Background Peptide vaccines offer the opportunity to elicit glioma-specific T cells with tumor killing ability. Using antigens eluted from the surface of glioblastoma samples, we designed a phase I/II study to test safety and immunogenicity of the IMA950 multipeptide vaccine adjuvanted with poly-ICLC (polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose) in human leukocyte antigen A2+ glioma patients. Methods Adult patients with newly diagnosed glioblastoma (n = 16) and grade III astrocytoma (n = 3) were treated with radiochemotherapy followed by IMA950/poly-ICLC vaccination. The first 6 patients received IMA950 (9 major histocompatibility complex [MHC] class I and 2 MHC class II peptides) intradermally and poly-ICLC intramuscularly (i.m.). After protocol amendment, IMA950 and poly-ICLC were mixed and injected subcutaneously (n = 7) or i.m. (n = 6). Primary endpoints were safety and immunogenicity. Secondary endpoints were overall survival, progression-free survival at 6 and 9 months, and vaccine-specific peripheral cluster of differentiation (CD)4 and CD8 T-cell responses. Results The IMA950/poly-ICLC vaccine was safe and well tolerated. Four patients presented cerebral edema with rapid recovery. For the first 6 patients, vaccine-induced CD8 T-cell responses were restricted to a single peptide and CD4 responses were absent. After optimization of vaccine formulation, we observed multipeptide CD8 and sustained T helper 1 CD4 T-cell responses. For the entire cohort, CD8 T-cell responses to a single or multiple peptides were observed in 63.2% and 36.8% of patients, respectively. Median overall survival was 19 months for glioblastoma patients. Conclusion We provide, in a clinical trial, using cell surface-presented antigens, insights into optimization of vaccines generating effector T cells for glioma patients. Trial registration Clinicaltrials.gov NCT01920191.

Background Prompt and accurate identification of stroke victims is essential to reduce time from symptom onset to adequate treatment and to improve neurological outcomes. Most neurologists evaluate the extent of neurological deficit according to the National Institutes of Health Stroke Scale (NIHSS), but the use of this scale by paramedics, the first healthcare providers to usually take care of stroke victims, has proven unreliable. This might be, at least in part, due to the teaching method. The video used to teach NIHSS lacks interactivity, while more engaging electronic learning (e-learning) methods might improve knowledge acquisition. Objective This study was designed to evaluate whether a highly interactive e-learning module could enhance NIHSS knowledge acquisition in paramedics. Methods A randomized controlled trial comparing a specially designed e-learning module with the original NIHSS video was performed with paramedics working in Geneva, Switzerland. A registration number was not required as our study does not come into the scope of the Swiss federal law on human research. The protocol was nevertheless submitted to the local ethics committee (Project ID 2017-00847), which issued a “Declaration of no objection.” Paramedics were excluded if they had prior knowledge of or previous training in the NIHSS, or if they had worked in a neurology or neurosurgery ward. The primary outcome was overall performance in the study quiz, which contained 50 questions. Secondary outcomes were performance by NIHSS item, time to course and quiz completion, user satisfaction regarding the learning method, user perception of the course duration, and probability the user would recommend the course to a colleague. Results The study was completed by 39 paramedics. There was a better overall median score (36/50 vs 33/50, P=.04) and a higher degree of satisfaction regarding the learning method in the e-learning group (90% vs 37%, P=.002). Users who had followed the e-learning module were more likely to recommend the course to a colleague (95% vs 63%, P=.02). Paramedics in the e-learning group took more time to complete the course (93 vs 59 minutes, P<.001), but considered the duration to be more adequate (75% vs 32%, P=.01). Time to quiz completion was similar between groups (25 vs 38 minutes, P=.12). Conclusions Use of an e-learning module shows promising results in teaching the NIHSS to paramedics.

Background The COVID-19 pandemic has considerably altered the regular medical education curriculum while increasing the need for health care professionals. Senior medical students are being incrementally deployed to the front line to address the shortage of certified physicians. These students, some of whom will be fast-tracked as physicians, may lack knowledge regarding the initial management of time-critical emergencies such as stroke. Objective Our aim was to determine whether an e-learning module could improve asynchronous distance knowledge acquisition of the National Institutes of Health Stroke Scale (NIHSS) in senior medical students compared to the traditional didactic video. Methods A randomized, data analyst–blinded web-based trial was conducted at the University of Geneva Faculty of Medicine between April and June 2020. Fifth year medical students followed a distance learning path designed to teach the NIHSS. The control group followed the traditional didactic video created by Patrick Lyden, while the e-learning group followed the updated version of a previously tested, highly interactive e-learning module. The main outcome was the score on a 50-question quiz displayed upon completion of the learning material. The difference in the proportion of correct answers for each specific NIHSS item was also assessed. Results Out of 158 potential participants, 88 started their allocated learning path and 75 completed the trial. Participants who followed the e-learning module performed better than those who followed the video (38 correct answers, 95% CI 37-39, vs 35 correct answers, 95% CI 34-36, P<.001). Participants in the e-learning group scored better on five elements than the video group: key NIHSS concepts (P=.02), the consciousness – global item (P<.001), the facial palsy item (P=.04), the ataxia item (P=.03), and the sensory item (P=.04). Conclusions Compared to the traditional didactic video, a highly interactive e-learning module enhances asynchronous distance learning and NIHSS knowledge acquisition in senior medical students.

BACKGROUND The COVID-19 pandemic has considerably altered the regular medical education curriculum while increasing the need for healthcare professionals. Senior medical students have been incrementally used on the front line to overcome the shortage of certified physicians. These students, some of whom will be fast-tracked as physicians, might lack knowledge regarding the initial management of time-critical emergencies such as stroke. OBJECTIVE Our aim was to determine whether an electronic learning (e-learning) module could improve distance knowledge acquisition of the National Institutes of Health Stroke Scale (NIHSS) in senior medical students compared to the traditional didactic video. METHODS A randomized, controlled, data-analyst blinded web-based trial was conducted at the University of Geneva Faculty of Medicine between April and June 2020. Fifth year medical students followed a learning path designed to distantly learn the NIHSS. The control group followed the traditional didactic video created by Patrick Lyden while the e-learning group followed the updated version of a previously tested highly-interactive e-learning module. The main outcome was the score on a 50-question quiz displayed upon completion of the learning material. Difference in the proportion of correct answers for each specific NIHSS item was also assessed. RESULTS Out of 158 potential participants, 88 started their allocated learning path, and 75 completed the trial. Participants who followed the e-learning module performed better than those who followed the video (38 [95%CI 37 to 39] correct answers versus 35 [95%CI 34 to 36], P<.001). Participants in the e-learning group scored five elements better than the video group: key NIHSS concepts (P=.02), the consciousness – global item (P<.001), the facial palsy item (P=.04), the ataxia item (P=.03) and the sensory item (P=.04). CONCLUSIONS Compared to the traditional didactic video, a highly-interactive e-learning module enhances distance learning and NIHSS knowledge acquisition in senior medical students.

Hemangioblastoma is a rare benign neoplasm, accounting for less than 2% of all primitive brain tumors. It may arise sporadically in a solitary form, or associated with Von Hippel-Lindau (VHL) disease with multiple tumors. Surgery is the mainstay treatment, but management is challenging in case of recurrent and/or multiple tumors. VHL protein is defective in both forms of hemangioblastoma, leading to the accumulation of hypoxia-inducible factor, stimulating angiogenesis via VEGF and PDGF mainly. Here, we report a 37-year-old woman's case with recurrent and rapidly progressive VHL-associated hemangioblastomas, causing severe disability. She was treated 24 months with pazopanib, a multityrosine kinase inhibitor (TKI) targeting VEGF and PDGF-β pathways. Despite moderate radiological changes, progressive improvement in her clinical condition persisting over 3 years was observed. Inhibiting angiogenesis is a therapeutic option that may improve the quality of life and the autonomy of VHL patients disabled with multiple hemangioblastomas.