Background: Causes of ischemic stroke in young adults (15–45 years) are diverse, but undetermined etiology is common in a majority of studies. Aims: The present series study aims to evaluate causes and changes in the etiological diagnosis of ischemic stroke in young adult patients admitted to a tertiary medical center over a period of 27 years. Methods: We retrospectively reviewed the records of patients with a first-ever stroke in the age range of 15–45 years who were admitted to the ‘12 de Octubre’ University Hospital between 1974 and 2002. Results: 272 young adults with ischemic stroke were identified. The etiological diagnoses were: undetermined in 36% of patients, large-artery atherosclerosis in 21%, cardioembolism in 17%, non-atherosclerotic vasculopathy in 17%, and other specific etiologies in 9%. While in the first study period (1974–1988) 45% of patients were diagnosed with uncertain etiology, in the last period (1989–2002) only 26% were diagnosed with cryptogenic stroke (45% with two or more potential etiologies identified; 45% with no identified cause despite complete evaluation, and 10% with incomplete evaluation). Conclusions: The etiological diagnosis of stroke in young adults has changed over time as a result of improvements in diagnostic workup. While cryptogenic stroke was the most frequent diagnosis in the past, today specific causes (non-atherosclerotic vasculopathy, large-artery atherosclerosis, cardioembolism and hematological disorder) are identified in the majority of patients.

Background: Spain has one of the highest incidences of coronavirus disease 2019 (COVID-19) worldwide, so Spanish health care workers (HCW) are at high risk of exposure. Our objective was to determine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody seroprevalence amongst HCW and factors associated with seropositivity. Methods: A cross-sectional study evaluating 6190 workers (97.8% of the total workforce of a healthcare-system of 17 hospitals across four regions in Spain) was carried out between April and June 2020, by measuring immunoglobulin G (IgG)-SARS-CoV-2 antibody titres and related clinical data. Exposure risk was categorized as high (clinical environment; prolonged/direct contact with patients), moderate (clinical environment; non-intense/no patient contact) and low (non-clinical environment). Results: A total of 6038 employees (mean age 43.8 years; 71% female) were included in the final analysis. A total of 662 (11.0%) were seropositive for IgG against SARS-CoV-2 (39.4% asymptomatic). Adding available PCR-testing, 713 (11.8%) employees showed evidence of previous SARS-CoV-2 infection. However, before antibody testing, 482 of them (67%) had no previous diagnosis of SARS-CoV-2-infection. Seroprevalence was higher in high- and moderate-risk exposure (12.1 and 11.4%, respectively) compared with low-grade risk subjects (7.2%), and in Madrid (13.8%) compared with Barcelona (7.6%) and Coruña (2.0%). High-risk [odds ratio (OR): 2.06; 95% confidence interval (CI): 1.63–2.62] and moderate-risk (OR: 1.77; 95% CI: 1.32–2.37) exposures were associated with positive IgG-SARS-CoV-2 antibodies after adjusting for region, age and sex. Higher antibody titres were observed in moderate–severe disease (median antibody-titre: 13.7 AU/mL) compared with mild (6.4 AU/mL) and asymptomatic (5.1 AU/mL) infection, and also in older (>60 years: 11.8 AU/mL) compared with younger (<30 years: 4.2 AU/mL) people. Conclusions: Seroprevalence of IgG-SARS-CoV-2 antibodies in HCW is a little higher than in the general population and varies depending on regional COVID-19 incidence. The high rates of subclinical and previously undiagnosed infection observed in this study reinforce the utility of antibody screening. An occupational risk for SARS-CoV-2 infection related to working in a clinical environment was demonstrated in this HCW cohort.

Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log₁₀ at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19.

Despite steady improvements in cardiovascular disease (CVD) prevention, a scarce proportion of patients achieve the recommended LDL-C goals, even under high-intensity lipid-lowering therapy (LLT). Our study aimed to evaluate the attainment rate of LDL-C targets recommended by the 2019 European guidelines, and to characterize potential factors associated with LDL-C goal achievement and change patterns in LLT. We conducted a retrospective, observational study on patients treated with high-intensity atorvastatin or rosuvastatin ± ezetimibe at cardiology and internal medicine clinics across Spain. It included 1570 evaluable patients (median age: 62 years; established CVD: 77.5% [myocardial infarction: 34.3%]; and 85.8% at very high cardiovascular risk). Rosuvastatin ± ezetimibe was the LLT in 52.2% of patients, and atorvastatin ± ezetimibe in 47.8%. LLT had been modified in 36.8% of patients (side effects: 10%), being the most common switch from atorvastatin- to rosuvastatin-based treatment (77.2%). The risk-based LDL-C goal attainment rate was 31.1%, with 78.2% high-risk and 71.7% very high-risk patients not achieving the recommended LDL-C targets. Established CVD and familial hypercholesterolemia were significantly associated with the non-achievement of LDL-C goals. Although having limitations, this study shows that the guideline-recommended LDL-C goal attainment rate is still suboptimal despite using high-intensity statin therapy in a real-world setting in Spain.