bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential benefits of ticagrelor plus aspirin in Chinese patients with stable coronary artery disease and diabetes
Authors: Sun W , Yan B
Published: October 2021

Purpose

Ticagrelor plus aspirin has been shown to reduce the incidence of cardiovascular (CV) events compared to asprin alone in patients with stable coronary artery disease and diabetes in the THEMIS trial. This study aimed to estimate the potential CV benefit of adding ticagrelor to aspirin among a THMEIS-like Chinese population.

Methods

We retrospectively analyzed 13,322 patients with stable coronary artery disease and diabetes from 16 public hospitals in Hong Kong between August 2015 and July 2020. 5,642 (42.4%) patients who met inclusion and exclusion criteria of the THEMIS trial were included in final analysis. Estimated absolute risk reduction (eARR) in major adverse CV event (MACE, composite of myocardial infarction (MI), ischemic stroke or CV death) and number needed to treat (eNNT) were extrapolated based on results of the THEMIS trial.

Results

Of 5,642 THEMIS-like patients (62.1% male; mean age 69.6±10.4 years), 26.5% had history of percutaneous coronary intervention (PCI). During a median follow-up of 17.5 (IQR: 9.3–41.3) months, rates of MACE, MI, stroke and CV-death were 10.7% (n=605), 5.3% (n=298), 2.5% (n=139) and 5.5% (n=308), respectively. Kaplan-Meier estimates at 36 months stratified by history of PCI or not were 16.9% vs. 14.0% for MACE and 9.0% vs 6.7% for MI (both Log-rank p<0.01). Among THEMIS-like and THEMIS-PCI-like patients, eARR with ticagrelor plus aspirin was 1.4% (eNNT=71) and 1.6% (eNNT=63) for MACE and 1.5% (eNNT=67) and 1.9% (eNNT=53) for MI, respectively.

Conclusion

Approximately one third of Chinese patients with stable coronary artery disease and diabetes met THEMIS trial criteria. Combined therapy of ticagrelor and aspirin might provide similar clinical benefit in our population observed in the THEMIS trial, with low number needed to treat, especially in patients with previous PCI.

Funding Acknowledgement

Type of funding sources: None.
Features of secondary prevention in young STEMI patients
Authors: Bilyi D , Parkhomenko A N , Irkin O I , Lutai Y M , Stepura A O , Dovhan O V
Published: October 2021

Among patients who underwent a myocardial infarction (MI), one in five patients has a second cardiovascular event (MI, acute cerebrovascular accident, arrhythmias, etc.) during the first year, even with optimal treatment and care. Young patients often do not take the prescribed treatment or do not take it for a long time after discharge from the hospital. The issue of secondary prevention among the population is well studied, while in the literature such data for young people are lacking.

Methods

The data of 160 STEMI young patients (18–46 years) who admitted and treated in the intensive care unit were evaluated. We studied the effect of the main groups of medicines on the course of AMI in young patients. The remote observation lasted 5 years after discharge from the hospital. The following cardiovascular events during 1 (365 days), 2 (730 days), 3 (1095 days), and 5 years (1800 days) of the FU were used as the endpoint: death from any cause, combined endpoint (cardiovascular death, myocardial infarction, stroke, revascularization (CABG, stenting).

Results

It was noted that taking one of the antithrombotic drugs (clopidogrel or ticagrelor) in young patients, after 2, 3, and 5 years of follow-up, significantly affected the development of the combined endpoint, reducing the number of events (p=0.013, p=0.004 and p=0.048, respectively). Statins had a better effect on the number of combined endpoints (reduced their number) in young patients during 2-year and 3-year follow-up (p=0.041) and (p=0.034), respectively. In young patients, ACEI or ARB tended to influence the development of a combined endpoint at 2, 3, and 5 years of follow-up (p=0.061, p=0.080, and p=0.067, respectively). In our study, we found that taking aspirin at a dose of 75–100 mg tends to reduce the development of death from any cause (p=0.054) within 5 years (1800 days) from discharge. Patients under 45 years after undergoing AMI were significantly less likely to take the minimum necessary medication, like aspirin, and statins than older patients (45–65 years) (24.2% vs. 42%, p<0.001, respectively).

Conclusion

Young patients after AMI for secondary prevention must take an antithrombotic drug (clopidogrel or ticagrelor), statins, and an ACEI or ARB. In order to increase compliance, it is recommended to take a combination drug.

Funding Acknowledgement

Type of funding sources: None.
Cannabis use is associated with prevalent coronary artery disease
Authors: Skipina T M S , Patel N P , Upadhya B U , Soliman E Z S
Published: October 2021

Background

Cannabis is the most commonly used illicit drug in the United States and has been associated with an increased risk of acute coronary syndrome (ACS) in multiple observational studies.

Purpose

The association of cannabis use with prevalent coronary artery disease (CAD) remains unclear. We hypothesized that cannabis use would also be associated with prevalent CAD among a nationally representative sample of patients.

Methods

This analysis included 12,543 participants (age 39.3±11.6 years, 48.8% male, 35.3% Caucasians) from the National Health and Nutrition Examination Survey years 2011–2018. Cannabis use was defined by self-report. Prevalent CAD was defined by physician diagnosis. Multivariable logistic regression was used to examine the association between cannabis use and prevalent CAD. The consistency of this association was tested among subgroups stratified by race, gender, tobacco smoking status, and comorbidities.

Results

In this analysis, 53.1% (n=6,650) of participants were ever-cannabis users and 1.1% (n=137) had prevalent CAD. After adjusting for covariates, ever-cannabis users had a 90% increased odds of prevalent CAD compared to never users (p=0.003). Those who had used cannabis at least once per month for at least one year had a 68% increased odds of prevalent CAD (p<0.001). Current cannabis users had a near two-fold increased odds of prevalent CAD [OR (95% CI): 1.98 (1.11 – 3.54), p=0.02]. Similar results were seen with heavy cannabis users [OR (95% CI): 1.99 (1.02 – 3.89), p=0.045]. Multiplicative interaction yielded consistent results among the subgroups analyzed.

Conclusion

Cannabis use is associated with prevalent CAD. This association remains consistent after adjusting for traditional cardiovascular disease risk factors. This is a novel finding that underscores the potential harmful effects of cannabis use on cardiovascular health and highlights the need for further controlled studies as the drug becomes more accepted by the general population.

Funding Acknowledgement

Type of funding sources: None.
Effect of colchicine on reducing C-reactive protein levels among patients with acute coronary syndrome: a meta-analysis
Authors: Divinagracia R Z , Vistal G , Tiongco R H
Published: October 2021

Background

Patients who have undergone Acute Coronary syndrome (ACS), whether ST segment or Non ST Segment elevated myocardial infarction, are more prone to have increased inflammation, as measured by C-reactive protein (CRP). Persistence of this inflammation may lead to future plaque instability and recurrence of ACS. Colchicine is known to have anti-inflammatory properties that aid in lowering ACS recurrence. This meta-analysis aims to investigate the current data for colchicine and its efficacy in reducing markers of acute inflammation such as CRP in the setting of patients with ACS.

Methods

The four studies considered for this meta-analysis were randomized control trials published from 2012 to 2016 that included patients who had ACS and were given Colchicine as an adjunctive therapy compared to placebo. The primary outcome investigated was CRP levels during hospital admission and 30 days after administration of colchicine.

Results

The pooled evidence showed that there is no heterogeneity among the studies I-squared = 0%. These studies, which compared 264 patients on colchicine and 277 patients on placebo, showed a decrease in CRP values after taking colchicine (p=0.97, Mean Difference −0.03, 95% CI [−1.94, 1.88]). This decrease, however, was not statistically significant.

Conclusion

Colchicine has no statistically significant evidence in reducing CRP levels in patients with ACS. Therefore, the use of colchicine routinely in ACS, particularly for the reduction of CRP, may not be warranted given the current level of evidence

Funding Acknowledgement

Type of funding sources: None.
Plasma apoC-III levels predict coronary severity and cardiovascular risks in stable coronary artery disease patients with diabetes or pre-diabetes: a prospective cohort study
Authors: Peng J , Li J.-J
Published: October 2021

Background

Apolipoprotein C-III (apoC-III) has been proposed to be involved in lipid and glucose metabolism and related to cardiovascular risks. The aim of this study is to investigate the association of apoC-III levels with coronary severity and cardiovascular outcomes in coronary artery disease (CAD) patients under different glucose metabolism status.

Methods

A total of 4342 consecutive patients with newly angiography-proven stable CAD were enrolled and categorized into three groups according to apoC-III levels and further stratified by glucose metabolism status [diabetes mellitus (DM), pre-DM, normal glucose regulation (NGR)]. Patients were followed for the occurrence of cardiovascular events (CVEs). Plasma apoC-III concentration was measured by enzyme immunoassay and coronary severity was assessed by number of diseased vessels, Gensini score and syntax score. The relationships of apoC-III levels with coronary severity and CVEs were evaluated.

Results

389 (9.0%) CVEs were developed during a follow-up of 5.1 years. Plasma apoC-III levels were increased in prediabetic and diabetic patients with stable CAD. Elevated apoC-III levels were associated with more severe coronary lesion and the risk for CVEs. No significant differences in incident CVEs and coronary severity were observed between pre-DM and NGR groups. When combined glucose metabolism status and apoC-III levels as stratifying factors, patients with the highest apoC-III levels and pre-diabetic or diabetic patients with any levels of apoC-III had more sever coronary lesion and higher risk of subsequent CVEs compared to those with the lowest apoC-III levels and NGR.

Conclusion

Our data firstly found that elevated apoC-III levels were greatly associated with coronary severity and adverse cardiovascular events in stable CAD patients with pre-DM and DM, which suggested apoC-III may be a prognostic predictor among CAD patient with impaired glucose metabolism.

Funding Acknowledgement

Type of funding sources: None.
Acute myocardial infarction in the Covid-19 era: incidence, clinical characteristics and in-hospital outcomes – a multicenter registry
Authors: Fardman A , Zahger D , Orvin K , Kofman N , Mohsen J , Tsafrir O , Asher E , Rubinshtein R , Jamal J , Efraim R , Halabi M , Shacham Y , Fortis L H , Beigel R , Matetzky S
Published: October 2021

Background

A reduction in acute myocardial infarction (AMI) hospitalizations during the coronavirus pandemic has been previously documented. We aimed to describe the characteristics and in-hospital outcomes of AMI patients during the Covid-19 era compared to a recent previous registry.

Methods

We conducted a prospective, multicenter, observational study involving 13 intensive cardiac care units (ICCUs) to evaluate consecutive AMI patients admitted throughout an 8-week period during the Covid-19 outbreak. Data were compared to the corresponding period in 2018 using an acute coronary syndrome survey conducted in all ICCUs in Israel. The primary end-point was defined as a composite of sustained ventricular arrhythmia, pulmonary congestion, and/or in-hospital mortality.

Results

The study cohort comprised 1466 patients, of whom 774 (53%) were hospitalized during the Covid-19 outbreak. Overall, 841 patients were diagnosed with ST-elevation MI (STEMI): 424 (50.4%) during the Covid-19 era and 417 (49.6%) during the parallel period in 2018. No differences were detected in the admission rate of patients between the two study periods. STEMI patients admitted during the Covid-19 period tended to have fewer co-morbidities, but a higher Killip class (p value = 0.03). The median time from symptom onset to reperfusion was extended from 180 minutes (IQR 122–292) in 2018 to 290 minutes (IQR 161–1080, p<0.001) in 2020. Hospitalization during the Covid-19 era was independently associated with an increased risk of the combined endpoint of heart failure, malignant arrhythmia, or death in the multivariable logistic regression model (OR 1.63, 95% CI 1.02–2.65, p value = 0.05).

Conclusion

While the admission rate of AMI and STEMI in Israel remained similar during both the Covid-19 era and the corresponding period in 2018, total ischemic time extended significantly during the Covid-19 period, which translated into a more severe disease status upon hospital admission, and a higher rate of in-hospital adverse events.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by a grant from a Fefer foundation for medical research
Carotid plaque vulnerability assessed by combined shear wave elastography and ultrafast doppler compared to histology: the UF-plaque study
Authors: Goudot G , Sitruk J , Jimenez A , Khider L , Julia P , Alsac J M , El Batti S , Bruneval P , Amemyia K , Pedreira O , Calvet D , Tanter M , Mirault T , Pernot M , Messas E
Published: October 2021

Purpose

New biomarkers are needed to assess the vulnerability of carotid plaque to guide carotid surgery decision. Ultrafast Ultrasound Imaging (UUI) provides an estimation of plaque stiffness by Shear Wave Elastography (SWE) and the quantification of wall shear stress (WSS) by ultrafast Doppler. We aimed at evaluating the plaque stiffness and WSS applied on the plaque as potential biomarkers of plaque vulnerability.

Methods

Patients were referred for carotid endarterectomy because of symptomatic or asymptomatic carotid stenosis. Their plaques were evaluated by UUI within 48 hours before surgery. For each plaque, WSS and SWE were obtained on a longitudinal view at the stenosis. After endarterectomy, gross analysis and histology were performed on each removed plaque.

Results

46 plaques with SWE data and 29 with WSS data were analysed. Histological analysis revealed 29 vulnerable and 17 stable plaques. Analysis of the Gray Scale Median by B mode, mean and standard deviation of stiffness by SWE were not helpful in identifying vulnerable plaques. Figure 1 presents the SWE acquisition on one plaque (A) and the distribution of plaque's stiffness average over all plaques showing the 4 ranges of stiffness (B). SWE analysis revealed that the percentage of stiffness range of [3–5] m/s was significantly increased in vulnerable plaques (p=0.048) (Figure 2A). WSS alone showed no significant difference between stable and vulnerable plaques regardless of which segment of the plaque was analysed. A multiparametric score using maximal WSS at the peak of the plaque associated with SWE texture analysis parameters was created by a stepwise analysis, leading to a score with a sensitivity of 80% and a specificity of 78%. The ROC curve of this score found an AUC of 0.85 (Figure 2B).

Conclusions

Multiparameter scoring including plaque stiffness and flow analysis using ultrafast ultrasound imaging allows an effective identification of histologically vulnerable carotid plaques.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Fédération Française de cardiologieSociété Française de Cardiologie Figure 1Figure 2
Epicardial adipose tissue is associated with exercise intolerance in patients with diabetes with asymptomatic left ventricular structural and functional abnormalities
Authors: Sugita Y , Sakai S
Published: October 2021

Background

The volume of epicardial adipose tissue (EAT), which is an index of visceral fat, is high in patients with type 2 diabetes mellitus (T2DM) and may affect the myocardial performances. However, the association between EAT and left ventricular (LV) structure and function, and exercise capacity in patients with asymptomatic heart failure has not been studied.

Aims

To elucidate whether the volume of EAT deteriorates the exercise capacity in patients with T2DM.

Methods

EAT thickness and LV structural and functional abnormality components (e.g., global longitudinal strain, E/e', LV mass index, relative wall thickness) were measured with echocardiography in 176 patients with asymptomatic heart failure (Stage A and B) and 62 healthy controls (HC). To evaluate exercise capacity, peak oxygen uptake (peakVO2) was measured by using the cardiopulmonary exercise testing.

Results

Lipid metabolism, glucose metabolism, brain natriuretic peptide and estimated glomerular filtration rate at cystatin were worse in the heart failure (HF) group than in the HC. The EAT was significantly thicker and peakVO2 was lower in patients with LV structural and functional abnormalities than in individuals without these abnormalities (p<0.001). As the number of LV structural and functional abnormality components increased, the thickness of the EAT increased and peakVO2 decreased (p<0.001). The EAT thickness (β=−0.207) was negatively correlated with peakVO2, even after adjusting for multivariates (R2=0.724).

Conclusions

In patients with T2DM with asymptomatic heart failure, EAT is associated with LV structural and functional abnormalities. It also suggests that increase of visceral fat around myocardium contributes to exercise intolerance.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): National University Corporation Tsukuba University of Technology education and research Grant
Outcome in elderly patients with myocardial infarction undergoing PCI using radial versus femoral access
Authors: Kanic V , Naji F H , Kompara G
Published: October 2021

Background

Radial access (RA) is increasingly used in interventional cardiology and has become the dominant access site for percutaneous coronary intervention (PCI). Data on the association between RA and outcome in elderly patients with myocardial infarction (MI) undergoing PCI are sparse and inconclusive.

Purpose

The aim of our study was to assess whether RA per se is associated with 30-day mortality in patients over 80 years of age with MI who underwent PCI at our center.

Methods

We retrospectively studied 639 consecutive patients aged over 80 years with MI who underwent PCI between January 2011 and December 2017. RA was used in 232 (36.3%) patients. Thirty-day mortality in the RA and femoral access (FA) groups was observed. Data were analyzed using descriptive statistics.

Results

RA patients had a significantly lower 30-day unadjusted mortality [30 (12.9%) patients died in the RA group compared to 102 (25.1%) patients in the FA group; p<0.0001] (Figure 1). After adjusting for confounders, RA independently predicted better outcome (adjusted OR: 0.55; 95% CI: 0.32 to 0.90; p=0.025). Hypertension, ST-elevation MI, TIMI flow 0/1 after PCI, dual antiplatelet therapy, glomerular filtration rate, and bleeding predicted 30-day mortality.

Conclusion

RA leads to a better 30-day outcome in patients over 80 years of age with MI (ST-elevation MI and non-ST- elevation MI) who underwent PCI. RA was independently associated with mortality. This finding strengthens existing evidence that RA should be preferred whenever possible in the elderly with Mi.

Funding Acknowledgement

Type of funding sources: None.
Low and full dose apixaban in patients with atrial fibrillation and renal dysfunction: findings from a national registry
Authors: Gurevitz C , Giladi E , Klempfner R , Goldenberg I , Barsheshet A , Kornowski R , Elis A
Published: October 2021

Background

The use of direct oral anticoagulants for stroke prevention in patients with non-valvular atrial fibrillation is robust. However, the efficacy and safety of different dosage in patients with renal dysfunction is still a clinical challenge. We aimed to evaluate the clinical characteristics and outcomes of patients treated with apixaban in its different doses.

Methods

A multicenter prospective cohort study, where consecutive eligible apixaban or warfarin treated patients with non-valvular atrial fibrillation and renal impairment (eGFR MDRD <60 ml/min/BSA) were registered. All patients were prospectively followed-up for clinical events and dosing adjustments over a mean period of 1 year. Analyses were performed according to the dose of apixaban given, with consideration to the standard indications for dose reduction. The primary outcomes were 1 year: mortality, stroke or systemic embolism, major bleeding and myocardial infarction as well as their composite occurrence.

Results

Among the study population (n=2140), the risk for composite outcome and for mortality were both significantly lower in the high dose apixaban group (n=491) than that of the warfarin group (n=976) and the low dose apixaban group (n=673, figure 1); Dosing analysis revealed Dosing analysis revealed that only 65% of the apixaban treated patients were appropriately dosed (figure 2), and 53% of the patients who were treated by low dose apixaban were under-dosed. Treatment with inappropriately under-dose apixaban was associated with improved survival rate and composite endpoint than treatment with appropriately low dose apixaban. Appropriately high dose apixaban compared to inappropriately over-dosed patients resulted in no significant difference. Overall, appropriately dosed apixaban treated patients (any dose) had better prognosis than matched warfarin treated patients.

Conclusion

Apixaban at any dose is a reasonable alternative to warfarin in patients with renal impairment, possibly associated with improved outcomes. Apixaban is still largely under-dosed in patients with renal dysfunction.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Educational grant from Pfizer Figure 1Figure 2
Isolated superfused rats atrial model for the investigation of atrial fibrillation mechanisms and treatment
Authors: Glatstein S , Ghiringhelli M , Maizels L , Heller E , Maor E , Gepstein L
Published: October 2021

Background

One of the major barriers to an improved mechanistic understanding of atrial fibrillation (AF), and thus in the pipeline of drug development, has been a lack of appropriate tissue models, especially in small animals.

Aim

We propose an advanced anatomical ex-vivo model based on rat atria for acute assessment of AF susceptibility. This novel model could yield a better understanding of arrhythmia mechanisms as well as the development of potential therapeutic strategies for the prevention or termination of atrial arrhythmias.

Methods

Wistar rats atria (N=25) were isolated, flattened and pinned to a custom-made silicon plate. Atria were superfused with an oxygenized Tyrode's solution. Tissues were then loaded with a voltage-sensitive dye and mapped using a high-resolution optical mapping system. AF was induced with 1uM carbamylcholine (N=23) coupled with pacing maneuvers and treated with 30uM Vernakalant (N=10) or 10uM Flecainide (N=10). Finally, the feasibility of a new ablation technique (electroporation) was evaluated.

Results

Optical mapping results suggested that the superfusion procedure led to a fast atrial recovery. Sinus activity was conserved for all atria for a long period. All the anatomical landmarks were clearly visualized. The acquired optical signals were analyzed during sinus rhythm and pacing, which allowed the creation of detailed activation maps and measurements of action potential duration (APD) and conduction velocity (CV) at different pacing rates. The resulting APD restitution curves revealed electrical excitation at high pacing rates (cycle length between 50ms and 300ms) with a relatively flattened curve. AF was successfully induced and optically mapping confirmed the presence of reentrant activity. AF was successfully treated using Vernacalant and Flecainide. Finally, we demonstrated the feasibility of a new ablation approach (electroporation) for creation of a continuous linear lesion serving as a functional block.

Conclusion

The isolated superfused atria model, coupled with voltage-sensitive dyes, can be utilized for long-term high-resolution functional imaging of the atria during sinus rhythm, pacing and arrhythmogenic activity. This allows the study of the atrial electrophysiological properties, the mechanisms involved in AF initiation, perpetuation, and termination as well as the study of drug and new ablation modalities.

Funding Acknowledgement

Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research Council (ERC) Spontaneous activation of isolated atria
Monoamine oxidase contributes to the valvular oxidative stress in patients with mitral valve regurgitation
Authors: Sosdean R , Ionica L N , Pescariu S A , Mornos C , Muntean D M , Sturza A , Luca C T , Feier H
Published: October 2021

Background

Oxidative stress plays a central role in the pathogenesis of cardiovascular diseases but the role of enzymatic sources of reactive oxygen species (ROS) remains elusive. There is scarce information in the literature regarding valvular oxidative stress. Monoamine oxidases (MAOs), with 2 isoforms, A and B, have emerged as important sources of oxidative stress in the cardiovascular system.

Purpose

To assess whether MAOs-related oxidative stress occurs in the pathological valves in patients with severe mitral regurgitation (due to valve degeneration and chordae rupture) and surgical indication and its interference with the activation of the renin-angiotensin aldosterone (RAAS) system.

Material and methods

Samples of mitral valve (n=17) were harvested during the valvular replacement procedure and used for reactive oxygen species (ROS) assessment (immune-fluorescence, spectrophotometry) and MAO mRNA and protein expression (qPCR and immune-fluorescence) measurement. Inflammatory markers, biochemical parameters and echocardiography (GE, Vivid 9, Vivid E95) data were also collected.

Results

Both MAO isoforms are expressed in the diseased mitral valves, with a predominance of MAO-A isoform. Ex vivo incubation with angiotensin 2 (12 h, 100 nM) of samples obtained from patients without RAAS medication lead to MAO upregulation and high ROS production. MAO-related oxidative stress was mitigated by MAO inhibition with clorgyline (MAO-A inhibitor, 10 microM) and selegyline (MAO-B inhibitor, 10 microM) and also by the angiotensin II receptor type 1 (AT1) antagonist, irbersartan (10 microM).

Conclusions

Monoamine oxidase is expressed in the pathological mitral valves, regardless the etiology. Its expression and the related-oxidative stress are modulated by angiotensin 2, irbesartan. Whether the latter effect is present in valvular patients treated with RAAS inhibitors is currently under investigation.

Funding Acknowledgement

Type of funding sources: None.
Vitamin K epoxide reductase complex subunit 1-like 1 (VKORC1L1) inhibition induces a proliferative and pro-inflammatory vascular smooth muscle cell phenotype
Authors: Al Zaidi M , Aksoy A , Repges E , Becher M U , Mueller C , Oldenburg J , Zimmer S , Nickenig G , Tiyerili V
Published: October 2021

Background

Vitamin K antagonists (VKA) like Warfarin are known to promote adverse cardiovascular remodelling. Contrarily, vitamin K supplementation has been discussed to decelerate cardiovascular disease. The recently described VKOR-isoenzyme Vitamin K epoxide reductase complex subunit 1-like 1 (VKORC1L1) is involved in vitamin K maintenance and exerts antioxidant properties. In this study, we sought to investigate the role of VKORC1L1 in neointima formation and on vascular smooth muscle cell (VSMC) function.

Methods and results

Treatment of wild-type mice with Warfarin increased maladaptive neointima formation after carotid artery injury. This was accompanied by reduced vascular mRNA expression of VKORC1L1.

In vitro, Warfarin was found to reduce VKORC1L1 mRNA expression in VSMC. VKORC1L1 downregulation by siRNA promoted viability, migration and formation of reactive oxygen species. VKORC1L1 knockdown further increased expression of key markers of vascular inflammation (NFκB, IL-6). Additionally, downregulation of the endoplasmic reticulum (ER) membrane resident VKORC1L1 increased expression of the main ER Stress moderator, glucose-regulated protein 78 kDa (GRP78). Moreover, treatment with the ER Stress inducer Tunicamycin promoted VKORC1L1, but not VKORC1 expression.

Finally, we sought to investigate, if treatment with vitamin K can mediate the protective properties of VKORC1L1. Thus, we examined effects of menaquinone-7 (MK7) on VSMC phenotype switch. MK7 treatment dose-dependently alleviated PDGF-induced proliferation and migration. In addition, we detected a reduction in expression of inflammatory and ER Stress markers.

Conclusion

VKA-induced neointima formation is associated with reduced vascular VKORC1L1 expression. VKORC1L1 inhibition contributes to an adverse VSMC phenotype while MK7 restores VSMC function. Thus, MK7 supplementation might be a feasible therapeutic option to modulate vitamin K- and VKORC1L1-mediated vasculoprotection.

Funding Acknowledgement

Type of funding sources: None.
Not-high before-treatment platelet reactivity in patients with STEMI:prevalence, clinical characteristics, response to therapy and outcomes
Authors: Canonico M E , Sanna G D , Siciliano R , Guarino S , Bellandi B , Scudiero F , Saba P S , Esposito G , Alexopoulos D , Parodi G
Published: October 2021

Background

Platelet reactivity (PR) has been indicated as a pathophysiological key element for ST-Elevation Myocardial Infarction (STEMI) development. In STEMI patients, PR following pharmacological treatment has been extensively studied with focus on patients with on-treatment high platelet reactivity (HPR). Patients with before-treatment not-high platelet reactivity (NHPR) have been poorly studied so far.

Purpose

Aim of the study is to investigate the prevalence, clinical characteristics, response to therapy and outcomes of baseline prior to treatment NHPR among patients with STEMI undergoing primary PCI.

Methods

We analysed the data from 358 STEMI patients with assessment of PR by VerifyNowbefore P2Y12 inhibitor loading dose (LD). All patients received a P2Y12 inhibitor (ticagrelor or prasugrel) LDafter baseline PR assessment. Blood samples were obtained at baseline (T0), and after 1 hour (T1), 2 hours (T2), 4–6 hours (T3) and 8–12 hours (T4) after LD. HPR was defined as Platelet Reactivity Unit values ≥208, while patients with values <208 at baseline were defined as having NHPR.

Results

Overall, 20% patients had NHPR. Patients with before-treatment NHPR values were more frequently young, of male gender and more frequently smokers (p=0.005), overweight or obese (p=0.009), affected by dyslipidemia (p=0.03) and with a family history of coronary artery disease (p=0.04). Age and male gender resulted both independent predictors of NHPR, even after propensity score adjustment. The percentage of inhibition of PR after ticagrelor or prasugrel LD was similar between HPR and NHPR patients at each time point (figure 1) and residual PR was constantly lower in patients with before-treatment PRU <208 from baseline to 8–12 hours from LD (figure 2). However, patients with HPR showed worse in-hospital clinical outcomes, and the composite adverse outcome endpoint of death, reinfarction, stroke, acute kidney injury or heart failure was significantly higher (10.0% vs 1.4%; p=0.017) as compared with the NHPR group.

Conclusions

A significant proportion of patients presenting with STEMI has a baseline NHPR; they are predominantly young males with a high-risk cardiovascular profile. NHPR is associated with better in-hospital outcomes as compare with patients with HPR. Further studies are needed to better understand the underlying pathophysiology in order to find out potential personalized treatments in this setting.

Funding Acknowledgement

Type of funding sources: None.
Capacity building in participatory stakeholder groups: results from a German research consortium on active lifestyles
Authors: Sauter Alexandra , Loss Julika
Published: October 2021

To implement sustainable health-promoting structures in a setting, various agents must work together. In the Capital4Health research network, participatory stakeholder groups consisting of key persons, stakeholders, representatives of the target group, and facilitating experts are assembled in five settings (child care center, school, company, rural community, nursing home). In a Cooperative Planning process, the various groups meet regularly to plan and implement strategies to promote physical activity across different settings. This study evaluates whether participatory stakeholder groups have been established and also examines the capacity-building processes that took place in these stakeholder groups. For process evaluation, 78 group meetings were documented in 16 different stakeholder groups using a semi-structured protocol based on established capacity-building domains. For outcome evaluation, six semi-structured interviews (1–2 per setting) with facilitating experts were conducted. Data were analyzed by content analysis. Across all settings, capacity-building processes were successful to a certain degree (e.g. problem assessment, resource mobilization). However, in most groups it was difficult to broadly assess problems, to establish sustainable networks, or to find persons with leadership characteristics. Also, irregular participation, lack of motivation to take over responsibility, and minimal institutional readiness for structural and personal changes often hindered the progress of the projects. Stakeholder groups can actively involve setting members in the development of physical activity promotion programs. It seems challenging, however, to sustainably establish such groups that continue working independently without assistance from a facilitating expert.
You Are Wrong Because I Am Right! The Perceived Causes and Ideological Biases of Misinformation Beliefs
Authors: Hameleers Michael , Brosius Anna
Published: October 2021

In the context of increasing concerns about false and deceptive information in public opinion, this research note explores which causes and sources news users associate with the dissemination of misinformation. Based on representative survey data collected in the Netherlands (N = 1,994), we found that news users distinguish unintentional causes related to uncertain evidence and lacking expert knowledge from politically or financially motivated falsehoods. People on the left-wing of the political spectrum associate falsehoods more with the radical-right, whereas those on the right-wing tend to associate misinformation with the radical-left. Right-wing participants, however, are most likely to perceive misinformation as driven by a deliberate attempt to hide reality. Our findings point to an ideological bias in information credibility that could foster polarization along epistemic lines.
Association of Statins and 28-Day Mortality Rates in Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 Infection
Authors: Memel Zoe N , Lee Jenny J , Foulkes Andrea S , Chung Raymond T , Thaweethai Tanayott , Bloom Patricia P
Published: October 2021

Background

Statins may be protective in severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 infection. The aim of the current study was to evaluate the effect of in-hospital statin use on 28-day mortality rates and intensive care unit (ICU) admission among patients with SARS-CoV-2, stratified into 4 groups: those who used statins before hospitalization (treatment continued or discontinued in the hospital) and those who did not (treatment newly initiated in the hospital or never initiated).

Methods

In a cohort study of 1179 patients with SARS-CoV-2, record review was used to assess demographics, laboratory measurements, comorbid conditions, and time from admission to death, ICU admission, or discharge. Using marginal structural Cox models, we estimated hazard ratios (HRs) for death and ICU admission.

Results

Among 1179 patients, 676 (57%) were male, 443 (37%) were >65 years old, and 493 (46%) had a body mass index ≥30 (calculated as weight in kilograms divided by height in meters squared). Inpatient statin use reduced the hazard of death (HR, 0.566; P=.008). This association held among patients who did and those who did not use statins before hospitalization (HR, 0.270 [P=.003] and 0.493 [P=.04], respectively). Statin use was associated with improved time to death for patients aged >65 years but not for those ≤65 years old.

Conclusion

Statin use during hospitalization for SARS-CoV-2 infection was associated with reduced 28-day mortality rates. Well-designed randomized control trials are needed to better define this relationship.
Mapping the quality of basic and comprehensive emergency obstetric care services in Haiti
Authors: Adegbosin Adeyinka E , Warnken Jan , Sun Jing
Published: October 2021

Objective

To investigate geographical inequalities and changes in the quality of emergency obstetric care services available in Haiti over time.

Methods

We utilized data from the Service Provision Assessment survey of all health facilities in Haiti in 2013 and 2017.We developed a quality index for basic emergency obstetric care (BEmOC) and comprehensive emergency obstetric care (CEmOC) based on the items in the signal functions of an emergency obstetric care framework, using a structure, process and outcome framework. We measured the quality index of all facilities in 2013 and 2017. We also assessed geographical trends and changes in quality between 2013 and 2017 using geospatial analysis.

Result

Our analysis showed that basic structure items such as connection to electricity grid, manual vacuum extractors, vacuum aspirators and dilation and curettage kits were widely unavailable at healthcare facilities. There was a significant improvement in indicators of structure (P < 0.001) and BEmOC (P = 0.03) in primary facilities; however, there was no significant change in the quality of CEmOC in primary facilities (P = 0.18). Similarly, there was no significant change in any of the structure or process indicators at secondary care facilities.

Conclusion

The availability of BEmOC at several Haitian facilities remains poor; however, there was significant improvement at primary care facilities, with little to no change in overall quality at secondary health facilities.
Linezolid-resistant Enterococcus gallinarum isolate of swine origin carrying cfr, optrA and poxtA genes
Authors: Coccitto Sonia Nina , Cinthi Marzia , Fioriti Simona , Morroni Gianluca , Simoni Serena , Vignaroli Carla , Garofalo Cristiana , Mingoia Marina , Brenciani Andrea , Giovanetti Eleonora
Published: October 2021

Objectives

To characterize a linezolid-resistant Enterococcus gallinarum isolate of porcine origin co-carrying cfr, optrA and poxtA genes.

Methods

The genome was sequenced using the Illumina and Nanopore platforms. The presence of circular intermediates was examined by inverse PCR. Transferability of oxazolidinone resistance genes was investigated by transformation and conjugation.

Results

Two plasmids, the cfr- and optrA-carrying pEgFS4-1 (35 kb) and the poxtA-harbouring pEgFS4-2 (38 kb), were identified. pEgFS4-1 disclosed a distinctive mosaic structure with two cargo regions bounded by identical IS1216 elements interpolated into a backbone related to that of Enterococcus faecium vanA-containing pVEF2. The first cargo region included the cfr and optrA contexts, whereas the second one carried a Tn554 remnant and the lnu(A) gene. Both regions were able to excise in circular form as a unique translocable unit. pEgFS4-2 plasmid was 99% identical to a not fully described E. faecium pSBC1 plasmid. The poxtA environment, flanked by IS1216, was proved to be unstable. pEgFS4-2 also exhibited another cargo region containing the tet(M)–tet(L) genes arranged in tandem and its circular form was detected. Transformation and conjugation experiments failed to demonstrate the transferability of both plasmids to enterococcal recipients. Both plasmids persisted in the absence of selective pressure.

Conclusions

To the best of our knowledge, this is the first description of a linezolid-resistant E. gallinarum isolate of swine origin carrying cfr, optrA and poxtA genes. The co-presence of three linezolid resistance determinants in an intrinsically vancomycin-resistant enterococcal species is cause of concern.
Short communication: the effects of a semi-synthetic diet with inclusion of black soldier fly larvae meal on health parameters of healthy adult cats
Authors: Pezzali Julia Guazzelli , Shoveller Anna Kate
Published: October 2021

In recent years, black soldier fly larvae meal (Hermetia illucens; BSFLM) has gained attention as a high value alternative protein source that is of great interest to the pet food industry. However, little is known regarding the effects of BSFLM on health parameters in adult cats. Thus, the objective of the current study was to determine the short-term effects of a semi-synthetic diet containing 4.6% inclusion of BSFLM on complete blood count (CBC) and serum biochemistry profile of healthy adult cats. Healthy adult male cats (n = 8; 1.4 yr) were fed the experimental diet for 21 d (experimental period) to maintain BW. Cats were washed in on a commercial diet and blood samples were collected before the start and at the end of the experimental period to measure gross health parameters. Results were analyzed as one-way ANOVA using the GLIMMIX procedure in SAS with cat as a random effect (SAS v. 9.4, The SAS Institute, Cary, NC). Cats lost an average of 5% of their BW (P = 0.0003) due to a concurrent decrease in food intake. A significant increase of alanine aminotransferase, chloride, potassium, sodium, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration was observed on day 21 vs. baseline (P < 0.05). In contrast, albumin, amylase, calcium, cholesterol, eosinophil, lymphocyte, monocyte, mean platelet volume, red blood cells, total protein, total solid proteins, and urea decreased over time (P < 0.05). However, all CBC and serum biochemistry parameters stayed within reference range for adult cats, with exception of glucose and mean corpuscular hemoglobin concentration that were above and below the reference range, respectively. Transient increases in glucose concentrations were likely due to sedation with dexmedetomidine prior to blood collection. The changes observed over time in the aforementioned parameters are likely due to changes in macronutrient composition of the diets offered prior to and during the experimental period (commercial diet vs. semi-synthetic diet, respectively) and cannot be attributed solely to a unique property of BSFLM. In conclusion, cats fed a semi-synthetic diet containing 4% BSFLM inclusion for 21 d remained healthy with no clinically relevant changes in CBC and serum biochemistry parameters. Further research should focus on longer term feeding studies and the ability of BSFLM to support the health and well-being of cats.
‘Sèvres-mania’ and collaborative collecting networks: The 2nd Earl of Lonsdale, Henry Broadwood and Edward Holmes Baldock
Authors: McCaffrey-Howarth Caroline
Published: October 2021

This article examines the relationship between a rising mania for ‘old’ pâte-tendre Sèvres porcelain and a growing specialization in collecting practices during the 1830s in Paris and London. Using newly discovered archival evidence, it questions the idea that individuals make collecting histories, and instead posits the notion of collaboration in creating an art collection. It examines a series of interactions between collecting networks and prioritizes the process of collecting rather than the collection itself. This provides an opportunity to consider constructions of identity, class and gender, and also shines a light on the methods of acquisition and value structures of ‘old’ Sèvres and the market for it during this time. At its core, it proposes a collaborative paradigm of object and knowledge exchange between an art collector, the 2nd Earl of Lonsdale (1787–1872), his friend and agent Henry Broadwood (1793–1878) and the dealer Edward Holmes Baldock (1777–1845).
Arabidopsis EXO70B2 exocyst subunit contributes to papillae and encasement formation in antifungal defence
Authors: Ortmannová Jitka , Sekereš Juraj , Kulich Ivan , Šantrůček Jiří , Dobrev Petre , Žárský Viktor , Pečenková Tamara
Published: October 2021

In the reaction to non-adapted Blumeria graminis f. sp. hordei (Bgh), Arabidopsis thaliana leaf epidermal cells deposit cell wall reinforcements called papillae or seal fungal haustoria in encasements, both of which involve intensive exocytosis. A plant syntaxin, SYP121/PEN1, has been found to be of key importance for the timely formation of papillae, and the vesicle tethering complex exocyst subunit EXO70B2 has been found to contribute to their morphology. Here, we identify a specific role for the EXO70B2-containing exocyst complex in the papillae membrane domains important for callose deposition and GFP-SYP121 delivery to the focal attack sites, as well as its contribution to encasement formation. The mRuby2-EXO70B2 co-localizes with the exocyst core subunit SEC6 and GFP-SYP121 in the membrane domain of papillae, and EXO70B2 and SYP121 proteins have the capacity to directly interact. The exo70B2/syp121 double mutant produces a reduced number of papillae and haustorial encasements in response to Bgh, indicating an additive role of the exocyst in SYP121-coordinated non-host resistance. In summary, we report cooperation between the plant exocyst and a SNARE protein in penetration resistance against non-adapted fungal pathogens.
Implied Terms
Authors: Andrews Neil
Published: October 2021

The fertility of the implied term device in English law explains the traditional absence of a general doctrine of good faith in performance (on that doctrine see chapter 19, and [2.69] ff).
Termination by Notice or Consent
Authors: Andrews Neil
Published: October 2021

This chapter deals concisely with two situations. The first is where the contract is not limited in its duration and a party exercises an implied right to bring it to an end by unilateral notice. The second situation, which has produced some subtle judicial discussion, involves the issue whether the parties’ conduct objectively and clearly manifests a mutual intention to abandon the contract, so that it has been consensually
Breach
Authors: Andrews Neil
Published: October 2021

This is a fundamental feature of contract doctrine. In English law breach justifies a party in terminating the contract by reason of the other’s default if: there has been a renunciation; or a serious breach of a repudiatory nature; if a term classified as a condition has been breached; if a term not so classified has been breached so that the result of the default is extremely serious. Breach can occur before the date of expected performance. Anticipatory cancellation does not automatically end the contract. Instead the other party, if able to perform without the other’s cooperation, might decide to keep the contract in operation (that topic is also examined, in the context of debt claims, at [27.36] to [27.49]). The process of terminating and the consequences of termination is also carefully explained in the present chapter.
Force Majeure and Frustration
Authors: Andrews Neil
Published: October 2021

Force majeure clauses: these exonerate a party whose performance has become impossible in circumstances falling with the scope of the stipulated clause. Such a clause will normally broaden the relevant party’s immunity from liability for default beyond the narrow set of excuses applicable as a result of the Common Law doctrine of frustration.