Embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma,and medulloepithelioma share molecular similarity and comprise a single clinicopathological entity

Three histological variants are known within the family of embryonal rosette-forming neuroepithelial brain tumors. These include embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma (EBL), and medulloepithelioma (MEPL). In this study, we performed a comprehensive clinical, pathological, and molecular analysis of 97 cases of these rare brain neoplasms, including genome-wide DNA methylation and copy number profiling of 41 tumors. We identified uniform molecular signatures in all tumors irrespective of histological patterns, indicating that ETANTR, EBL, and MEPL comprise a single biological entity. As such, future WHO classification schemes should consider lumping these variants into a single diagnostic category, such as embryonal tumor with multilayered rosettes (ETMR). We recommend combined LIN28A immunohistochemistry and FISH analysis of the 19q13.42 locus for molecular diagnosis of this tumor category. Recognition of this distinct pediatric brain tumor entity based on the fact that the three histological variants are molecularly and clinically uniform will help to distinguish ETMR from other embryonal CNS tumors and to better understand the biology of these highly aggressive and therapy-resistant pediatric CNS malignancies, possibly leading to alternate treatment strategies.     

Nucleotide metabolic mismatches in mammalian hearts: implications for transplantation

Introduction

Human donor organ shortages have led surgeons and scientists to explore the use of animals as alternative organ sources. Acute thrombovascular rejection (AVR) is the main hurdle in xenotransplantation. Disparities in nucleotide metabolism in the vessels of different species may contribute significantly to the microvascular component of AVR.

Methods

We evaluated the extent of nucleotide metabolism mismatch in selected organs and endothelial cells of different mammals with particular focus on the changes in activity of ecto-5’-nucleotidase (E5’N) elicited by exposure of porcine hearts or endothelial cells to human blood (ex vivo) or human plasma (in vitro).

Results

E5’N activity in the rat heart was significantly higher than in other species. We noted a significant difference (p<0.001) in E5’N activity between human and pig endothelial cell lines. Initial pig aortic endothelial E5’N activity decreased in vitro after a three-hour exposure to human and porcine plasma while remaining constant in controls. Ex vivo perfusion with fresh human blood for four hours resulted in a significant decrease of E5’N activity in both wild type and transgenic pig hearts overexpressing human decay accelerating factor (p<0.001).

Conclusions

This study provides evidence that mismatches in basal mammalian metabolic pathways and humoral immunity interact in a xenogeneic environment. Understanding the role of nucleotide metabolism and signalling in xenotransplantation may identify new targets for genetic modifications and may lead to the development of new therapies extending graft survival.     

Plasminogen activator inhibitor 1 and visceral obesity during pronounced weight loss after bariatric surgery

Background and aimsElevated plasminogen activator inhibitor 1 (PAI-1) concentrations are a hallmark of obesity and are considered to contribute to the development of cardiovascular disease. As adipose tissue constitutes a major source for PAI-1 in obesity, we investigated the individual contribution of subcutaneous and intra-abdominal fat on PAI-1 concentrations during pronounced weight loss after bariatric surgery.Methods and resultsThirty-seven obese adults were examined before and 18 months after surgery. Abdominal fat distribution was determined by ultrasound, metabolic parameters and plasma PAI-1 levels by standard methods. BMI was reduced by 9.2 ± 4.9 kg/m², while total fat mass and visceral fat diameter (VFD) decreased by 20.7 ± 11.9 kg and 4.2 ± 2.3 cm, respectively. Concomitantly, PAI-1 levels diminished by 3.2 ± 5.6 ng/ml (all p ≤ 0.015). Change in PAI-1 levels was correlated with change in VFD (r = 0.441, p = 0.008), but not with subcutaneous fat diameter. In stepwise multiple regression analysis change in VFD was an independent predictor of change in PAI-1 concentrations. When adjusted for age and sex or total fat mass associations between PAI-1 and VFD remained significant.ConclusionWe demonstrate that VFD is a major determinant for PAI-1 concentrations during pronounced weight loss after bariatric surgery. Thus, significant reduction of visceral fat mass may contribute to the reduced cardiovascular morbidity and mortality after bariatric surgery by a concomitant decrease in PAI-1 concentrations.     

Embolic Protection Devices in Saphenous Vein Graft and Native Vessel Percutaneous Intervention: A Review

The clinical benefit of percutaneous intervention (PCI) depends on both angiographic success at the site of intervention as well as the restoration of adequate microvascular perfusion. Saphenous vein graft intervention is commonly associated with evidence of distal plaque embolization, which is correlated with worse clinical outcomes. Despite successful epicardial intervention in the acute MI patient treated with primary PCI, distal tissue perfusion may still be absent in up to 25% of cases [1-3]. Multiple devices and pharmacologic regimens have been developed and refined in an attempt to protect the microvascular circulation during both saphenous vein graft intervention and primary PCI in the acute MI setting. We will review the evidence for various techniques for embolic protection of the distal myocardium during saphenous vein graft PCI and primary PCI in the native vessel.