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Patients with glioblastoma (GBM) need bold new approaches to their treatment, yet progress has been hindered by a relative inability to dynamically track treatment response, mechanisms of resistance, evolution of targetable mutations, and changes in mutational burden. We are writing on behalf of a multidisciplinary group of academic neuro-oncology professionals who met at the collaborative Christopher Davidson Forum at Washington University in St Louis in the fall of 2019. We propose a dramatic but necessary change to the routine management of patients with GBM to advance the field: to routinely biopsy recurrent GBM at the time of presumed recurrence. Data derived from these samples will identify true recurrence vs treatment effect, avoid treatments with little chance of success, enable clinical trial access, and aid in the scientific advancement of our understanding of GBM.

Large calvarial defects in the setting of chronic infection and limited autologous donor sites present challenging problems for the reconstructive surgeon. We report on a novel osteogenic implant as a potential calvarial reconstruction solution. Two patients with an extensive history of severe traumatic brain injury and multiple cranial operations desired delayed calvarial reconstruction subsequent to removal of infected acrylic and titanium implants. These patients underwent harvesting of cancellous femoral bone and bone marrow, which was placed between 2 layers of recombinant bone morphogenic protein 2 impregnated in acellular collagen sponges and an outer layer of sturdily pliable Vicryl mesh to create a moldable osteogenic implant construct. The construct was molded into the shape of the defect and secured with sutures to the skull surrounding the defect. The osteogenic implant showed evidence of bone formation and maintained coverage over the original calvarial defect at 26 months postoperatively as well as subjective satisfaction by both patients and the senior surgeon. This technically straightforward technique with acceptable functional and aesthetic outcomes may be useful to reconstructing selected calvarial defects.

Background The degree of carotid artery stenosis has traditionally been used as a marker of hemodynamic compromise and increased stroke risk. However, the hemodynamic effect of carotid atherosclerotic plaque length on cerebral blood flow has not previously been studied. Objective To determine whether carotid plaque length, in addition to degree of stenosis, significantly affects carotid blood flow in patients with >65% carotid stenosis. Methods Consecutively treated surgical patients with unilateral >65% carotid stenosis at a single institution were analyzed. Quantitative measurements of plaque length, internal carotid artery (ICA) vessel diameter, and degree of stenosis were made from magnetic resonance angiography images. Quantitative phase-contrast magnetic resonance angiography flow maps were generated to estimate ICA flow compromise by calculating a ratio of the ipsilateral/contralateral ICA flow rates. Results Of 38 eligible patients, 23 had full anatomic and ICA flow data sets available for analysis. Univariate regression analysis demonstrated that longer carotid plaques and increasing percentage carotid stenosis were associated with a significant decline in ipsilateral ICA flow (P = .008 and P = .02, respectively). A multivariate regression identified both plaque length and vessel diameter as independent predictors of ICA flow (P = .001 and P = .002, respectively). Conclusion Carotid plaque length and vessel diameter appear to be significant variables, in addition to degree of stenosis, in predicting ipsilateral carotid blood flow compromise in patients undergoing carotid revascularization.

Objective Mutations in KRIT1 cause familial cerebral cavernous malformation, an autosomal dominant disorder affecting primarily the central nervous system vasculature. Although recent studies have suggested that Krev-1 interaction trapped 1 (KRIT1) is a microtubule-associated protein that interacts with integrin cytoplasmic domain-associated protein-1alpha, the function of KRIT1 remains elusive. Methods We used Western blotting and immunohistochemistry with specific KRIT1 polyclonal antibodies to investigate KRIT1 protein expression in diverse cerebral and extracerebral tissues. Results Immunostaining demonstrates that although KRIT1 is expressed in a broad variety of human organs, it localizes to the vascular endothelium of each, specifically to capillaries and arterioles. KRIT1 antibody fails to stain fenestrated capillaries in the kidney, the liver, or the red pulp of the spleen, where endothelial cells do not to adhere to one another. In contrast, intense staining is observed in the thymus and the white pulp of the spleen, where specialized blood-organ barriers are formed. Other cell types, including various epithelia, cardiac myocytes, and hepatocytes, also stain with KRIT1. Conclusion Although KRIT1 expression is seen in every endothelium studied, cerebral cavernous malformation lesions are seen almost exclusively in the central nervous system, suggesting that additional cell type(s) contribute to the pathophysiology of cerebral cavernous malformations. Here, we demonstrate that KRIT1 is also present in cells and structures integral to the cerebral angiogenesis and formation of the blood-brain barrier, namely, endothelial cells and astrocytic foot processes, as well as pyramidal neurons in the cerebral cortex.