Noah Brian Drewes

Background/Objectives: Sphenoid wing meningiomas are skull base meningiomas whose resection is often complicated by involvement of the optic canal, cavernous sinus, orbit, and internal carotid artery. However, prior studies use heterogeneous classification systems that may conflate tumor site of origin with patterns of extension, making comparisons by location difficult. We evaluated sphenoid wing meningiomas using an origin-based classification to assess differences in extent of resection according to tumor origin and cavernous sinus invasion. Methods: We retrospectively reviewed 39 patients who underwent resection of histopathologically confirmed sphenoid wing meningiomas at a single center between 2010 and 2024. Tumors were classified as medial or lateral according to their dominant dural attachment on MRI. An exploratory stratified analysis compared GTR rates between medial and lateral tumors according to cavernous sinus invasion status. Results: GTR was achieved in 4 of 15 medial tumors (26.7%) and 18 of 24 lateral tumors (75.0%; p = 0.007). Cavernous sinus invasion occurred in 9 of 15 medial and 2 of 24 lateral tumors. Among tumors without cavernous sinus invasion, GTR was achieved in 4 of 6 medial and 18 of 22 lateral tumors (66.7% vs. 81.8%; p = 0.58). All six events were progression after STR, with no recurrence after GTR. The 1-year recurrence-free survival after GTR and progression-free survival after less-than-GTR were 100% and 73.9%, respectively (p = 0.005). Conclusions: Medial sphenoid wing meningiomas more often involve critical skull base structures and are less likely to undergo GTR. The smaller observed difference among non-invaded tumors is hypothesis-generating because this subgroup only comprised six medial tumors.

The mammalian target of rapamycin (mTOR) signaling pathway is often aberrantly activated in cancers, including colorectal cancers. Long non-coding RNA (lncRNA) is a subset of non-coding transcripts with a minimum length of 200 nucleotides that can regulate multiple biological processes related to development, differentiation, metabolism, and carcinogenesis. By screening the lncRNAs required for short-chain fatty acids to suppress mTOR signaling, we have identified rhabdomyosarcoma 2-associated transcript (lncRNA RMST) as a novel regulator of mTOR and autophagy in colorectal cancer cells. Among its various transcript variants, linear RMST from exon 1 to exon 9 is sufficient to suppress mTOR signaling. Herein, we discuss the regulation of RMST gene expression, its expression patterns in cancers, and its clinical relevance. We also discuss the mechanism for RMST to suppress mTOR signaling and its possible abrogation during tumor growth and progression.

Background/Objectives: Preoperative antithrombotic therapy is common among patients undergoing subdural hematoma (SDH) evacuation. However, the association with postoperative outcomes remains uncertain. We evaluated this potential association using a multicenter electronic health record cohort and a single-center cohort. Methods: We performed a retrospective cohort study using TriNetX, a multicenter electronic health record (EHR) database, and a single-center cohort. TriNetX was used to identify adults undergoing evacuation of nontraumatic subdural hematoma between 2005 and 2025. The exposed cohort was defined as documented oral anticoagulant or antiplatelet exposure within 7 days before surgery, after which patients were propensity-score matched 1:1. The single-center cohort included surgically treated subdural hematoma patients with clinical, radiographic, laboratory, and operative data. Postoperative outcomes included 30-day mortality, short-term thrombotic complications, and 90-day repeat subdural hematoma surgery. Results: In TriNetX, 15,651 eligible patients were identified. Matched cohorts included 1455 exposed and 1455 unexposed patients. Preoperative antithrombotic exposure was associated with higher 90-day repeat surgery (9.7% vs. 6.5%; hazard ratio [HR] 1.52; p = 0.001), whereas 30-day mortality and 14-day thrombotic complications did not differ significantly. The single-center cohort included 164 surgically treated patients, including 103 exposed and 61 unexposed patients. The reoperation association was not reproduced. However, exposed patients had higher unadjusted 30-day and overall mortality that attenuated after multivariable Cox adjustment. Conclusions: Preoperative antithrombotic exposure was associated with repeat surgery in the TriNetX cohort but not in the single-center cohort. Together, these findings suggest that antithrombotic exposure may identify a medically complex surgical SDH population requiring individualized postoperative surveillance.

Background: Glioblastoma (GBM) adapts to therapy through coordinated malignant-cell and microenvironmental responses, but the mechanisms linking treatment-associated inflammation to tumor-cell phenotypic plasticity remain poorly defined. Here, we investigated whether preoperative temozolomide exposure is associated with inflammatory-repair remodeling and a ROCK-linked therapeutic vulnerability in recurrent GBM using a window-of-opportunity clinical trial cohort. Methods: We integrated patient-resolved single-cell transcriptomics, spatial RNA profiling and multiplex protein imaging with experimental perturbations and orthotopic glioblastoma models. In the presurgical window-of-opportunity subgroup of NCT05236036 , four patients with recurrent glioblastoma received additional preoperative temozolomide (TMZ; 150 mg/m2/day for 5 days) before resection and were compared with three recurrent comparators who did not receive additional preoperative TMZ. Results: Across seven tumors, malignant-cell inflammatory activity covaried with integrin-binding and wound-healing programs (median partial ρ = 0.45 and 0.42, respectively). Tumors exposed to preoperative TMZ showed enrichment of inflammatory, chemokine, adhesion and wound-healing programs (GSEA q < 0.05), with the direction of enrichment preserved in all leave-one-patient-out analyses. In two tumors exposed to preoperative TMZ, CXCL12 localized to vascular territories, whereas chemokine and wound-repair programs increased near injury-reference regions. Across seven specimens analyzed by multiplex protein imaging, MYL9 abundance correlated with local CXCL12 (ρ = 0.61), phosphorylated MYPT1 (ρ = 0.48) and nuclear phosphorylated STAT3 (ρ = 0.45), with positive associations in every specimen. Experimentally, TMZ increased CXCL8 and reactive-state markers and enhanced subsequent scratch closure, while CXCL8 and CXCL12 increased MLC2 phosphorylation. Fasudil attenuated TNF-NF-κB, inflammatory-response and IFN-γ-response programs in TMZ-treated cells and reduced scratch closure and p-MLC2 in complementary assays. Across three orthotopic models, fasudil plus TMZ prolonged survival versus TMZ alone (model-stratified HR, 0.21; 95% CI, 0.07-0.61; P = 0.001). Conclusions: These findings link treatment-associated inflammatory-repair programs with cytoskeletal remodeling and support further translational evaluation of fasudil plus TMZ in glioblastoma.

Neuronavigation, initially developed for cranial applications, has laid the groundwork for innovation in spine surgery. Recent advances in artificial intelligence (AI) and machine learning (ML) have elevated navigation techniques by improving image acquisition, registration and intraoperative tracking. Contemporary ML-driven neuronavigation systems now demonstrate higher pedicle screw placement accuracy and lower complication rates than traditional fluoroscopy- or stereotactic-guided approaches, while also reducing radiation exposure and surgeon fatigue. These frameworks frequently leverage architectures such as convolutional neural networks (CNNs), recurrent neural networks (RNNs), and generative adversarial networks (GANs) to enhance segmentation, anatomical mapping and real-time image reconstruction. Integrated into both standalone navigation systems and robot-assisted workflows, these algorithms support dynamic intraoperative adaptation to patient-specific anatomy even with complex tissue manipulation and instrumentation. Although fully autonomous execution is not yet realized, current FDA-cleared systems emphasize surgeon-directed control with progressive elements of computational assistance; future iterations of AI/ML-enabled technologies promise to incorporate greater levels of autonomy. This chapter highlights the transformative potential of intelligent navigation in spine surgery, situating algorithmic principles within clinical context to illustrate how AI/ML-based navigation can shape the future of neurosurgical precision medicine.

Purpose: Whether gross total resection (GTR) remains associated with survival among MGMT-methylated IDH-wildtype glioblastoma patients receiving chemoradiation remains uncertain. We evaluated whether GTR versus less-than-GTR (< GTR) was associated with overall survival across MGMT promoter methylation and chemoradiation strata. Methods: We retrospectively reviewed 261 patients undergoing biopsy or resection for newly diagnosed IDH-wildtype glioblastoma at a single institution from 2010 to 2024. Extent of resection was dichotomized as GTR versus < GTR, and chemoradiation was coded as receipt of postoperative radiation and temozolomide. Overall survival was assessed using Kaplan-Meier analysis and multivariable Cox models with prespecified EOR × MGMT × chemoradiation interaction testing, adjusted for age, KPS, tumor location, and mFI-5. Results: GTR was associated with longer overall survival than < GTR in the overall cohort and within all four MGMT × chemoradiation strata. MGMT-methylated patients receiving chemoradiation had a median overall survival of 17.02 months after GTR versus 10.65 months after < GTR (log-rank p = 0.001), and the model-derived adjusted hazard ratio for < GTR versus GTR was 2.12 (95% CI 1.27–3.54; p = 0.004). The three-way EOR × MGMT × chemoradiation interaction was not significant (likelihood-ratio p = 0.309). In a 6-week sensitivity analysis, all survival associations remained, but EOR × chemoradiation was no longer significant. Conclusion: GTR was associated with longer survival across all MGMT and chemoradiation-defined subgroups, including MGMT-methylated patients receiving chemoradiation. These findings are consistent with maximal safe resection when feasible but should be interpreted cautiously because of small subgroups as well as treatment-selection and immortal-time biases.

Background: Delta large-channel endoscopic decompression is an emerging, minimally invasive approach for lumbar degenerative disease, but its comparative effectiveness and perioperative performance have not been comprehensively synthesized. We performed a systematic review and meta-analysis to evaluate clinical, functional, and safety outcomes of Delta large-channel endoscopy relative to established decompression techniques. Methods: PubMed, Embase, and Scopus were searched from database inception through July 2025 (PROSPERO #CRD420251107750). Peer-reviewed English-language studies reporting extractable outcomes after Delta large-channel endoscopic surgery in adults were included. Random-effects meta-analyses were used for pooled comparisons. Results: Nine studies met the inclusion criteria, comprising 737 patients overall, including 379 treated with Delta large-channel endoscopy and 358 treated with comparator procedures. Reported outcome assessment generally ranged from 1 week to 12 months postoperatively, or variable latest follow-up timepoints, and mean follow-up was inconsistently reported. All studies originated in China and included five retrospective cohorts, two randomized controlled trials, one prospective cohort, and one case series. The pooled mean operative time for Delta procedures was 88.28 min (95% CI, 79.24–97.31), pooled mean intraoperative blood loss was 24.58 mL (95% CI, 11.14–38.02), and pooled mean hospital stay was 4.59 days (95% CI, 2.87–6.31). Compared with microscopic, endoscopic, and open techniques, Delta large-channel endoscopy showed no statistically significant differences in operative time (MD = 6.95 min, 95% CI: −11.51–25.40 min; p = 0.4037), intraoperative blood loss (MD, −40.62 mL; 95% CI, −83.68–2.44; p = 0.0598), 3-month ODI change from baseline (MD, 1.26; 95% CI, −2.17–4.69; p = 0.3661), or complication rates (OR, 0.67; 95% CI, 0.40–1.12; p = 0.1094). Delta procedures were associated with shorter hospital stay (MD, −1.69 days; 95% CI, −2.83 to −0.56; p = 0.0122) and marginally greater improvement in six-month VAS low back pain change from baseline (MD, 0.28; 95% CI, 0.26–0.29; p = 0.0002), though clinically insignificant. The pooled complication rate for Delta procedures was 6.0% (95% CI, 4–10%) and reported rates of excellent or good MacNab outcomes ranged from 80 to 93% across Delta cohorts. Conclusions: Delta large-channel endoscopy may provide clinical and functional outcomes comparable to established decompression techniques, with similar safety and potential perioperative benefits, including shorter hospitalization. However, these findings are based on limited, low-certainty evidence with high heterogeneity and should be interpreted as exploratory rather than definitive. Additional multicenter studies with longer follow-up, broader geographic representation, and higher methodological quality are necessary before definitive conclusions regarding comparative effectiveness can be established.

Mammalian target of rapamycin (mTOR) signaling pathway is often aberrantly activated in cancers including colorectal cancers. Long non-coding RNA (lncRNA) is a subset of non-coding transcripts with a minimum length of 200 nucleotides that can regulate multiple biological processes related to development, differentiation, metabolism, and carcinogenesis. Through screening of lncRNAs required for short chain fatty acids to suppress mTOR signaling, we have identified rhabdomyosarcoma 2 associated transcript (lncRNA RMST) as a novel regulator of mTOR and autophagy in colorectal cancer cells. Among its various transcript variants, linear RMST from exon 1 to exon 9 is sufficient to suppress mTOR signaling. Deletion of a segment of RMST gene between exon 5 and exon 6 enhances mTOR signaling. Herein we discuss the regulation of RMST gene expression, its expression patterns in cancers, and its clinical relevance. We also discuss the mechanism for RMST to suppress mTOR signaling and its possible abrogation during tumor growth and progression.

Undifferentiated pleomorphic sarcoma (UPS) is a rare and aggressive soft tissue tumor of unknown histogenesis. UPS most often arises in the extremities or trunk, where wide surgical excision is feasible. Rarely, UPS involves the intracranial space, where critical structures may inhibit complete resection. Given its rarity and historical misclassification as malignant fibrous histiocytoma (MFH), knowledge of intracranial UPS is limited, and there are no clear treatment guidelines. We systematically reviewed all available cases of intracranial UPS to consolidate existing literature and assess prognosis and management considerations. A systematic review was conducted according to PRISMA guidelines. PubMed and Embase were searched for reports of intracranial UPS or storiform-pleomorphic MFH. Eligible studies included at least one histologically confirmed case treated with surgery, chemotherapy, or radiotherapy and reported outcomes. Data on demographics, tumor location, treatment, follow-up, and survival were extracted. Event-free survival (EFS) and overall survival (OS) were analyzed by treatment modality, age, sex, and tumor location using Kaplan-Meier and log-rank tests. From 801 records, 40 studies with 48 patients were included. The median age was 45 years, and 50% were female. 15% had prior radiotherapy. Most tumors were extra-axial (45%) and nearly all patients underwent surgery, with 82.1% achieving gross total resection. Median EFS and OS were 18 and 24 months, respectively. No survival differences were seen by treatment modality, age, or sex. Overall survival was longer for extra-axial tumors compared to intra-axial or skull base tumors ( p = 0.016). Intracranial UPS is a rare and aggressive tumor, with worse prognosis compared to those that are extracranial. Among factors that we evaluated, extra-axial location was the strongest positive prognostic factor. Surgical resection with adjuvant chemoradiation showed the longest median survival. Ongoing case reports are required to refine management guidelines and improve patient outcomes.