Everolimus-eluting bioresorbable vascular scaffold in daily clinical practice: A single-centre experience

Background

Recent evidence has raised concerns regarding the safety of the everolimus-eluting bioresorbable vascular scaffold (E-BVS) (Absorb, Abbott Vascular, Santa Clara, CA, USA). Following these data, the use of this device has diminished in the Netherlands; however, daily practice data are limited. Therefore we studied the incidence of safety and efficacy outcomes with this device in daily clinical practice in a single large tertiary centre in the Netherlands.

Methods

All E?BVS treated patients were included in this analysis. The primary endpoint was target lesion failure (TLF), a composite of cardiac death, target vessel non-fatal myocardial infarction (TV-MI) and clinically-driven target lesion revascularisation (TLR). The secondary endpoint was the incidence of definite scaffold thrombosis.

Results

Between October 2013 and January 2017, 105 patients were treated with 147 E?BVS. This population contained 42 (40%) patients with diabetes mellitus and 43 (40.9%) undergoing treatment for acute coronary syndrome, and thus represents a high-risk patient cohort. Mean follow-up was 19.8 months. Intravascular imaging guidance during scaffold implantation was used in 64/105 (43.5%) patients. The primary endpoint (TLF) occurred in 3 (2.9%) patients. All-cause mortality and cardiac mortality occurred in 2 (2%) and 0 (0%) patients respectively. TV-MI occurred in 2 patients (1.9%): both were periprocedural and not related to the BVS implantation. TLR occurred in 1 patient (1.0%) during follow-up. No definite scaffold thrombosis occurred during follow-up.

Conclusion

This single-centre study examining the real-world experience of E?BVS implantation in a high-risk population shows excellent procedural safety and long-term clinical outcomes.

     

Short versus long duration of dual antiplatelet therapy following drug-eluting stents: a meta-analysis of randomised trials

Background

Dual antiplatelet therapy (DAPT) remains the cornerstone therapy in the prevention of ischaemic events following drug-eluting stent (DES) implantation. Mandatory duration of DAPT after DES however, is a matter of debate. We aimed to evaluate safety and efficacy of short-term (up to 6 months) versus long-term (12 months) DAPT after DES implantation.

Methods

We searched PubMed, EMBASE, Cochrane databases, and international meetings for randomised clinical trials (RCTs) comparing short with long DAPT. We performed a systematic review and meta-analysis of major trials with primary outcomes: all-cause death, myocardial infarction, definite or probable stent thrombosis, stroke, and major bleeding event.

Results

Nine RCTs with a total number of 19,099 patients were pooled in the present meta-analysis. When compared with long DAPT, short DAPT was associated with a significant reduction in major bleeding events (0.62% vs. 1.10%, risk ratio (RR) 0.58, 95% confidence interval (CI) 0.39 to 0.86, p?<?0.007, I²?=?21%), whereas all-cause death (1.65% vs. 1.84%, RR 0.90, 95% CI 0.73 to 1.11, p?=?0.34, I2?=?0%), myocardial infarction (1.91% vs. 1.68%, RR 1.14, 95% CI 0.92 to 1.40, p?=?0.23, I2?=?0%), definite or probable stent thrombosis (0.62% vs. 0.47%, RR 1.25, 95% CI 0.84 to 1.86, p?=?0.27, I2?=?0%), and stroke (0.60% vs. 0.67%, RR 0.91, 95% CI 0.63 to 1.31, p?=?0.61, I2?=?0%) were similar.

Conclusions

Short DAPT following DES implantation results in a significant reduction of major bleeding events with no apparent increase in all-cause death, myocardial infarction, stent thrombosis, or stroke. Future dedicated trials should investigate the optimal strategies for patient-tailored DAPT in various subgroups.

     

Appropriate use criteria for optical coherence tomography guidance in percutaneous coronary interventions

Introduction

Optical coherence tomography (OCT) enables detailed imaging of the coronary wall, lumen and intracoronary implanted devices. Responding to the lack of specific appropriate use criteria (AUC) for this technique, we conducted a literature review and a procedure for appropriate use criteria.

Methods

Twenty-one of all 184 members of the Dutch Working Group on Interventional Cardiology agreed to evaluate 49 pre-specified cases. During a meeting, factual indications were established whereupon members individually rated indications on a 9-point scale, with the opportunity to substantiate their scoring.

Results

Twenty-six indications were rated ‘Appropriate’, eighteen indications ‘May be appropriate’, and five ‘Rarely appropriate’. Use of OCT was unanimously considered ‘Appropriate’ in stent thrombosis, and ‘Appropriate’ for guidance in PCI, especially in distal left main coronary artery and proximal left anterior descending coronary artery, unexplained angiographic abnormalities, and use of bioresorbable vascular scaffold (BVS). OCT was considered ‘Rarely Appropriate’ on top of fractional flow reserve (FFR) for treatment indication, assessment of strut coverage, bypass anastomoses or assessment of proximal left main coronary artery.

Conclusions

The use of OCT in stent thrombosis is unanimously considered ‘Appropriate’ by these experts. Varying degrees of consensus exists on the appropriate use of OCT in other settings.

     

Perioperative management of antiplatelet treatment in patients undergoing isolated coronary artery bypass grafting in Dutch cardiothoracic centres

Background

International guidelines do not provide uniform recommendations regarding the use of antiplatelet treatment in the perioperative period in patients undergoing coronary artery bypass grafting (CABG).

Methods

A questionnaire was sent to all 16 cardiothoracic centres in the Netherlands to determine which antiplatelet treatment is used in the perioperative setting. Furthermore, a single-centre prospective observational cohort study was performed which included all patients undergoing isolated CABG in July 2014.

Results

Eleven centres responded to the survey. Acetylsalicylic acid monotherapy was discontinued before surgery in 6 centres. In patients with an acute coronary syndrome receiving dual antiplatelet therapy (DAPT), most centres discontinued the P2Y₁₂ inhibitor preoperatively. DAPT was restarted after surgery in 4 centres. However, 6 centres continued DAPT in patients who had undergone coronary stenting within one month of surgery. In patients with coronary stents, variation in the management of antiplatelet therapy increased in proportion to the interval between stenting and surgery. A total of 70 patients were included in the registry. Acetylsalicylic acid monotherapy was discontinued in 51% of patients and restarted in all patients. P2Y₁₂ inhibitor treatment was discontinued before surgery in 70% of patients and re-initiated after CABG in 29%.

Conclusions

Major differences were observed in the preoperative and postoperative management of antiplatelet treatment between different Dutch cardiothoracic centres and within a single centre. Part of this variation is probably due to lack of evidence and differences between the current guidelines; however, many of the strategies were not in accordance with any of these guidelines.

     

Citrate usage in the leading causes of blindness: new possibilities for the old metabolite

Introduction

Citrate is an old metabolite which is best known for the role in the Krebs cycle. Citrate is widely used in many branches of medicine. In ophthalmology citrate is considered as a therapeutic agent and an useful diagnostic tool—biomarker.

Objectives

To summarize the published literature on citrate usage in the leading causes of blindness and highlight the new possibilities for this old metabolite.

Methods

We conducted a systematic search of the scientific literature about citrate usage in ophthalmology up to January 2018. The reference lists of identified articles were searched for providing in-depth information.

Results

This systematic review included 30 articles. The role of citrate in the leading causes of blindness is presented.

Conclusions

Citrate might help inhibit cataract progression, in case of questions confirm glaucoma diagnosis or improve cornea repair treatment as adjuvant agent (therapy of ulcerating cornea after alkali injury, crosslinking procedure). However, the knowledge about possible citrate usage in ophthalmology is not widely known. Promoting recent scientific knowledge about citrate usage in ophthalmology may not only benefit of medical improvement but may also limit economic costs caused by leading causes of blindness. Further studies on citrate usage in ophthalmology should continuously be the field of scientific interest.

     

Lanthanum phosphate/chitosan scaffolds enhance cytocompatibility and osteogenic efficiency via the Wnt/β-catenin pathway

Background

Fabrication of porous scaffolds with great biocompatibility and osteoinductivity to promote bone defect healing has attracted extensive attention.

Methods

In a previous study, novel lanthanum phosphate (LaPO₄)/chitosan (CS) scaffolds were prepared by distributing 40- to 60-nm LaPO₄ nanoparticles throughout plate-like CS films.

Results

Interconnected three dimensional (3D) macropores within the scaffolds increased the scaffold osteoconductivity, thereby promoting cell adhesion and bone tissue in-growth. The LaPO₄/CS scaffolds showed no obvious toxicity and accelerated bone generation in a rat cranial defect model. Notably, the element La in the scaffolds was found to promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) through the Wnt/β-catenin signalling pathway and induced high expression of the osteogenesis-related genes alkaline phosphatase, osteocalcin and Collagen I (Col-I). Moreover, the LaPO₄/CS scaffolds enhanced bone regeneration and collagen fibre deposition in rat critical-sized calvarial defect sites.

Conclusion

The novel LaPO₄/CS scaffolds provide an admirable and promising platform for the repair of bone defects.

     

Metallic small y stent placement at primary right carina for bronchial disease

Background

Metallic large Y stent placement has been used mainly for airway disease around the main carina. However, few studies have reported this treatment for bronchial disease around the primary right carina.

Methods

Twenty-eight patients were treated by small y stent. All stents were custom-designed and placed under fluoroscopic guidance. Clinical and imaging data were analyzed retrospectively.

Results

Thirty-one stents were successfully inserted in 28 patients. Twenty-five patients succeed at the first attempt (89.3%), and 3 patients needed a second attempt. Twelve complications occurred in 10 patients (35.7%). Stent restenosis and sputum retention were the most common complications. Five patients underwent successful stent removal due to complications or cure efficacy. During follow up, 17 patients died of tumors and one died of myocardial infarction. The 1-, 3-, and 5-year survival rates were 49.3, 19.6 and 19.6%, respectively.

Conclusions

Metallic small y stent placement is technically feasible, effective and safe for bronchial disease around the primary right carina.

     

Optimization of fecal sample preparation for untargeted LC-HRMS based metabolomics

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.

     

Mid-term and long-term safety and efficacy of bioresorbable vascular scaffolds versus metallic everolimus-eluting stents in coronary artery disease: A weighted meta-analysis of seven randomised controlled trials including 5577 patients

Aims

Mid- and long-term safety and efficacy of the Absorb bioresorbable vascular scaffold (BVS) have been studied in randomised trials; however, most were not individually powered for clinical endpoints. We performed a weighted meta-analysis comparing mid- and long-term outcomes in patients treated with the BVS compared with the Xience metallic stent.

Methods and results

Randomised trials comparing the BVS and Xience were identified by searching MEDLINE, EMBASE and conference abstracts. Seven trials were included (BVS n = 3258, Xience n = 2319) with follow-up between 1–3 years. The primary outcome of target lesion failure occurred more frequently in BVS compared with Xience [OR 1.34; 95% CI 1.11–1.62, p = 0.003]. Overall definite or probable device thrombosis occurred more frequently with the BVS [OR 2.86; 95% CI 1.88–4.36, p < 0.001] and this extended beyond 1 year of follow-up [OR 4.13; 95% CI 1.99–8.57, p < 0.001]. Clinically indicated or ischaemia driven target lesion revascularisation [OR 1.43; 95% CI 1.11–1.83, p = 0.005] and myocardial infarction (all MI) [OR 1.64; 95% CI 1.20–2.23, p = 0.002] were more frequently seen in the BVS compared with Xience. Rates of target vessel failure [OR 1.15; 95% CI 0.91–1.46, p = 0.25] and cardiac death [OR 0.91; 95% CI 0.57–1.46, p = 0.71] were not significantly different between BVS and Xience.

Conclusion

This meta-analysis shows a higher rate of target lesion failure and an almost threefold higher rate of device thrombosis in BVS compared with Xience, which extends beyond the first year. Device thrombosis did not lead to an overall increased (cardiac) mortality.

     

Numerical simulation on the effects of drug eluting stents at different Reynolds numbers on hemodynamic and drug concentration distribution

Background

The changes of hemodynamics and drug concentration distribution caused by the implantation of drug eluting stents (DESs) in curved vessels have significant effects on In-Stent Restenosis.

Methods

A 3D virtual stent with 90°curvature was modelled and the distribution of wall shear stress (WSS) and drug concentration in this model were numerically studied at Reynolds numbers of 200, 400, 600, 800.

Results

The results showed that (1) the intensity of secondary flow at the 45° cross-section was stronger than that at the 90° cross-section; (2) As the Reynolds number increases, the WSS decreases. When the Reynolds number reaches 600, the low-WSS region only accounts for 3% of the total area. (3) The effects of Reynolds number on drug concentration in the vascular wall decreases in proportionally and then the blood velocity increased 4 times, the drug concentration in the vascular wall decreased by about 30%. (4) The size of the high drug concentration region is inversely proportional to the Reynolds number. As the blood velocity increases, the drug concentration in the DES decreases, especially at the outer bend.

Conclusions

It is beneficial for the patient to decrease vigorous activities and keep calm at the beginning of the stent implantation, because a substantial amount of the drug is released in the first two months of stent implantation, thus a calm status is conducive to drug release and absorption; Subsequently, appropriate exercise which increases the blood velocity is helpful in decreasing regions of low-WSS.

     

Three dimensional rotational angiography for assessment of coronary arteries during melody valve implantation: introducing a technique that may improve outcomes

Background

Adverse events from Melody valve implantation may be catastrophic. To date a role for three dimensional rotational angiography of the aortic root (3DRAA) during Melody valve implantation has not been established.

Objectives

To describe the role of 3DRAA in the assessment of Melody valve candidacy and to demonstrate that it may improve outcomes.

Methods

All patients who underwent cardiac catheterisation for Melody valve implantation and 3DRAA between August 2013 and February 2015 were reviewed.

Results

31 patients had 3DRAA with balloon sizing. Ten were deemed not Melody candidates (5 coronary compression, 2 aortic root distortion with cusp flattening, 2 RVOT was too large, and 1 had complex branch stenosis and a short landing zone). Of the 21 patients who were Melody candidates, 12 had conduits, 6 prosthetic valves and 3 native RVOTs. In patients with conduits, the technique of stenting the conduit prior to dilation was used after measuring the distance between the conduit and the coronary arteries on 3DRAA. In the Melody patients, we had 100% procedural success and no serious adverse events (coronary compression, tears, stent fracture or endocarditis).

Conclusion

As a tool for case selection, 3DRAA may facilitate higher procedural success and decreased risk of serious adverse events. Furthermore, 3D rotational angiography allows stenting of the conduit prior to dilation, which may prevent tears and possibly endocarditis.

     

Modeling the behavior of human induced pluripotent stem cells seeded on melt electrospun scaffolds

Background

Human induced pluripotent stem cells (hiPSCs) can form any tissue found in the body, making them attractive for regenerative medicine applications. Seeding hiPSC aggregates into biomaterial scaffolds can control their differentiation into specific tissue types. Here we develop and analyze a mathematical model of hiPSC aggregate behavior when seeded on melt electrospun scaffolds with defined topography.

Results

We used ordinary differential equations to model the different cellular populations (stem, progenitor, differentiated) present in our scaffolds based on experimental results and published literature. Our model successfully captures qualitative features of the cellular dynamics observed experimentally. We determined the optimal parameter sets to maximize specific cellular populations experimentally, showing that a physiologic oxygen level (～?5%) increases the number of neural progenitors and differentiated neurons compared to atmospheric oxygen levels (～?21%) and a scaffold porosity of ～?63% maximizes aggregate size.

Conclusions

Our mathematical model determined the key factors controlling hiPSC behavior on melt electrospun scaffolds, enabling optimization of experimental parameters.

     

A lost opportunity for science: journals promote data sharing in metabolomics but do not enforce it

Introduction

Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.

Objectives

(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.

Methods

A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.

Results

Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.

Conclusion

Further efforts are required to improve data sharing in metabolomics.

     

Untargeted metabolomics suffers from incomplete raw data processing

Introduction

Untargeted metabolomics is a powerful tool for biological discoveries. To analyze the complex raw data, significant advances in computational approaches have been made, yet it is not clear how exhaustive and reliable the data analysis results are.

Objectives

Assessment of the quality of raw data processing in untargeted metabolomics.

Methods

Five published untargeted metabolomics studies, were reanalyzed.

Results

Omissions of at least 50 relevant compounds from the original results as well as examples of representative mistakes were reported for each study.

Conclusion

Incomplete raw data processing shows unexplored potential of current and legacy data.

     

Pseudo current density maps of electrophysiological heart,nerve or brain function and their physical basis

Background

In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.

Methods

The physical basis of these intuitive maps is clarified by means of analytically solvable problems.

Results

Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.

Conclusion

Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.

     

Quantitative analysis of tetrahydrofolate metabolites from <Emphasis Type="Italic">clostridium autoethanogenum</Emphasis>

Introduction

Quantification of tetrahydrofolates (THFs), important metabolites in the Wood–Ljungdahl pathway (WLP) of acetogens, is challenging given their sensitivity to oxygen.

Objective

To develop a simple anaerobic protocol to enable reliable THFs quantification from bioreactors.

Methods

Anaerobic cultures were mixed with anaerobic acetonitrile for extraction. Targeted LC–MS/MS was used for quantification.

Results

Tetrahydrofolates can only be quantified if sampled anaerobically. THF levels showed a strong correlation to acetyl-CoA, the end product of the WLP.

Conclusion

Our method is useful for relative quantification of THFs across different growth conditions. Absolute quantification of THFs requires the use of labelled standards.

     

Metabolomic profiling of maternal hair suggests rapid development of intrahepatic cholestasis of pregnancy

Introduction

Intrahepatic cholestasis of pregnancy (ICP) is a common maternal liver disease; development can result in devastating consequences, including sudden fetal death and stillbirth. Currently, recognition of ICP only occurs following onset of clinical symptoms.

Objective

Investigate the maternal hair metabolome for predictive biomarkers of ICP.

Methods

The maternal hair metabolome (gestational age of sampling between 17 and 41 weeks) of 38 Chinese women with ICP and 46 pregnant controls was analysed using gas chromatography–mass spectrometry.

Results

Of 105 metabolites detected in hair, none were significantly associated with ICP.

Conclusion

Hair samples represent accumulative environmental exposure over time. Samples collected at the onset of ICP did not reveal any metabolic shifts, suggesting rapid development of the disease.

     

Three-dimensional image fusion guidance of percutaneous pulmonary valve implantation to reduce radiation exposure and contrast dose: A comparison with traditional two-dimensional and three-dimensional rotational angiographic guidance

Introduction

Three-dimensional rotational angiography (3DRA) has been used in the guidance of various transcatheter therapies including percutaneous pulmonary valve implantation (PPVI). The most recently available 3D image fusion software (VesselNavigator, Philips) extends this technology to use pre-registered computed tomography or magnetic resonance imaging datasets, promising reductions in contrast and radiation exposure along with shorter procedural times.

Methods

In this retrospective review, patients were assigned to three groups according to the mode of imaging guidance: two-dimensional angiography (2DA), 3DRA and VesselNavigator (VN) assisted valve implantation. Patient characteristics and catheterisation data were reviewed with a focus on contrast and radiation exposure, fluoroscopy, and procedural times.

Results

Between July 2012 and June 2016, 21 patients underwent PPVI: 8 with 2D guidance, 6 patients with 3DRA and most recently 7 patients with VN assistance. Patents in the VN group received significantly less absolute and weight indexed contrast when compared with those with 2DA or 3DRA guided PPVI. Patients in the 2DA group received a significantly higher total dose area product radiation dose and air kerma in comparison with patients with 3DRA and VN guided intervention. Application of VN resulted in the shortest fluoroscopy time, although not statistically significant, and a significantly shorter study time when compared with 2DA.

Conclusions

Utilisation of pre-intervention image manipulation with VesselNavigator for 3D guidance of PPVI results in a reduction in contrast and radiation exposure and study time as compared with traditional 2D guidance, and contrast usage as compared with 3DRA.

     

A methodology for elucidating regulatory mechanisms leading to changes in lipid profiles

Introduction

It is difficult to elucidate the metabolic and regulatory factors causing lipidome perturbations.

Objectives

This work simplifies this process.

Methods

A method has been developed to query an online holistic lipid metabolic network (of 7923 metabolites) to extract the pathways that connect the input list of lipids.

Results

The output enables pathway visualisation and the querying of other databases to identify potential regulators. When used to a study a plasma lipidome dataset of polycystic ovary syndrome, 14 enzymes were identified, of which 3 are linked to ELAVL1—an mRNA stabiliser.

Conclusion

This method provides a simplified approach to identifying potential regulators causing lipid-profile perturbations.