Clinical Uncertainty and Equipoise in the Management of Recurrent Glioblastoma.

BACKGROUND: A significant proportion of glioblastoma (GBM) patients are considered for repeat resection, but evidence regarding best management remains elusive. Our aim was to measure the degree of clinical uncertainty regarding reoperation for patients with recurrent GBM. METHODS: We first performed a systematic review of agreement studies examining the question of repeat resection for recurrent GBM. An electronic portfolio of 37 pathologically confirmed recurrent GBM patients including pertinent magnetic resonance images and clinical information was assembled. To measure clinical uncertainty, 26 neurosurgeons from various countries, training backgrounds, and years' experience were asked to select best management (repeat surgery, other nonsurgical management, or conservative), confidence in recommended management, and whether they would include the patient in a randomized trial comparing surgery with nonsurgical options. Agreement was evaluated using κ statistics. RESULTS: The literature review did not reveal previous agreement studies examining the question. In our study, agreement regarding best management of recurrent GBM was slight, even when management options were dichotomized (repeat surgery vs. other options; κ=0.198 [95% confidence interval: 0.133-0.276]). Country of practice, years' experience, and training background did not change results. Disagreement and clinical uncertainty were more pronounced within clinicians with (κ=0.167 [0.055-0.314]) than clinicians without neuro-oncology fellowship training (κ=0.601 [0.556-0.646]). A majority (51%) of responders were willing to include the patient in a randomized trial comparing repeat surgery with nonsurgical alternatives in 26/37 (69%) of cases. CONCLUSION: There is sufficient uncertainty and equipoise regarding the question of reoperation for patients with recurrent glioblastoma to support the need for a randomized controlled trial.

Organization of the reach and grasp in head-fixed vs freely-moving mice provides support for multiple motor channel theory of neocortical organization.

Multiple motor channel (MMC) theory of neocortical organization proposes that complex movements, such as reaching for a food item to eat, are produced by the coordinated action of separate neural channels. For example, the human reach-to-grasp act is mediated by two visuo-parieto-motor cortex channels, one for the reach and one for the grasp. The present analysis asked whether there is a similar organization of reach-and-grasp movements in the mouse. The reach-to-eat movements of the same mice were examined from high-shutter speed, frame-by-frame video analysis in three tasks in which the mice obtained equivalent success scores: when freely-moving reaching for food pellets, when head-fixed reaching for food pellets, and when head-fixed reaching for pieces of pasta. To reach, the mice used egocentric cues to vary upper arm movements in a task-appropriate manner to place an open hand on the food or to locate the food using a "touch-release-grasp" strategy. Although mice could not hand-shape offline when reaching, they could hand-shape using online touch-related cues from the mouth to manipulate the food at the mouth. That the reach can be performed offline in relation to egocentric cues whereas hand shaping for the grasp requires online cues supports the idea that for the mouse, as for primates, the reach and grasp are separate acts. The results are further discussed in relation to the use of the head-fixed behavioral procedure to identify the independent neural substrates of the reach and the grasp using mesoscale stimulation/imaging methods.