Diagnostic performance of transthyretin measurement in fat tissue of patients with ATTR amyloidosis

In this article, the diagnostic performance of a transthyretin (TTR) ELISA for detection and characterization of transthyretin-derived (ATTR) amyloid in abdominal subcutaneous fat tissue was studied. Fat tissue specimens were analyzed of 38 patients with ATTR amyloidosis, 70 controls, and 17 carriers of a TTR mutation. Amyloid amount was graded semi-quantitatively in Congo red-stained specimens (0-4+). Amyloid was extracted from tissue in guanidine, and the TTR concentration was measured using a sandwich TTR-ELISA. The TTR concentration of patients with ATTR amyloidosis (mean 0.84 ng/mg fat tissue) was significantly higher than controls (p<0.001). With a TTR concentration of 0.13 ng/mg fat tissue as cut-off value, 32 of the 38 ATTR patients were identified resulting in a sensitivity of 84%. Sixty-seven of the 70 controls had values below the cut-off value resulting in a specificity of 96%. Thus, measuring TTR in fat tissue is useful for detecting ATTR amyloidosis and for characterizing amyloid as ATTR type

Observation of Ground-State Two-Neutron Decay

Neutron decay spectroscopy has become a successful tool to explore nuclear properties of nuclei with the largest neutron-to-proton ratios. Resonances in nuclei located beyond the neutron dripline are accessible by kinematic reconstruction of the decay products. The development of two-neutron detection capabilities of the Modular Neutron Array (MoNA) at NSCL has opened up the possibility to search for unbound nuclei which decay by the emission of two neutrons. Specifically this exotic decay mode was observed in 16Be and 26O.Comment: To be published in Acta Physica Polonica

Exploring the neutron dripline two neutrons at a time: The first observations of the 26O and 16Be ground state resonances

The two-neutron unbound ground state resonances of $^{26}$O and $^{16}$Be were populated using one-proton knockout reactions from $^{27}$F and $^{17}$B beams. A coincidence measurement of 3-body system (fragment + n + n) allowed for the decay energy of the unbound nuclei to be reconstructed. A low energy resonance, $<$ 200 keV, was observed for the first time in the $^{24}$O + n + n system and assigned to the ground state of $^{26}$O. The $^{16}$Be ground state resonance was observed at 1.35 MeV. The 3-body correlations of the $^{14}$Be + n + n system were compared to simulations of a phase-space, sequential, and dineutron decay. The strong correlations in the n-n system from the experimental data could only be reproduced by the dineutron decay simulation providing the first evidence for a dineutron-like decay.Comment: Invited Talk given at the 11th International Conference on Nucleus-Nucleus Collisions (NN2012), San Antonio, Texas, USA, May 27-June 1, 2012. To appear in the NN2012 Proceedings in Journal of Physics: Conference Series (JPCS

Improved and standardized method for assessing years lived with disability after burns and its application to estimate the non-fatal burden of disease of burn injuries in Australia, New Zealand and the Netherlands

Background: Burden of disease estimates are an important resource in public health. Currently, robust estimates are not available for the burn population. Our objectives are to adapt a refined methodology (INTEGRIS method) to burns and to apply this new INTEGRIS-burns method to estimate, and compare, the burden of disease of burn injuries in Australia, New Zealand and the Netherlands. Methods: Existing European and Western-Australian health-related quality of life (HRQL) datasets were combined to derive disability weights for three homogenous burn injury groups based on percentage total body surface area (%TBSA) burned. Subsequently, incidence data from Australia, New Zealand, and the Netherlands from 2010 to 2017 were used to compute annual non-fatal burden of disease estimates for each of these three countries. Non-fatal burden of disease was measured by years lived w

Trends in liver transplantation for primary biliary cirrhosis in the Netherlands 1988-2008

Background: A decrease in the need for liver transplantations (LTX) in Primary Biliary Cirrhosis (PBC), possibly related to treatment with ursodeoxycholic acid (UDCA), has been reported in the USA and UK. The aim of this study was to assess LTX require

Population vulnerability to COVID-19 in Europe: A burden of disease analysis

Background: Evidence has emerged showing that elderly people and those with pre-existing chronic health conditions may be at higher risk of developing severe health consequences from COVID-19. In Europe, this is of particular relevance with ageing populations living with non-communicable diseases, multi-morbidity and frailty. Published estimates of Years Lived with Disability (YLD) from the Global Burden of Disease (GBD) study help to characterise the extent of these effects. Our aim was to identify the countries across Europe that have populations at highest risk from COVID-19 by using estimates of population age structure and YLD for health conditions linked to severe illness from COVID-19. Methods: Population and YLD estimates from GBD 2017 were extracted for 45 countries in Europe. YLD was restricted to a list of specific health conditions associated with being at risk of developing severe consequences from COVID-19 based on guidance from the United Kingdom Government. This guidance also identified individuals aged 70 years and above as being at higher risk of developing severe health consequences. Study outcomes were defined as: (i) proportion of population aged 70 years and above; and (ii) rate of YLD for COVID-19 vulnerable health conditions across all ages. Bivariate groupings were established for each outcome and combined to establish overall population-level vulnerability. Results: Countries with the highest proportions of elderly residents were Italy, Greece, Germany, Portugal and Finland. When assessments of population-level YLD rates for COVID-19 vulnerable health conditions were made, the highest rates were observed for Bulgaria, Czechia, Croatia, Hungary and Bosnia and Herzegovina. A bivariate analysis indicated that the countries at high-risk across both measures of vulnerability were: Bulgaria; Portugal; Latvia; Lithuania; Greece; Germany; Estonia; and Sweden. Conclusion: Routine estimates of population structures and non-fatal burden of disease measures can be usefully combined to create composite indicators of vulnerability for rapid assessments, in this case to severe health consequences from COVID-19. Countries with available results for sub-national regions within their country, or national burden of disease studies that also use sub-national levels for burden quantifications, should consider using non-fatal burden of disease estimates to estimate geographical vulnerability to COVID-19

Variation in amount of wild-type transthyretin in different fibril and tissue types in ATTR amyloidosis

Familial transthyretin (TTR) amyloidosis is caused by a mutation in the TTR gene, although wild-type (wt) TTR is also incorporated into the amyloid fibrils. Liver transplantation (LT) is the prevailing treatment of the disease and is performed in order to eliminate the mutant TTR from plasma. The outcome of the procedure is varied; especially problematic is a progressive cardiomyopathy seen in some patients, presumably caused by continued incorporation of wtTTR. What determines the discrepancy in outcome is not clear. We have previously shown that two structurally distinct amyloid fibrils (with or without fragmented ATTR) are found among ATTRV30M patients. In this study, we investigated the proportion of wtATTR in cardiac and adipose amyloid from patients having either fibril type. It was found that cardiac amyloid more easily incorporates wtTTR than adipose amyloid, offering a potential explanation for the vulnerability of cardiac tissue for continued amyloidosis after LT. In cardiac tissue, fibrils with fragmented ATTR contained a higher wt proportion than fibrils without, suggesting that continued incorporation of wtTTR after LT, perhaps, can take place more easily in these patients. In adipose tissue, a rapid increase in wt proportion after LT indicates that a rather fast turnover of the deposits must occur. A difference in wt proportion between the fibril types was seen post-LT but not pre-LT, possibly caused by differences in turnover rate. Conclusively, this study further establishes the basic dissimilarities between the two fibril types and demonstrates that their role in LT outcome needs to be further investigated

The burden of breast, cervical, and colon and rectum cancer in the Balkan countries, 1990–2019 and forecast to 2030.

Background Despite effective prevention and control strategies, in countries of the Balkan region, cancers are the second leading cause of mortality, closely following circulatory system diseases. Objective To describe trends in the burden of breast, cervical, and colon and rectum cancer in the Balkan region and per country between 1990 and 2019, including a forecast to 2030. Methods We described the 2019 Global Burden of Disease (GBD) estimates for breast, cervical, and colon and rectum cancers in eleven Balkan countries over the period 1990–2019, including incidence, years lived with disability (YLD), years of life lost (YLL), and disability-adjusted life years (DALYs) rates per 100,000 population and accompanied 95% uncertainty interval. With the Autoregressive Integrated Moving Average, we forecasted these rates per country up to 2030. Results In the Balkan region, the highest incidence and DALYs rates in the study period were for colon and rectum, and breast cancers. Over the study period, the DALYs rates for breast cancer per 100,000 population were the highest in Serbia (reaching 670.84 in 2019) but the lowest in Albania (reaching 271.24 in 2019). In 2019, the highest incidence of breast cancer (85 /100,000) and highest YLD rate (64 /100,000) were observed in Greece. Romania had the highest incidence rates, YLD rates, DALY rates, and YLL rates of cervical cancer, with respective 20.59%, 23.39% 4.00%, and 3.47% increases for the 1990/2019 period, and the highest forecasted burden for cervical cancer in 2030. The highest incidence rates, YLD rates and DALY rates of colon and rectum cancers were continuously recorded in Croatia (an increase of 130.75%, 48.23%, and 63.28%, respectively), while the highest YLL rates were in Bulgaria (an increase of 63.85%). The YLL rates due to colon and rectum cancers are forecasted to progress by 2030 in all Balkan countries. Conclusion As most of the DALYs burden for breast, cervical, and colon and rectum cancer is due to premature mortality, the numerous country-specific barriers to cancer early detection and quality and care continuum should be a public priority of multi-stakeholder collaboration in the Balkan region

Methodological considerations in injury burden of disease studies across Europe: a systematic literature review

Background Calculating the disease burden due to injury is complex, as it requires many methodological choices. Until now, an overview of the methodological design choices that have been made in burden of disease (BoD) studies in injury populations is not available. The aim of this systematic literature review was to identify existing injury BoD studies undertaken across Europe and to comprehensively review the methodological design choices and assumption parameters that have been made to calculate years of life lost (YLL) and years lived with disability (YLD) in these studies. Methods We searched EMBASE, MEDLINE, Cochrane Central, Google Scholar, and Web of Science, and the grey literature supplemented by handsearching, for BoD studies. We included injury BoD studies that quantified the BoD expressed in YLL, YLD, and disability-adjusted life years (DALY) in countries within the European Region between early-1990 and mid-2021. Results We retrieved 2,914 results of which 48 performed an injury-specific BoD assessment. Single-country independent and Global Burden of Disease (GBD)-linked injury BoD studies were performed in 11 European countries. Approximately 79% of injury BoD studies reported the BoD by external cause-of-injury. Most independent studies used the incidence-based approach to calculate YLDs. About half of the injury disease burden studies applied disability weights (DWs) developed by the GBD study. Almost all independent injury studies have determined YLL using national life tables. Conclusions Considerable methodological variation across independent injury BoD assessments was observed; differences were mainly apparent in the design choices and assumption parameters towards injury YLD calculations, implementation of DWs, and the choice of life table for YLL calculations. Development and use of guidelines for performing and reporting of injury BoD studies is crucial to enhance transparency and comparability of injury BoD estimates across Europe and beyond