A genetic analysis of a Spanish population with early onset Parkinson's disease.

INTRODUCTION: Both recessive and dominant genetic forms of Parkinson's disease have been described. The aim of this study was to assess the contribution of several genes to the pathophysiology of early onset Parkinson's disease in a cohort from central Spain. METHODS/PATIENTS: We analyzed a cohort of 117 unrelated patients with early onset Parkinson's disease using a pipeline, based on a combination of a next-generation sequencing panel of 17 genes previously related with Parkinson's disease and other Parkinsonisms and CNV screening. RESULTS: Twenty-six patients (22.22%) carried likely pathogenic variants in PARK2, LRRK2, PINK1, or GBA. The gene most frequently mutated was PARK2, and p.Asn52Metfs*29 was the most common variation in this gene. Pathogenic variants were not observed in genes SNCA, FBXO7, PARK7, HTRA2, DNAJC6, PLA2G6, and UCHL1. Co-occurrence of pathogenic variants involving two genes was observed in ATP13A2 and PARK2 genes, as well as LRRK2 and GIGYF2 genes. CONCLUSIONS: Our results contribute to the understanding of the genetic architecture associated with early onset Parkinson's disease, showing both PARK2 and LRRK2 play an important role in Spanish Parkinson's disease patients. Rare variants in ATP13A2 and GIGYF2 may contribute to PD risk. However, a large proportion of genetic components remains unknown. This study might contribute to genetic diagnosis and counseling for families with early onset Parkinson's disease.

HIGH VERSUS STANDARD DOSES OF CORTICOSTEROIDS IN COVID-19 PATIENTS WITH AN ACUTE RESPIRATORY DISTRESS SYNDROME: a controlled observational comparative study.

INTRODUCTIONDespite the increasing evidence of the benefit of corticosteroids for the treatment of moderate-severe Coronavirus disease 2019 (COVID-19) patients, no data are available about the potential role of high doses of steroids for these patients. METHODSAll consecutive confirmed COVID-19 patients admitted to a single center were selected, including those treated with steroids and an acute respiratory distress syndrome (ARDS). Patients were allocated to the high doses (HD, [≥]250mg/day of methylprednisolone) of corticosteroids or the standard doses (SD, [≤]1.5mg/kg/day of methylprednisolone) at discretion of treating physician. The primary endpoint was the mortality between both cohorts and secondary endpoints were the risk of need for mechanical ventilation (MV) or death and the risk of developing a severe ARDS. RESULTS573 patients were included: 428 (74.7%) men, with a median (IQR) age of 64 (54-73) years. In HD cohort, a worse baseline respiratory situation was observed and male sex, older age and comorbidities were significantly more common. After adjusting by baseline characteristics, HD were associated with a higher mortality than SD (adjusted-OR 2.46, 95% CI 1.58 - 3.83, p<0.001) and with an increased risk of needing MV or death (adjusted-OR 2.50, p=0.001). Conversely, the risk of developing a severe ARDS was similar between groups. Interaction analysis showed that HD increased mortality exclusively in elderly patients. CONCLUSIONOur real-world experience advises against exceeding 1-1.5mg/kg/day of corticosteroids for severe COVID-19 with an ARDS, especially in older subjects. This reinforces the rationale of modulating rather than suppressing immune responses in these patients. SUMMARYIn patients with severe COVID-19, high doses of corticosteroids are associated with a higher mortality and risk of need for mechanical ventilation or death compared to standard doses. This deleterious effect is mainly observed in the elderly.