Human breast cancer metastases to the brain display GABAergic properties in the neural niche.

Dispersion of tumors throughout the body is a neoplastic process responsible for the vast majority of deaths from cancer. Despite disseminating to distant organs as malignant scouts, most tumor cells fail to remain viable after their arrival. The physiologic microenvironment of the brain must become a tumor-favorable microenvironment for successful metastatic colonization by circulating breast cancer cells. Bidirectional interplay of breast cancer cells and native brain cells in metastasis is poorly understood and rarely studied. We had the rare opportunity to investigate uncommonly available specimens of matched fresh breast-to-brain metastases tissue and derived cells from patients undergoing neurosurgical resection. We hypothesized that, to metastasize, breast cancers may escape their normative genetic constraints by accommodating and coinhabiting the neural niche. This acquisition or expression of brain-like properties by breast cancer cells could be a malignant adaptation required for brain colonization. Indeed, we found breast-to-brain metastatic tissue and cells displayed a GABAergic phenotype similar to that of neuronal cells. The GABAA receptor, GABA transporter, GABA transaminase, parvalbumin, and reelin were all highly expressed in breast cancer metastases to the brain. Proliferative advantage was conferred by the ability of breast-to-brain metastases to take up and catabolize GABA into succinate with the resultant formation of NADH as a biosynthetic source through the GABA shunt. The results suggest that breast cancers exhibit neural characteristics when occupying the brain microenvironment and co-opt GABA as an oncometabolite.

Building Geriatric Trauma Programs in Resource-Constrained Environments: Trauma Quality Improvement Program Guideline Implementation at Two Safety Net Hospitals in Southern California.

Background: To improve care of geriatric trauma patients, the American College of Surgeons (ACS) Trauma Quality Improvement Program (TQIP) updated guidelines in 2021. Amid geriatrician shortages in Southern California, 2 Los Angeles County safety net hospitals were tasked with creating a strategy to meet geriatric trauma guidelines despite constrained resources. Methods: All trauma patients ≥ 60 years admitted to a safety net hospital in Southern California were enrolled without exclusions (August 2022-April 2023). Primary outcome was frailty screening with documentation to identify older trauma patients at a high risk for adverse outcomes. Results: Needs assessment discovered no standardized process to identify high-risk geriatric patients, no geriatric care guidelines, and no inpatient geriatric consultation service. An action plan composed of a resident-led frailty screen resulted in identification of high-risk patients. Overall, 217 patients met criteria. Ninety-six patients (44%) successfully underwent frailty screening. Frailty screening compliance increased over the study, beginning at 37% capture in the first month and increasing to 81% in the final study month. After achieving nearly uniform frailty screening, a form was developed for the EMR for ease of documentation, data capture/tracking, and compliance monitoring. Discussion: In this study, creativity, collaboration, and resourcefulness allowed TQIP guideline implementation at 2 county hospitals. A systematic process is now in place to identify and triage high-risk geriatric trauma patients based on frailty screen to receive inpatient medicine consultation for medical comorbidity optimization. Continued interdisciplinary and interfacility collaboration will be crucial for continued delivery of the optimal care to older injured patients.

Pediatric neurosurgery outreach: sustainability appraisal of a targeted teaching model in Kiev, Ukraine.

PURPOSE: This study evaluates the efficacy of operative skill transfer in the context of targeted pediatric outreach missions completed in Kiev, Ukraine. In addition the ability to create sustainable surgical care improvement is investigated as an efficient method to improve global surgical care. METHODS: Three 1-week targeted neurosurgical missions were performed (2005-2007) to teach neuroendoscopy, which included donation of the necessary surgical equipment, so the host team can deliver newly acquired surgical skills to their citizens after the visiting mission team departs. The neuroendoscopy data for the 4 years after the final mission in 2007 was obtained. RESULTS: After performing pediatric neurosurgery missions in 2005-2007, with a focus on teaching neuroendoscopy, the host team demonstrated the sustainability of our educational efforts in the subsequent 4 years by performing cases independently for their citizens. Since the last targeted mission of 2007, neuroendoscopic procedures have continued to be performed by the trained host surgeons. In 2008, 33 cases were performed. In 2009 and 2010, 29 and 22 cases were completed, respectively. In 2011, local neurosurgeons accomplished 27 cases. To date, a total of 111 operations have been performed over the past 4 years independent of any visiting team, illustrating the sustainability of educational efforts of the missions in 2005-2007. CONCLUSIONS: Effective operative skill transfer to host neurosurgeons can be accomplished with limited international team visits using a targeted approach that minimizes expenditures on personnel and capital. With the priority being teaching of an operative technique, as opposed to perennially performing operations by a visiting mission team, sustainable surgical care was achieved and perpetuated after missions officially concluded.