ABSTRACT
The mechanism underlying the association between elevated red cell distribution width (RDW) and poor prognosis in variety of diseases is unknown although many researchers consider RDW a marker of inflammation. We hypothesized that RDW directly affects intravascular hemodynamics, interactions between circulating cells and vessel wall, inducing local changes predisposing to atherothrombosis. We applied different human and animal models to verify our hypothesis. Carotid plaques harvested from patients with high RDW had increased expression of genes and proteins associated with accelerated atherosclerosis as compared to subjects with low RDW. In microfluidic channels samples of blood from high RDW subjects showed flow pattern facilitating direct interaction with vessel wall. Flow pattern was also dependent on RDW value in mouse carotid arteries analyzed with Magnetic Resonance Imaging. In different mouse models of elevated RDW accelerated development of atherosclerotic lesions in aortas was observed. Therefore, comprehensive biological, fluid physics and optics studies showed that variation of red blood cells size measured by RDW results in increased interactions between vascular wall and circulating morphotic elements which contribute to vascular pathology.
Subject(s)
Atherosclerosis , Erythrocyte Indices , Animals , Atherosclerosis/pathology , Blood Cells , Carotid Arteries/pathology , Erythrocytes/pathology , Humans , Mice , Prognosis , Risk FactorsABSTRACT
BACKGROUND: We examined whether molecular characterization of high-grade epithelial ovarian cancer can inform the diagnosis and/or identify potential actionable targets. METHODS: All of the consecutively sequenced high-grade ovarian tumours with consent between 2014 until 2019 were included. A total of 274 tumours underwent next generation sequencing using a targeted panel. RESULTS: Patients with high-grade ovarian epithelial cancer were consented to prospective molecular characterization. Clinical information was extracted from their medical record. Tumour DNA was subjected to sequencing, and selected patients received PARP inhibitor therapy. CONCLUSIONS: Tumours from 274 women were sequenced, including high-grade serous carcinoma (n = 252), clear cell carcinoma (n = 4), carcinosarcoma (n = 9), endometrioid carcinoma (n = 3), undifferentiated carcinoma (n = 1), and mixed tumours (n = 5). Genomic profiling did not influence histologic diagnosis. Mutations were identified in TP53, BRCA1, BRCA2, as well as additional homologous recombination repair pathway genes BARD1, ATR, CHEK2, PALB2, RAD51D, RAD50, SLX4, FANCA, RAD51C, and RAD54L. In addition, mutations in PTEN and CDKN2A were identified. Several somatic mutations with implications for germline testing were identified, including RMI1, STK11, and CDH1. Germline testing identified 16 previously unknown BRCA1/2 carriers. Finally, 20 patients were treated with the PARP inhibitor olaparib based on the sequencing results.
ABSTRACT
INTRODUCTION: The results of intravitreal ranibizumab treatment for exsudative age-related macular degeneration have been favourable until this time. AIM: To evaluate the two-year functional and anatomic results of intravitreal ranibizumab treatment. METHOD: 46 patients (age: 75 ± 9.1 years) were included in a prospective single center study. Treatment regimen was the following: monthly 0.5 mg ranibizumab was administered in the first 3 months, and later as required (pro re nata). The change of best corrected visual acuity and central retinal thickness was followed. RESULTS: The visus change at the end of the follow-up time was not statistically significant compared to baseline (p = 0.760) and the at the end of the first year (p = 0.154). Central retinal thickness decreased significantly compared to baseline (p = 0.000001), but the change was not statistically significant compared to the end of the first year (p = 0.875). CONCLUSIONS: Patients with neovascular macular degeneration treated with intravitreal ranibizumab using pro re nata regimen have stable visus for long term, and the exsudation could be reduced efficiently.
