To collect sensitive patient data during clinical trials, the Informed Consent (IC) of the participants must be obtained beforehand. If the IC is not correct and complete, the document cannot be used to represent the will of the participant and will not be considered a legally valid document. However, few studies have examined the quality of the IC and the IC-quality found is unfortunately not satisfactory. The aim of this article is to describe the development of an IC quality assurance concept and to report the results of an evaluation using the example of a German Centre for Cardiovascular Research (DZHK) registry. All quality issues identified during the study were documented. These were aggregated into the quality indicators "Completeness", "Consistency of Data", "Correctness" and "Validity". Of 2,453 ICs, 1,588 had at least one quality issue; 99.8% of them were resolved. In addition, training sessions were conducted with study staff to raise awareness of the importance of correct IC collection, including documentation, and to minimize quality issues. Our data exemplify that improvements in the recording of ICs by the study staff can be achieved. This evaluation shows the value and importance of continuous IC quality control.

BACKGROUND AND OBJECTIVES:Ageing populations in high-income countries reduce the proportion of potential blood donors while increasing transfusion demand. Sustaining an adequate blood supply requires higher donor motivation among younger age groups. We analysed long-term trends in whole blood donations (WBDs) in one German federal state as an indicator for challenges that may arise in other high-income countries. MATERIALS AND METHODS:In our prospective longitudinal study (starting 2005), we obtained the age and sex of the donors of all WBDs in the German federal state Mecklenburg-Western Pomerania in 2019 and 2020 and compared them with the data from 2005 to 2015. Population data from the German statistical office were used to predict future WBD in two models, population-based and population-based with behaviour-adjusted prediction. RESULTS:WBD decreased from 118,419 in 2005 to 83,871 in 2019 (-29.2%) and 76,912 in 2020 (-35.1%). Donation rates per 1000 inhabitants declined by 19.1% between 2005 and 2019, indicating a loss of donor motivation beyond demographic effects. Based on the donation numbers of 2019, we predict a further decline of WBD in 2030 by -12.7% (population-based projection) or -15.1% (behaviour-adjusted projection), respectively. CONCLUSION:The decline in blood donations is no longer solely driven by demographic changes but also by reduced motivation among younger donors. As ageing populations and changing donor behaviour are common to many high-income countries, these findings likely reflect an emerging international trend. Targeted strategies to recruit and retain young donors are urgently needed to ensure sustainable blood supplies in ageing societies.

Introduction: The objective of this study is to compare the 5 year overall survival of patients with stage I–III colon cancer treated by laparoscopic colectomy versus open colectomy. Methods: Using Mecklenburg-Western Pomerania Cancer Registry data from 2008 to 2018, we will emulate a phase III, multicenter, open-label, two-parallel-arm hypothetical target trial in adult patients with stage I–III colon cancer who received laparoscopic or open colectomy as an elective treatment. An inverse-probability weighted Royston‒Parmar parametric survival model (RPpsm) will be used to estimate the hazard ratio of laparoscopic versus open surgery after confounding factors are balanced between the two treatment arms. Further to the hazard ratio, we will also compute differences in the absolute risk (at 1, 3, and 5 years) and restricted mean survival time (up to 1, 3, and 5 years). A weighted Kaplan‒Meier curve will be used to compare five-year overall survival in both treatment arms. Various comparator and sensitivity analyses will be performed to check the robustness of the results that will be estimated by the RPpsm main model. Treatment period- and stage-specific results will also be provided. Discussion: This study aims to causally model the effect of laparoscopic versus open colectomy on 5 year overall survival using a target trial emulation approach. As the cancer registry data do not cover BMI, comorbidity, and previous abdominal surgery for non-malignant indications, the potential for residual confounding arising from these factors is a limitation of this study. This will be approached in a quantitative bias analysis using the E-method. The results will substantiate existing evidence on the comparative effectiveness of laparoscopic versus open colectomy in patients with stage I–III colon cancer and may guide clinical decisions as to whether a laparoscopic approach is as safe as an open approach in terms of improving 5-year overall survival in these patient groups.

The aim of this study is the analysis of cancer incidence and mortality among the firefighters of the municipal fire brigade in the city of Neubrandenburg in Germany. To asses cancer risk standardized incidence ratios and standardized mortality ratios were computed. The risk of the firefighter cohort was compared to the risk of two reference populations: the county Mecklenburg Lake District, where the city of Neubrandenburg is located, and the federal state Mecklenburg-Western Pomerania. Results are based on data from 100 firefighters. No statistically significant results were observed for the incidence or mortality of all cancers (ICD-10 C00-C97 without C44). The SIR and SMR for bladder cancer were significantly elevated. The overall cancer incidence and mortality among Neubrandenburg’s firefighters were not higher than among the reference population. The increased incidence and mortality from bladder cancer are in line with published results, especially with the monograph by the International Agency for Research on Cancer on occupational exposure as a firefighter.

Breast cancer (BC) is a heterogeneous disease, traditionally classified by hormone receptor and HER2 (human epidermal growth factor receptor 2) status. HER2-low, characterized by low HER2 expression without gene amplification, recently gained attention. While new therapies are promising, its clinical significance remains unclear. We analysed 241,510 BC patients diagnosed between 2000 and 2020 in Germany using data from the German Cancer Registry Group. HER2 status was determined using immunohistochemistry and fluorescence in situ hybridization results, and patients were classified as HER2-positive, HER2-low or HER2-zero. Clinical features, chemosensitivity and long-term outcomes - metastasis-free survival (MFS), recurrence-free survival (RFS), and overall survival (OS) - were analysed using Cox models. HER2-low comprised 42% of female and 47% of male patients, predominantly hormone receptor positive. Metastatic patterns in HER2-low and HER2-zero were similar but differed from HER2-positive, which showed more liver metastasis and multiple metastatic sites. HER2-positive showed worse MFS, RFS, and OS than HER2-zero and HER2-low subtypes. Pathological complete response (pCR) rates after neoadjuvant chemotherapy were highest in HER2-positive. HER2-low has higher hormone receptor positivity, distinguishing it from HER2-zero. While metastatic behaviour, treatment and long-term response in HER2-low were comparable to HER2-zero, the hormone receptor status seems to play a critical role in these outcomes.

Malignant ovarian germ cell tumors (MOGCT) and ovarian sex cord stromal tumors (SCST) are rare ovarian tumors. Since 2013, all German federal states are obliged to record data on diagnosis, pathology, therapy, and clinical course of tumor diseases. We gathered data on MOGCT and SCST from thirteen federal cancer registries and the German Childhood Cancer Registry. Each of the participating registries provided aggregated data on MOGCT and SCST with date of diagnosis between 01.01.2016 and 31.12.2021. 629 MOGCT and 872 SCST were included, age peaks at diagnosis for MOGCT and SCST were between 20 and 24 years and between 55 and 59 years, respectively. Of all MOGCT, 23%, 22%, 13% and 12% were malignant teratoma, dysgerminoma, neuroendocrine tumors and yolk sac tumors, respectively. The large majority (94%) of SCST represented malignant granulosa cell tumors. Most tumors were diagnosed in FIGO stage I (66% of MOGCT and 85% of SCST). Surgery was reported in 58% of patients with MOGCT and in 73% of patients with SCST. Chemotherapy was administered to 26% of MOGCT patients and 8% of SCST patients. This study highlights the great potential of cancer registries as high numbers of patients are recorded, however, data are highly dependent on the reporting institutions.

BACKGROUND:Employees at the Ihlenberg toxic waste landfill in northern Germany were found to have an increased risk of cancer and cancer-related deaths in previous analyses covering the time period from 1983 to 2008. The present study aimed to quantify cancer risk and all-cause mortality in the employee cohort in 2009 to 2021. METHODS:In this retrospective cohort study, cancers were identified by linkage with cancer registries, and employee deaths were obtained from population registries. Standardized incidence ratios (SIRs) for cancers and standardized mortality ratios (SMRs) were calculated to quantify cancer and mortality risk in the employee cohort. The effects of employment duration and different latency periods up to 30 years were additionally considered. RESULTS:The cohort of 590 employees (432 men, 158 women) who worked at the landfill for at least 3 months between 1983 and 2018 was established from human resource management documentation and followed from January 1, 2009 until December 31, 2021. During this follow-up period, the SIR for all cancers combined was 0.69 (95% confidence interval (CI): 0.47, 0.98) and the SMR for all-cause mortality was 0.51 (95% CI: 0.35, 0.73). Longer employment at the landfill was not associated with increased cancer incidence or mortality. CONCLUSIONS:Employment at the landfill, expected to reflect occupational exposure to toxic waste, was not associated with increased cancer incidence or mortality in the employee cohort. Preventive measures to reduce exposure and to promote a healthy lifestyle should be maintained at the landfill.

The German Centre for Cardiovascular Research (DZHK) is one of the German Centres for Health Research and aims to conduct early and guideline-relevant studies to develop new therapies and diagnostics that impact the lives of people with cardiovascular disease. Therefore, DZHK members designed a collaboratively organised and integrated research platform connecting all sites and partners. The overarching objectives of the research platform are the standardisation of prospective data and biological sample collections among all studies and the development of a sustainable centrally standardised storage in compliance with general legal regulations and the FAIR principles. The main elements of the DZHK infrastructure are web-based and central units for data management, LIMS, IDMS, and transfer office, embedded in a framework consisting of the DZHK Use and Access Policy, and the Ethics and Data Protection Concept. This framework is characterised by a modular design allowing a high standardisation across all studies. For studies that require even tighter criteria additional quality levels are defined. In addition, the Public Open Data strategy is an important focus of DZHK. The DZHK operates as one legal entity holding all rights of data and biological sample usage, according to the DZHK Use and Access Policy. All DZHK studies collect a basic set of data and biosamples, accompanied by specific clinical and imaging data and biobanking. The DZHK infrastructure was constructed by scientists with the focus on the needs of scientists conducting clinical studies. Through this, the DZHK enables the interdisciplinary and multiple use of data and biological samples by scientists inside and outside the DZHK. So far, 27 DZHK studies recruited well over 11,200 participants suffering from major cardiovascular disorders such as myocardial infarction or heart failure. Currently, data and samples of five DZHK studies of the DZHK Heart Bank can be applied for.

Introduction: Germany has established a national mammography screening program (MSP). Despite extensive awareness campaigns, the participation rate is only 54%, which is considerably below the European guidelines’ recommendation of at least 70%. Several reasons why women do not participate are already known. Telephone consultations along with invitation letters have improved the participation rate. Here, we analyzed the reasons for non-participation and offered barrier-specific counseling to examine which impediments can be overcome to improve participation. Study Design: In a randomized controlled trial, women who had not attended their proposed screening appointment in the MSP after a written invitation were contacted by telephone and asked why they did not attend. Barrier-specific counseling via telephone was then offered. Participation in the MSP was rechecked 3 months after counseling. Setting: 1772 women, aged 50–69 years, who had not scheduled a mammography screening after a written invitation were contacted by telephone and asked for their reasons for non-participation. Intervention: The reasons were recorded by the calling consultant and categorized either during the call or later based on their recorded statements. Afterward, the women received counseling specific to their statements and were given general information about the MSP. Main outcome measures: We categorized the reasons given, calculated their frequency, and analyzed the probabilities to which they could be successfully addressed in individual counseling. Participation rates were determined post-consultation according to the reason(s) indicated. Results: The data were analyzed in 2022. After exclusions, 1494 records were analyzed. Allowing for multiple reasons to be stated by every individual 3280 reasons for not attending were abstracted. The most frequent reason was participation in “gray screening” (51.5%), which included various breast cancer prevention measures outside the national MSP. Time problems (26.6%) and health reasons (17.3%) were also important. Counseling was most effective when women had not participated for scheduling reasons. Conclusion: Several reasons prevented women from participating in the MSP. Some reasons, such as time-related issues, could be overcome by telephone counseling, but others, like barriers resulting from fear of the examination procedure or its result, could not.

Survival analysis of patients with primary GBM dependent on therapy and resection status

Expression and survival analyses of CPT1A and CPT1C in GBM specimens

Additional information on the immunoblot analysis, cell line characteristics and our glioma mouse model

Introduction: In 2013, a new federal law obligated all German federal states to collect additional clinical data in population-based cancer registries as an active tool for monitoring and improving the quality of cancer care, increasing transparency and promoting health research. Now, 10 years later, the current status of the expanded cancer registration is presented, including current figures on cancer in Germany. Methods: Reporting of cancer is mandatory for physicians, and about 5 to 10 reports from different healthcare providers are expected for each case. A uniform national dataset of about 130 items is used, and reports are usually sent electronically to the registry. We used the most recent data available from cancer registries up to the year of diagnosis in 2019. We calculated incidence rates and 5-year relative survival (5YRS) for common cancers. Data on clinical outcomes and benchmarking based on quality indicators (QIs) from guidelines were provided by the Cancer Registry Schleswig-Holstein (CR SH). Results: All federal state cancer registries met most of the previously defined national eligibility criteria. Approximately 505,000 cancer cases were registered in 2019, with breast, prostate, colorectal and lung cancer being the most common cancers. The age-standardised cancer incidence has slightly decreased during the last decade. and spatial heterogeneity can be observed within Germany. 5YRS for all cancers was 67% and 63% for women and men, respectively. Therapy data for rectal cancer in 2019–2021 from the CR SH are shown as an example: 69% of the registered patients underwent surgery, mostly with curative intent (84%) and tumour-free resection (91%). Radiotherapy was given to 33% of the patients, and chemotherapy was given to 40%. Three selected QIs showed differences between involved healthcare providers. Discussion: The implementation of population-based clinical cancer registration can be considered a success. Comprehensive recording of diagnosis, treatment and disease progression and the use of registry data for quality assurance, benchmarking and feedback have been implemented.

Dilated cardiomyopathy (DCM) is characterized by ventricular chamber enlargement and impaired myocardial function. Endomyocardial biopsies (EMB) enable immunohistochemical and molecular characterization of this disease. However, knowledge about specific molecular patterns and their relation to cardiac function in both ventricles is rare. Therefore, we performed a mass spectrometric analysis of 28 paired EMBs of left (LV) and right ventricles (RV) of patients with DCM or suspected myocarditis allowing quantitative profiling of 743 proteins. We analysed associations between protein abundance of LV and RV as well as the echocardiographic parameters LVEF, TAPSE, LVEDDI, and RVEDDI by linear regression models. Overall, more LV than RV proteins were associated with LV parameters or with RVEDDI. Most LV and RV proteins increasing in level with impairing of LVEF were annotated to structural components of cardiac tissue. Additionally, a high proportion of LV proteins with metabolic functions decreased in level with decreasing LVEF. Results were validated with LV heart sections of a genetic murine heart failure model. The study shows, that remodelling and systolic dysfunction in DCM is mirrored by distinct alterations in protein composition of both ventricles. Loss of LV systolic function is reflected predominantly by alterations in proteins assigned to metabolic functions in the LV whereas structural remodelling was more obvious in the RV. Alterations related to intermediate filaments were seen in both ventricles and highlight such proteins as early indicators of LV loss of function. SIGNIFICANCE: The present study report protein sets in the RV and the LV being associated with ventricular function and remodelling in DCM. Protein abundances in the LV and the RV emphasize and expand current knowledge on pathophysiological changes in heart failure and DCM. While RV and LV EMBs do not differ concerning diagnostic assessment of inflammatory status and virus persistence, additional information reflecting disease severity associated protein alterations can be gained by EMB protein profiling. RV and LV protein data provided complementary information. The protein pattern of the LV reflects metabolic changes and an impaired energy production, which is associated with the degree of LV systolic dysfunction and remodelling and may yield important information about the disease status in DCM. On the other hand, at this disease stage of DCM with still preserved RV function, RV alterations in structural proteins may reflect myocardial compensatory protective mechanisms for maintenance of structure and cellular function. The study highlight particular proteins being of interest as heart failure biomarkers in both ventricles which seem to reflect the severity of the disease. Further comparative studies between different HF aetiologies have to evaluate those proteins as markers specific for DCM.

Diagnostic radiology is a leading cause of man-made radiation exposure to the population. It is an important factor in many epidemiological studies as variable of interest or as potential confounder. The effective dose as a risk related quantity is the most often stated patient dose. Nevertheless, there exists no comprehensive quantification model for retrospective analysis for this quantity. This paper gives a catalog of effective dose values for common and rare examinations and demonstrates how to modify the dose values to adapt them to different calendar years using a quantification concept already used for retrospective analysis of the red bone marrow dose. It covers the time period of 1946 to 1995 and allows considering technical development and different practical standards over time. For an individual dose assessment, if the dose area product is known, factors are given for most examinations to convert the dose area product into the effective dose. Additionally factors are stated for converting the effective dose into the red bone marrow dose or vice versa.