Comparison of Botulinum neurotoxin efficiency in dystonia associated with Parkinson's disease and atypical parkinsonism: a retrospective study with a self-reported improvement scale.

Botulinum neurotoxin (BoNT) is a useful therapeutic option to treat dystonic manifestations. Data on its efficiency on dystonia associated with Parkinson's disease (PD) or atypical parkinsonism (AP) are scarce and no comparison of the efficiency of BoNT has been performed between these diseases and between the different localizations of dystonia in these pathologies. We retrospectively collected from patients' medical records the result of 611 BoNT injections in 63 dystonic parkinsonian patients (44 PD and 19 AP) using a self-reported clinical improvement scale and duration of effect. Using these data, we modeled the degree of improvement and its duration after BoNT treatment with a linear mixed model. This allowed us to assess the influence of clinical parameters on the reported treatment efficiency. On a scale from 0 to 100, patients with PD and AP, respectively, report a mean improvement of 69% and 55% after BoNT injection and it is similar regarding the different localizations of dystonia. Duration of effect is, however, longer in PD compared to AP (P = 0.023). Patients' demographic and clinical characteristics had no effect on the degree of improvement or duration of effect. Overall, our results support the use of BoNT in the various dystonic phenomena associated with degenerative parkinsonian syndromes. Shorter delays between injection sessions should be considered in AP compared to PD.Trial registration: This study was registered on Clinicaltrial.gov (NCT04948684).

Impairment of neutrophil functions and homeostasis in COVID-19 patients: association with disease severity.

BACKGROUND: A dysregulated immune response is emerging as a key feature of critical illness in COVID-19. Neutrophils are key components of early innate immunity that, if not tightly regulated, contribute to uncontrolled systemic inflammation. We sought to decipher the role of neutrophil phenotypes, functions, and homeostasis in COVID-19 disease severity and outcome. METHODS: By using flow cytometry, this longitudinal study compares peripheral whole-blood neutrophils from 90 COVID-19 ICU patients with those of 22 SARS-CoV-2-negative patients hospitalized for severe community-acquired pneumonia (CAP) and 38 healthy controls. We also assessed correlations between these phenotypic and functional indicators and markers of endothelial damage as well as disease severity. RESULTS: At ICU admission, the circulating neutrophils of the COVID-19 patients showed continuous basal hyperactivation not seen in CAP patients, associated with higher circulating levels of soluble E- and P-selectin, which reflect platelet and endothelial activation. Furthermore, COVID-19 patients had expanded aged-angiogenic and reverse transmigrated neutrophil subsets-both involved in endothelial dysfunction and vascular inflammation. Simultaneously, COVID-19 patients had significantly lower levels of neutrophil oxidative burst in response to bacterial formyl peptide. Moreover patients dying of COVID-19 had significantly higher expansion of aged-angiogenic neutrophil subset and greater impairment of oxidative burst response than survivors. CONCLUSIONS: These data suggest that neutrophil exhaustion may be involved in the pathogenesis of severe COVID-19 and identify angiogenic neutrophils as a potentially harmful subset involved in fatal outcome.