Highlights Largest cohort of patients with COVID-19 and neurological symptoms who underwent LP. In all 30 cases, RT-PCR for SARS-CoV-2 from CSF was negative. CSF analysis findings, including WBC, were normal in most patients with COVID-19. Neurological symptoms in COVID-19 seem to be caused mainly by indirect mechanism.

Purpose: Genetically engineered T cells are powerful anticancer treatments but are limited by safety and specificity issues. We herein describe an MHC-unrestricted modular platform combining autologous T cells, transduced with a targetable synthetic agonistic receptor (SAR), with bispecific antibodies (BiAb) that specifically recruit and activate T cells for tumor killing.Experimental Design: BiAbs of different formats were generated by recombinant expression. T cells were retrovirally transduced with SARs. T-cell activation, proliferation, differentiation, and T-cell-induced lysis were characterized in three murine and human tumor models in vitro and in vivo.Results: Murine T cells transduced with SAR composed of an extracellular domain EGFRvIII fused to CD28 and CD3z signaling domains could be specifically recruited toward murine tumor cells expressing EpCAM by anti-EGFRvIII Â anti-EpCAM BiAb. BiAb induced selective antigen-dependent activation, proliferation of SAR T cells, and redirected tumor cell lysis. Selectivity was dependent on the monovalency of the antibody for EGFRvIII. We identified FAS ligand as a major mediator of killing utilized by the T cells. Similarly, human SAR T cells could be specifically redirected toward mesothelin-expressing human pancreatic cancer cells. In vivo, treatment with SAR T cells and BiAb mediated antitumoral activity in three human pancreatic cancer cell xenograft models. Importantly, SAR activity, unlike CAR activity, was reversible in vitro and in vivo.Conclusions: We describe a novel ACT platform with antitumor activity in murine and human tumor models with a distinct mode of action that combines adoptive T-cell therapy with bispecific antibodies.

BackgroundSocial networking sites, in particular Facebook, are not only predominant in students’ social life but are to varying degrees interwoven with the medical curriculum. Particularly, Facebook groups have been identified for their potential in higher education. However, there is a paucity of data on user types, content, and dynamics of study-related Facebook groups.ObjectiveThe aim of this study was to identify the role of study-related Facebook group use, characterize medical students that use or avoid using Facebook groups (demographics, participation pattern, and motivation), and analyze student posting behavior, covered topics, dynamics, and limitations in Facebook groups with regards to educational usage.MethodsUsing a multi-method approach (interviews, focus groups, and qualitative and quantitative analysis of Facebook posts), we analyzed two representative Facebook groups of medical preclinical semesters at Ludwig-Maximilians-University (LMU) Munich. Facebook primary posts and replies over one semester were extracted and evaluated by using thematic content analysis. We developed and applied a coding scheme for studying the frequency and distribution of these posts. Additionally, we interviewed students with various degrees of involvement in the groups, as well as “new minorities,” students not registered on Facebook.ResultsFacebook groups seem to have evolved as the main tool for medical students at LMU to complement the curriculum and to discuss study-related content. These Facebook groups are self-organizing and quickly adapt to organizational or subject-related challenges posed by the curriculum. A wide range of topics is covered, with a dominance of organization-related posts (58.35% [6916/11,853] of overall posts). By measuring reply rates and comments per category, we were able to identify learning tips and strategies, material sharing, and course content discussions as the most relevant categories. Rates of adequate replies in these categories ranged between 78% (11/14) and 100% (13/13), and the number of comments per post ranged from 8.4 to 13.7 compared with the average overall reply rate of 68.69% (1167/1699) and 3.9 comments per post. User typology revealed social media drivers (>30 posts per semester) as engines of group function, frequent users (11-30 posts), and a majority of average users acting rather as consumers or lurkers (1-10 posts).ConclusionsFor the moment, the medical faculty has no active involvement in these groups and therefore no influence on accuracy of information, professionalism, and ethical issues. Nevertheless, faculty could in the future benefit by extracting relevant information, identifying common problems, and understanding semester-related dynamics.

Background Neurologic manifestations are increasingly reported in patients with coronavirus disease 2019 (COVID-19). Yet, data on prevalence, predictors and relevance for outcome of neurological manifestations in patients requiring intensive care are scarce. We aimed to characterize prevalence, risk factors and impact on outcome of neurologic manifestations in critically ill COVID-19 patients. Methods In the prospective, multicenter, observational registry study PANDEMIC (Pooled Analysis of Neurologic DisordErs Manifesting in Intensive care of COVID-19), we enrolled COVID-19 patients with neurologic manifestations admitted to 19 German intensive care units (ICU) between April 2020 and September 2021. We performed descriptive and explorative statistical analyses. Multivariable models were used to investigate factors associated with disorder categories and their underlying diagnoses as well as to identify predictors of outcome. Results Of the 392 patients included in the analysis, 70.7% (277/392) were male and the mean age was 65.3 (SD ± 3.1) years. During the study period, a total of 2681 patients with COVID-19 were treated at the ICUs of 15 participating centers. New neurologic disorders were identified in 350 patients, reported by these centers, suggesting a prevalence of COVID-19-associated neurologic disorders of 12.7% among COVID-19 ICU patients. Encephalopathy (46.2%; 181/392), cerebrovascular (41.0%; 161/392) and neuromuscular disorders (20.4%; 80/392) were the most frequent categories identified. Out of 35 cerebrospinal fluid analyses with reverse transcriptase PCR for SARS-COV-2, only 3 were positive. In-hospital mortality was 36.0% (140/389), and functional outcome (mRS 3 to 5) of surviving patients was poor at hospital discharge in 70.9% (161/227). Intracerebral hemorrhage (OR 6.2, 95% CI 2.5–14.9, p < 0.001) and acute ischemic stroke (OR 3.9, 95% CI 1.9–8.2, p < 0.001) were the strongest predictors of poor outcome among the included patients. Conclusions Based on this well-characterized COVID-19 ICU cohort, that comprised 12.7% of all severe ill COVID-19 patients, neurologic manifestations increase mortality and morbidity. Since no reliable evidence of direct viral affection of the nervous system by COVID-19 could be found, these neurologic manifestations may for a great part be indirect para- or postinfectious sequelae of the infection or severe critical illness. Neurologic ICU complications should be actively searched for and treated.