RESUMO
PURPOSE: COVID-19 patients on anti-CD20 treatment can suffer a delayed viral clearance and worse clinical outcome. We aim to present our experience with remdesivir treatment in anti-CD20-treated patients with prolonged symptoms, a patient population for which no data from randomized controlled trials are available. METHODS: From the beginning of the pandemic until February 2021, we included all consecutive patients from our healthcare network on anti-CD20 treatment with prolonged COVID-19 symptoms, who received remdesivir. Patient informed consent was gathered and patients' charts were reviewed to collect baseline data, COVID-19 history including time of symptom onset, diagnosis, data on treatment and disease course. Patients or their next of kin were contacted in March 2022 to assess long-term outcomes. RESULTS: We included 11 patients, who received remdesivir at a median of 33 days after diagnosis. Eight patients showed clinical improvement along with reductions in viral loads, one patient with relapsing infection recovered after administration of convalescent plasma, and two patients died. No clinical relapses were reported (median follow-up 13 months), while follow-up PCRs were not performed. One patient died of underlying malignancy 8 months after recovery from COVID-19. CONCLUSIONS: We observed a benefit of antiviral therapy in a majority of COVID-19 patients on anti-CD20 treatment, without any clinical relapses in the 1-year follow-up. Although these data suggest that remdesivir might be a promising management option in patients with delayed viral clearance, the lack of a control group is an important limitation of the study design. TRIAL REGISTRATION: Ethikkommission Ostschweiz, Scheibenackerstrasse 4, CH-9000 St. Gallen approved this case series. Project-ID 2021-00349 EKOS 21/027.
Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Anticorpos Monoclonais/uso terapêutico , Antivirais/uso terapêutico , COVID-19/terapia , Humanos , Imunização Passiva , Recidiva , SARS-CoV-2 , Resultado do Tratamento , Soroterapia para COVID-19RESUMO
Neurodegenerative diseases of the central nervous system frequently affect the locomotor system resulting in impaired movement and gait. In this study we performed a whole-body high-speed video gait analysis in three different mouse lines of neurodegenerative movement disorders to investigate the motor phenotype. Based on precise computerized motion tracking of all relevant joints and the tail, a custom-developed algorithm generated individual and comprehensive locomotor profiles consisting of 164 spatial and temporal parameters. Gait changes observed in the three models corresponded closely to the classical clinical symptoms described in these disorders: Muscle atrophy due to motor neuron loss in SOD1 G93A transgenic mice led to gait characterized by changes in hind-limb movement and positioning. In contrast, locomotion in huntingtin N171-82Q mice modeling Huntington's disease with basal ganglia damage was defined by hyperkinetic limb movements and rigidity of the trunk. Harlequin mutant mice modeling cerebellar degeneration showed gait instability and extensive changes in limb positioning. Moreover, model specific gait parameters were identified and were shown to be more sensitive than conventional motor tests. Altogether, this technique provides new opportunities to decipher underlying disease mechanisms and test novel therapeutic approaches.
Assuntos
Algoritmos , Modelos Animais de Doenças , Marcha , Processamento de Imagem Assistida por Computador , Doenças Neurodegenerativas/fisiopatologia , Gravação em Vídeo , Animais , Fenômenos Biomecânicos , Progressão da Doença , Marcha/fisiologia , Membro Posterior/fisiopatologia , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Camundongos Transgênicos , Doenças Neurodegenerativas/diagnóstico , Fenótipo , Teste de Desempenho do Rota-Rod , Fatores de Tempo , Tronco/fisiopatologia , Gravação em Vídeo/métodosRESUMO
Despite its economic and technological importance, the Swiss life sciences sector faces severe challenges in attracting enough venture capital for its own development. Although biotechnology and medical technology have been the most important areas of venture financing from 1999 through 2012 according to our own data, average investment volumes nevertheless remain on a low level of only 0.05 percent of Swiss GDP. After 2008, there was a pronounced shift away from early-stage financing. While business angels still play an important role at the early stage, venture capitalists are the most important investor type by volumes having their main focus on expansion financing. The industry faces predominant challenges in securing capital availability for entrepreneurs, in transforming the highly skewed and back-loaded payoff profile of investments into a more stable return stream, and in defining appropriate business and collaboration models.