Superselective intraarterial cerebral infusion of cetuximab with blood brain barrier disruption combined with Stupp Protocol for newly diagnosed glioblastoma.

OBJECTIVE: We describe the first case of a novel treatment for a newly diagnosed glioblastoma (GBM) using superselective intraarterial cerebral infusion (SIACI) of cetuximab after osmotic disruption of the blood-brain barrier (BBB) with mannitol. A 51year-old female underwent craniotomy for removal of a right frontal GBM. Pathology confirmed EGFR amplification, and she underwent three treatments of SIACI of cetuximab to the tumor site. The first treatment was given within a week of starting standard of care chemoradiation (Stupp protocol), which is a combination of radiation treatment (2 Gy per/ day x 30 days, total of 60 Gy) and oral temozolomide (75 mg/m2). The second and third SIACI of cetuximab were administered 3 and 6 months later, while the patient continued on maintenance temozolomide. Post-radiation changes on MRI were stable, and there were no signs of recurrence at 4 and 6 months post-resection. Herein, we detail the technical aspects of this novel treatment paradigm and suggest that SIACI of cetuximab after BBB disruption using mannitol, combined with the standard of care chemoradiation therapy, may be an effective treatment method for newly diagnosed EGFR amplified glioblastoma.

Long-term benefit of intra-arterial bevacizumab for recurrent glioblastoma.

OBJECTIVE: Standard treatment for recurrent GBM is not yet established. We present a case demonstrating the benefit of intra-arterial (IA) bevacizumab with blood brain barrier disruption (BBBD) for the treatment of recurrent GBM. A 31 year-old man diagnosed with GBM, following primary resection, received temozolomide. After a second resection, he received one dose of IA bevacizumab with BBBD using mannitol, preventing regrowth for 2.5 years. Following tumor regrowth, the patient received another dose of IA bevacizumab with BBBD, which has prevented regrowth for another year.

State emergency medical services guidance and protocol changes in response to the COVID-19 pandemic: A national investigation.

OBJECTIVES: The COVID-19 pandemic has had an impact on emergency medical services (EMS) and its guidelines, which aid in patient care. This study characterizes state and territory EMS office recommendations to EMS statewide operational and clinical guidelines and describes the mechanisms of distribution and implementation during the COVID-19 pandemic. METHODS: A mixed-methods study was conducted in 2 phases. In phase 1, changes and development of COVID-19 guidance and protocols for EMS clinical management and operations were identified among 50 states, the District of Columbia, and 5 territories in publicly available online documents and information. In phase 2, structured interviews were conducted with state/territory EMS officials to confirm the protocol changes or guidance and assess dissemination and implementation strategies for COVID-19. RESULTS: In phase 1, publicly available online documents for 52 states/territories regarding EMS protocols and COVID-19 guidance were identified and reviewed. Of 52 (33/52) states/territories, 33 had either formal protocol changes or specific guidance for the pandemic. In phase 2, 2 state and territory EMS officials were interviewed regarding their protocols or guidance for COVID-19 and the dissemination and implementation practices they used to reach EMS agencies (response rate = 65%). Of the 34 state/territory officials interviewed, 22 had publicly available online COVID-19 protocols or guidance. Of the 22 officials with online COVID-19 protocols, all reported providing operational direction, and 19 of 22 officials reported providing clinical direction. CONCLUSIONS: Most states provided guidance to EMS agencies and/or updated protocols in response to the COVID-19 pandemic.

Pooling Morphometric Estimates: A Statistical Equivalence Approach.

Changes in hardware or image-processing settings are a common issue for large multicenter studies. To pool MRI data acquired under these changed conditions, it is necessary to demonstrate that the changes do not affect MRI-based measurements. In these circumstances, classical inference testing is inappropriate because it is designed to detect differences, not prove similarity. We used a method known as statistical equivalence testing to address this limitation. Equivalence testing was carried out on 3 datasets: (1) cortical thickness and automated hippocampal volume estimates obtained from healthy individuals imaged using different multichannel head coils; (2) manual hippocampal volumetry obtained using two readers; and (3) corpus callosum area estimates obtained using an automated method with manual cleanup carried out by two readers. Equivalence testing was carried out using the "two one-sided tests" (TOST) approach. Power analyses of the TOST were used to estimate sample sizes required for well-powered equivalence testing analyses. Mean and standard deviation estimates from the automated hippocampal volume dataset were used to carry out an example power analysis. Cortical thickness values were found to be equivalent over 61% of the cortex when different head coils were used (q < .05, false discovery rate correction). Automated hippocampal volume estimates obtained using the same two coils were statistically equivalent (TOST P = 4.28 × 10(-15) ). Manual hippocampal volume estimates obtained using two readers were not statistically equivalent (TOST P = .97). The use of different readers to carry out limited correction of automated corpus callosum segmentations yielded equivalent area estimates (TOST P = 1.28 × 10(-14) ). Power analysis of simulated and automated hippocampal volume data demonstrated that the equivalence margin affects the number of subjects required for well-powered equivalence tests. We have presented a statistical method for determining if morphometric measures obtained under variable conditions can be pooled. The equivalence testing technique is applicable for analyses in which experimental conditions vary over the course of the study.