Vascular effects of advanced glycation end-products : content of immunohistochemically detected AGEs in radial artery samples as a predictor for arterial calcification and cardiovascular risk in asymptomatic patients with chronic kidney disease

Objectives. Our aim was to determine whether vascular deposition of advanced glycation end-products (AGEs) is associated with arterial calcification and cardiovascular mortality in chronic kidney disease (CKD) patients and to assess the relationships between vascular content of AGEs and selected clinical and biochemical parameters. Materials and Methods. The study comprised 54 CKD patients (33 hemodialyzed, 21 predialyzed). Examined parameters included BMI, incidence of diabetes, plasma fasting glucose, AGEs, soluble receptor for AGEs and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging, serum C-reactive protein (hsCRP), plasminogen activator inhibitor-1 (PAI-1), and fetuin-A. Fragments of radial artery obtained during creation of hemodialysis access were stained for calcifications using alizarin red. AGEs deposits were identified immunohistochemically and their relative content was quantified. Results. Vascular content of AGEs was positively correlated with BMI, hsCRP, fetuin-A, PAI-1, and DPPH scavenging in simple regression; only fetuin-A was an independent predictor in multiple regression.There was a significant positive trend in the intensity of AGEs immunostaining among patients with grades 1, 2, and 3 calcifications. AGEs immunostaining intensity predicted 3-year cardiovascular mortality irrespective of patient’s age. Conclusions. The present study demonstrates an involvement of AGEs in the development of medial arterial calcification and the impact of arterial AGE deposition on cardiovascular mortality in CKD patient

Cardiovascular risk in chronic kidney disease patients : intima-media thickness predicts the incidence and severity of histologically assessed medial calcification in radial arteries

BACKGROUND: The objective of the study was to determine the relationship between common carotid artery intima-media thickness (CCA-IMT) and histologically assessed calcification of radial artery in relation to clinical features and laboratory markers of bone and mineral metabolism, inflammation, and oxidative stress in patients with stage 5 chronic kidney disease (CKD). METHODS: The study comprised 59 patients (36 hemodialyzed, 23 predialysis). CCA-IMT was measured by ultrasonography; the biochemical parameters examined were assessed using routine laboratory methods, ELISA micro-plate immunoassays and spectrophotometry. Fragments of radial artery obtained during creation of hemodialysis access were cryosectioned and stained for calcifications using von Kossa method and alizarin red. RESULTS: Glucose, osteoprotegerin, pentraxin 3 and Framingham risk score significantly correlated with CCA-IMT. In multiple regression analysis, OPG positively predicted CCA-IMT. Radial artery calcifications were found in 34 patients who showed higher CCA-IMT (0.98 ± 0.13 vs 0.86 ± 0.14 mm; P = 0.006). Higher CCA-IMT values were also associated with more advanced calcifications. CCA-IMT and the presence of plaques in common carotid artery were positive predictors of radial artery calcifications, independent of dialysis status, Framingham risk score, CRP and Ca x Pi [OR for calcifications 2.19 (1.08-4.45) per 0.1 mm increase in CCA-IMT]. The presence of radial artery calcifications was a significant predictor of mortality, independent of dialysis status and Framingham risk score [HR 3.16 (1.03-9.64)]. CONCLUSIONS: In CKD patients, CCA-IMT examination can be used as a surrogate measure to assess the incidence and severity of arterial medial calcification which is associated with poor clinical outcome in these patients

Proteoglycan / glycosaminoglycan and collagen content in the arterial wall of patients with end-stage renal disease : new indicators of vascular disease

Introduction: The prevalence of cardiovascular (CV) comorbidity in patients with chronic kidney disease (CKD) is high, particularly in end-stage renal disease (ESRD). There is an ongoing search for novel biomarkers of CV disease in this population. Objectives: We aimed to investigate the associations of matrix proteoglycans (PGs) and glycosaminoglycans (GAGs), collagen, and arterial calcifications with selected serum and plasma markers of endothelial dysfunction, inflammation, oxidative stress, and bone turnover in patients with ESRD. Patients and methods: We enrolled 47 adult patients (32 men) with stage 5 CKD. The following parameters were investigated: fibrinogen, soluble thrombomodulin (sTM), plasminogen activator inhibitor 1 (PAI-1), stromal cell-derived factor 1α (SDF-1α), calcium (Ca), phosphate (Pi), intact parathormone, interleukin 6, high-sensitivity C-reactive protein (hs-CRP), ferric reducing ability of plasma, 2,2-diphenyl-1-picrylhydrazyl scavenging, ferric reducing ability of ascorbate in plasma, fetuin-A, fibroblast growth factor 23, osteopontin, osteoprotegerin, osteocalcin, transforming growth factor β (TGF-β), hepatocyte growth factor, secreted protein acidic and rich in cysteine, as well as matrix metalloproteinase 2. Radial artery specimens were stained with alizarin red for calcifications, alcian blue for PGs and GAGs, and sirius red for collagen. Results: We observed positive correlations between PG and GAG, collagen, and calcification staining. The most intense (grade 3) alcian blue staining was significantly correlated with diabetes as well as higher levels of Ca×Pi product, hs-CRP, fibrinogen, SDF-1α, PAI-1, and sTM. However, PAI-1 was the only significant predictor of grade 3 alcian blue staining in a multiple logistic regression model adjusted for hemodialysis, Ca×Pi product, and hs-CRP levels. Conclusions: Coagulation disorders and endothelial dysfunction are the hallmarks of ESRD. The levels of SDF-1α, PAI-1, sTM, and fibrinogen may be novel predictors of early vascular wall alterations and may serve as CV risk markers.biomarkersend‑stage renal diseaseglycosaminoglycansplasminogen activator inhibitor 1proteoglycan

Interplay of nitric oxide metabolites and markers of endothelial injury, inflammation and vascular disease in the spectrum of advanced chronic kidney disease

Background: Chronic kidney disease is linked to cardiovascular morbidity; therefore, relevant biomarkers are widely investigated. Aims: We aimed to assess the relationship between nitric oxide (as measured by its metabolites, NOx), a key endothelial molecule, with markers of endothelial dysfunction, inflammation, antioxidant status, and mineral disorders as well as histologically assessed vascular calcification in uremic and hemodialysis patients with chronic kidney disease. Methods: Plasma and serum samples were obtained from 62 patients with renal failure. NOx was assessed by the Griess method, while the other biomarkers were measured by the immunoenzymatic assay. Morphological analysis of arterial calcification was performed in a blinded, semiquantitative manner. Common carotid intima‑media thickness and atherosclerotic plaques were assessed by ultrasonography. Results: In the simple analysis, NOx levels correlated positively with the parameters of renal function, mineral metabolism, endothelial injury, and inflammation. NOx predicted carotid intima‑media thickness in simple (P = 0.014) and multiple analysis (P = 0.036) adjusted for the Framingham risk score, C‑reactive protein, serum creatinine, and parathormone. The occurrence of atherosclerotic plaques in the common carotid artery was correlated with higher NOx concentrations (P = 0.021). Conclusions: In chronic renal failure, NOx is associated with surrogate markers of atherosclerosis, even after adjustment for traditional cardiovascular risk factors, inflammation, and renal function, but not with the presence or grade of medial arterial calcification. Endothelial injury, inflammation, and mineral metabolism markers are associated with NOx levels, though a causal link requires further study

Erotetic Reasoning Corpus. A data set for research on natural question processing

The aim of this paper is to present the Erotetic Reasoning Corpus (ERC) which constitutes a data set for research on natural question processing. We describe the theoretical background, linguistic data and tags used for the annotation process. We also discuss potential areas of ERC exploitation

Efficacy of double vs. standard empagliflozin dose for METabolic syndromE tReatment (DEMETER — SIRIO 11) study. Rationale and protocol of the study

Complex metabolic disorders associated with obesity and diabetes pose a serious therapeutic challenge. The DEMETER-SIRIO 11 study is a phase III, multicenter, randomized, open-label, investigator-initiated clinical trial with a 6-month follow-up aimed at performing a comparative evaluation of the effect of two empagliflozin doses (10 mg vs. 20 mg) on selected metabolic parameters in patients with metabolic syndrome. The primary hypothesis of the study is that a higher dose of empagliflozin will result in a significant reduction of BMI and HbA1c in patients with obesity and MS receiving empagliflozin 20 mg as compared to 10 mg. Sample size and power calculation were based on a superiority assumption for the primary efficacy endpoint (the difference in decrease of body weight by > 1.5 kg and HbA1c by > 0.4%) for the higher vs. standard dose arm at 6-months of follow-up. Therefore, a sample size of 79 patients per arm is required to provide 80% power to detect a higher decrease in BMI, and 85 patients per arm is required to provide 80% power to detect a higher decrease in HbA1c in the 20 mg versus 10 mg arm with a type I error rate of 0.05. Summing up, enrollment of a total of 200 patients (100 in each arm) is planned to compensate for the potential drop-out rate from the study of up to 15%. Prespecified subanalyses will be performed according to: 1) diabetes mellitus; 2) chronic kidney disease (GFR < 60 mL/min/1.73 m2); 3) gender; and 4) age. A greater comprehensive improvement in biochemical, functional, and anthropometric parameters reflecting favorable metabolic changes is expected at the higher dose of empagliflozin compared to the standard dose

Praktyka kliniczna oceny minimalnej choroby resztkowej u chorych na szpiczaka plazmocytowego w Polsce: badanie ankietowe Polskiego Konsorcjum Szpiczakowego

Studies exploring the significance of minimal residual disease (MRD) in plasma cell myeloma (PCM) have proven its prognostic value, regardless of the type of administered treatment. In order to assess the current practice for evaluating MRD in Poland, we conducted a survey on the methods for assessing MRD and on the MRD testing time points at Polish hematological centres. Seven out of 15 institutions surveyed use of the flow cytometry (FC) method for MRD assessment. The FC-MRD assessment is performed uniformly only in those patients achieving complete remission(CR). However, the specific indications and assessment time points differed at the tested centres including: testing MRD only after autologous hematopoietic stem cell transplantation (auto-HSCT), after auto-HSCT and consolidation, after completion of first line chemotherapy or after obtaining CR in any line of treatment. The study also showed considerable heterogeneity in the FC-MRD methodology, which affects test sensitivity (from 10–3 to 10–5). None of the surveyed centres uses molecular techniques for MRD assessment. In 8 of the 15 institutions, patients are monitored by imaging techniques. Our survey may thus be useful for developing guidelines and standardization of MRD assessment in PCM in Poland.W badaniach nad znaczeniem minimalnej choroby resztkowej (MRD) w szpiczaku plazmocytowym (PCM) dowiedziono, że status MRD ma wartość prognostyczną niezależnie od zastosowanego leczenia. W celu poznania zasad monitorowania MRD u chorych na PCM w polskich ośrodkach hematologicznych przeprowadzono badanie ankietowe. W ankiecie zadano pytania dotyczące stosowanych metod wykrywania MRD oraz punktów czasowych, w których badania są wykonywane. W 7 z 15 ośrodków objętych badaniem ankietowym oznaczenia MRD w PCM wykonuje się w aspiratach szpiku kostnego metodą cytometrii przepływowej (FC). We wszystkich ośrodkach oznaczenia FC-MRD są wykonywane jedynie u chorych w całkowitej remisji (CR), jednak w różnych punktach czasowych — tylko po autologicznym przeszczepieniu krwiotwórczych komórek macierzystych (allo-HSCT), po allo-HSCT i konsolidacji, po zakończeniu leczenia pierwszej linii lub, w przypadku uzyskania CR, po dowolnej linii leczenia. Stwierdzono ponadto znaczne różnice w sposobie wykonywania badania FC-MRD wpływające na osiąganą czułość detekcji MRD (od 10–3 do 10–5). W żadnym z ankietowanych ośrodków nie ocenia się MRD w szpiku kostnym technikami molekularnymi. Monitorowanie choroby resztkowej metodami obrazowymi stosuje personel 8 z 15 ośrodków. Wyniki przeprowadzonej ankiety mogą posłużyć wypracowaniu wspólnych wytycznych i standaryzacji oceny MRD w PCM w Polsce

SARS-CoV-2 infection in patients with multiple myeloma: survey in 23 centers across Europe and USA

Introduction: Despite several studies, the impact of coronavirus disease 2019 on patients with multiple myeloma remains uncertain. Material and methods: We performed a survey that covered the period of the first and second waves of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in 23 centers inseven countries. Out of 352 patients with myeloma and SARS-CoV-2, 23% died. Results/Conclusions: Logistic regression showed a lower risk of death among patients treated with proteasome inhibitor and a higher risk of death for those who had a severe or a very severe course of disease