Angiogenesis, the formation of new blood vessels, is controlled by a balance between positive and negative endothelial regulatory factors. Soluble vascular endothelial growth factor receptor-1 (sVEGFR1), a naturally occurring soluble form of VEGFR1, is a negative counterpart of the vascular endothelial growth factor (VEGF) signaling pathway, which has been characterized as one of the most important endothelial regulators in human tumor angiogenesis. In our study, we examined the expression of sVEGFR1 in 110 primary breast carcinomas, and assessed its clinical significance. Ninety-four of 110 tumors showed >0.1 ng/mg protein of sVEGFR1 (range: 0.1-6.9 ng/mg protein; median: 1.03 ng/mg protein) as determined by a specific enzyme-linked immunosorbent assay (ELISA). Immunoblot analysis confirmed the presence of sVEGFR1 in breast tumor tissues. The levels of sVEGFR1 were correlated significantly with the levels of VEGF. There was no significant correlation between the levels of sVEGFR1 and any clinico-pathological factors including age, menopause, nodal involvement and hormone receptor status. A univariate prognosis analysis showed that the intratumoral VEGF status, as determined by ELISA, was a significant prognostic indicator, but sVEGFR1 status was not. In the combined analysis, however, the ratio of sVEGFR1 and VEGF levels provided more statistically significant prognostic value than VEGF status alone. Tumors in which the sVEGFR1 levels exceeded VEGF levels 10-fold had a markedly favorable prognosis. Multivariate analysis also demonstrated that the ratio of sVEGFR1 and VEGF was an independent prognostic indicator after nodal status. In conclusion, sVEGFR1, an intrinsic inhibitor of VEGF, frequently co-expressed with VEGF in primary breast cancer tissues. The intratumoral balance between sVEGFR1 and VEGF levels might be crucial for the progression of breast cancer.
The interaction of blood with artificial surfaces is of particular interest during hemodialysis treatments with extracorporeal blood circuits. Components of the extracorporeal blood circuit are known to have only a moderate, sometimes even an unfavorable hemocompatibility, and thus may provoke adverse biochemical or clinical sequelae. This article describes a newly established hemocompatibility assessment score. This score is based on on a standardized series of in vitro tests and is applied to commercially available hemodialysis membranes. It relates to a variety of membrane polymers, such as regenerated cellulose, diethylaminoethyl-modified cellulose, polyethersulfone/polyarylate blends and polysulfone. In order to compare different polymers used in the manufacturing of dialysis membranes, a set of the following hemocompatibility parameters was assessed and assembled to an overall score: generation of complement factor 5a, thrombin-antithrombin III-complex, release of platelet factor 4, generation and release of elastase from polymorphonuclear granulocytes, and platelet count. With respect to these parameters, the results reveal major differences between the selected dialysis membranes. This new score model proves to be an efficient tool to derive objective results, and it may, thus, be used in the future to facilitate the selection of membrane polymers with an appropriate hemocompatibility pattern for dialysis therapy.
As the prevalence of chronic kidney disease is expected to rise worldwide over the next decades, provision of renal replacement therapy (RRT), will further challenge budgets of all healthcare systems. Most patients today requiring RRT are treated with haemodialysis (HD) therapy and are elderly. This article demonstrates the interdependence of clinical and sustainability criteria that need to be considered to prepare for the future challenges of delivering dialysis to all patients in need. Newer, more sustainable models of high-value care need to be devised, whereby delivery of dialysis is based on value-based healthcare (VBHC) principles, i.e. improving patient outcomes while restricting costs. Essentially, this entails maximizing patient outcomes per amount of money spent or available. To bring such a meaningful change, revised strategies having the involvement of multiple stakeholders (i.e. patients, providers, payers and policymakers) need to be adopted. Although each stakeholder has a vested interest in the value agenda often with conflicting expectations and motivations (or motives) between each other, progress is only achieved if the multiple blocs of the delivery system are advanced as mutually reinforcing entities. Clinical considerations of delivery of dialysis need to be based on the entire patient disease pathway and evidence-based medicine, while the non-clinical sustainability criteria entail, in addition to economics, the societal and ecological implications of HD therapy. We discuss how selection of appropriate modes and features of delivery of HD (e.g. treatment modalities and schedules, selection of consumables, product life cycle assessment) could positively impact decision-making towards value-based renal care. Although the delivery of HD therapy is multifactorial and complex, applying cost-effectiveness analyses for the different HD modalities (conventional in-centre and home HD) can support in guiding payability (balance between clinical value and costs) for health systems. For a resource intensive therapy like HD, concerted and fully integrated care strategies need to be urgently implemented to cope with the global demand and burden of HD therapy.
Background: This systematic review was performed to identify recent published comparative evidence on the efficacy, effectiveness, and safety of expanded hemodialysis (HDx) versus high-flux HD and/or hemodiafiltration (HDF) for long-term outcomes in end-stage kidney disease.Methods: Systematic literature review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Medline, Medline ® Epub Ahead of Print, EconLit, Embase, and EBM reviews were searched to identify relevant publications from 2013 onwards. Eligibility criteria included clinical studies reporting mortality, hospitalizations, cardiovascular outcomes, economic evaluations, cost studies, and quality of life (QoL) studies.Results: A total of 79 relevant studies were identified with 29 prioritized for detailed analysis; four compared HDx to HD, one compared HDF and HDx, and 24 compared HDF with HD. A total of 13 randomized controlled trial (RCT)-based studies were identified; 11 compared HDF with HD, one compared HDx with HD, and one compared HDF with HDx. Follow-up duration ranged from 16 weeks to 7 years for HDF studies and from 12 weeks to 1 year for HDx studies. HDF showed significant improvements in mortality, cardiovascular outcomes, hospitalizations, and QoL versus high-flux HD. One study reported mortality outcomes for HDx and found no difference versus HDF. QoL benefits with HDx were reported in a small number of studies. Conclusion:The efficacy and safety of HDF is supported by a robust evidence base that includes several RCTs. While HDx may offer benefits over high-flux HD, longterm studies are required to compare HDx with online high volume HDF.
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