Hiltrud Merzenich

Decreasing sperm quality: a global problem?

BackgroundCarlsen and coworkers (1992) reviewed 61 heterogeneous observational studies on semen quality published between 1938 and 1990. This review indicates that mean sperm density decreased significantly between 1940 and 1990. An extended meta-analysis with 101 studies confirmed a decline in sperm density for the period from 1934 to 1996 (2000). The key message of the meta-analyses is that sperm counts have decreased globally by about 50% over the past decades. This assessment has been questioned.DiscussionA major methodological problem of the meta-analysis is the use of data collected in different countries, at different times, on different populations and with different methods of semen analysis. Furthermore, the results of studies concerning semen analysis are frequently biased e.g. by selection criteria of volunteers. In most studies on human semen characteristics the populations under study are insufficiently defined and the study participants are not a representative population sample. The incidence of testicular cancer has increased in Caucasian men worldwide. The investigation of common risk factors for male reproductive disorders requires well designed epidemiological studies and the collection of individual data.SummaryFormer meta-analyses of sperm count data show a global downward trend. This conclusion should be interpreted with caution. The included studies are of great heterogeneity due to geographical and/or ethnical variation, different study designs and different methodological standards. Population-based prospective studies are needed to investigate secular trends in male reproductive disorders.

Childhood leukemia in relation to radio frequency electromagnetic fields in the vicinity of TV and radio broadcast transmitters.

A case-control study of radio frequency electromagnetic fields (RF-EMFs) and childhood leukemia was conducted in West Germany. The study region included municipalities near high-power radio and TV broadcast towers, including 16 amplitude-modulated and 8 frequency-modulated transmitters. Cases were aged 0-14 years, were diagnosed with leukemia between 1984 and 2003, and were registered at the German Childhood Cancer Registry. Three age-, gender-, and transmitter-area-matched controls per case were drawn randomly from population registries. The analysis included 1,959 cases and 5,848 controls. Individual exposure to RF-EMFs 1 year before diagnosis was estimated with a field strength prediction program. Considering total RF-EMFs, the odds ratio derived from conditional logistic regression analysis for all types of leukemia was 0.86 (95% confidence interval: 0.67, 1.11) when upper (>or=95%/0.701 V/m) and lower (<90%/0.504 V/m) quantiles of the RF-EMF distribution were compared. An analysis of amplitude-modulated and frequency-modulated transmitters separately did not show increased risks of leukemia. The odds ratio for all types of leukemia was 1.04 (95% confidence interval: 0.65, 1.67) among children living within 2 km of the nearest broadcast transmitter compared with those living at a distance of 10-<15 km. The data did not show any elevated risks of childhood leukemia associated with RF-EMFs.

An evaluation of exposure metrics in an epidemiologic study on radio and television broadcast transmitters and the risk of childhood leukemia

Electric field strength values calculated by wave propagation modeling were applied as an exposure metric in a case-control study conducted in Germany to investigate a possible association between radio frequency electromagnetic fields (RF-EMF) emitted from television and radio broadcast transmitters and the risk of childhood leukemia. To validate this approach it was examined at 850 measurement sites whether calculated RF-EMF are an improvement to an exposure proxy based on distance from the place of residence to a transmitter. Further, the agreement between measured and calculated RF-EMF was explored. For dichotomization at the 90% quantiles of the exposure distributions it was found that distance agreed less with measured RF-EMF (Kappa coefficient: 0.55) than did calculated RF-EMF (Kappa coefficient: 0.74). Distance was a good exposure proxy for a single transmitter only which uses the frequency bands of amplitude modulated radio, whereas it appeared to be of limited informative value in studies involving several transmitters, particularly if these are operating in different frequency bands. The analysis of the agreement between calculated RF-EMF and measured RF-EMF showed a sensitivity of 76.6% and a specificity of 97.4%, leading to an exposure misclassification that still allows one to detect a true odds ratio as low as 1.4 with a statistical power of >80% at a two-sided significance level of 5% in a study with 2,000 cases and 6,000 controls. Thus, calculated RF-EMF is confirmed to be an appropriate exposure metric in large-scale epidemiological studies on broadcast transmitters.

Radiation dose distribution in functional heart regions from tangential breast cancer radiotherapy

BACKGROUND AND PURPOSE To analyze the distribution of individually-determined radiation dose to the heart and its functional sub-structures after radiotherapy in breast cancer patients treated in Germany during 1998-2008. MATERIAL AND METHODS We obtained electronic treatment planning records for 769 female breast cancer patients treated with megavoltage tangential field radiotherapy. All dose distributions were re-calculated using Eclipse with the anisotropic analytical algorithm (AAA) for photon fields, and the electron Monte Carlo algorithm for electron boost fields. Based on individual dose volume histograms for the complete heart and several functional sub-structures, we estimated various dose measures in patient groups. RESULTS Mean heart dose spanned a range of 0.9-19.1Gy for left-sided radiotherapy and 0.3-11.6Gy for right-sided radiotherapy. Average (median) mean heart dose was 4.6Gy (3.7Gy) for left-sided radiotherapy, and 1.7Gy (1.4Gy) for right-sided RT. With left-sided radiotherapy, 66% of the patients had 2cm(3) of the complete heart exposed to at least 40Gy. Younger age, higher body mass index, tumor location in a medial quadrant, and presence of a parasternal field were also associated with higher heart dose. CONCLUSION Tumor location and treatment choices influence cardiac dose with complex interactions. There is considerable variability in heart dose, with dose metrics of different cardiac sub-structures showing different patterns in their dependency on external influences. Dose-response analysis of late cardiac effects after radiotherapy requires detailed individual dosimetry.

Burden of cardiovascular risk factors and cardiovascular disease in childhood cancer survivors: data from the German CVSS-study

Aims The cardiac and vascular late sequelae in long-term survivors of childhood cancer (CVSS)-study aimed to quantify the prevalence of cardiovascular risk factors (CVRF) and cardiovascular disease (CVD) in German childhood cancer survivors (CCS). Methods and results In the CVSS-study (NCT02181049), 1002 CCS (age range 23-48 years) diagnosed with neoplasia prior to 15 years of age between 1980 and 1990 prospectively underwent a systematic, standardized clinical and laboratory cardiovascular screening, identical to the population-based Gutenberg Health Study (GHS) cohort. For 951 individuals, prevalences of CVRF and CVD were primarily compared to the GHS sample and to two further German population-based cohorts. Using log-binomial regression models, an increased risk for occurrence of arterial hypertension [relative risk (RR) 1.38, 95% confidence interval (95% CI 1.21-1.57)] and dyslipidaemia [RR 1.26 (95% CI 1.12-1.42)] was found. This indicates a premature occurrence compared to the general population of approximately 6 and 8 years, respectively [rate advancement period estimator, RAPhypertension 5.75 (95% CI 3.5-8.0) and RAPdyslipidaemia 8.16 (95% CI 4.4-11.9)]. Overall, no differences were observed for obesity and diabetes. Overt CVD was present in 4.5% (95% CI 3.0-6.6%) of CCS [RR 1.89 (95% CI 1.34-2.66), RAPCVD 7.9 (95% CI 4.1-11.7)], of which the most frequent entities were congestive heart failure and venous thromboembolism. Prevalences of CVRF and CVD increased with age without reaching a plateau over time. Conclusion This large CCS screening examination revealed consistently in comparison to three population samples a considerably increased risk for premature CVD. The findings in these young adult CCS indicate a high burden of cardiovascular morbidity and mortality in the long term. Clinicaltrials. gov-Nr NCT02181049.

Prevalence of cardiovascular late sequelae in long-term survivors of childhood cancer: A systematic review and meta-analysis

Cardiovascular diseases are well‐known late effects of childhood cancer and research on these late effects is a highly important emerging field. We conducted a systematic review with a meta‐analysis to give an overview of the current evidence and the prevalence of late cardiovascular events.

Predicting Heart Dose in Breast Cancer Patients Who Received 3D Conformal Radiation Therapy

Abstract Cardiac late effects are a major health concern for long-term survivors after radiotherapy for breast cancer. Large cohort studies to better understand the exact dose–response relationship require individual estimates of radiation dose to the heart. To predict individual cardiac dose from information that is typically available for all members of a retrospective epidemiological cohort study, 774 female breast cancer patients treated with megavoltage tangential field radiotherapy in 1998–2008 were examined. All dose distributions were calculated using Eclipse with the anisotropic analytical algorithm (AAA) for photon fields and the electron Monte Carlo algorithm for electron boost fields. Based on individual dose volume histograms, the authors calculated absorbed dose in the complete heart as well as in six functional substructures. Statistical models were developed to predict absorbed dose using only covariate information from patients’ clinical records on tumor location, patient anatomy and radiotherapy prescription. The out-of-sample prediction error for mean heart dose was 54% (coefficient of variation). The prediction error in functional substructures ranged from 49–68% for mean dose and from 52–86% for extreme dose. The authors conclude that based on a patient sample with exact heart dosimetry, it is possible to use clinical information alone to predict absorbed heart dose in the remaining cohort with a quantified error suitable for dose–response analyses of cardiac late effects.

Pediatric computed tomography practice in Japanese university hospitals from 2008-2010: did it differ from German practice?

Computed tomography (CT) is an essential tool in modern medicine and is frequently used to diagnose a wide range of conditions, particularly in industrial countries, such as Japan and Germany. However, markedly higher doses of ionizing radiation are delivered during CT imaging than during conventional X-ray examinations. To assess pediatric CT practice patterns, data from three university hospital databases (two in Japan and one in Germany) were analyzed. Anonymized data for patients aged 0 to 14 years who had undergone CT examinations between 2008 and 2010 were extracted. To assess CT practice, an interdisciplinary classification scheme for CT indications, which incorporated the most common examination types and radiosensitive tissues, was developed. The frequency of CT examinations was determined according to sex, age at examination, and indications. A total of 5182 CT examinations were performed in 2955 children. Overall, the frequency of CT examinations at the Japanese university hospitals did not differ significantly from that at the German hospital. However, differences were detected in the age distribution of the patients who underwent CT examinations (the proportion of patients <5 years of age was significantly higher in Japan than in Germany) and in the indications for CT. Substantial practice differences regarding the use of CT in pediatric health care were detected between the three hospitals. The results of this study point towards a need for approaches such as clinical guidelines to reduce unwarranted medical radiation exposures, particularly abdominal and head CT, in the Japanese health system.

Cardiovascular risk factors are important determinants of platelet-dependent thrombin generation in adult survivors of childhood cancer

Cardiovascular disease is the most frequent non-malignant cause of morbidity and mortality in adult survivors of childhood or adolescent cancer. Thrombin generation (TG) analysis gives insight in hypercoagulability as an important mechanism linked to cardiovascular risk factors (CVRFs). In 200 individuals, from the cardiac and vascular late sequelae in long-term survivors of childhood cancer study, TG in platelet-rich plasma (PRP) and platelet-free plasma (PFP) at 1pM tissue factor was investigated. Endogenous thrombin potential (ETP) and peak height were the analysed parameters of a TG curve. Sex-specific multivariable linear regression analysis adjusted for age and CVRFs was used to assess the clinical determinants of TG. Females presented with higher ETP and peak height compared to males, both in PRP and PFP. Hypertension (beta estimate, ß: 184.8 [90.7; 278.8]), obesity (ß: 161.9 [63.9; 259.5]), and HbA1c (ß: 715.6 [97.4; 1333.8]) were associated with higher ETP in PRP only. ETP in PRP was positively associated with obesity and HbA1c in both males and females and with dyslipidemia (ß: 253.07 [72.92; 433.22]) and systolic hypertension (ß: 436.7 [119.02; 754.39]) in females only. CVRFs showed no association with TG variables in PFP. In conclusion, this study presents an important relation between traditional CVRFs and TG in the presence of platelets only. Sex-specific differences in TG with females presenting with higher TG, particularly those with dyslipidemia and systolic hypertension, were demonstrated. These results highlight the potential of the platelet-coagulant function in identifying cancer survivors at higher risk for adverse cardiovascular events.

Prevalence of Cardiac Disease in Breast Cancer Patients at Time of Diagnosis Compared to the General Female Population in Germany

Background: Advances in oncological therapy have significantly improved breast cancer survival; therefore comorbid conditions are becoming more relevant. We investigated the prevalence of prior cardiovascular diseases and risk factors in patients with breast cancer compared to those in the general female population in Germany. Methods: The PASSOS heart study is a retrospective multicenter cohort study on cardiac late effects in breast cancer patients treated between 1998 and 2008. We analyzed the frequencies of cardiac diseases and cardiovascular risk factors in patients from this cohort as documented in anesthesia protocols compared to self-reported frequencies in the general female population in Germany. Results: 3,496 patients aged between 40 and 79 years who underwent breast surgery were considered for analysis. The age-standardized prevalence of cardiac diseases or cardiovascular risk factors was 6.75 versus 7.52% and 69 versus 80.92%, respectively. Coronary heart disease (3.96 vs. 5.18%) and angina pectoris (0.37 vs. 1.03%) prevalence was lower in breast cancer patients, while non-fatal myocardial infarction (2.06 vs. 1.81%) and stroke (2.64 vs. 2.34%) were more frequent (not statistically significant). Conclusion: Pre-existing cardiac diseases and cardiovascular risk factors are common in both study populations, being slightly less frequent in the PASSOS cohort. When making therapy decisions, the cardiac risk profile should be carefully monitored and taken into account.