Racial and socioeconomic disparities in glioblastoma outcomes: A single-center, retrospective cohort study.

BACKGROUND: Glioblastoma (GBM) is the most common malignant primary brain tumor. Emerging reports have suggested that racial and socioeconomic disparities influence the outcomes of patients with GBM. No studies to date have investigated these disparities controlling for isocitrate dehydrogenase (IDH) mutation and O-6-methylguanine-DNA methyltransferase (MGMT) status. METHODS: Adult patients with GBM were retrospectively reviewed at a single institution from 2008 to 2019. Univariable and multivariable complete survival analyses were performed. A Cox proportional hazards model was used to assess the effect of race and socioeconomic status controlling for a priori selected variables with known relevance to survival. RESULTS: In total, 995 patients met inclusion criteria. Of these, 117 patients (11.7%) were African American (AA). The median overall survival for the entire cohort was 14.23 months. In the multivariable model, AA patients had better survival compared with White patients (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.2-0.69). The observed survival difference was significant in both a complete case analysis model and a multiple imputations model accounting for missing molecular data and controlling for treatment and socioeconomic status. AA patients with low income (HR, 2.17; 95% CI, 1.04-4.50), public insurance (HR, 2.25; 95% CI, 1.04-4.87), or no insurance (HR, 15.63; 95% CI, 2.72-89.67) had worse survival compared with White patients with low income, public insurance, or no insurance, respectively. CONCLUSIONS: Significant racial and socioeconomic disparities were identified after controlling for treatment, GBM genetic profile, and other variables associated with survival. Overall, AA patients demonstrated better survival. These findings may suggest the possibility of a protective genetic advantage in AA patients. PLAIN LANGUAGE SUMMARY: To best personalize treatment for and understand the causes of glioblastoma, racial and socioeconomic influences must be examined. The authors report their experience at the O'Neal Comprehensive Cancer Center in the deep south. In this report, contemporary molecular diagnostic data are included. The authors conclude that there are significant racial and socioeconomic disparities that influence glioblastoma outcome and that African American patients do better.

Targeting glioma-initiating cells via the tyrosine metabolic pathway.

OBJECTIVE: Despite an aggressive multimodal therapeutic regimen, glioblastoma (GBM) continues to portend a grave prognosis, which is driven in part by tumor heterogeneity at both the molecular and cellular levels. Accordingly, herein the authors sought to identify metabolic differences between GBM tumor core cells and edge cells and, in so doing, elucidate novel actionable therapeutic targets centered on tumor metabolism. METHODS: Comprehensive metabolic analyses were performed on 20 high-grade glioma (HGG) tissues and 30 glioma-initiating cell (GIC) sphere culture models. The results of the metabolic analyses were combined with the Ivy GBM data set. Differences in tumor metabolism between GBM tumor tissue derived from within the contrast-enhancing region (i.e., tumor core) and that from the peritumoral brain lesions (i.e., tumor edge) were sought and explored. Such changes were ultimately confirmed at the protein level via immunohistochemistry. RESULTS: Metabolic heterogeneity in both HGG tumor tissues and GBM sphere culture models was identified, and analyses suggested that tyrosine metabolism may serve as a possible therapeutic target in GBM, particularly in the tumor core. Furthermore, activation of the enzyme tyrosine aminotransferase (TAT) within the tyrosine metabolic pathway influenced the noted therapeutic resistance of the GBM core. CONCLUSIONS: Selective inhibition of the tyrosine metabolism pathway may prove highly beneficial as an adjuvant to multimodal GBM therapies.

Helicobacter pylori antimicrobial resistance and antibiotic consumption in the low-resource Central America setting.

BACKGROUND: Antimicrobial resistance is a global public health problem, particularly in low- and middle-income countries (LMICs), where antibiotics are often obtained without a prescription. H. pylori antimicrobial resistance patterns are informative for patient care and gastric cancer prevention programs, have been shown to correlate with general antimicrobial consumption, and may guide antimicrobial stewardship programs in LMICs. We report H. pylori resistance and antimicrobial utilization patterns for western Honduras, representative of rural Central America. METHODS: In the context of the western Honduras gastric cancer epidemiology initiative, gastric biopsies from 189 patients were studied for culture and resistance patterns. Antimicrobial utilization was investigated for common H. pylori treatment regimens from regional public (7 antimicrobials) and national private (4 antimicrobials) data, analyzed in accordance with WHO anatomical therapeutic chemical defined daily doses (DDD) method and expressed as DDD/1000 inhabitants per day (DID) and per year (DIY). RESULTS: H. pylori was successfully cultured from 116 patients (56% males, mean age: 54), and nearly all strains were cagA+ and vacAs1m1+ positive (99% and 90.4%, respectively). Unexpectedly, high resistance was noted for levofloxacin (20.9%) and amoxicillin (10.7%), while metronidazole (67.9%) and clarithromycin (11.2%) were similar to data from Latin America. Significant associations with age, gender, or histology were not noted, with the exception of levofloxacin (28%, P = 0.01) in those with histology limited to non-atrophic gastritis. Total antimicrobial usage in western Honduras of amoxicillin (17.3 DID) and the quinolones had the highest relative utilizations compared with other representative nations. CONCLUSIONS: We observed significant H. pylori resistance to amoxicillin and levofloxacin in the context of high community antimicrobial utilization. This has implications in Central America for H. pylori treatment guidelines as well as antimicrobial stewardship programs.

Reducing inequities in preventable neural tube defects: the critical and underutilized role of neurosurgical advocacy for folate fortification.

Neural tube defects (NTDs) are one of the greatest causes of childhood mortality and disability-adjusted life years worldwide. Global prevalence at birth is approximately 18.6 per 10,000 live births, with more than 300,000 infants with NTDs born every year. Substantial strides have been made in understanding the genetics, pathophysiology, and surgical treatment of NTDs, yet the natural history remains one of high morbidity and profound impairment of quality of life. Direct and indirect costs of care are enormous, which ensures profound inequities and disparities in the burden of disease in countries of low and moderate resources. All indices of disease burden are higher for NTDs in developing countries. The great tragedy is that the majority of NTDs can be prevented with folate fortification of commercially produced food. Unequivocal evidence of the effectiveness of folate to reduce the incidence of NTDs has existed for more than 25 years. Yet, the most comprehensive surveys of effectiveness of implementation strategies show that more than 100 countries fail to fortify, and consequently only 13% of folate-preventable spina bifida is actually prevented. Neurosurgeons harbor a disproportionate, central, and fundamental role in the management of NTDs and enjoy high standing in society. No organized group in medicine can speak as authoritatively or convincingly. As a result, neurosurgeons and organized neurosurgery harbor disproportionate potential to advocate for more comprehensive folate fortification, and thereby prevent the most common and severe birth defect to impact the human nervous system. Assertive, proactive, informed advocacy for folate fortification should be a central and integral part of the neurosurgical approach to NTDs. Only by making the prevention of dysraphism a priority can we best address the inequities often observed worldwide.