Optimal long-term antithrombotic treatment of patients with stable coronary artery disease and atrial fibrillation: "OLTAT registry".

BACKGROUND: The optimal long-term antithrombotic treatment of patients with stable coronary artery disease (CAD) and atrial fibrillation (AF) is a challenge in daily practice. We sought to determine the prevalence of hemorrhagic complications and ischaemic events depending on antithrombotic strategy in patients with stable CAD and AF. METHODS: The primary outcome was major adverse cardiac and cerebrovascular events (MACCE) defined as a composite of cardiovascular mortality, myocardial infarction and ischaemic stroke. The subsequent risks of MACCE and clinically significant bleedings requiring hospitalisation (major safety outcome) were analyzed in a propensity score-matched analysis by adjusted Cox regression models. RESULTS: Six hundred and six patients with high thrombotic and bleeding risks (mean age 73.4 ±â€¯9.8 years, 25.2% female, CHA2DS2-VASc score:4.7 ±â€¯1.5, and HAS-BLED score:3.1 ±â€¯1.0) were included, and 127 propensity-matched pairs were analyzed. At inclusion, 172 patients (28.4%) were on oral anticoagulation (OAC) alone (75.6% on VKA and 24.4% on DOAC) and 434 patients (71.6%) on OAC + single antiplatelet therapy (SAPT) (71.9% on VKA and 28.1% on DOAC). At 5-year follow-up, MACCE rate did not significantly differ in both groups (30.9% in OAC + SAPT vs. 26.8% in OAC alone; adjusted HR 1.1 [0.8-1.5], p = 0.58), but clinically significant bleedings (28.3% vs. 18.5%; adjusted HR 1.8 [1.2-2.8], p = 0.005) and total deaths (29.5% vs. 20.8%; adjusted HR 1.4 [95% CI 1.0-2.2], p = 0.049) were higher in patients with OAC + SAPT than in patients with OAC alone. CONCLUSIONS: In patients with stable CAD and AF, the addition of antiplatelet therapy to VKA or DOAC therapy was independently associated with a higher risk of bleeding and overall mortality, without significant reduction in cardiac and cerebral ischaemic events.

Dynamic properties of retino-geniculate synapses in the cat.

Simultaneous recordings from relay cells in the lateral geniculate nucleus (LGN) and their retinal afferents were used to examine the rules governing the transmission of spikes across the retino-geniculate synapse. Retinal spikes that terminate short retinal interspike intervals are much more likely to be transmitted across the synapse than spikes terminating longer intervals. This facilitation can be observed for interspike intervals as long as 50 ms when retinal firing rates are low, but the range of effective intervals decreases exponentially as retinal firing rate increases. Contribution, the fraction of LGN spikes triggered by an individual retinal afferent, is typically much higher during visual stimulation than during maintained activity, and these differences are unrelated to presynaptic or postsynaptic firing rate. It is suggested that this effect is a manifestation of increased synchronization of spikes among retinal afferents to the geniculate cell during structured visual stimulation, and that this synchronization offers a means of enhancing signal-to-noise ratio at the retino-geniculate synapse. Cross-correlograms between geniculate burst spikes and retinal afferents often contain two distinct peaks; a short latency peak that results from direct coupling between burst spikes and retinal input spikes, and a longer latency peak that represents indirect coupling in which retinal spikes trigger the calcium spike underlying the burst. Direct coupling is most likely to occur for the later spikes in the burst, and is present regardless of whether the calcium spike underlying the burst is triggered by the same or a different retinal afferent. These results further illuminate the relationship between tonic and burst modes of retino-geniculate transmission and indicate that bursts in LGN relay cells can be viewed as a mechanism of signal amplification, producing signals whose timing is potentially related to the temporal structure of a stimulus, independent of presynaptic and postsynaptic firing rate. This mechanism also appears to capitalize on the synchronization that is present among parallel retinal afferents to a geniculate cell.

Cyclic AMP-dependent protein kinase mediates ocular dominance shifts in cat visual cortex.

Visual experience during a critical period early in postnatal development can change connections within mammalian visual cortex. In a kitten at the peak of the critical period (approximately P28-42), brief monocular deprivation can lead to complete dominance by the open eye, an ocular dominance shift. This process is driven by activity from the eyes, and depends on N-methyl-D-aspartate (NMDA) receptor activation. The components of the intracellular signaling cascade underlying these changes have not all been identified. Here we show that inhibition of protein kinase A (PKA) by Rp-8-Cl-cAMPS blocks ocular dominance shifts that occur following monocular deprivation early in the critical period. Inhibition of protein kinase G by Rp-8-Br-PET-cGMPS had no effect, indicating a specificity for the PKA pathway. Enhancement of PKA activity late in the critical period with Sp-8-Cl-cAMPS did not increase plasticity. PKA is a necessary component of the pathway leading to cortical plasticity during the critical period.

Number and distribution of retinal ganglion cells in anubis baboons (Papio anubis).

The number of retinal ganglion cells in Papio anubis was determined from light microscopic observations of wholemounted and vertically sectioned retinal tissue and electron microscopic examination of optic nerve cross sections. The total number of ganglion cells ranged from 1.41 to 1.81 million (mean 1.58 million, n = 6, SD = 169,927) per retina. The distribution of ganglion cells in cresyl violet stained wholemounts was also examined. Isodensity contours were almost circular perifoveally, but became horizontally elongated outside of the central retina, providing strong evidence for a visual streak. Ganglion cell somata within the streak were found to be significantly smaller than those outside of the streak in comparing regions of equal density. Finally, the distribution of blood vessels within the retina formed a watershed pattern with its crux centered on the ridge of this horizontally oriented high-density zone. Combined, these features indicate that anubis baboons possess a visual streak specialization as reported for lagomorphs, felines, and several primate species. Further, the visual streak appears more pronounced in anubis baboons than in any other primate species studied to date, with the possible exception of Homo sapiens, a similarly ground-dwelling/foraging and secondarily terrestrial species.