Somatic Variants in SVIL in Cerebral Aneurysms.

Background and Objectives: While somatic mutations have been well-studied in cancer, their roles in other complex traits are much less understood. Our goal is to identify somatic variants that may contribute to the formation of saccular cerebral aneurysms. Methods: We performed whole-exome sequencing on aneurysm tissues and paired peripheral blood. RNA sequencing and the CRISPR/Cas9 system were then used to perform functional validation of our results. Results: Somatic variants involved in supervillin (SVIL) or its regulation were found in 17% of aneurysm tissues. In the presence of a mutation in the SVIL gene, the expression level of SVIL was downregulated in the aneurysm tissue compared with normal control vessels. Downstream signaling pathways that were induced by knockdown of SVIL via the CRISPR/Cas9 system in vascular smooth muscle cells (vSMCs) were determined by evaluating changes in gene expression and protein kinase phosphorylation. We found that SVIL regulated the phenotypic modulation of vSMCs to the synthetic phenotype via Krüppel-like factor 4 and platelet-derived growth factor and affected cell migration of vSMCs via the RhoA/ROCK pathway. Discussion: We propose that somatic variants form a novel mechanism for the development of cerebral aneurysms. Specifically, somatic variants in SVIL result in the phenotypic modulation of vSMCs, which increases the susceptibility to aneurysm formation. This finding suggests a new avenue for the therapeutic intervention and prevention of cerebral aneurysms.

The Continuum of Neurosurgical Care: Increasing the Neurosurgeon's Role and Responsibility.

The Health Care Reform Act has fostered a shift toward capitation and shared risk among providers to improve quality and reduce the escalating costs of healthcare. Like all physicians, neurosurgeons are increasingly being incentivized to participate in efforts to streamline care through the use of surgical pathways to reduce hospital length of stay and prevent readmissions. These changes have expanded the role of the neurosurgeon along the continuum of care for the neurosurgery patient. This paper predicts and advocates for a further broadening of neurosurgery participation from programs that reward physicians for helping to prevent a high-risk patient's need for surgery to management of postacute rehabilitation. It also introduces the concept of risk reduction more generally at the community level through collaborative interventions that improve health through changes to the built environment, innovations in transportation, and improved access to healthy food and recreation opportunities.

In-training factors predictive of choosing and sustaining a productive academic career path in neurological surgery.

BACKGROUND: Factors during neurosurgical residency that are predictive of an academic career path and promotion have not been defined. OBJECTIVE: To determine factors associated with selecting and sustaining an academic career in neurosurgery by analyzing in-training factors for all graduates of American College of Graduate Medical Education (ACGME)-accredited programs between 1985 and 1990. METHODS: Neurological surgery residency graduates (between 1985 and 1990) from ACGME-approved training programs were analyzed to determine factors associated with choosing an academic career path and having academic success. RESULTS: Information was available for 717 of the 720 (99%) neurological surgery resident training graduates (678 male, 39 female). One hundred thirty-eight graduates (19.3%) held full-time academic positions. One hundred seven (14.9%) were professors and 35 (4.9%) were department chairs/chiefs. An academic career path/success was associated with more total (5.1 vs 1.9; P < .001) and first-author publications (3.0 vs 1.0; P < .001) during residency. Promotion to professor or chair/chief was associated with more publications during residency (P < .001). Total publications and first-author publications were independent predictors of holding a current academic position and becoming professor or chair/chief. Although male trainees published more than female trainees (2.6 vs 0.9 publications; P < .004) during training, no significant sex difference was observed regarding current academic position. Program size (≥ 2 graduates a year; P = .02) was predictive of an academic career but not predictive of becoming professor or chair/chief (P > .05). CONCLUSION: Defined in-training factors including number of total publications, number of first-author publications, and program size are predictive of residents choosing and succeeding in an academic career path.