The Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) trial was a non-inferiority trial that compared percutaneous coronary intervention (PCI) using first-generation paclitaxel-eluting ...stents with coronary artery bypass grafting (CABG) in patients with de-novo three-vessel and left main coronary artery disease, and reported results up to 5 years. We now report 10-year all-cause death results.
The SYNTAX Extended Survival (SYNTAXES) study is an investigator-driven extension of follow-up of a multicentre, randomised controlled trial done in 85 hospitals across 18 North American and European countries. Patients with de-novo three-vessel and left main coronary artery disease were randomly assigned (1:1) to the PCI group or CABG group. Patients with a history of PCI or CABG, acute myocardial infarction, or an indication for concomitant cardiac surgery were excluded. The primary endpoint of the SYNTAXES study was 10-year all-cause death, which was assessed according to the intention-to-treat principle. Prespecified subgroup analyses were performed according to the presence or absence of left main coronary artery disease and diabetes, and according to coronary complexity defined by core laboratory SYNTAX score tertiles. This study is registered with ClinicalTrials.gov, NCT03417050.
From March, 2005, to April, 2007, 1800 patients were randomly assigned to the PCI (n=903) or CABG (n=897) group. Vital status information at 10 years was complete for 841 (93%) patients in the PCI group and 848 (95%) patients in the CABG group. At 10 years, 248 (28%) patients had died after PCI and 212 (24%) after CABG (hazard ratio 1·19 95% CI 0·99–1·43, p=0·066). Among patients with three-vessel disease, 153 (28%) of 546 had died after PCI versus 114 (21%) of 549 after CABG (hazard ratio 1·42 95% CI 1·11–1·81), and among patients with left main coronary artery disease, 95 (27%) of 357 had died after PCI versus 98 (28%) of 348 after CABG (0·92 0·69–1·22, pinteraction=0·023). There was no treatment-by-subgroup interaction with diabetes (pinteraction=0·60) and no linear trend across SYNTAX score tertiles (ptrend=0·20).
At 10 years, no significant difference existed in all-cause death between PCI using first-generation paclitaxel-eluting stents and CABG. However, CABG provided a significant survival benefit in patients with three-vessel disease, but not in patients with left main coronary artery disease.
German Foundation of Heart Research (SYNTAXES study, 5–10-year follow-up) and Boston Scientific Corporation (SYNTAX study, 0–5-year follow-up).
Plaque disruption (PD) causes most acute cardiovascular events. Although cholesterol crystals (CCs) have been observed in plaques, their role in PD was unknown. However, cholesterol expands with ...crystallization tearing and perforating fibrous tissues. This study tested the hypothesis that CCs can damage plaques and intima, triggering PD, as observed in tissues prepared without ethanol solvents that dissolve CCs. Coronary arteries of patients who died of acute coronary syndrome (n = 19) and non–acute coronary syndrome causes (n = 12) and carotid plaques from patients with (n = 51) and without (n = 19) neurologic symptoms were studied. Samples were examined for CCs perforating the intima using light and scanning electron microscopy (SEM) with ethanol or vacuum dehydration. In addition, fresh unfixed carotid plaques were examined at 37°C using confocal microscopy. Crystal content using SEM was scored from 0 to +3. SEM using vacuum dehydration had significantly higher crystal content compared with SEM using ethanol dehydration (+2.5 ± 0.53 vs +0.25 ± 0.46; p <0.0003), with enhanced detection of CC perforations. The presence of CCs using SEM and confocal microscopy was similar, suggesting that CC perforation can occur in vivo at 37°C. All patients with acute coronary syndrome had perforating CCs, but none was present in patients without acute coronary syndrome (p = 0.0001). For all plaques, there were strong associations of CCs with PD, thrombus, symptoms (p <0.0001), and plaque size (p <0.02). Crystal content was an independent predictor of thrombus and symptoms. In conclusion, by avoiding ethanol in tissue preparation, CCs perforating the intima were shown to be associated with PD. Crystal content was significantly associated with clinical events, suggesting that cholesterol crystallization may have a role in PD.
Objectives This study sought to determine whether variations in NOS1AP affect drug-induced long QT syndrome (LQTS). Background Use of antiarrhythmic drugs is limited by the high incidence of serious ...adverse events including QT prolongation and torsades de pointes. NOS1AP gene variants play a role in modulating QT intervals in healthy subjects and severity of presentation in LQTS. Methods This study carried out an association study using 167 single nucleotide polymorphisms (SNP) spanning the NOS1AP gene in 58 Caucasian patients experiencing drug-induced LQTS (dLQTS) and 87 Caucasian controls from the DARE (Drug-Induced Arrhythmia Risk Evaluation) study. Results The rs10800397 SNP was significantly associated with dLQTS (odds ratio OR: 3.3, 99.95% confidence interval CI: 1.0 to 10.8, p = 3.7 × 10–4 ). The associations were more pronounced in the subgroup of amiodarone users, in which 3 SNPs, including rs10800397, were significantly associated (most significant SNP: rs10919035: OR: 5.5, 99.95% CI: 1.1 to 27.9, p = 3.0 × 10–4 ). We genotyped rs10919035 in an independent replication cohort of 28 amiodarone dLQTS cases versus 173 control subjects (meta-analysis of both studies: OR: 2.81, 99.95% CI: 1.62 to 4.89, p = 2.4 × 10–4 ). Analysis of corrected QT interval among 74 control subjects from our dataset showed a similar pattern of significance over the gene region as the case-control analysis. This pattern was confirmed in 1,480 control subjects from the BRIGHT (British Genetics of Hypertension Study) cohort (top SNP from DARE: rs12734991 in meta-analysis: increase in corrected QT interval per C allele: 9.1 ± 3.2 ms, p = 1.7 × 10–4 ). Conclusions These results provide the first demonstration that common variations in the NOS1AP gene are associated with a significant increase in the risk of dLQTS. This study suggests that common variations in the NOS1AP gene may have relevance for future pharmacogenomic applications in clinical practice permitting safer prescription of drugs for vulnerable patients.
Abstract
OBJECTIVES
The very long-term mortality of off-pump and on-pump coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in a randomized complex coronary artery ...disease population is unknown. This study aims to investigate the impact of on-pump and off-pump CABG versus PCI on 10-year all-cause mortality.
METHODS
The SYNTAX trial randomized 1800 patients with three-vessel and/or left main coronary artery disease to PCI or CABG and assessed their survival at 10 years. In this sub-study, the hazard of mortality over 10 years was compared according to the technique of revascularization: on-pump CABG (n = 725), off-pump CABG (n = 128) and PCI (n = 903).
RESULTS
There was substantial inter-site variation in the use of off-pump CABG despite baseline characteristics being largely homogeneous among the 3 groups. The crude rate of mortality was significantly lower following on-pump CABG versus PCI 25.6% vs 28.4%, hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.65–0.96, while it was comparable between off-pump CABG and PCI (28.5% vs 28.4%, HR 0.98, 95% CI 0.69–1.40). After adjusting for the 9 variables included in the SYNTAX score II 2020, 10-year mortality remained significantly lower with on-pump CABG than PCI (HR 0.75 against PCI, P = 0.009).
CONCLUSIONS
In the SYNTAXES trial, 10-year mortality adjusted for major confounders was significantly lower following on-pump CABG compared to PCI. There was no evidence for unadjusted difference between off-pump CABG and PCI, although the unadjusted estimated HR had a wide CI. Site heterogeneity in the technique used in bypass surgery has had measurable effects on treatment performance.
For 30 years, the risks and benefits of the off-pump versus on-pump approach to coronary artery bypass grafting (CABG) surgery have been debated extensively 1.
Evidence is growing on the adverse neurodevelopmental effects of exposure to combustion-related air pollution. Project TENDR (Targeting Environmental Neurodevelopmental Risks), a unique collaboration ...of leading scientists, health professionals, and children's and environmental health advocates, has identified combustion-related air pollutants as critical targets for action to protect healthy brain development. We present policy recommendations for maintaining and strengthening federal environmental health protections, advancing state and local actions, and supporting scientific research to inform effective strategies for reducing children's exposures to combustion-related air pollution. Such actions not only would improve children's neurological development but also would have the important co-benefit of climate change mitigation and further improvements in other health conditions.
Cervical spinal cord injury (SCI) is a devastating condition with very few treatment options. It remains unclear if early surgery correlated with conversion of American Spinal Injury Association ...Impairment Scale (AIS) grade A injuries to higher grades.
To determine the optimal time to surgery after cervical SCI through retrospective analysis.
We collected data from 48 patients with cervical SCI. Based on the time from Emergency Department (ED) presentation to surgical decompression, we grouped patients into ultra-early (decompression within 12 h of presentation), early (within 12-24 h), and late groups (>24 h). We compared the improvement in AIS grade from admission to discharge, controlling for confounding factors such as AIS grade on admission, injury severity, and age. The mean time from injury to ED for this group of patients was 17 min.
Patients who received surgery within 12 h after presentation had a relative improvement in AIS grade from admission to discharge: the ultra-early group improved on average 1.3. AIS grades compared to 0.5 in the early group (P = .02). In addition, 88.8% of patients with an AIS grade A converted to a higher grade (AIS B or better) in the ultra-early group, compared to 38.4% in the early and late groups (P = .054).
These data suggest that surgical decompression after SCI that takes place within 12 h may lead to a relative improved neurological recovery compared to surgery that takes place after 12 h.
Aldehydes, pervasive in various environments, pose health risks at elevated levels due to their collective toxic effects
via
shared mechanisms. Monitoring total aldehyde content in living systems is ...crucial due to their cumulative impact. Current methods for detecting cellular aldehydes are limited to UV and visible ranges, restricting their analysis in living systems. This study introduces an innovative reaction-based trigger that leverages the exceptional selectivity of 2-aminothiophenol for aldehydes, leading to the production of dihydrobenzothiazole and activating a fluorescence response. Using this trigger, we developed a series of fluorescent probes for aldehydes by altering the fluorophore allowing for excitation and emission wavelengths across the visible to near-infrared spectral regions without compromising the reactivity of the bioorthogonal moiety. These probes exhibit remarkable aldehyde chemoselectivity, rapid kinetics, and high quantum yields, enabling the detection of diverse aldehyde types, both exogenous and endogenous, within complex biological contexts. Notably, we employed the most red-shifted near-infrared probe from this series to detect aldehydes in living systems, including biliary organoids and mouse organs. These probes provide valuable tools for exploring the multifaceted roles of aldehydes in biological functions and diseases within living systems, laying the groundwork for further investigations.
Introducing 4-amino-3-thiophenol BODIPY "turn on" probe tunable to NIR wavelengths for monitoring aldehydes in tissues and living organoids by forming dihydrobenzothiazole products with aldehydes, exhibiting a remarkable fluorescence increase.
Abstract Background Traumatic spinal cord injury (SCI) guidelines recommend to maintain mean arterial pressures (MAPs) above 85 mmHg for 7d following SCI to minimize spinal cord ischemia. Some doubt ...that patients with initially complete injuries benefit. Objective To assess the relationship between MAP augmentation and neurological improvement in SCI patients stratified by initial AIS score. Methods High-frequency MAP values of acute SCI patients admitted over a six-year period were recorded and values were correlated with degree of neurological recovery in an analysis stratified by post-resuscitation AIS score. Results 62 patients with SCI were analyzed. 33 patients were determined to have complete injuries and of those 11 improved at least 1 AIS grade by discharge. The average MAP of initially AIS A patients who improved versus those who did not was significantly higher (96.6 +/- 0.07 mmHg vs 94.4 +/- 0.06 mmHg, respectively; p < 0.001) and the proportion of MAP values < 85mmHg was significantly lower (13.5% vs 25.6%, respectively; p<0.001). A positive correlation between MAP values and outcome was also observed in AIS B and C patients, but was not observed in patients who were initially AIS D. Conclusion A positive correlation was observed between MAP values and neurological recovery in AIS A, B and C patients but not AIS D patients. These data raise the possibility that patients with an initially complete SCI may derive greater benefit from MAP augmentation than patients with initial AIS D injuries.
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