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.

The coronary vasodilating action of 1,5-benzothiazepine derivatives and the structureactivity relationship were examined in the anesthetized dog. 2-(4-Methoxyphenyl), 3-acyloxy or alkyloxy, 5-dimethylaminoethyl and 7-hydrogen moieties were important for vasodilation.The action of the derivatives was found to be stereospecific for the d-cis-isomer.Based on these findings, it can be concluded that d-3-acetoxy-cis-2,3-(5H) -one hydrochloride (CRD-401) was the most potent compound among the derivatives tested. The metabolites of dl-isomer of CRD-401, i.e. deacetyl and deacetyl-O-or N-demethyl compounds, were less active and less toxic than the parent compound.

Overall arrhythmia burden is similar between the 2 groups, but the extracardiac Fontan group had a higher incidence of early bradyarrhythmias. There was no difference in the incidence of late tachyarrhythmias over time between the 2 operations. Therefore, the type of Fontan performed should be based on factors other than an anticipated reduction in arrhythmia burden from the extracardiac conduit.

Abstract-Diltiazem, a new 1,5-benzothiazepine derivative, antagonized calcium ion and thus caused a reduction in the contractile force of isolated papillary muscle. The antagonistic ratio of diltiazem to calcium ion was estimated to be approx. 1 : 100. A lower concentration of diltiazem (2.2 yX 10-13 M) decreased the contractile force without affecting significantly the intracellularly recorded resting and action potentials. When the concentration of the compound was increased to 2.2 x 10-5 M, only the maximum rate of rise of the action potential was reduced, while the other parameters of the ac tion potential were also affected at 1

Uniparental disomy denotes a situation when an individual has inherited two copies of a specific chromosome from a single parent. Uniparental disomy has been demonstrated to be involved in the pathogenesis of recessively inherited diseases in rare cases. Here we report a patient of Japanese origin with Herlitz junctional epidermolysis bullosa (OMIM no. 226700), who died at the age of 8 mo from complications of the disease. The mutation analysis revealed that the proband was homozygous for a nonsense mutation C553X in the LAMC2 gene encoding the gamma2 chain of laminin 5. The father was a heterozygous carrier of this mutation whereas the mother had two normal alleles of this gene. The patient showed homozygosity for 15 known intragenic polymorphisms in the LAMC2 gene. Furthermore, genotype analysis, performed from the parents and the proband, using 16 microsatellite markers spanning the entire chromosome 1, revealed that the patient was homozygous for all markers tested, and that these alleles originated from the father. Among the 16 markers, eight were fully informative for the absence of the maternal chromosome 1 in the proband, suggesting that the patient had complete paternal isodisomy of this chromosome. Thus, the Herlitz junctional epidermolysis bullosa phenotype in this patient is caused by homozygous LAMC2 mutation C553X that is of paternal origin and results from nondisjunction and uniparental disomy involving monosomy rescue. This is a novel mechanism resulting in Herlitz junctional epidermolysis bullosa and has implications for assessment of the risk in subsequent pregnancies.