mutation analysis showed that oncogenes exhibited a higher degree of spatial heterogeneity than tumor suppressor genes, regardless of MRI status. While the mesenchymal transcriptional subtype with extracellular matrix remodeling, stress response, and immune programs were preferentially enriched in enhancing cores, proneural tumors with neurological processes favored non-enhancing margins. Using a 15-drug GBM-targeted panel, ERK (ulixertinib) and PI3K pathway (paxalisib, CC-115) inhibitors showed preferential efficacy in enhancing cores and non-enhancing margins, respectively. The anti-apoptosis, pan-Bcl2 agent navitoclax and the epigenetic drug trotabresib represented the most effective, tumor-wide monotherapies. Importantly, drug combinations generally outperformed single agents across all regions. Conclusions This work demonstrates the regional heterogeneity of therapeutic vulnerabilities in GBM ex vivo, showing various drugs with tumor-wide or MRI-enhancement informed activity. These findings offer preclinical bases of numerous monotherapies and drug combinations for future clinical trial design.

Objectives: Despite advantages of titanium mesh, hardware exposure affects up to 25% of cases reported in the literature. We aim to identify risk factors associated with titanium mesh exposure following cranioplasty and characterize early wound changes that may signal impending hardware exposure. Methods: A review of 34 patients who underwent titanium mesh cranioplasty between 2015 and 2025 was performed. Seventeen patients with hardware exposure were matched 1:1 with 17 controls. Data on demographics, comorbidities, operative details, and postoperative complications were collected. Statistical analysis included Fisher exact test and t tests, with significance set at P <0.05. Results: Significant risk factors for titanium hardware exposure included a history of metal allergy and reconstruction with advancement flaps. Significant protective factors included patients undergoing postoperative radiation therapy and reconstruction with rotational flaps. Conclusions: Titanium mesh exposure risk increases with metal allergy history, postoperative radiotherapy, and use of advancement flaps for reconstruction. Recognition of early wound changes is crucial for timely intervention. These findings support individualized surgical planning and highlight the need for close postoperative monitoring to reduce complications and improve reconstructive outcomes.

Purpose: Subcortical functional brain mapping is a valuable technique, especially involving lesions within or near white matter tracts. Motor and language deficits caused by intraoperative damage to these subcortical fibers are associated with worse outcomes. However, there are variable approaches to performing subcortical functional brain mapping. This systematic review was performed to better understand indications and optimal stimulation parameters. Methods: A systematic review was performed by PRISMA guidelines, using PubMed, Scopus, and Medline databases. Search dates ranged from inception to November 30th, 2024. Studies included adults who underwent subcortical electrical stimulation for functional brain mapping. Results: A total of 55 articles (249 patients, mean age 44.8 years, 114 female) were included. The most common pathology was brain tumor (96.3%), primarily gliomas and metastases, and 24.4% of all cases had a history of epilepsy. The most frequently mapped white matter tracts were the arcuate fasciculus, corticospinal/pyramidal tract, and inferior fronto-occipital fasciculus, involving motor, language, and cognitive functions. Bipolar stimulation (50–60 Hz, 0.5–1 millisecond, 1–10 mA) was preferred over monopolar stimulation. Among 147 patients with outcome data, 89.1% did not suffer permanent adverse outcomes including neurologic deficits, although long-term outcomes were inconsistently reported. Conclusions: The methodologic variability of subcortical functional brain mapping and lack of long-term follow-up reported limits determination of optimal parameter selection for electrical stimulation although common trends are reported. Functional brain mapping approaches may be guided by the tract and network involved. Further studies are needed to develop a standardized approach and more definitive guideline to its performance.

OBJECTIVE The aim of this study was to compare 3 electrode designs—a novel 22-contact circular grid, standard 6-contact strip, and high-density (HD) grid between 32 and 64 contacts—for the detection of epileptiform activity during awake craniotomy. METHODS This study included patients who underwent functional brain mapping with and without direct electrical stimulation during awake craniotomy. Demographic, clinical, and electrocorticography (ECoG) data were collected. RESULTS A total of 194 patients were included, with 264 instances of electrode use: 113 circular grid, 96 strip electrode, and 55 HD grid. The HD grid (15%) was used less to record ECoG during direct electrical stimulation than the circular grid (80%, p < 0.001) and strip electrodes (69%, p < 0.001). Sporadic interictal epileptiform activity was better detected with circular (45%, p < 0.001) and HD (40%, p = 0.006) grids compared with strip electrodes (16%). Spontaneous seizures were recorded more frequently with the circular grid (16%, p = 0.018) compared with the strip electrode (9.4%) and HD grid (1.8%). Afterdischarges were more frequently detected by the circular grid (69%, p = 0.031) and with circular and HD grids (combined) compared with strip electrodes (67% vs 48%, p = 0.024), at lower median intensity (3 mA vs 5 mA, p < 0.001). Multivariable analyses demonstrated circular grids (p < 0.001) to be more sensitive in detecting spontaneous epileptiform activity than strip and HD grid electrodes, and grids (circular and HD) to be better in recording stimulus-induced epileptiform activity (p = 0.01). CONCLUSIONS This study demonstrates a higher rate of detection of epileptiform activity with circular and standard grids when compared with strip electrodes. The standard HD grid was used less during electrical stimulation, demonstrating the importance of both the number of contacts and design array when considering optimal conditions for ECoG and functional brain mapping.

Abstract This study aimed to investigate the association between objective and subjective olfactory assessments in patients with recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection undergoing endoscopic endonasal skull base surgery (EESBS). Retrospective cohort study. Academic medical center. Adult patients with and without recent SARS-CoV-2 infection who underwent EESBS for sellar and parasellar lesion resection between 2020 and 2024 at the Mayo Clinic in Florida, Jacksonville, FL. Pre- and postoperative self-reported olfactory dysfunction and University of Pennsylvania Smell Identification Test (UPSIT) scores were collected. Patients with recent SARS-CoV-2 infection had a similar rate of discrepant preoperative objective olfactory assessments (38.2%, 26/68) compared with SARS-CoV-2-negative patients (39.9%, 127/318). SARS-CoV-2-positive patients were twice as likely to report postoperative subjective olfactory dysfunction (46.2%, 12/26) compared with SARS-CoV-2-negative patients (18.1%, 23/127, p = 0.002). There was no statistically significant difference in the mean preoperative (p = 0.162) or postoperative (p = 0.724) UPSIT scores between both groups. Patients with recent SARS-CoV-2 infection and discrepant preoperative objective olfactory assessments were twice as likely to self-report olfactory dysfunction following EESBS compared with SARS-CoV-2-negative controls. This increase in self-reported olfactory dysfunction was not accompanied by changes in objective psychophysical testing. These findings suggest that SARS-CoV-2 infection may impact subjective olfactory recovery following EESBS.