Abstract Background High levels of anxiety are associated with worse outcomes in coronary artery disease patients. Little is known about anxiety levels in patients undergoing coronary procedures. Our ...objective is to examine the levels of anxiety in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) during the different phases of hospital stay and to evaluate which patient characteristics are associated with increased anxiety. Methods Patients undergoing CAG or PCI between April 2009 and April 2010 were included in this prospective cohort study. Anxiety levels were measured using the self reported Visual Analogue Scale (VAS) of Anxiety, ranging from 0 to 100. VAS anxiety scores were obtained at hospital intake, pre- and post-procedure, and at hospital discharge. Multivariate linear regression analyses were performed to assess correlations between baseline characteristics and anxiety levels at the different time points. Results In total 2604 patients were included, with 70.4% male participants with a mean age of 65 ± 12 years. VAS anxiety scores were highest pre-procedure (44.2 ± 27.0 mm). Female patients reported a significantly higher pre procedure VAS anxiety score (50.4 ± 26.5) compared to males (41.5 ± 26.8, p = 0.02). Other factors associated with higher levels of anxiety at different time points were age < 65 years, low level of education and an acute primary PCI. Conclusion In the largest cohort to date, we examined anxiety among patients undergoing PCI or CAG was highest immediately around the procedure, particularly in patients aged < 65 years, of female gender, undergoing primary PCI, or with a lower level of education. Better pre-procedural information or pharmacological strategies may reduce anxiety in these patients.
Tungsten oxide nanoparticles were synthesized via a sol–gel route using metallic tungsten as precursor, and were printed on a flexible electrode using inkjet printing in order to build solid-state ...electrochromic cells. Several spectroscopic techniques were used to characterize and compare tungsten oxide particles obtained from different origins. FTIR, Raman and X-ray diffraction spectroscopic measurements showed that the sol–gel synthesis described here produces nanoparticles mainly in an amorphous state with hexagonal crystalline domains and allowed the analysis of the hydration extent of those nanoparticles. The size was measured combining dynamic light scattering, sedimentation, and microscopic techniques (AFM), showing a consistent size of about 200 nm. The tungsten oxide nanoparticles were used to produce an ink formulation for application in inkjet printing. Solid-state electrochromic devices were assembled at room temperature, without sintering the tungsten oxide printed films, showing excellent contrast between on/off states. Electrochemical characterization of those films is described using cyclic voltammetry. The devices were then tested through spectroelectrochemistry by Visible/NIR absorption spectroscopy (400–2200 nm range), showing a dual spectroscopic response depending on the applied voltage. This phenomenon is attributed to the presence of two different crystalline states in accordance with results obtained from the spectroscopic characterization of the nanoparticles. The electrochromic cells had a good cycling stability showing high reversibility and a cyclability up to more than 50 000 cycles with a degradation of 25%.
Aims Cardioprotective effects of erythropoietin (EPO) have been shown in experimental and smaller clinical studies. We performed a prospective, multicentre, randomized trial to assess the effects of ...a single high dose of EPO after primary coronary intervention (PCI) for an ST-elevation myocardial infarction (STEMI). Methods and results Patients with a successful PCI for a first STEMI were randomized to receive either standard medical care alone, or in combination with a single bolus with 60 000IU i.v. of epoetin alfa within 3 h after PCI. Primary endpoint was left ventricular ejection fraction (LVEF) after 6 weeks, assessed by planar radionuclide ventriculography. Pre-specified secondary endpoints included enzymatic infarct size and major adverse cardiovascular events. A total of 529 patients were enrolled (EPO n = 263, control n = 266). At baseline (before EPO administration), groups were well-matched for all relevant characteristics. After a mean of 6.5 (±2.0) weeks, LVEF was 0.53 (±0.10) in the EPO group and 0.52 (±0.11) in the control group (P = 0.41). Median area under the curve (inter-quartile range) after 72 h for creatinine kinase was 50 136 (28 212–76 664)U/L per 72 h in the EPO group and 53 510 (33 973–90 486)U/L per 72 h in the control group (P = 0.058). More major adverse cardiac events occurred in the control than in the EPO group (19 vs. 8; P = 0.032). Conclusion A single high dose of EPO after a successful PCI for a STEMI did not improve LVEF after 6 weeks. However, the use of EPO was related to less major adverse cardiovascular events and a favourable clinical safety profile. Clinical Trial Registration Information: NCT00449488; http://www.clinicaltrials.gov/ct2/show/NCT00449488?term=voors&rank=2.
Arenicin-3 is an amphipathic β-hairpin antimicrobial peptide that is produced by the lugworm Arenicola marina. In this study, we have investigated the mechanism of action of arenicin-3 and an ...optimized synthetic analogue, AA139, by studying their effects on lipid bilayer model membranes and Escherichia coli bacterial cells. The results show that simple amino acid changes can lead to subtle variations in their interaction with membranes and therefore alter their pre-clinical potency, selectivity and toxicity. While the mechanism of action of arenicin-3 is primarily dependent on universal membrane permeabilization, our data suggest that the analogue AA139 relies on more specific binding and insertion properties to elicit its improved antibacterial activity and lower toxicity, as exemplified by greater selectivity between lipid composition when inserting into model membranes i.e. the N-terminus of AA139 seems to insert deeper into lipid bilayers than arenicin-3 does, with a clear distinction between zwitterionic and negatively charged lipid bilayer vesicles, and AA139 demonstrates a cytoplasmic permeabilization dose response profile that is consistent with its greater antibacterial potency against E. coli cells compared to arenicin-3.
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•Arenicin-3, a cationic β-hairpin disulfide-constrained antimicrobial peptide (AMP) isolated from the sandworm Arenicola marina, is highly attractive due to its broad and potent spectrum of antimicrobial activity. A structure-activity-relationship campaign of arenicin-3 gave rise to the more potent and less toxic analogue AA139. We recently published the in vitro and in vivo efficacy of lead drug candidate AA139 in Nature Communications, Elliott et al 2020 11 (1), 3184. In Elliott et al., we showed AA139 to be highly effective in infection models of peritonitis, urinary tract and pneumonia, and like many other AMPs is membrane active. Simple amino acid changes can lead to subtle variations in the peptide interaction with membranes and therefore alter their pre-clinical potency, selectivity and toxicity. In this current study we show while the mechanism of action of arenicin-3 is primarily dependent on universal membrane permeabilization, our data suggest that the analogue AA139 relies on more specific binding and insertion properties to elicit its improved antibacterial activity and lower toxicity, as exemplified by greater selectivity between lipid composition when inserting into model membranes i.e. the N-terminus of AA139 seems to insert deeper into lipid bilayers than arenicin-3 does, with a clear distinction between zwitterionic and negatively charged lipid bilayer vesicles, and AA139 demonstrates a cytoplasmic permeabilization dose response profile that is consistent with its greater antibacterial potency against Escherichia coli cells compared to arenicin-3.•The use of lipid bilayer model membranes and bacterial cells, allowed us to propose a model for the mechanism of action of AA139 (1) binding to the outer membrane through electrostatic interactions, (2) insertion into the hydrophobic core of the outer membrane creating partial permeabilization, (3) access to, and permeabilization of the cytoplasmic membrane ultimately leading to cell death.•We now have a better understanding of the mechanism of action of arenicin peptides and how the mutation of only three amino acids has led to a significant increase in the therapeutic value of the peptide. Natural AMPs offer great potential for the fight against resistant bacteria. The redesign of AMPs can lead to improved pre-clinical candidates. The differences seen in the membrane-binding and -disrupting properties of arenicin-3 and AA139 may provide a pathway to better design and screen for optimized peptide antibiotics in the future.
Objectives
Patient-tailored contrast delivery protocols strongly reduce the total iodine load and in general improve image quality in CT coronary angiography (CTCA). We aim to use machine learning to ...predict cases with insufficient contrast enhancement and to identify parameters with the highest predictive value.
Methods
Machine learning models were developed using data from 1,447 CTs. We included patient features, imaging settings, and test bolus features. The models were trained to predict CTCA images with a mean attenuation value in the ascending aorta below 400 HU. The accuracy was assessed by the area under the receiver operating characteristic (AUROC) and precision-recall curves (AUPRC). Shapley Additive exPlanations was used to assess the impact of features on the prediction of insufficient contrast enhancement.
Results
A total of 399 out of 1,447 scans revealed attenuation values in the ascending aorta below 400 HU. The best model trained using only patient features and CT settings achieved an AUROC of 0.78 (95% CI: 0.73–0.83) and AUPRC of 0.65 (95% CI: 0.58–0.71). With the inclusion of the test bolus features, it achieved an AUROC of 0.84 (95% CI: 0.81–0.87), an AUPRC of 0.71 (95% CI: 0.66–0.76), and a sensitivity of 0.66 and specificity of 0.88. The test bolus’ peak height was the feature that impacted low attenuation prediction most.
Conclusion
Prediction of insufficient contrast enhancement in CT coronary angiography scans can be achieved using machine learning models. Our experiments suggest that test bolus features are strongly predictive of low attenuation values and can be used to further improve patient-specific contrast delivery protocols.
Key Points
• Prediction of insufficient contrast enhancement in CT coronary angiography scans can be achieved using machine learning models.
• The peak height of the test bolus curve is the most impacting feature for the best performing model.
The lack of small-diameter vascular grafts (inner diameter <5 mm) to substitute autologous grafts in arterial bypass surgeries has a massive impact on the prognosis and progression of cardiovascular ...diseases, the leading cause of death globally. Decellularized arteries from different sources have been proposed as an alternative, but their poor mechanical performance and high collagen exposure, which promotes platelet and bacteria adhesion, limit their successful application. In this study, these limitations were surpassed for decellularized umbilical cord arteries through the coating of their lumen with graphene oxide (GO). Placental and umbilical cord arteries were decellularized and perfused with a suspension of GO (C/O ratio 2:1) with ∼1.5 μm lateral size. A homogeneous GO coating that completely covered the collagen fibers was obtained for both arteries, with improvement of mechanical properties being achieved for umbilical cord decellularized arteries. GO coating increased the maximum force in 27%, the burst pressure in 29%, the strain in 25%, and the compliance in 10%, compared to umbilical cord decellularized arteries. The achieved theoretical burst pressure (1960 mmHg) and compliance (13.9%/100 mmHg) are similar to the human saphenous vein and mammary artery, respectively, which are used nowadays as the gold standard in coronary and peripheral artery bypass surgeries. Furthermore, and very importantly, coatings with GO did not compromise the endothelial cell adhesion but decreased platelet and bacteria adhesion to decellularized arteries, which will impact on the prevention of thrombosis and infection, until full re-endothetialization is achieved. Overall, our results reveal that GO coating has an effective role in the improvement of decellularized umbilical cord artery performance, which is a huge step toward their application as a small-diameter vascular graft.
The authors sought to evaluate the relative performance of a drug-eluting balloon (DEB) and a drug-eluting stent (DES) in patients with any (bare-metal or drug-eluting stent) in-stent restenosis ...(ISR).
The treatment of ISR remains challenging in contemporary clinical practice.
In a multicenter randomized noninferiority trial, patients with any ISR were randomly allocated in a 1:1 fashion to treatment with a DEB (SeQuent Please paclitaxel-eluting balloon, B. Braun Melsungen, Melsungen, Germany), or a DES (XIENCE everolimus-eluting stent, Abbott Vascular, Santa Clara, California). The primary endpoint was noninferiority in terms of in-segment minimal lumen diameter (MLD) at 6-month angiographic follow-up. Secondary endpoints included angiographic parameters at 6 months and clinical follow-up up to 12 months.
A total of 278 patients, of whom 56% had DES-ISR, were randomized at 8 sites to treatment with DEB (n = 141) or DES (n = 137). As compared with DEB, DES was associated with larger MLD and lower % stenosis immediately post-procedure (1.84 ± 0.46 vs. 1.72 ± 0.35; p = 0.018; and 26 ± 10% vs. 30 ± 10%; p = 0.03). Angiographic follow up was completed at 196 ± 53 days in 79% of patients. With respect to the primary endpoint of in-segment MLD at 6 months, DEB was noninferior to DES (DEB 1.71 ± 0.51 mm vs. DES 1.74 ± 0.61 mm; p for noninferiority <0.0001). Target vessel revascularization at 12-month follow-up was similar in both groups (DES 7.1% vs. DEB 8.8%; p = 0.65).
In patients with ISR, treatment with DEB was noninferior compared with DES in terms of 6-month MLD. There were no differences in clinical endpoints, including target vessel revascularization up to 12 months. Therefore, use of a DEB is an attractive treatment option for in-stent restenosis, withholding the need for additional stent implantation.
Aims Although recognized as an important feature of atherosclerotic coronary disease, little is known about the frequency and prognostic importance of distal embolization during primary angioplasty ...for acute myocardial infarction. Methods and Results As part of a randomized trial of thrombolysis vs primary angioplasty, 178 patients with acute myocardial infarction were treated with primary angioplasty. In these patients the occurrence of distal embolization after angioplasty was assessed. Embolization was defined as a distal filling defect with an abrupt ‘cutoff’ in one of the peripheral coronary artery branches of the infarct-related vessel, distal to the site of angioplasty. We analysed myocardial blush grade, ST-T segment elevation resolution, enzymatic infarct size and left ventricular ejection fraction in patients with and without distal embolization. Clinical information was collected for a mean of 5 years. Distal embolization was present in 27 patients (15·2%). Mean age and gender were not different from patients without distal embolization. Angiographic success (thrombolyis in myocardial infarction flow grade 3 and residual stenosis <50%) after primary angioplasty was less frequently observed in patients with distal embolization (70% vs 90%,P <0·01). Myocardial blush and ST-T segment elevation resolution after angioplasty were reduced when distal embolization was present. Patients with distal embolization had a larger enzymatic infarct size (mean cumulative lactate dehydrogenase measured over 72h, 1612 vs 847, P<0·05) and a lower left ventricle ejection fraction at discharge (42% vs 51%, P<0·01). Long-term mortality was higher in patients with distal embolization (44% vs 9%, P<0·001). Conclusion Distal embolization in patients treated with primary angioplasty is visible on the coronary angiogram in 15·2% of patients. It is related to reduced myocardial reperfusion, more extensive myocardial damage and a poor prognosis. Additional pharmacological interventions and/ or mechanical devices should be studied to prevent and/or treat distal embolization. Copyright 2001 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.
This study aimed to characterize Escherichia coli present in irrigation water and vegetables from 16 household farms. Isolates were obtained from 50% of water (n=210 isolates) and 38% of vegetable ...samples (n=239). Phylogroups B1 (56% of isolates) and A (22%) were the most prevalent both in water and vegetables. Diarrheagenic strains were detected in vegetables. Irrespective of the source (i.e. water or vegetables), the most common antibiotic resistance was against streptomycin (89% resistant isolates) and tetracycline (24%). Common acquired genes (e.g. blaTEM, tetA, tetB) were found in isolates from both sources. Class I integrons were detected in water (arrays dfrA1-aadA1 and dfr16-blaP1b-aadA2-ereA) and vegetables (unknown arrays). intI2 was detected in water (dfrA1-sat2-aadA1). Plasmids were detected in 14 isolates (IncFIC, IncFIB, IncFrep, IncI1 in both samples; IncY in vegetables). Plasmids from seven isolates were transferrable by conjugation, conferring resistance to antibiotics to the recipient strain. Multidrug-resistant (MDR) strains were isolated from water (12% of the unique isolates) and vegetables (21%). Predominant sequence types (STs) among MDR isolates were ST10, ST297 and ST2522. In some cases, the same STs and identical clones (as showed by rep-PCR typing) were detected in water and vegetables, suggesting cross-contamination. This study identified several risk factors in E. coli isolates from vegetables and irrigation water, raising health concerns. Also, results suggest that irrigation groundwater constitutes a source of E. coli that may enter the food chain through vegetables ingestion.
•E. coli resistant to antibiotics crucial to human health were found in both sources.•Multiresistance was more prevalent among vegetable isolates than water isolates.•Isolates carried conjugative plasmids encoding antibiotic resistance.•Virulent determinants for EIEC and ETEC were found in vegetable isolates.•Detection of identical clones in both sources suggests cross-contamination.
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