Nomograms including the UBC® Rapid test to detect primary bladder cancer based on a multicentre dataset

Objectives: To evaluate the clinical utility of the urinary bladder cancer antigen test UBC Rapid for the diagnosis of bladder cancer (BC) and to develop and validate nomograms to identify patients at high risk of primary BC. Patients and Methods: Data from 1787 patients from 13 participating centres, who were tested between 2012 and 2020, including 763 patients with BC, were analysed. Urine samples were analysed with the UBC Rapid test. The nomograms were developed using data from 320 patients and externally validated using data from 274 patients. The diagnostic accuracy of the UBC Rapid test was evaluated using receiver-operating characteristic curve analysis. Brier scores and calibration curves were chosen for the validation. Biopsy-proven BC was predicted using multivariate logistic regression. Results: The sensitivity, specificity, and area under the curve for the UBC Rapid test were 46.4%, 75.5% and 0.61 (95% confidence interval [CI] 0.58–0.64) for low-grade (LG) BC, and 70.5%, 75.5% and 0.73 (95% CI 0.70–0.76) for high-grade (HG) BC, respectively. Age, UBC Rapid test results, smoking status and haematuria were identified as independent predictors of primary BC. After external validation, nomograms based on these predictors resulted in areas under the curve of 0.79 (95% CI 0.72–0.87) and 0.95 (95% CI: 0.92–0.98) for predicting LG-BC and HG-BC, respectively, showing excellent calibration associated with a higher net benefit than the UBC Rapid test alone for low and medium risk levels in decision curve analysis. The R Shiny app allows the results to be explored interactively and can be accessed at www.blucab-index.net. Conclusion: The UBC Rapid test alone has limited clinical utility for predicting the presence of BC. However, its combined use with BC risk factors including age, smoking status and haematuria provides a fast, highly accurate and non-invasive tool for screening patients for primary LG-BC and especially primary HG-BC

Identification of historical mediteranean dyes and pigments by means of Double-Shot-Pyrolysis-Capillary Gas Chromatography/MS (FID)

Abweichender Titel nach Übersetzung der Verfasserin/des VerfassersZiel dieser Arbeit war die Entwicklung einer neuen pyrolyse-gaschromatographischen massenspektrometrischen Methode zur Untersuchung von mediterranen organischen Naturfarbstoffen auf gefärbten Materialien wie Schafwolle, Baumwolle, Seide, Papier und Pergament ohne aufwändige Probenvorbereitung. Dieses neu entwickelte Verfahren wurde für folgende Farbstoffe optimiert: Krapp, Cochenille, Saflor, Safran, Kurkuma, Färberwau, Gelbbeere, Indigo, Waid, Purpur, Alkanna, Rotholz und Blauholz. Die Rohstoffe stammten von der Historischen Wiesner-Rohstoffsammlung der TU Wien, der Firma Kremer Pigmente sowie der Aristoteles-Universität Thessaloniki. Das gefärbte Material wurde mit Hilfe der Gaschromatographie/ Massenspektrographie unter Verwendung der Double-Shot-Pyrolyse (Thermische Desorption und Pyrolyse) untersucht. Auf Basis der Methodenoptimierung für die oben genannten Pigmente gelang es, diese in weiterer Folge auch direkt auf der gefärbten Schafwolle sowie auf mit Purpur gefärbter Schafwolle, Baumwolle, Seide, Papier und Pergament nachzuweisen, ohne sie vorher mit einem organischen Lösungsmittel vom Trägermaterial extrahieren zu müssen. Dazu war es notwendig, das Massenspektrometer im Selected-Ion-Monitoring-Modus zu betreiben.Aim of this work was the development of a new pyrolysis gas chromatographic mass spectrometric method to examine Mediterranean organic natural dyes on materials like sheep´s wool, cotton, silk, paper and parchment, which could be performed without difficult sample preparation. This experimental assembly allowed the differentiation of a selection of dyes (madder, cochineal, safflower, saffron, turmeric, weld, Persian berries, indigo, woad, purple, alkanna, brazilwood und campeche wood) of different origin (historic Wiesner collection of the Vienna University of Technology, company Kremer Pigmente and Aristotle University in Thessaloniki). The analytical part was done with gas chromatography/mass spectrometry combined with a pyrolyser, which allowed double shot pyrolysis, so the solid sample could be exposed to both, thermal desorption and pyrolysis. There were analysed with this technique sheep´s wool samples dyed with the above mentioned organic natural dyes as well as purple on sheep´s wool, cotton, silk, paper and parchment. By the use of selected ion monitoring mode of the mass spectrometer the organic carrier materials were made invisible and thus the low amounts of dyes could be detected without prior removal from their supports.14

Nomograms including UBC® Rapid Test to detect primary bladder cancer based on a multicenter data set

Objectives: To evaluate the clinical utility of the urinary bladder cancer antigen UBC® Rapid Test for the diagnosis of bladder cancer (BC) and to develop and validate nomograms to identify patients at high-risk of primary BC. Patients and methods: Data from 1,787 patients from 13 participating centers tested between 2012 and 2020, including 763 patients with BC, were analyzed. Urine samples were analyzed with the UBC® Rapid Test. The nomograms were developed using data from 320 patients and externally validated using data from 274 patients. The diagnostic accuracy of the UBC® Rapid Test was evaluated using receiver operating characteristics analysis. Brier scores and calibration curves were chosen for validation. Biopsy-proven BC was predicted using multivariate logistic regression. Results: The sensitivity, specificity, and area under the curve for the UBC® Rapid Test were 46.4%, 75.5%, and 0.61 (95% CI: 0.58–0.64) for low-grade (LG-) BC, and 70.5%, 75.5%, and 0.73 (95% CI: 0.70–0.76) for high-grade (HG-) BC, respectively. Age, UBC® Rapid Test results, smoking status, and hematuria were identified as independent predictors of primary BC. After external validation, nomograms based on these predictors resulted in an area under the curve of 0.79 (95% CI: 0.72–0.87) and 0.95 (95% CI: 0.92–0.98) in predicting LG-BC and HG-BC, respectively, showing excellent calibration associated with a higher net benefit than the UBC® Rapid Test alone for low and medium risk levels in decision curve analysis. An R Shiny app allows the results to be explored interactively and can be accessed at www.blucab-index.net. Conclusion: The UBC® Rapid Test alone has limited clinical utility for predicting the presence of BC. However, its combined use with BC risk factors including age, smoking status, and hematuria provides a fast, highly accurate, and non-invasive tool for screening patients for primary LG-BC and especially primary HG-BC

Osteogenic monocytes within the coronary circulation and their association with plaque vulnerability in patients with early atherosclerosis

OBJECTIVES: This study tests the hypothesis that circulating mononuclear cells expressing osteocalcin (OCN) and bone alkaline phosphatase (BAP) are associated with distinct plaque tissue components in patients with early coronary atherosclerosis. BACKGROUND: Plaque characteristics implying vulnerability develop at the earliest stage of coronary atherosclerosis. Increasing evidence indicates that cells from the myeloid lineage might serve as important mediators of destabilization. Plaque burden and its components were assessed regarding their relationship to monocytes carrying both pro-inflammatory (CD14) and osteogenic surface markers OCN and BAP. METHODS: Twenty-three patients with angiographically non-obstructive coronary artery disease underwent coronary endothelial function assessment and virtual histology-intravascular ultrasound of the left coronary artery. Plaque composition was characterized in the total segment (TS) and in the target lesion (TL) containing the highest amount of plaque burden. Blood samples were collected simultaneously from the aorta and the coronary sinus. Circulating cell counts were then identified from each sample and a gradient across the coronary circulation was determined. RESULTS: Circulating CD14+/BAP+/OCN+ monocytes correlate with the extent of necrotic core and calcification (r=0.53, p=0.010; r=0.55, p=0.006, respectively). Importantly, coronary retention of CD14+/OCN+ cells also correlates with the amount of necrotic core and calcification (r=0.61, p=0.003; r=0.61, p=0.003) respectively. CONCLUSIONS: Our study links CD14+/BAP+/OCN+ monocytes to the pathologic remodeling of the coronary circulation and therefore associates these cells with plaque destabilization in patients with early coronary atherosclerosis

Polyphenol-rich cranberry juice has a neutral effect on endothelial function but decreases the fraction of osteocalcin-expressing endothelial progenitor cells

PURPOSE: Cranberry juice (CJ) contains a remarkably high concentration of polyphenols, considered to be beneficial for cardiovascular and bone health. The current double-blind, randomized study was designed to test whether daily consumption of double-strength Ocean Spray light CJ (2 x 230 ml) over 4 months has beneficial effects on vascular function and on endothelial progenitor cells (EPCs) carrying the osteoblastic marker osteocalcin in particular. METHODS: A total of 84 participants (49.5 +/- 16.2 years) with peripheral endothelial dysfunction and cardiovascular risk factors were enrolled in this double-blind, randomized, controlled trial (69 completed the 4-month protocol-32 in the CJ group and 37 in the placebo group, respectively). Vascular responses to reactive hyperemia were measured non-invasively by peripheral arterial tonometry (EndoPAT). Peripheral blood mononuclear cells were stained for EPC markers, as well as osteocalcin, and counted by flow cytometry. RESULTS: Baseline characteristics were similar in both groups. The effect of CJ on peripheral endothelial function and on circulating EPC counts (CD34(+)/CD133(+)/KDR(+)) did not change during the study. A high percentage of EPCs expressed osteocalcin (59.4 +/- 35.7%). CJ, as compared to placebo, induced a decrease in the fraction of EPCs expressing osteocalcin (-8.64 +/- 48.98 and 19.13 +/- 46.11%, respectively, p = 0.019). Systemic levels of the adhesion marker ICAM correlated significantly with the number of EPCs expressing osteocalcin. CONCLUSIONS: The study demonstrated that long-term supplementation of polyphenol-rich CJ did not improve peripheral endothelial function. However, the decrease in the fraction of osteocalcin+ EPCs suggests a potential beneficial effect of polyphenol-rich CJ