Time course of ischemic and bleeding burden in consecutive patients undergoing transcatheter aortic valve replacement (FOCUS-ONE Registry).

BACKGROUND AND AIMS: Ischemic or bleeding events might occur after transcatheter aortic valve replacement (TAVR), with the potential to hamper clinical outcomes. This study aimed to characterize the average daily ischemic risks (ADIRs) and the average daily bleeding risks (ADBRs) over 1-year in all consecutive patients undergoing TAVR. METHODS: ADBR included all bleeding events according to VARC-2 definition, and ADIR included cardiovascular deaths, myocardial infarction and ischemic stroke. ADIRs and ADBRs were assessed within different timeframes post TAVR: acute (0-30 days), late (31-180 days), and very late (>181 days). Generalized estimating equations were used to test the least squares mean differences for the pairwise comparison of ADIRs and ADBRs. Our analysis was performed in the overall cohort and according to antithrombotic strategy (LT-OAC vs No LT-OAC). RESULTS: Ischemic burden was higher than bleeding burden, independently from the indication to LT-OAC, and in all timeframes examined. In the overall population, ADIRs were three-fold ADBRs (0.0467 [95% CI, 0.0431-0.0506] vs 0.0179 [95% CI, 0.0174-0.0185]; p < 0.001*). While ADIR was significantly higher in the acute phase, ADBR was relatively stable in all timeframes analysed. Of note, in LT-OAC population, OAC + SAPT group showed lower ischemic risk and higher bleeding events compared with OAC alone (ADIR: 0.0447 [95% CI: 0.0417-0.0477] vs 0.0642 [95% CI: 0.0557-0.0728]; p < 0.001*, ADBR 0.0395 [95% CI: 0.0381-0.0409] vs 0.0147 [95% CI: 0.0138-0.0156]; p < 0.001*). CONCLUSIONS: In patients undergoing TAVR Average daily risk fluctuates over time. However, ADIRs overcome ADBRs in all timeframes, especially in the acute phase and regardless of antithrombotic strategy adopted.

Adjusted indirect comparison of new oral anticoagulants for stroke prevention in atrial fibrillation.

BACKGROUND: Vit-K antagonists are the therapy of choice to prevent thromboembolic events due to atrial fibrillation since many years. New oral anticoagulants (NOA) showed encouraging results vs. warfarin but there are no data directly comparing different NOA. We performed an adjusted indirect meta-analysis. METHODS: Randomized controlled trials (RCTs) were searched. Efficacy end points were the cumulative rate of thomboembolic stroke (TES) and systemic embolism (SE). Main safety end point was the rate of hemorrhagic stroke (HS). RESULTS: Three RCTs (50578 patients) were included. Overall, NOA were comparable to warfarin according to the cumulative risk of TES and SE, as well as for TES alone. NOA were associated with a reduced rate of SE [OR 0.64 (0.44, 0.94], P=0.02]. Compared to warfarin, NOA were associated with a significantly reduced risk of HS [OR 0.43 (0.34, 0.55), P<0.001, NNT to avoid a HS 153] and all cause death [OR 0.90 [0.84, 0.96], P=0.03, NNT to save one fatality 43]. Head to head comparison showed that in terms of cumulative rate of TES/SE, as well as of TES, none of the NOA was significantly superior to the others (all Ps>0.05). Rivaroxaban showed superiority in the prevention of SE. Dabigatran 150 mg/twice daily was associated with the largest reduction in the risk of HS vs. warfarin and vs. other NOA. Overall mortality was quite comparable across NOA. CONCLUSION: Overall superiority of NOA over warfarin is largely influenced by the reduction of HS. Dabigatran 150 mg/twice daily seems to have the best risk/benefit profile.

Percutaneous coronary interventions in cardiac allograft vasculopathy: a single-center experience.

OBJECTIVE: Cardiac allograft vasculopathy represents an accelerated form of obstructive coronary disease. It is the main cause of late death following heart transplantation. Percutaneous coronary intervention is considered a palliative procedure due to high restenosis rates. The aim of this study was to review our experience with percutaneous coronary interventions using stents in cardiac transplant recipients. METHODS: The present analysis included all primary adult heart transplanted patients who had been discharged from the hospital after transplantation, had a clinical follow-up of 12 months and underwent percutaneous coronary intervention (PCI). RESULTS: Seventy heart transplanted patients underwent percutaneous revascularization. Our analysis comprised 85 first-vessel procedures resulting in treatment of 135 lesions. The mean time from heart transplantation to first intervention was 9.3 +/- 4.8 years. Primary success was obtained in 96% lesions; at least 1 recurrent stenosis event occurred in 16 patients with primarily successful PCI. Lesions treated with drug-eluting stents experienced recurrent stenosis in 16% of cases. During a mean follow-up after PCI of 45.2 +/- 41.7 months, 27 deaths (19 cardiac) and 1 late re-transplantation occurred after PCI. CONCLUSION: In cardiac transplant recipients, percutaneous coronary intervention with stents can be performed safely with high rates of primary success. Restenosis rates were higher compared with coronary interventions in native coronary arteries. Drug-eluting stents seemed to favorably impact restenosis compared with bare-metal stents. The clinical benefit from percutaneous coronary intervention may be reduced due to disease progression in untreated coronary segments.

Isolation and characterization of a priB mutant of Escherichia coli influencing plasmid copy number of delta rop ColE1-type plasmids.

The lethality induced by the overproduction in Escherichia coli of a heterologous protein was used to select bacterial mutants. In one of these, the mutation responsible was mapped to priB. We describe the isolation of this mutant, the sequencing of the mutated gene, and its in vivo effect on plasmid replication.

Structure of the gene complementing uvr-402 in Streptococcus pneumoniae: homology with Escherichia coli uvrB and the homologous gene in Micrococcus luteus.

The repair ability for UV-induced damage observed for Streptococcus pneumoniae proceeds through a system similar to the Uvr-dependent system in Escherichia coli. The DNA sequence of a gene complementing uvr-402, a mutation conferring UV sensitivity, was determined. Alignments of the deduced amino acid sequence revealed an extensive sequence homology of 55% with the UvrB protein of E. coli and 59% with the UvrB-homologous protein of Micrococcus luteus. Nucleotide-binding site consensus was observed. The high conservation of the uvrB-like gene among these three species suggests that the role of the UvrB protein and excision repair in general might be very important for cell survival.

Transfer of plasmid DNA to Brevibacterium lactofermentum by electrotransformation.

The Escherichia coli-Brevibacterium lactofermentum shuttle vector pBLA was introduced into intact cells of B. lactofermentum by electrotransformation. Several parameters of this procedure such as voltage and cell concentration were analysed. Optimal conditions gave an efficiency of 10(6) transformants per microgram of DNA. Two recalcitrant strains could be electrotransformed when an ampicillin pretreatment step was used. Electrotransformation experiments using DNAase or different structural forms of plasmid DNA showed that the electrotransformation process is quite different from natural transformation involving competence development. Restriction-modification-proficient B. lactofermentum could be efficiently electrotransformed with pBLA DNA isolated from E. coli. This restriction-modification system therefore seems to be overcome by electrotransformation. Thus electrotransformation may efficiently replace the protoplast bacterial transformation method.

Isolation and characterization of a restriction and modification deficient mutant of Brevibacterium lactofermentum.

In order to facilitate genetic engineering in amino-acid producing bacteria we have isolated two restriction-deficient Brevibacterium lactofermentum strains. They have been selected for their ability to obtain a high yield of plaques from CL31 phage which was grown on Corynebacterium lilium. These mutant strains do not restrict either phage DNA by transfection or DNA from the shuttle vector pBLA extracted from Escherichia coli by protoplast transformation. These mutants have also lost modification activity. We also report the presence of a restriction modification system in C. lilium ATCC 15990.

A shuttle vector system for Brevibacterium lactofermentum.

We have constructed a shuttle vector that replicates in Escherichia coli, Corynebacterium glutamicum and Brevibacterium lactofermentum, by fusion of a 4.4-kb cryptic plasmid isolated from B. lactofermentum and a derivative of pBR322. Resistance to erythromycin which is expressed in all three bacteria has been a useful selective marker. The frequency of homospecific transformation was 1.5 X 10(5) transformants/micrograms of hybrid plasmid DNA.

Transfection of Corynebacterium lilium protoplasts.

A protoplast transfection system has been developed for a lysine-producing bacterium, Corynebacterium lilium, using the DNA of phage CL31. Phage CL31 is lytic and specific to C. lilium and has a genome of approximately 48 kb. The transfection procedure involves a polyethylene-glycol-mediated introduction of the DNA into lysozyme-treated cells and has a maximum efficiency of 3 X 10(4) transfectants per microgram DNA.

[Lethality of the dnaB thermosensitive mutation of E. coli : comparison with thymine-less death]. / Léthalité de la mutation thermosensible dnaB de la bactérie E. coli : comparaison avec la mort des bactéries carencées en thymine

In a dnaB thermosensitive mutant of the bacterium E. coli, a shift to non-permissive conditions leads to the immediate cessation of DNA synthesis and results in a sizable loss of viability. Under conditions where protein synthesis is inhibited, either by addition of antibiotics (chloramphenicol, rifampicin) or by amino-acids starvation, there is a marked increase in viability. This is reminiscent of the behavior of thymine-deprived bacteria and suggests that both types of death, induced by a block in the displacement of the DNA-replicative fork, follow the same pattern.