Dynamic Assessment of Pulmonary Artery Pulsatility Index Provides Incremental Risk Assessment for Early Right Ventricular Failure After Left Ventricular Assist Device.

BACKGROUND: The pulmonary artery pulsatility index (PAPi) has been studied to predict right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation, but only as a single time point before LVAD implantation. Multiple clinical factors and therapies impact RV function in pre-LVAD patients. Thus, we hypothesized that serial PAPi measurements during cardiac intensive care unit (CICU) optimization before LVAD implantation would provide incremental risk stratification for early RVF after LVAD implantation. METHODS AND RESULTS: Consecutive patients who underwent sequential pulmonary artery catherization with cardiac intensive care optimization before durable LVAD implantation were included. Serial hemodynamics were reviewed retrospectively across the optimization period. The optimal PAPi was defined by the initial PAPi + the PAPi at optimized hemodynamics. RVF was defined as need for a right ventricular assist device or prolonged inotrope use (>14 days postoperatively). Patients with early RVF had significantly lower mean optimal PAPi (3.5 vs 7.5, P < .001) compared with those who did not develop RVF. After adjusting for established risk factors of early RVF after LVAD implantation, the optimal PAPi was independently and incrementally associated with early RVF after LVAD implantation (odds ratio 0.64, 95% confidence interval 0.532-0.765, P < .0001). CONCLUSIONS: Optimal PAPi achieved during medical optimization before LVAD implantation provides independent and incremental risk stratification for early RVF, likely identifying dynamic RV reserve.

Radial artery occlusion after transradial approach to cardiac catheterization.

Radial artery occlusion (RAO) is the most common complication of the transradial approach (TRA) to cardiac catheterization, with a reported incidence between 0.8 % and 30 %. RAO is likely the result of acute thrombus formation and complicated by neointimal hyperplasia. Most RAO are asymptomatic with rare cases of acute hand or digit ischemia reported in the literature. The role of testing for dual circulation to the hand in determining the safety of TRA as it relates to symptomatic RAO is controversial; however, modifiable risk factors like low sheath-to-artery ratio, adequate anticoagulation, and non-occlusive ("patent") hemostasis are likely to prevent RAO. This review examines the incidence of RAO, potential mechanisms leading to RAO, and strategies to prevent and treat RAO.

Graph neural networks and cross-protocol analysis for detecting malicious IP addresses.

An internet protocol (IP) address is the foundation of the Internet, allowing connectivity between people, servers, Internet of Things, and services across the globe. Knowing what is connecting to what and where connections are initiated is crucial to accurately assess a company's or individual's security posture. IP reputation assessment can be quite complex because of the numerous services that may be hosted on that IP address. For example, an IP might be serving millions of websites from millions of different companies like web hosting companies often do, or it could be a large email system sending and receiving emails for millions of independent entities. The heterogeneous nature of an IP address typically makes it challenging to interpret the security risk. To make matters worse, adversaries understand this complexity and leverage the ambiguous nature of the IP reputation to exploit further unsuspecting Internet users or devices connected to the Internet. In addition, traditional techniques like dirty-listing cannot react quickly enough to changes in the security climate, nor can they scale large enough to detect new exploits that may be created and disappear in minutes. In this paper, we introduce the use of cross-protocol analysis and graph neural networks (GNNs) in semi-supervised learning to address the speed and scalability of assessing IP reputation. In the cross-protocol supervised approach, we combine features from the web, email, and domain name system (DNS) protocols to identify ones which are the most useful in discriminating suspicious and benign IPs. In our second experiment, we leverage the most discriminant features and incorporate them into the graph as nodes' features. We use GNNs to pass messages from node to node, propagating the signal to the neighbors while also gaining the benefit of having the originating nodes being influenced by neighboring nodes. Thanks to the relational graph structure we can use only a small portion of labeled data and train the algorithm in a semi-supervised approach. Our dataset represents real-world data that is sparse and only contain a small percentage of IPs with verified clean or suspicious labels but are connected. The experimental results demonstrate that the system can achieve 85.28 % accuracy in detecting malicious IP addresses at scale with only 5 % of labeled data.

Caffeine blocks disruption of blood brain barrier in a rabbit model of Alzheimer's disease.

High levels of serum cholesterol and disruptions of the blood brain barrier (BBB) have all been implicated as underlying mechanisms in the pathogenesis of Alzheimer's disease. Results from studies conducted in animals and humans suggest that caffeine might be protective against Alzheimer's disease but by poorly understood mechanisms. Using rabbits fed a cholesterol-enriched diet, we tested our hypothesis that chronic ingestion of caffeine protects against high cholesterol diet-induced disruptions of the BBB. New Zealand rabbits were fed a 2% cholesterol-enriched diet, and 3 mg caffeine was administered daily in drinking water for 12 weeks. Total cholesterol and caffeine concentrations from blood were measured. Olfactory bulbs (and for some studies hippocampus and cerebral cortex as well) were evaluated for BBB leakage, BBB tight junction protein expression levels, activation of astrocytes, and microglia density using histological, immunostaining and immunoblotting techniques. We found that caffeine blocked high cholesterol diet-induced increases in extravasation of IgG and fibrinogen, increases in leakage of Evan's blue dye, decreases in levels of the tight junction proteins occludin and ZO-1, increases in astrocytes activation and microglia density where IgG extravasation was present. Chronic ingestion of caffeine protects against high cholesterol diet-induced increases in disruptions of the BBB, and caffeine and drugs similar to caffeine might be useful in the treatment of Alzheimer's disease.

Lower Repeat Revascularization Rates Among Patients With Prior Coronary Artery Bypass Graft Surgery are Due to Lack of Adequate Target Vessels.

BACKGROUND: Studies comparing percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery in patients with multivessel coronary artery disease (CAD) have shown lower repeat revascularization rates in patients who undergo CABG. The reason remains unclear. METHODS: We identified patients with multivessel CAD who received CABG or PCI enrolled in the Duke Databank for Cardiovascular Disease (2003 to 2012). We compared the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) between the two groups. Clinically performed follow-up angiograms for CABG patients were reviewed to determine adequacy of intervenable targets. RESULTS: A total of 1555 patients were included: 861 underwent PCI and 694 underwent CABG. Patients with index PCI were more often female, African-American, presented with ST-elevation myocardial infarction (MI), and had previous MI; they were less often diabetic and had less heart failure or proximal left anterior descending disease. The adjusted hazard ratio of MACCE for CABG vs PCI was 0.68 (95% confidence interval, 0.58-0.80; P<.001). The adjusted odds ratio for repeat revascularization for CABG vs PCI was 0.45 (95% confidence interval, 0.28-0.72; P<.001). Fifty-seven patients with index CABG were found to have ≥1 occluded graft on subsequent angiography without repeat revascularization; 48 patients (6.9%) had inadequate targets for intervention. CONCLUSION: Among patients with multivessel CAD, repeat revascularization rates are lower among CABG patients compared with PCI patients. However, a high proportion of CABG patients with occluded grafts on repeat angiography lack targets for repeat revascularization. This may partially explain the disparity in repeat revascularization rates and suggests that future comparison studies should additionally assess angiographic outcomes.

Role of Endolysosomes in Skeletal Muscle Pathology Observed in a Cholesterol-Fed Rabbit Model of Alzheimer's Disease.

Deficits in skeletal muscles contribute not only to the functional decline in people living with Alzheimer's disease (AD), but also to AD pathogenesis. We have shown that endolysosome dysfunction plays an important role in the development of AD pathological features in a cholesterol-fed rabbit model of AD. Interestingly we observed in skeletal muscle from the rabbit AD model increased deposition of Aß, phosphorylated tau, and ubiquitin. Here, we tested the hypothesis that endolysosome dysfunction commonly occurs in skeletal muscle and brain in this rabbit model of AD. In skeletal muscle of rabbits fed a 2% cholesterol-enriched diet for 12 weeks we observed the presence of abnormally enlarged endolysosomes, in which were increased accumulations of free cholesterol and multiple AD marker proteins subject to misfolding and aggregation including Aß, phosphorylated tau, and ubiquitin. Moreover, in skeletal muscle of rabbits fed the cholesterol-enriched diet we observed decreased specific activities of three different lysosome enzymes. Our results suggest that elevated levels of plasma cholesterol can disturb endolysosome structure and function as well as promote the development of AD-like pathological features in skeletal muscle and that these organellar changes might contribute to the development of skeletal muscle deficits in AD.

A comparison of radial and femoral access for cardiac catheterization.

Over the past several years, the transradial approach (TRA) for cardiac catheterization has become increasingly adopted in the United States. The increased utilization of the TRA is grounded on 2 decades of research, showing reduced bleeding and vascular complications to complement improved patient quality of life. However, the concern over cost, radiation exposure, and acknowledged "learning curve" has kept the transfemoral approach (TFA) the mainstay of most US catheterization laboratories. More recent larger multi-centered randomized studies have aimed to address outcomes and these concerns between the TR and TF approaches. This article will review the changing trends in TRA in the US, discuss clinical (bleeding and mortality) and non-clinical (quality of life and cost) outcomes from recent randomized studies, and finally discuss certain aspects when it comes to adopting TRA.

Endolysosome mechanisms associated with Alzheimer's disease-like pathology in rabbits ingesting cholesterol-enriched diet.

Alzheimer's disease (AD) is characterized clinically by progressive disturbances in memory, judgment, reasoning, and olfaction, and pathologically by loss of synaptic integrity, extracellular accumulations of amyloid-ß (Aß) containing plaques, and intraneuronal tangles composed of hyperphosphorylated tau. Endolysosome dysfunction is one of the earliest pathological features of AD and cholesterol, a known risk factor for sporadic AD, is up-taken into neurons via receptor-mediated endocytosis. Accordingly, we determined the extent to which endolysosome dysfunction is associated with pathological features observed in rabbits fed cholesterol-enriched diet; a well-characterized model of sporadic AD. Olfactory bulbs were taken from rabbits fed for 12 weeks a diet enriched with 2% cholesterol and endolysosome morphology and function as well as AD-like pathology were investigated using enzyme activity measurements, immunoblotting and immunostaining techniques. In olfactory bulbs of rabbits fed cholesterol-enriched diet, we observed enlarged endolysosomes containing increased accumulations of ApoB containing cholesterol and increased accumulations of synaptophysin, Aß, and phosphorylated tau. The cholesterol-enriched diet also significantly decreased specific enzyme activities of the endolysosome enzymes acid phosphatase and cathepsin D. Decreased synaptic area was present in olfactory bulbs of cholesterol-fed rabbits as indicated by significant decreases in protein expression levels of the synaptic area marker protein synaptophysin. Our results suggest strongly that elevated circulating cholesterol plays an important role in the pathogenesis of AD, and that alterations in endolysosome structure and function are associated with cholesterol diet-induced AD-like pathology.