Aims The EURO-ENDO registry aimed to study the management and outcomes of patients with infective endocarditis (IE). Methods and results Prospective cohort of 3116 adult patients (2470 from Europe, 646 from non-ESC countries), admitted to 156 hospitals in 40 countries between January 2016 and March 2018 with a diagnosis of IE based on ESC 2015 diagnostic criteria. Clinical, biological, microbiological, and imaging [echocardiography, computed tomography (CT) scan, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)] data were collected. Infective endocarditis was native (NVE) in 1764 (56.6%) patients, prosthetic (PVIE) in 939 (30.1%), and device-related (CDRIE) in 308 (9.9%). Infective endocarditis was community-acquired in 2046 (65.66%) patients. Microorganisms involved were staphylococci in 1085 (44.1%) patients, oral streptococci in 304 (12.3%), enterococci in 390 (15.8%), and Streptococcus gallolyticus in 162 (6.6%). 18F-fluorodeoxyglucose positron emission tomography/computed tomography was performed in 518 (16.6%) patients and presented with cardiac uptake (major criterion) in 222 (42.9%) patients, with a better sensitivity in PVIE (66.8%) than in NVE (28.0%) and CDRIE (16.3%). Embolic events occurred in 20.6% of patients, and were significantly associated with tricuspid or pulmonary IE, presence of a vegetation and Staphylococcus aureus IE. According to ESC guidelines, cardiac surgery was indicated in 2160 (69.3%) patients, but finally performed in only 1596 (73.9%) of them. In-hospital death occurred in 532 (17.1%) patients and was more frequent in PVIE. Independent predictors of mortality were Charlson index, creatinine > 2 mg/dL, congestive heart failure, vegetation length > 10 mm, cerebral complications, abscess, and failure to undertake surgery when indicated. Conclusion Infective endocarditis is still a life-threatening disease with frequent lethal outcome despite profound changes in its clinical, microbiological, imaging, and therapeutic profiles.

Polymorphism at the ADH2 and ADH3 loci of alcohol dehydrogenase (ADH) has been shown to have an effect on the predisposition to alcoholism in Asian individuals. However, the results are not conclusive for white individuals. We have analyzed the ADH genotype of 876 white individuals from Spain (n ‫؍‬ 251), France (n ‫؍‬ 160), Germany (n ‫؍‬ 184), Sweden (n ‫؍‬ 88), and Poland (n ‫؍‬ 193). Peripheral blood samples from healthy controls and groups of patients with viral cirrhosis and alcohol-induced cirrhosis, as well as alcoholics with no liver disease, were collected on filter paper. Genotyping of the ADH2 and ADH3 loci was performed using polymerase chain reactionrestriction fragment length polymorphism methods on white cell DNA. In healthy controls, ADH2*2 frequencies ranged from 0% (France) to 5.4% (Spain), whereas ADH3*1 frequencies ranged from 47.6% (Germany) to 62.5% (Sweden). Statistically significant differences were not found, however, between controls from different countries, nor between patients with alcoholism and/or liver disease. When all individuals were grouped in nonalcoholics (n ‫؍‬ 451) and alcoholics (n ‫؍‬ 425), ADH2*2 frequency was higher in nonalcoholics (3.8%) than in alcoholics (1.3%) (P ‫؍‬ .0016), whereas the ADH3 alleles did not show differences. Linkage disequilibrium was found between ADH2 and ADH3, resulting in an association of the alleles ADH2*2 and ADH3*1, both coding for the most active enzymatic forms. In conclusion, the ADH2*2 allele decreases the risk for alcoholism, whereas the ADH2*2 and ADH3*1 alleles are found to be associated in the European population. (HEPATOLOGY 2000;31:984-989.)Ingested alcohol is mostly metabolized in the liver by the successive action of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Both enzymes exhibit genetic polymorphisms that influence the rate of conversion of ethanol to acetaldehyde, and of acetaldehyde to acetate. It has been consistently reported that ALDH2 is the most important alcohol-metabolizing gene affecting predisposition to alcoholism in Asian populations. The prevalence of the ALDH2*2 allele, which codes for a physiologically inactive mitochondrial ALDH form, is lower in alcoholics than in nonalcoholics. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] However, this allele has not been found in white individuals. 21 Regarding ADH, polymorphism is detected at the ADH2 and ADH3 loci. Alleles of ADH2 found in whites and Asians are ADH2*1 and ADH2*2, which encode for the low activity (␤1) and high activity (␤2) subunits, respectively. The kcat values for the resulting dimeric isozymes are very different: 9.2 min Ϫ1 for ␤1␤1 and 400 min Ϫ1 for ␤2␤2. 22 The ADH2*2 frequency is much higher in Asians (60%-80%) than in whites (0%-10%). 21 ADH3 alleles are ADH3*1 and ADH3*2, which produce the ␥1 and ␥2 subunits. The ␥1␥1 isozyme (kcat ϭ 87 min Ϫ1 ) is moderately more active than the ␥2␥2 isozyme (kcat ϭ 35 min Ϫ1 ). 22 ADH3*1 frequency is about 50% to 60% in whites and higher than 90% in Asians. 3,23 ...

Background Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19), exhibit a wide spectrum of disease behaviour. Since DNA methylation has been implicated in the regulation of viral infections and the immune system, we performed an epigenome-wide association study (EWAS) to identify candidate loci regulated by this epigenetic mark that could be involved in the onset of COVID-19 in patients without comorbidities. Methods Peripheral blood samples were obtained from 407 confirmed COVID-19 patients ≤ 61 years of age and without comorbidities, 194 (47.7%) of whom had mild symptomatology that did not involve hospitalization and 213 (52.3%) had a severe clinical course that required respiratory support. The set of cases was divided into discovery ( n = 207) and validation ( n = 200) cohorts, balanced for age and sex of individuals. We analysed the DNA methylation status of 850,000 CpG sites in these patients. Findings The DNA methylation status of 44 CpG sites was associated with the clinical severity of COVID-19. Of these loci, 23 (52.3%) were located in 20 annotated coding genes. These genes, such as the inflammasome component Absent in Melanoma 2 (AIM2) and the Major Histocompatibility Complex, class I C (HLA-C) candidates, were mainly involved in the response of interferon to viral infection. We used the EWAS-identified sites to establish a DNA methylation signature (EPICOVID) that is associated with the severity of the disease. Interpretation We identified DNA methylation sites as epigenetic susceptibility loci for respiratory failure in COVID-19 patients. These candidate biomarkers, combined with other clinical, cellular and genetic factors, could be useful in the clinical stratification and management of patients infected with the SARS-CoV-2. Funding The Unstoppable campaign of the Josep Carreras Leukaemia Foundation, the Cellex Foundation and the CERCA Programme/Generalitat de Catalunya.