Objectives Three intravascular ultrasound (IVUS) signatures have been associated with coronary artery disease instability: echo attenuation, an intraplaque echolucent zone, and spotty calcification. ...The aim of this study was to investigate the substrates responsible for these IVUS signatures in a relatively large series of post-mortem human coronary samples. Background The exact mechanisms and pathological correlates underlying echo attenuation, an intraplaque echolucent zone, and spotty calcification remain poorly understood. Methods IVUS was compared with near-infrared spectroscopic detection of lipid core plaque and histopathology in 2,294 vessel segments from 151 coronary specimens from 62 patients at necropsy using the modified American Heart Association classification. Results IVUS detected echo-attenuated plaques in 18.3% of segments, echolucent plaques in 10.5% of segments, and spotty calcification in 14.4% of segments. Histopathologically, 91.4% of echo-attenuated plaques corresponded to either a fibroatheroma (FA) with a necrotic core (NC) or pathological intimal thickening with a lipid pool; almost all segments with superficial echo attenuation indicated the presence of an FA with an advanced NC. Echolucent plaques indicated the presence of a relatively smaller lipid or NC compared with echo-attenuated plaques (thickness: 0.51 mm interquartile range (IQR): 0.35 to 0.64 mm vs. 0.70 mm IQR: 0.54 to 0.92 mm p < 0.001; arc: 74.5° IQR: 59.0° to 101.0° vs. 90° IQR: 70.0° to 112.0° p < 0.001), although 82.8% of superficial echolucent zones indicated an NC-containing FA. IVUS spotty calcification, especially when superficial in location (72.6%), was often associated with an FA with calcium deposits and had smaller arcs of calcium in the setting of FA compared with fibrocalcific plaques (37.5° IQR: 23.0° to 53.0° vs. 59.0° IQR: 46.0° to 69.0°; p < 0.001). Comparisons between IVUS and near-infrared spectroscopy revealed that echo-attenuated plaques contained the highest probability of near-infrared spectroscopy–derived lipid core plaque, followed by echolucent plaques and spotty calcifications. Conclusions This study demonstrated that echo-attenuated plaque, especially superficial echo attenuation, was the most reliable IVUS signature for identifying a high-risk plaque (i.e., an FA containing a large NC).
Aerobic exercise intensity prescription is a key issue in cardiac rehabilitation, being directly linked to both the amount of improvement in exercise capacity and the risk of adverse events during ...exercise. This joint position statement aims to provide professionals with up-to-date information regarding the identification of different exercise intensity domains, the methods of direct and indirect determination of exercise intensity for both continuous and interval aerobic training, the effects of the use of different exercise protocols on exercise intensity prescription and the indications for recommended exercise training prescription in specific cardiac patients' groups. The importance of functional evaluation through exercise testing prior to starting an aerobic training program is strongly emphasized, and ramp incremental cardiopulmonary exercise test, when available, is proposed as the gold standard for a physiologically comprehensive exercise intensity assessment and prescription. This may allow a shift from a 'range-based' to a 'threshold-based' aerobic exercise intensity prescription, which, combined with thorough clinical evaluation and exercise-related risk assessment, could maximize the benefits obtainable by the use of aerobic exercise training in cardiac rehabilitation.
Abstract Since the publication of the 2012 guidelines new literature has emerged to inform decision-making. The 2016 guidelines primary panel selected a number of clinically relevant questions and ...has produced updated recommendations, on the basis of important new findings. In subjects with clinical atherosclerosis, abdominal aortic aneurysm, most subjects with diabetes or chronic kidney disease, and those with low-density lipoprotein cholesterol ≥ 5 mmol/L, statin therapy is recommended. For all others, there is an emphasis on risk assessment linked to lipid determination to optimize decision-making. We have recommended nonfasting lipid determination as a suitable alternative to fasting levels. Risk assessment and lipid determination should be considered in individuals older than 40 years of age or in those at increased risk regardless of age. Pharmacotherapy is generally not indicated for those at low Framingham Risk Score (FRS; <10%). A wider range of patients are now eligible for statin therapy in the FRS intermediate risk category (10%-19%) and in those with a high FRS (> 20%). Despite the controversy, we continue to advocate for low-density lipoprotein cholesterol targets for subjects who start therapy. Detailed recommendations are also presented for health behaviour modification that is indicated in all subjects. Finally, recommendation for the use of nonstatin medications is provided. Shared decision-making is vital because there are many areas in which clinical trials do not fully inform practice. The guidelines are meant to be a platform for meaningful conversation between patient and care provider so that individual decisions can be made for risk screening, assessment, and treatment.
Dental calculus (calcified dental plaque) is prevalent in archaeological skeletal collections and is a rich source of oral microbiome and host-derived ancient biomolecules. Recently, it has been ...proposed that dental calculus may provide a more robust environment for DNA preservation than other skeletal remains, but this has not been systematically tested. In this study, shotgun-sequenced data from paired dental calculus and dentin samples from 48 globally distributed individuals are compared using a metagenomic approach. Overall, we find DNA from dental calculus is consistently more abundant and less contaminated than DNA from dentin. The majority of DNA in dental calculus is microbial and originates from the oral microbiome; however, a small but consistent proportion of DNA (mean 0.08 ± 0.08%, range 0.007-0.47%) derives from the host genome. Host DNA content within dentin is variable (mean 13.70 ± 18.62%, range 0.003-70.14%), and for a subset of dentin samples (15.21%), oral bacteria contribute > 20% of total DNA. Human DNA in dental calculus is highly fragmented, and is consistently shorter than both microbial DNA in dental calculus and human DNA in paired dentin samples. Finally, we find that microbial DNA fragmentation patterns are associated with guanine-cytosine (GC) content, but not aspects of cellular structure.
Coevolutionary models suggest that herbivores drive diversification and community composition in plants. For herbivores, many questions remain regarding how plant defenses shape host choice and ...community structure. We addressed these questions using the tree genus Inga and its lepidopteran herbivores in the Amazon. We constructed phylogenies for both plants and insects and quantified host associations and plant defenses. We found that similarity in herbivore assemblages between Inga species was correlated with similarity in defenses. There was no correlation with phylogeny, a result consistent with our observations that the expression of defenses in Inga is independent of phylogeny. Furthermore, host defensive traits explained 40% of herbivore community similarity. Analyses at finer taxonomic scales showed that different lepidopteran clades select hosts based on different defenses, suggesting taxon-specific histories of herbivore–host plant interactions. Finally, we compared the phylogeny and defenses of Inga to phylogenies for the major lepidopteran clades. We found that closely related herbivores fed on Inga with similar defenses rather than on closely related plants. Together, these results suggest that plant defenses might be more evolutionarily labile than the herbivore traits related to host association. Hence, there is an apparent asymmetry in the evolutionary interactions between Inga and its herbivores. Although plants may evolve under selection by herbivores, we hypothesize that herbivores may not show coevolutionary adaptations, but instead “chase” hosts based on the herbivore’s own traits at the time that they encounter a new host, a pattern more consistent with resource tracking than with the arms race model of coevolution.
Background
Transcarotid artery revascularization (TCAR) was approved by the Food and Drug Administration in 2015 for patients with carotid artery stenosis. However, no randomized trial to evaluate ...TCAR has been performed to date, and previous reports have important limitations. Accordingly, we measured stroke or death after TCAR compared with carotid endarterectomy (CEA) and transfemoral carotid artery stenting (TF‐CAS).
Methods and Results
We used the Vascular Quality Initiative registry to study patients who underwent TCAR, CEA, or TF‐CAS from September 2016 to June 2021. Our primary outcomes were perioperative and 1‐year stroke or death. We used logistic regression for risk adjustment for perioperative outcomes and Cox regression for risk adjustment for 1‐year outcomes. We used a 2‐stage residual inclusion instrumental variable (IV) method to adjust for selection bias and other unmeasured confounding. Our instrument was a center's preference to perform TCAR versus CEA or TF‐CAS. We performed a subgroup analysis stratified by presenting neurologic symptoms. We studied 21 234 patients who underwent TCAR, 82 737 who underwent CEA, and 14 595 who underwent TF‐CAS across 662 centers. The perioperative rate of stroke or death was 2.0% for TCAR, 1.7% for CEA, and 3.7% for TF‐CAS (
P
<0.001). Compared with TCAR, the IV‐adjusted odds ratio of perioperative stroke or death for CEA was 0.74 (95% CI, 0.55–0.99) and for TF‐CAS was 1.66 (95% CI, 0.99–2.79). Results were similar among both symptomatic and asymptomatic patients. The 1‐year rate of stroke or death was 6.4% for TCAR, 5.2% for CEA, and 9.7% for TF‐CAS (
P
<0.001). Compared with TCAR, the IV‐adjusted hazard ratio of 1 year stroke or death for CEA was 0.97 (95% CI, 0.80–1.17), and for TF‐CAS was 1.45 (95% CI, 1.04–2.02). IV analysis further demonstrated that symptomatic patients with carotid stenosis had the lowest 1‐year likelihood of stroke or death with TCAR (compared with TCAR, symptomatic IV‐adjusted hazard ratio for CEA: 1.30 95% CI, 1.04–1.64, and TF‐CAS: 1.86 95% CI, 1.27–2.71).
Conclusions
Perioperative stroke or death was greater following TCAR when compared with CEA. However, at 1 year there was no statistically significant difference in stroke or death between the 2 procedures. TCAR performed favorably compared with TF‐CAS at both time points. Although CEA remains the gold standard procedure for patients with carotid stenosis, TCAR appears to be a safe alternative to CEA and TF‐CAS when used selectively and may be useful when treating symptomatic patients.
Ceftibuten is an established, oral, third-generation cephalosporin in early clinical development in combination with an oral prodrug of avibactam for the treatment of complicated urinary tract ...infections, including acute pyelonephritis. We evaluated the
activity of ceftibuten-avibactam against 1,165 Enterobacterales isolates selected from the 2016-2020 ATLAS global surveillance program based upon their β-lactamase genotype, β-lactam-susceptible phenotype, species identification, and specimen source (95.8% urine). MICs were determined by CLSI broth microdilution. Avibactam was tested at a fixed concentration of 4 μg/mL. Molecular methods were used to identify β-lactamase genes. Ceftibuten-avibactam inhibited 90% (MIC
) of ESBL-producing (
= 645), KPC-producing (
= 60), chromosomal AmpC-positive (
= 100), OXA-48-like-producing (
= 50), and acquired AmpC-producing (
= 110) isolates at concentrations of 0.12, 0.5, 1, 2, and 4 μg/mL, respectively. At concentrations of ≤1 and ≤8 μg/mL, ceftibuten-avibactam inhibited 98.4 and 99.2% of ESBL-positive isolates; 96.7 and 100% of KPC-positive isolates; 91.0 and 99.0% of chromosomal AmpC-positive isolates; 86.0 and 96.0% of OXA-48-like-positive isolates; and 85.5 and 91.8% of acquired AmpC-positive isolates. Against ESBL-producing, KPC-producing, chromosomal AmpC-positive, OXA-48-like-producing, and acquired AmpC-producing isolates, ceftibuten-avibactam was 256-, 128-, >64-, >32-, and > 16-fold more potent than ceftibuten alone. The potency of ceftibuten-avibactam was 4-fold greater than ceftazidime-avibactam against ESBL-producing (ceftibuten-avibactam MIC
, 0.12 μg/mL; ceftazidime-avibactam MIC
, 0.5 μg/mL) and KPC-producing (0.5 μg/mL; 2 μg/mL) isolates, equivalent to ceftazidime-avibactam (MIC
, 2 μg/mL) against OXA-48-like-producing isolates, 2-fold less active than ceftazidime-avibactam (1 μg/mL; 0.5 μg/mL) against chromosomal AmpC-positive isolates, and 4-fold less active than ceftazidime-avibactam (4 μg/mL; 1 μg/mL) against acquired AmpC-producing isolates. Continued development of ceftibuten-avibactam appears justified.
Cardiac rehabilitation (CR) is an efficacious yet underused treatment for patients with coronary artery disease. The objective of this study was to determine the association between CR completion and ...mortality and resource use.
We conducted a prospective cohort study of 5886 subjects (20.8% female; mean age, 60.6 years) who had undergone angiography and were referred for CR in Calgary, AB, Canada, between 1996 and 2009. Outcomes of interest included freedom from emergency room visits, hospitalization, and survival in CR completers versus noncompleters, adjusted for clinical covariates, treatment strategy, and coronary anatomy. Hazard ratios for events for CR completers versus noncompleters were also constructed. A propensity model was used to match completers to noncompleters on baseline characteristics, and each outcome was compared between propensity-matched groups. Of the subjects referred for CR, 2900 (49.3%) completed the program, and an additional 554 subjects started but did not complete CR. CR completion was associated with a lower risk of death, with an adjusted hazard ratio of 0.59 (95% confidence interval, 0.49-0.70). CR completion was also associated with a decreased risk of all-cause hospitalization (adjusted hazard ratio, 0.77; 95% confidence interval, 0.71-0.84) and cardiac hospitalization (adjusted hazard ratio, 0.68; 95% confidence interval, 0.55-0.83) but not with emergency room visits. Propensity-matched analysis demonstrated a persistent association between CR completion and reduced mortality.
Among those coronary artery disease patients referred, CR completion is associated with improved survival and decreased hospitalization. There is a need to explore reasons for nonattendance and to test interventions to improve attendance after referral.
Evolutionary radiations are prominent and pervasive across many plant lineages in diverse geographical and ecological settings; in neotropical rainforests there is growing evidence suggesting that a ...significant fraction of species richness is the result of recent radiations. Understanding the evolutionary trajectories and mechanisms underlying these radiations demands much greater phylogenetic resolution than is currently available for these groups. The neotropical tree genus Inga (Leguminosae) is a good example, with ~300 extant species and a crown age of 2-10 MY, yet over 6 kb of plastid and nuclear DNA sequence data gives only poor phylogenetic resolution among species. Here we explore the use of larger-scale nuclear gene data obtained though targeted enrichment to increase phylogenetic resolution within Inga. Transcriptome data from three Inga species were used to select 264 nuclear loci for targeted enrichment and sequencing. Following quality control to remove probable paralogs from these sequence data, the final dataset comprised 259,313 bases from 194 loci for 24 accessions representing 22 Inga species and an outgroup (Zygia). Bayesian phylogenies reconstructed using either all loci concatenated or a gene-tree/species-tree approach yielded highly resolved phylogenies. We used coalescent approaches to show that the same targeted enrichment data also have significant power to discriminate among alternative within-species population histories within the widespread species I. umbellifera. In either application, targeted enrichment simplifies the informatics challenge of identifying orthologous loci associated with de novo genome sequencing. We conclude that targeted enrichment provides the large volumes of phylogenetically-informative sequence data required to resolve relationships within recent plant species radiations, both at the species level and for within-species phylogeographic studies.
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