OBJECT The object of this study was to identify and quantify predictors of burnout and career satisfaction among US neurosurgeons. METHODS All US members (3247) of the American Association of Neurological Surgeons (AANS) were invited to participate in a survey between September and December 2012. Responses were evaluated through univariate analysis. Factors independently associated with burnout and career satisfaction were determined using multivariable logistic regression. Subgroup analysis of academic and nonacademic neurosurgeons was performed as well. RESULTS The survey response rate was 24% (783 members). The majority of respondents were male, 40–60 years old, in a stable relationship, with children, working in a group or university practice, and trained in a subspecialty. More than 80% of respondents reported being at least somewhat satisfied with their career, and 70% would choose a career in neurosurgery again; however, only 26% of neurosurgeons believed their professional lives would improve in the future, and 52% believed it would worsen. The overall burnout rate was 56.7%. Factors independently associated with both burnout and career satisfaction included achieving a balance between work and life outside the hospital (burnout OR 0.45, satisfaction OR 10.0) and anxiety over future earnings and/or health care reform (burnout OR 1.96, satisfaction OR 0.32). While the burnout rate for nonacademic neurosurgeons (62.9%) was higher than that for academic neurosurgeons (47.7%), academicians who had practiced for over 20 years were less likely to be satisfied with their careers. CONCLUSIONS The rates of burnout and career satisfaction were both high in this survey study of US neurosurgeons. The negative effects of burnout on the lives of surgeons, patients, and their families require further study and probably necessitate the development of interventional programs at local, regional, and even national levels.
PURPOSE Precision medicine trials in glioblastoma (GBM) are often conducted at tumor recurrence. However, second surgeries for recurrent GBM are not routinely performed, and therefore, molecular data for trial inclusion are predominantly derived from the primary sample. This study aims to establish whether molecular targets change during tumor progression and, if so, whether this affects precision medicine trial design. MATERIALS AND METHODS We collected 186 pairs of primary-recurrent GBM samples from patients receiving chemoradiotherapy with temozolomide and sequenced approximately 300 cancer genes. MGMT, TERT, and EGFRvIII status was individually determined. RESULTS The molecular profile of our cohort was identical to that of other GBM cohorts ( IDH wild-type [WT], 95%; EGFR amplified, approximately 50%), indicating that patients amenable to second surgery do not represent a specific molecular subtype. Molecular events in IDH WT GBMs were stable in approximately 80% of events, but changes in mutation status were observed for all examined genes (range, approximately 90% and 60% for TERT and EGFR mutations, respectively), and such changes strongly affected targeted trial size and design. A similar pattern of GBM driver instability was observed within MGMT promoter–methylated tumors. MGMT promoter methylation status remained prognostic at tumor recurrence. The observation that hypermutation at GBM recurrence was rare (8%) and not correlated with outcome was relevant for immunotherapy-based treatments. CONCLUSION This large cohort of matched primary and recurrent IDH WT tumors establishes the frequency of GBM driver instability after chemoradiotherapy with temozolomide. This allows per gene or pathway calculation of trial size at tumor recurrence, using molecular data of the primary tumor only. We also identify genes for which repeat surgery is necessary because of low mutation retention rate.
A physical hydrogel cross-linked via the host-guest interactions of cucurbit[8]uril and utilised as an implantable drug-delivery vehicle for the brain is described herein. Constructed from hyaluronic acid, this hydrogel is biocompatible and has a high water content of 98%. The mechanical properties have been characterised by rheology and compared with the modulus of human brain tissue demonstrating the production of a soft material that can be moulded into the cavity it is implanted into following surgical resection. Furthermore, effective delivery of therapeutic compounds and antibodies to primary human glioblastoma cell lines is showcased by a variety of in vitro and ex vivo viability and immunocytochemistry based assays.
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