Fewer Circulating Endothelial Progenitor Cells in Newly Diagnosed Neovascular AMD Patients

Abstract: Objective: Patients with age-related macular degeneration (AMD) exhibit pathologic neovascularization under the retina, with choroidal neovascularization (CNV) suggestive of defective angiogenesis. The endothelial progenitor cells (EPCs) present in the peripheral blood contribute to angiogenesis and vasculogenesis, and their regulation is altered in several vascular disorders. We investigated whether the numbers and functional properties of EPCs may be disordered in newly diagnosed neovascular AMD. Methods Fifteen suitable AMD patients and 10 controls matched for age, risk factors for atherosclerosis and use of medication that could influence the circulating pool of EPCs were studied. Circulating EPCs were assayed by the colony-forming unit (CFU) method. The EPCs' adhesive capacity was studied by evaluating their ability to attach to fibronectin and cultured endothelial cells. Serum levels of vascular endothelial growth factor (VEGF) were studied and correlated with EPC numbers. Results: The patients had significantly fewer circulating EPCs(16.5±2.8) compared to their controls (31±4.6; p=0.0085). The functional properties of both groups' EPCs were similar. Conclusions: The peripheral circulating pool of endothelial stem cells is altered in patients with newly diagnosed neovascular AMD, suggesting that pathologic angiogenesis may result from or influence the regulation of endothelial precursor circulation

An optical coherence tomography-based grading of diabetic maculopathy proposed by an international expert panel: The European School for Advanced Studies in Ophthalmology classification.

Aims:To present an authoritative, universal, easy-to-use morphologic classification of diabetic maculopathy based on spectral domain optical coherence tomography.Methods:The first draft of the project was developed based on previously published classifications and a literature search regarding the spectral domain optical coherence tomography quantitative and qualitative features of diabetic maculopathy. This draft was sent to an international panel of retina experts for a first revision. The panel met at the European School for Advanced Studies in Ophthalmology headquarters in Lugano, Switzerland, and elaborated the final document.Results:Seven tomographic qualitative and quantitative features are taken into account and scored according to a grading protocol termed TCED-HFV, which includes foveal thickness (T), corresponding to either central subfoveal thickness or macular volume, intraretinal cysts (C), the ellipsoid zone (EZ) and/or external limiting membrane (ELM) status (E), presence of disorganization of the inner retinal layers (D), number of hyperreflective foci (H), subfoveal fluid (F), and vitreoretinal relationship (V). Four different stages of the disease, that is, early diabetic maculopathy, advanced diabetic maculopathy, severe diabetic maculopathy, and atrophic maculopathy, are based on the first four variables, namely the T, C, E, and D. The different stages reflect progressive severity of the disease.Conclusion:A novel grading system of diabetic maculopathy is hereby proposed. The classification is aimed at providing a simple, direct, objective tool to classify diabetic maculopathy (irrespective to the treatment status) even for non-retinal experts and can be used for therapeutic and prognostic purposes, as well as for correct evaluation and reproducibility of clinical investigations

Biosimilars in ophthalmology: "Is there a big change on the horizon?"

Retinal disease management has witnessed remarkable advances in posterior segment pharmacotherapy with the development of anti-VEGF molecules such as Lucentis® (ranibizumab), Eylea® (aflibercept), and off-label bevacizumab (Avastin). The US patents for ranibizumab and aflibercept will expire in 2020 (though Regeneron has indicated that it might attempt to extend its US patent to June 2023 with additional patent claims), and their European patents will expire in 2022 and 2025. Aflibercept comes off patent in 2022 in People's Republic of China and Japan. As soon as each patent expires, biosimilar molecules could potentially come in the mainstream clinical practice as a more cost-efficient choice in the form of generic biosimilars. It is difficult to predict how significant this shift would be in terms of more cost-effective clinical management and how it will impact the care in developed and developing world. It is important for clinicians to have a clear understanding about ophthalmic biosimilars before the industry brings these molecules to the mainstream clinical use globally

Biosimilars in ophthalmology: "Is there a big change on the horizon?"

Retinal disease management has witnessed remarkable advances in posterior segment pharmacotherapy with the development of anti-VEGF molecules such as Lucentis® (ranibizumab), Eylea® (aflibercept), and off-label bevacizumab (Avastin). The US patents for ranibizumab and aflibercept will expire in 2020 (though Regeneron has indicated that it might attempt to extend its US patent to June 2023 with additional patent claims), and their European patents will expire in 2022 and 2025. Aflibercept comes off patent in 2022 in People's Republic of China and Japan. As soon as each patent expires, biosimilar molecules could potentially come in the mainstream clinical practice as a more cost-efficient choice in the form of generic biosimilars. It is difficult to predict how significant this shift would be in terms of more cost-effective clinical management and how it will impact the care in developed and developing world. It is important for clinicians to have a clear understanding about ophthalmic biosimilars before the industry brings these molecules to the mainstream clinical use globally

CXCR4 increases in-vivo glioma perivascular invasion, and reduces radiation induced apoptosis: A genetic knockdown study

Glioblastoma (GBM) is a highly invasive brain tumor. Perivascular invasion, autovascularization and vascular co-option occur throughout the disease and lead to tumor invasion and progression. The molecular basis for perivascular invasion, i.e., the interaction of glioma tumor cells with endothelial cells is not well characterized. Recent studies indicate that glioma cells have increased expression of CXCR4. We investigated the in-vivo role of CXCR4 in perivascular invasion of glioma cells using shRNA-mediated knock down of CXCR4. We show that primary cultures of human glioma stem cells HF2303 and mouse glioma GL26-Cit cells exhibit significant migration towards human (HBMVE) and mouse (MBVE) brain microvascular endothelial cells. Blocking CXCR4 on tumor cells with AMD3100 in-vitro, inhibits migration of GL26-Cit and HF2303 toward MBVE and HBMVE cells. Additionally, genetic down regulation of CXCR4 in mouse glioma GL26-Cit cells inhibits their in-vitro migration towards MBVE cells; in an in-vivo intracranial mouse model, these cells display reduced tumor growth and perivascular invasion, leading to increased survival. Quantitative analysis of brain sections showed that CXCR4 knockdown tumors are less invasive. Lastly, we tested the effects of radiation on CXCR4 knock down GL26-Cit cells in an orthotopic brain tumor model. Radiation treatment increased apoptosis of CXCR4 downregulated tumor cells and prolonged median survival. In summary, our data suggest that CXCR4 signaling is critical for perivascular invasion of GBM cells and targeting this receptor makes tumors less invasive and more sensitive to radiation therapy. Combination of CXCR4 knock down and radiation treatment might improve the efficacy of GBM therapy

Beyond the hospital infection control guidelines: a qualitative study using positive deviance to characterize gray areas and to achieve efficacy and clarity in the prevention of healthcare-associated infections

Abstract Background The literature is replete with attempts to design and promote customized guidelines to reduce infections during the care continuum. Paradoxically, these efforts sometimes result in gray areas where many staff members are unaware of what is required of them, which then leads to confusion, frustration, and uncertainty. We coined the phrase “gray areas” in this context to encompass the variety of situations on the care continuum that are not addressed in the accepted guidelines, and where staff members are unsure of how to proceed. The purpose of the present study was to characterize the gray areas that were reported by staff and to identify the practices of Positive Deviance (PD) individuals. We define to PD individuals as people who independently develop creative solutions to solve problems not identified by the majority in their community. Methods A qualitative constructivist research methodology was used that included personal interviews, observations and video recordings of identified PD practices to enhance infection control. The study was conducted January through March 2018, in two Intensive Care Units (ICU) units at Hadassah Hospital, Jerusalem, Israel. Personal interviews were conducted with 82 staff members from the General ICU (GICU) and Medical ICU (MICU). Results The study confirmed that guidelines cannot cover all the different situations that arise during the care continuum and can paradoxically result in the increased spread of hospital infections. Our study found there are numerous individuals who independently develop and implement solutions for gray areas. The creative and practical solutions of PD individuals can address the barriers and difficulties on the care continuum that were encountered by the staff in their communities. For example, inserting a central venous line is a complex practice in the general guidelines, while the PDs provided clear situation-specific solutions not covered in the guidelines. Conclusions The recommendations of the present study are to encourage hospital personnel to create their own solutions for various situations on the care continuum, and to disseminate them within their units to achieve a bottom up change, in lieu of investing in new or specific written guidelines