Socioeconomic Disparities Affecting the Presentation and Outcomes in Pediatric Subdural Empyema Patients.

BACKGROUND AND OBJECTIVES: Pediatric subdural empyemas (SDE) carry significant morbidity and mortality, and prompt diagnosis and treatment are essential to ensure optimal outcomes. Nonclinical factors affect presentation, time to diagnosis, and outcomes in several neurosurgical conditions and are potential causes of delay in presentation and treatment for patients with SDE. To evaluate whether socioeconomic status, race, and insurance status affect presentation, time to diagnosis, and outcomes for children with subdural empyema. METHODS: We conducted a retrospective cohort study with patients diagnosed with SDE between 2005 and 2020 at our institution. Information regarding demographics (age, sex, zip code, insurance status, race/ethnicity) and presentation (symptoms, number of prior visits, duration of symptoms) was collected. Outcome measures included mortality, postoperative complications, length of stay, and discharge disposition. RESULTS: 42 patients were diagnosed with SDE with a mean age of 9.5 years. Most (85.7%) (n = 36) were male ( P = .0004), and a majority, 28/42 (66.7%), were African American ( P < .0001). There was no significant difference in socioeconomic status based on zip codes, although a significantly higher number of patients were on public insurance ( P = .015). African American patients had a significantly longer duration of symptoms than their Caucasian counterparts (8.4 days vs 1.8 days P = .0316). In total, 41/42 underwent surgery for the SDE, most within 24 hours of initial neurosurgical evaluation. There were no significant differences in the average length of stay. The average length of antibiotic duration was 57.2 days and was similar for all patients. There were no significant differences in discharge disposition based on any of the factors identified with most of the patients (52.4%) being discharged to home. There was 1 mortality (2.4%). CONCLUSION: Although there were no differences in outcomes based on nonclinical factors, African American men on public insurance bear a disproportionately high burden of SDE. Further investigation into the causes of this is warranted.

Targeting protein arginine methyltransferase 5 sensitizes glioblastoma to trametinib.

Background: The prognosis of glioblastoma (GBM) remains dismal because therapeutic approaches have limited effectiveness. A new targeted treatment using MEK inhibitors, including trametinib, has been proposed to improve GBM therapy. Trametinib had a promising preclinical effect against several cancers, but its adaptive treatment resistance precluded its clinical translation in GBM. Previously, we have demonstrated that protein arginine methyltransferase 5 (PRMT5) is upregulated in GBM and its inhibition promotes apoptosis and senescence in differentiated and stem-like tumor cells, respectively. We tested whether inhibition of PRMT5 can enhance the efficacy of trametinib against GBM. Methods: Patient-derived primary GBM neurospheres (GBMNS) with transient PRMT5 knockdown were treated with trametinib and cell viability, proliferation, cell cycle progression, ELISA, and western blot were analyzed. In vivo, NSG mice were intracranially implanted with PRMT5-intact and -depleted GBMNS, treated with trametinib by daily oral gavage, and observed for tumor progression and mice survival rate. Results: PRMT5 depletion enhanced trametinib-induced cytotoxicity in GBMNS. PRMT5 knockdown significantly decreased trametinib-induced AKT and ERBB3 escape pathways. However, ERBB3 inhibition alone failed to block trametinib-induced AKT activity suggesting that the enhanced antitumor effect imparted by PRMT5 knockdown in trametinib-treated GBMNS resulted from AKT inhibition and not ERBB3 inhibition. In orthotopic murine xenograft models, PRMT5-depletion extended the survival of tumor-bearing mice, and combination with trametinib further increased survival. Conclusion: Combined PRMT5/MEK inhibition synergistically inhibited GBM in animal models and is a promising strategy for GBM therapy.

Minimally invasive surgery for intradural extramedullary spinal cord pathologies: A case series and technical note.

BACKGROUND: Intradural spinal cord pathologies have traditionally been managed with open surgical procedures and require the completion of a durotomy. Minimally invasive techniques are emerging as alternative procedures with the goal of reducing complications, but often require specialized equipment with additional training. METHODS: We conduct a single institution retrospective review from 2016 to 2019 of patients undergoing minimally invasive durotomy closure for intradural extramedullary pathologies using a novel technique that utilizes standard operating room equipment. This cohort is compared to a cohort of patients treated with a traditional open approach. RESULTS: Patients treated with minimally invasive surgery (MIS) had no statistically significant differences in baseline characteristics compared to patients treated with open procedures. Patients treated with MIS had decreases in complication rates, estimated blood loss, and length of stay in the hospital compared to the patients treated with open procedures, but these differences did not reach levels of statistical significance. CONCLUSIONS: Our novel MIS technique for intradural extramedullary pathologies appears to be safe and effective in creating a watertight dural closure using standard operating room equipment, while avoiding the costs and training associated with specialized equipment and possibly improving surgical outcome measures when compared to open approaches.

Middle meningeal artery embolization with subdural evacuating port system for primary management of chronic subdural hematomas.

Optimal treatment for chronic subdural hematomas remains controversial and perioperative risks and comorbidities may affect management strategies. Minimally invasive procedures are emerging as alternatives to the standard operative treatments. We evaluate our experience with middle meningeal artery (MMA) embolization combined with Subdural Evacuating Port System (SEPS) placement as a first-line treatment for patients with cSDH. A single institution retrospective review was performed of all patients undergoing intervention. Patients were stratified by treatment with MMA embolization and SEPS placement, MMA embolization and surgery, SEPS placement only, and surgery only for cSDH from 2017 to 2020, and cohorts were compared against each other. Patients treated with MMA/SEPS were more likely to be older, be on anticoagulation, have significant comorbidities, have shorter length of stay, and less likely to have symptomatic recurrence compared to SEPS only cohort. Thus, MMA/SEPS appears to be a safe and equally effective minimally invasive treatment for cSDH patients with significant comorbidities who are poor surgical candidates.