Biological dosimetry after radiosynoviorthesis with rhenium-186 sulphide and erbium-169 citrate

Zur Abschätzung der radiobiologischen Sicherheit des Verfahrens wird in dieser Arbeit die Radiosynoviorthese (RSO) mit Re-186 und Er-169 hinsichtlich biologischer Strahleneffekte untersucht. Bei 23 Patienten wurde eine RSO mit Rhenium-186-Sulfid- (10 Patienten) oder Erbium-169-Zitratkolloid (13 Patienten) durchgeführt. Das behandelte Gelenk wurde anschließend ruhig gestellt. Bei allen Patienten erfolgte vor und 17–19 Tage (Re-186) bzw. 45–50 Tage (Er-169) nach der RSO eine venöse Blutentnahme. Zur Analyse der Strahlenexposition wurde die Häufigkeit von dizentrischen Chromosomen in Lymphozyten der ersten Zellteilung in vitro bestimmt. Pro Patient wurden mindestens 1000 Zellen vor und nach der RSO untersucht, was nach längerer Einwirkung niederenergetischer Strahlung ausreichend ist, um im bestrahlten Kollektiv die im Rahmen der RSO erwarteten Strahlendosen nachzuweisen. Ergänzend wurde bei den mit Re-186 behandelten Patienten der Aktivitätsabtransport aus dem Gelenk mittels Ganzkörperszintigraphie bestimmt. In der Untersuchung von insgesamt 47017 Zellen fanden sich vor RSO mit Re-186 bzw. Er-169 40 bzw. 88, danach 59 bzw. 105 dizentrische Chromosomen in Lymphozyten des peripheren Blutes. Eine signifikante Zunahme der dizentrischen Chromosomen nach der RSO zeigte sich nicht. Der Aktivitätsabtransport nach RSO mit Re-186 lag durchschnittlich unter 5 % (unter 3 MBq) und ist damit als gering einzustufen. Die Ergebnisse der Untersuchung von Chromosomenaberrationen und des Aktivitätsabtransports nach Radiosynoviorthese mit Rhenium-186 und Erbium-169 sprechen für eine geringe Strahlenexposition der Patienten und damit für die Sicherheit des Verfahrens.The aim of the present studies was to investigate the biological radiation effect of radiosynoviorthesis (RSO) with Re-186 and Er-169 in order to evaluate the safety of this procedure. RSO with rhenium-186 sulfide colloid (10 patients) or erbium-169 citrate colloid (13 patients) was carried out in a total of 23 patients. Afterwards, the treated joint was immobilised for three days using splints. From all patients, blood was drawn immediately before and 17 to 19 days (Re-186) or 45 to 50 days (Er-169) after RSO. To evaluate the radiation dose, the yield of dicentric chromosomes in lymphocytes was determined exclusively in metaphases of the first cell cycle in vitro. At least 1000 cells per patient have been analysed before and after RSO which is sufficient to find potential radiation effects after long-term exposure to low energy radiation such as to expect after RSO. In addition, for Re-186 the activity leakage from the treated joint was measured by whole-body scintigraphy. In a total of 47017 cells analysed from 46 blood samples, 40 and 88 before and 59 and 105 dicentrics after RSO with Re-186 and Er-169 were found. This showed no statistically significant increase in the number of dicentric chromosomes. The measured average activity leakage of less than 5 % (less than 3 MBq) was considered to be low. The results of chromosome analysis and activity measurement after RSO prove that this procedure is associated with a low effective dose in treated patients and thus can be considered a safe treatment

Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown

Community evaluation of glycoproteomics informatics solutions reveals high-performance search strategies for serum glycopeptide analysis

Glycoproteomics is a powerful yet analytically challenging research tool. Software packages aiding the interpretation of complex glycopeptide tandem mass spectra have appeared, but their relative performance remains untested. Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. Although the results were variable, several high-performance glycoproteomics informatics strategies were identified. Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions. This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions