Trends in female breast cancer incidence, mortality, and survival in Austria, with focus on age, stage, and birth cohorts (1983-2017)

Breast cancer (BC) is the most commonly diagnosed malignant disease and the leading cause of cancer death in women in Austria. We investigated overall and subgroup-specific female breast cancer rates to provide a comprehensive analysis of trends over several decades. Incidence, mortality, and survival, as well as age-, stage-, and birth cohort-specific incidence were analysed using nationwide cancer registry data on 163,694 cases of female breast cancer in Austria (1983-2017). Annual percentage changes were estimated using joinpoint regression. BC incidence underwent linear increases until 1997 and reversed with statistically non-significant declines until 2017. After initial increases in BC-specific mortality, rates were stable from 1989 through 1995 and started declining thereafter, although statistically non-significantly after 2011. Overall BC-specific survivals, as well as survivals according to the calendar period of diagnosis, increased throughout the observation period. Incidence in younger women (aged 44 and lower) showed linear increases, whereas for women aged 45 and higher mostly stable or decreasing rates were observed. Localised BC incidence increased markedly and started declining only in 2012. Distant disease-BC incidence decreased through the whole observation period and incidence of regionalised BC started declining in 2000. Birth cohort-specific incidence peaked in women born between 1935 and 1949 (ages 45-74). In conclusion, the incidence of BC in younger women is increasing, while overall female BC incidence and mortality are stable with non-significant declines. Further, increases in the incidence of early-stage BC (localised) seem disproportionately high in comparison to more modest decreases in late-stage BC incidence (regionalised and distant disease)

Anti-CD3 antibody treatment reduces scar formation in a rat model of myocardial infarction

Introduction: Antibody treatment with anti-thymocyte globulin (ATG) has been shown to be cardioprotective. We aimed to evaluate which single anti-T-cell epitope antibody alters chemokine expression at a level similar to ATG and identified CD3, which is a T-cell co-receptor mediating T-cell activation. Based on these results, the effects of anti-CD3 antibody treatment on angiogenesis and cardioprotection were tested in vitro and in vivo. Methods: Concentrations of IL-8 and MCP-1 in supernatants of human peripheral blood mononuclear cell (PBMC) cultures following distinct antibody treatments were evaluated by Enzyme-linked Immunosorbent Assay (ELISA). In vivo, anti-CD3 antibodies or vehicle were injected intravenously in rats subjected to acute myocardial infarction (AMI). Chemotaxis and angiogenesis were evaluated using tube and migration assays. Intracellular pathways were assessed using Western blot. Extracellular vesicles (EVs) were quantitatively evaluated using fluorescence-activated cell scanning, exoELISA, and nanoparticle tracking analysis. Also, microRNA profiles were determined by next-generation sequencing. Results: Only PBMC stimulation with anti-CD3 antibody led to IL-8 and MCP-1 changes in secretion, similar to ATG. In a rat model of AMI, systemic treatment with an anti-CD3 antibody markedly reduced infarct scar size (27.8% (Inter-quartile range; IQR 16.2–34.9) vs. 12.6% (IQR 8.3–27.2); p < 0.01). The secretomes of anti-CD3 treated PBMC neither induced cardioprotective pathways in cardiomyocytes nor pro-angiogenic mechanisms in human umbilical vein endothelial cell (HUVECs) in vitro. While EVs quantities remained unchanged, PBMC incubation with an anti-CD3 antibody led to alterations in EVs miRNA expression. Conclusion: Treatment with an anti-CD3 antibody led to decreased scar size in a rat model of AMI. Whereas cardioprotective and pro-angiogenetic pathways were unaltered by anti-CD3 treatment, qualitative changes in the EVs miRNA expression could be observed, which might be causal for the observed cardioprotective phenotype. We provide evidence that EVs are a potential cardioprotective treatment target. Our findings will also provide the basis for a more detailed analysis of putatively relevant miRNA candidates

Seasonal variations in the diagnosis of testicular germ cell tumors: a national cancer registry study in austria

SIMPLE SUMMARY: Seasonal variations in cancer diagnosis could already be demonstrated in prostate and breast cancer. The reasons for this observed seasonal pattern are still unclear. The health care system or other determinants such as the protective function of vitamin D3 in carcinogenesis could be assumed as one explanation. Testicular germ cell tumors are the most common developed malignancy among young men. The aim of our study was to investigate, for the first time, the seasonal variations in the clinical diagnosis of testicular germ cell tumors. We have been able to confirm that the frequency of monthly newly diagnosed cases of testicular cell tumors in Austria has a strong seasonality, with a significant reduction in the tumor incidence during the summer months and an increase during the winter months. ABSTRACT: We conducted a retrospective National Cancer Registry study in Austria to assess a possible seasonal variation in the clinical diagnosis of testicular germ cell tumors (TGCT). In total, 3615 testicular cancer diagnoses were identified during an 11-year period from 2008 to 2018. Rate ratios for the monthly number of TGCT diagnoses, as well as of seasons and half-years, were assessed using a quasi-Poisson model. We identified, for the first time, a statistically significant seasonal trend (p < 0.001) in the frequency of monthly newly diagnosed cases of TGCT. In detail, clear seasonal variations with a reduction in the tumor incidence during the summer months (Apr–Sep) and an increase during the winter months (Oct–Mar) were observed (p < 0.001). Focusing on seasonality, the incidence during the months of Oct–Dec (p = 0.008) and Jan–Mar (p < 0.001) was significantly higher compared to the months of Jul–Sep, respectively. Regarding histopathological features, there is a predominating incidence in the winter months compared to summer months, mainly concerning pure seminomas (p < 0.001), but not the non-seminoma or mixed TGCT groups. In conclusion, the incidence of TGCT diagnoses in Austria has a strong seasonal pattern, with the highest rate during the winter months. These findings may be explained by a delay of self-referral during the summer months. However, the hypothetical influence of vitamin D3 in testicular carcinogenesis underlying seasonal changes in TGCT diagnosis should be the focus of further research

Catalyzing Transcriptomics Research in Cardiovascular Disease : The CardioRNA COST Action CA17129

Cardiovascular disease (CVD) remains the leading cause of death worldwide and, despite continuous advances, better diagnostic and prognostic tools, as well as therapy, are needed. The human transcriptome, which is the set of all RNA produced in a cell, is much more complex than previously thought and the lack of dialogue between researchers and industrials and consensus on guidelines to generate data make it harder to compare and reproduce results. This European Cooperation in Science and Technology (COST) Action aims to accelerate the understanding of transcriptomics in CVD and further the translation of experimental data into usable applications to improve personalized medicine in this field by creating an interdisciplinary network. It aims to provide opportunities for collaboration between stakeholders from complementary backgrounds, allowing the functions of different RNAs and their interactions to be more rapidly deciphered in the cardiovascular context for translation into the clinic, thus fostering personalized medicine and meeting a current public health challenge. Thus, this Action will advance studies on cardiovascular transcriptomics, generate innovative projects, and consolidate the leadership of European research groups in the field.COST (European Cooperation in Science and Technology) is a funding organization for research and innovation networks (www.cost.eu)

Changing geographical patterns and trends in cancer incidence in children and adolescents in Europe, 1991–2010 (Automated Childhood Cancer Information System): a population-based study

Background: A deceleration in the increase in cancer incidence in children and adolescents has been reported in several national and regional studies in Europe. Based on a large database representing 1·3 billion person-years over the period 1991–2010, we provide a consolidated report on cancer incidence trends at ages 0–19 years. Methods: We invited all population-based cancer registries operating in European countries to participate in this population-based registry study. We requested a listing of individual records of cancer cases, including sex, age, date of birth, date of cancer diagnosis, tumour sequence number, primary site, morphology, behaviour, and the most valid basis of diagnosis. We also requested population counts in each calendar year by sex and age for the registration area, from official national sources, and specific information about the covered area and registration practices. An eligible registry could become a contributor if it provided quality data for all complete calendar years in the period 1991–2010. Incidence rates and the average annual percentage change with 95% CIs were reported for all cancers and major diagnostic groups, by region and overall, separately for children (age 0–14 years) and adolescents (age 15–19 years). We examined and quantified the stability of the trends with joinpoint analyses. Findings: For the years 1991–2010, 53 registries in 19 countries contributed a total of 180 335 unique cases. We excluded 15 162 (8·4%) of 180 335 cases due to differing practices of registration, and considered the quality indicators for the 165 173 cases included to be satisfactory. The average annual age-standardised incidence was 137·5 (95% CI 136·7–138·3) per million person-years and incidence increased significantly by 0·54% (0·44–0·65) per year in children (age 0–14 years) with no change in trend. In adolescents, the combined European incidence was 176·2 (174·4–178·0) per million person-years based on all 35 138 eligible cases and increased significantly by 0·96% (0·73–1·19) per year, although recent changes in rates among adolescents suggest a deceleration in this increasing trend. We observed temporal variations in trends by age group, geographical region, and diagnostic group. The combined age-standardised incidence of leukaemia based on 48 458 cases in children was 46·9 (46·5–47·3) per million person-years and increased significantly by 0·66% (0·48–0·84) per year. The average overall incidence of leukaemia in adolescents was 23·6 (22·9–24·3) per million person-years, based on 4702 cases, and the average annual change was 0·93% (0·49–1·37). We also observed increasing incidence of lymphoma in adolescents (average annual change 1·04% [0·65–1·44], malignant CNS tumours in children (average annual change 0·49% [0·20–0·77]), and other tumours in both children (average annual change 0·56 [0·40–0·72]) and adolescents (average annual change 1·17 [0·82–1·53]). Interpretation: Improvements in the diagnosis and registration of cancers over time could partly explain the observed increase in incidence, although some changes in underlying putative risk factors cannot be excluded. Cancer incidence trends in this young population require continued monitoring at an international level. Funding: Federal Ministry of Health of the Federal German Government, the European Union's Seventh Framework Programme, and International Agency for Research on Cancer

Combining population projections with quasi-likelihood models: A new way to predict cancer incidence and cancer mortality in Austria up to 2030

Background: The current demographic changes with a shift toward older ages contribute to more cancer cases in the next decades in Western countries. Thus, forecasting the demand for expected healthcare services and expenditures is relevant for planning purposes and resource allocation. Objective: In this study, we provide a new method to estimate future numbers of cancer cases (newly diagnosed cancers and cancer deaths) using Austrian data. Methods: We used 1983-2009 data to estimate cancer burden trends using quasi-Poisson regression models, which we then applied to official population projections up to 2030. Specific regression models were estimated for cancer incidence and mortality, disaggregated by sex and 16 tumor sites. Results: The absolute number of cancer cases increased continuously during the last decades in Austria. The trend will also continue in the near future, as the number of newly diagnosed cancers and cancer deaths will increase by +14Š and +16Š between 2009 and 2030. Age-standardized individual risk of being newly diagnosed with or die from cancer will be substantially lower in 2030 compared to 2009 (-14Š and -16Š, respectively). Contribution: Our novel method combining population projections with quasi-likelihood models found a falling individual risk for cancer burden in the Austrian population. However, the absolute number of new cancer cases and deaths will increase due to the aging of the population. These estimates should be considered when planning future healthcare demands

Moderate Altitude Residence Reduces Male Colorectal and Female Breast Cancer Mortality More Than Incidence: Therapeutic Implications?

Simple Summary Living at moderate altitudes has been reported to be associated with health benefits, including reduced mortality from male colorectal and female breast cancer. The aim of this study was to evaluate altitude-dependent incidence rates and to compare them with mortality rates of those cancers. We further explored whether altitude-associated differences in lifestyle behaviour exist. Analyses including all incidence cases and deaths over a 10-year observation period of an Alpine country (Austria) revealed that the age-standardized incidence and mortality rates of male colorectal cancer decreased by 24.0% and 44.2%, and that of female breast cancer by 6.5% and 26.2%, from the lowest (<251 m) to the highest (1000-2000) altitude level. The population-based survey indicated higher physical activity levels and lower body mass index for both sexes living at a moderate altitude compared to those living below 251 m. These observations may, in certain cases, support decision making when changing residence. Background: Living at moderate altitude may be associated with health benefits, including reduced mortality from male colorectal and female breast cancer. We aimed to determine altitude-dependent incidence and mortality rates of those cancers and put them in the context of altitude-associated lifestyle differences. Methods: Incidence cases and deaths of male colorectal cancer (n = 17,712 and 7462) and female breast cancer (n = 33,803 and 9147) from altitude categories between 250 to about 2000 m were extracted from official Austrian registries across 10 years (2008-2017). Altitude-associated differences in health determinants were derived from the Austrian Health Interview Survey (2014). Results: The age-standardized incidence and mortality rates of male colorectal cancer decreased by 24.0% and 44.2%, and that of female breast cancer by 6.5% and 26.2%, respectively, from the lowest to the highest altitude level. Higher physical activity levels and lower body mass index for both sexes living at higher altitudes were found. Conclusions: Living at a moderate altitude was associated with a reduced incidence and (more pronounced) mortality from colorectal and breast cancer. Our results suggest a complex interaction between specific climate conditions and lifestyle behaviours. These observations may, in certain cases, support decision making when changing residence

Changing Epidemiological Trends of Hepatobiliary Carcinomas in Austria 2010–2018

Using national registries, we investigated the epidemiological trends of hepatobiliary carcinomas in Austria between 2010 and 2018 and compared them to those reported for the periods of 1990–1999 and 2000–2009. In total, 12,577 patients diagnosed with hepatocellular carcinoma (n = 7146), intrahepatic cholangiocarcinoma (n = 1858), extrahepatic cholangiocarcinoma (n = 1649), gallbladder carcinoma (n = 1365), and ampullary carcinoma (n = 559), between 2010 and 2018, were included. The median overall survival of all patients was 9.0 months. The best median overall survival was observed in patients with ampullary carcinoma (28.5 months) and the worst median overall survival was observed in patients with intrahepatic carcinoma (5.6 months). The overall survival significantly improved in all entities over the period 2010–2018 as compared with over the periods of 2000–2009 and 1990–1999. Age-adjusted incidence and mortality rates remained stable for most entities in both, men and women; only in gallbladder carcinoma, the incidence and mortality rates significantly decreased in women, whereas, in men, the incidence rates remained stable and mortality rates showed a decreasing trend. We showed that age-adjusted incidence and mortality rates were stable in most entities, except in gallbladder carcinoma. The overall survival improved in almost all entities as compared with those during 1990–2009

Prothrombotic response to norepinephrine infusion, mimicking norepinephrine stress-reactivity effects, is partly mediated by α-adrenergic mechanisms

BACKGROUND: Stress-induced prothrombotic changes are mediated by the sympathetic nervous system and critically involved in mental triggering of acute coronary syndromes, but the underlying psychobiology is not fully understood. We tested the hypothesis that a norepinephrine (NE) infusion to mimic effects of stress-induced NE release on blood coagulation elicits prothrombotic changes and examined to what extent these would be mediated by an alpha-adrenergic mechanism.METHODS AND RESULTS: In a single-blind placebo-controlled within-subjects design, 24 middle-aged, non-smoking, non-obese and normotensive men participated in three experimental trials with an interval between one and two weeks. Each trial applied two sequential infusions of 1 and 15min duration with varying substances [i.e., saline as placebo, the non-specific alpha-blocker phentolamine (2.5mg/min), and NE (5mug/min)]: trial 1=saline+saline; trial 2=saline+NE, and trial 3=phentolamine+NE. Plasma levels of clotting factor VIII activity (FVIII:C), fibrinogen, and D-dimer were assessed from blood samples collected immediately before and 1min and 20min after infusion procedures. Compared to saline+saline, saline+NE induced increases over time in FVIII:C, fibrinogen, and D-dimer levels. With phentolamine+NE, fibrinogen levels remained increased compared to saline+saline, but changes in FVIII:C and D-dimer levels were no more different. Coagulation changes did not differ between saline+NE and phentolamine+NE.CONCLUSIONS: NE infusion activates blood coagulation. The resulting prothrombotic state could be one psychobiological mechanism underlying mental triggering of acute coronary syndromes. Blockade of alpha-adrenergic receptors partly attenuated NE effects on coagulation and could be implied to have preventive potential in susceptible individuals.Copyright © 2018 Elsevier Ltd. All rights reserved