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.

     

Proteomic investigations into hypertension: what’s new and how might it affect clinical practice?

Introduction: Hypertension is a multifactorial disease that has, thus far, proven to be a difficult target for pharmacological intervention. The application of proteomic strategies may help to identify new biomarkers for the early diagnosis and prompt treatment of hypertension, in order to control blood pressure and prevent organ damage.

Areas covered: Advances in proteomics have led to the discovery of new biomarkers to help track the pathophysiological processes implicated in hypertension. These findings not only help to better understand the nature of the disease, but will also contribute to the clinical needs for a timely diagnosis and more precise treatment. In this review, we provide an overview of new biomarkers identified in hypertension through the application of proteomic techniques, and we also discuss the difficulties and challenges in identifying biomarkers in this clinical setting. We performed a literature search in PubMed with the key words ‘hypertension’ and ‘proteomics’, and focused specifically on the most recent literature on the utility of proteomics in hypertension research.

Expert opinion: There have been several promising biomarkers of hypertension identified by proteomics, but too few have been introduced to the clinic. Thus, further investigations in larger cohorts are necessary to test the feasibility of this strategy for patients. Also, this emerging field would profit from more collaboration between clinicians and researchers.     

From Mitochondrial Dysfunction to Amyloid Beta Formation: Novel Insights into the Pathogenesis of Alzheimer’s Disease

The non-Mendelian sporadic Alzheimer's disease (AD) is the most frequent form of dementia diagnosed worldwide. The most important risk factor to develop sporadic AD is aging itself. Next to hyperphosphorylated Tau, intracellular amyloid beta (A?) oligomers are known to initiate a cascade of pathological events ranging from mitochondrial dysfunction, synaptic dysfunction, oxidative stress, and loss of calcium regulation, to inflammation. All these events are considered to play an important role in the progressive loss of neurons. The molecular mechanisms determining the balance between A? production and clearance during the progression of the disease are not well understood. Furthermore, there is cumulating evidence that A? formation impairs mitochondrial function and that mitochondrial dysfunction is an early event in the pathogenesis of AD. On the other hand, mitochondrial dysfunction, in particular increased formation of mitochondrially derived reactive oxygen species, promote A? formation. Here, we review these latest findings linking mitochondrial dysfunction and A? formation. We propose that mitochondrial dysfunction, which is well-known to increase with age, is an initial trigger for A? production. As A? itself further accelerates mitochondrial dysfunction and oxidative stress, its formation is self-stimulated. Taken together, a vicious cycle is initiated that originates from mitochondrial dysfunction, implying that AD can be viewed as an age-associated mitochondrial disorder. The proposed mechanism sheds new light on the pathophysiological changes taking place during the progression of AD as well as in the aging process.     

Insights into Strata Use of Forest Animals Using the ‘Canopy Effect’

Stable carbon isotope ratios (δ¹³C) of plants increase linearly from ground to canopy. Accordingly, I used δ¹³C for estimating strata use of fig-eating bats. Data suggest that, overall, bats commuted at lower but fed at higher forest strata, and that small bats foraged at lower forest strata than large bats.     

Making sense of ‘mixture’: states and the classification of ‘mixed’ people

Caribbean diaspora intellectuals have contributed significantly to African-American political struggles over the years, despite arguments by some African-American intellectuals about what they discern as West Indian negativism, extremism, and divisiveness in American political life. This essay examines the legacy of a representative sample of diasporic Caribbean intellectuals since the time of the Harlem Renaissance in the 1920s and culminating in the 1970s, notably, Garvey, members of the African Blood Brotherhood [ABB], C.L.R. James, and Walter Rodney, to demonstrate the phenomenal ideological vision, organizational capability, and political activism they have brought into fostering solidarity with African Americans in the struggle for fundamental change. The focus here is on their respective contributions to the debate on the relationship between class and race in America and the black diaspora generally, which has helped to shape the form, and orient the direction of African-American and Caribbean diasporic struggles for the better part of the twentieth century.     

Rethinking translational nanomedicine: insights from the ‘bottom-up’ design of the Porphysome for guiding the clinical development of imageable nanomaterials

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An analysis of the synthetic tryptamines AMT and 5-MeO-DALT: Emerging ‘Novel Psychoactive Drugs’

Novel Psychoactive Drugs (NPD) can be sold without restriction and are often synthetic analogues of controlled drugs. The tryptamines are an important class of NPD as they bind to the various serotonin (5-HT) receptor subtypes and cause psychosis and hallucinations that can lead to injury or death through misadventure. Here we report on the structure elucidation and receptor binding profiles of two widely marketed tryptamine-derived NPDs, namely alpha-methyl-tryptamine and 5-methoxy-N,N-diallyl-tryptamine.     

Novel insights into the development and maintenance of the blood–brain barrier

The blood–brain barrier (BBB) is essential for maintaining homeostasis within the central nervous system (CNS) and is a prerequisite for proper neuronal function. The BBB is localized to microvascular endothelial cells that strictly control the passage of metabolites into and out of the CNS. Complex and continuous tight junctions and lack of fenestrae combined with low pinocytotic activity make the BBB endothelium a tight barrier for water soluble moleucles. In combination with its expression of specific enzymes and transport molecules, the BBB endothelium is unique and distinguishable from all other endothelial cells in the body. During embryonic development, the CNS is vascularized by angiogenic sprouting from vascular networks originating outside of the CNS in a precise spatio-temporal manner. The particular barrier characteristics of BBB endothelial cells are induced during CNS angiogenesis by cross-talk with cellular and acellular elements within the developing CNS. In this review, we summarize the currently known cellular and molecular mechanisms mediating brain angiogenesis and introduce more recently discovered CNS-specific pathways (Wnt/β?catenin, Norrin/Frizzled4 and hedgehog) and molecules (GPR124) that are crucial in BBB differentiation and maturation. Finally, based on observations that BBB dysfunction is associated with many human diseases such as multiple sclerosis, stroke and brain tumors, we discuss recent insights into the molecular mechanisms involved in maintaining barrier characteristics in the mature BBB endothelium.     

Novel cap-independent translation with the 5′-noncoding region of L-A virus mRNA

A novel cap-independent translation has been performed where the ribosome entry is regulated by the 5-noncoding region (NCR) of L-A virus mRNA. Despite L-A virus mRNA containing neither cap structure nor a poly(A) tail, the reconstructed mRNA encoding the 5 NCR of L-A virus mRNA and a reporter gene (luciferase) was translated, in yeast lysate, 60 times more efficiently than control mRNA. The 5 NCR from L-A virus was effective in regulating the recruitment of ribosome in vitro. A possible mechanism in Saccharomyces cerevisiae is also suggested, whereby the ribosome entry is regulated by the 5 NCR of L-A virus mRNA.     

‘Make-up’: Personhood through the lens of biotechnology

This paper looks through the ethnographic lens of ‘new reproductive and genetic technologies’ (NRGT) at the idiom of ‘make-up’ in English understandings of personhood and relatedness. In the kinship thinking of interest here, persons are both ‘made’ and ‘made-up’. There are both unpredictable and inevitable elements in the way in which people ‘turn-out’ and their character or personality is meant to be idiosyncratic, lumpy and unique. The paper draws on the way in which residents of a town in the north of England explore possibilities presented by NRGT in ways that make explicit their understandings of personal identity, interpersonal relatedness and communal belonging. The paper attempts to integrate the quotidian and personal narratives of residents with broader social and economic changes occurring in their town.     

From ‘ecologist’ to ‘conceptual ecologist’: the utility of the conceptual ecology analogy for teachers of biology

This paper advocates the application of established teaching models to the professional development of biology teachers. This is achieved by using the analogy of conceptual ecologies, made explicit through concept mapping. The approach is designed to support teachers' developing understanding of pupils' conceptual change by using familiar terminology and biological analogies. Monitoring of students' understanding at an ecosystemic level may also help distinguish between instances of conceptual change and contextual switching (described here with reference to photosynthesis).     

Nationalism and the ‘idiocy’ of the countryside: The case of Serbia

The mobilization of the countryside has direct consequences for political discourse about national values and in times of social crisis, the ‘conservatism’ of the countryside has the potential to assume an aggressive, offensive posture. When rural mobilization is accompanied by religious revival, group loyalty and so‐called ‘traditional’ values are sacralized. When rural mobilization, ethnic mobilization, and religious revival occur simultaneously, it signifies that the society is undergoing profound destabilization. Examining the case of Serbia, this article argues that while Serbia is, in cultural and social terms, predominantly rural in character, Titoist Communism imposed the values of the city on that culture, while the 1987 coup by Slobodan Milosevic represented, among other things, the triumph of the countryside over the city in Serbia.

This article begins by characterizing the countryside in cultural terms, provides documentation of the importance of rural traditions in Serbian society, documents the rural character of the Serbian national movement, connecting its ideology and behaviour with populist appeals, and examines the contribution made by the Serbian Orthodox Church to the mobilization of the Serbian countryside.     

‘Heparin’ – from anticoagulant drug into the new biology

This overview attempts to cover, from a personal viewpoint, the development of the heparin field during the last four decades. In particular, it emphasizes the metamorphosis of heparan sulfate (HS), from a disturbing contaminant in heparin production to the present-day key player in cell and developmental biology. Our understanding of the structural properties of the polysaccharides has been greatly promoted by studies of their biosynthesis. We now have a fairly detailed view of the various enzymatic reactions, that convert the initial [4GlcA1-4GlcNAc1-]_n polymer into sulfated products with highly variable proportions of GlcA/IdoA and of N-acetyl, N-sulfate and O-sulfate substituents. It is also recognized that the variously substituted domains of the polysaccharide serve to interact, in more or less specific fashion, with a multitude of proteins, and that these interactions are essential to the biological functions of the proteins. Molecular genetics has unravelled the gene structures for almost all of the enzymes required to synthesize a heparin or HS chain, and has shown that several of these proteins exhibit genetic polymorphism. While differences in substrate specificity between enzyme isoforms may help to explain the structural variability of, in particular, HS chains, we still only partly understand the key features of heparin/HS biosynthesis and its regulation.     

Biocultural Diversity: Moving Beyond the Realm of ‘Indigenous’ and ‘Local’ People

During the past decade the relationship between biodiversity and human diversity has received increased attention, resulting in the identification of what the Declaration of Belém calls an ‘inextricable link’ between biological and cultural diversity. Although the term biocultural diversity, introduced to denote this link, is being used increasingly, there has been little critical reflection on what it precisely refers to. I argue that it is used with particular reference to ‘indigenous traditional’ people, but that there is scope for extending its application within biocultural discourse. I therefore review the concept of culture and discuss what constitutes cultural values of the natural environment. I conclude that the concept of culture must be understood as involving a dynamic process of transcultural exchange and constant re-articulations of tradition resulting in the persistence of certain cultural practices. This approach ultimately reveals that the concept of biocultural diversity is also applicable to non-indigenous traditional communities.