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Background: Despite considerable improvements in oral health in recent decades, caries and periodontitis are still widespread, ranking among the most prevalent diseases worldwide and requiring future research. The German National Cohort (NAKO Gesundheitsstudie, NAKO) is a large-scaled, multidisciplinary, nationwide, multi-centre, population-based, prospective cohort study with oral examinations that aims to provide a resource to study risk factors for major diseases. The aim of the present article is to provide the methodological background, to report on the data quality, and to present initial results of the oral examinations., Methods: During baseline examinations (2014-2019), a total of 205,184 persons aged 19-74 years has been examined in 18 study centres, including, among others, a dental interview, stimulated saliva sampling, and recording of the numbers of present teeth and prostheses (standard Level 1 program). As part of the Level 2 program that was offered to 20% randomly selected participants, each study centre selected one of three modules, one of them being the Level 2 oral examination. This extended program was carried out in a subgroup of 20,828 participants, including collection of detailed information on the dental and prosthetic status as well as on periodontal, cariological and functional aspects. To ensure reliability and reproducibility, study nurses were trained and calibrated by dental experts. In addition, a reliability study was conducted among 794 Level 1 and 359 Level 2 participants, reporting intra class correlation and kappa coefficients., Results: Intra class correlation and kappa coefficients for observer agreement and reliability were consistently above 0.7, indicating good to excellent reliability of all dental measurements. For example, intra class correlation was 0.937 for the number of present teeth (Level 1), 0.740 for mean probing depth (PD) and 0.797 for active mouth opening. An initial inspection of the data showed that the median number of present teeth was 27, of which on average 6.9 teeth were healthy and caries-free. Average mean PD was 1.92 mm. An orthodontic treatment was reported by 35.5% of participants., Discussion: Overall, the dental study protocol was feasible and successfully integrated into the NAKO's overall assessment program. However, rigorous support of the study centres by dental professionals was required to ensure high quality data. In summary, high-quality data collection within the NAKO pave the way for future investigation of potential risk factors for oral diseases and links between oral and systemic diseases and conditions., Competing Interests: Declarations. Ethics approval and consent to participate: All procedures performed involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and is in accordance with national law and with the Declaration of Helsinki of 1975 (in the current, revised version). The research protocol was approved by the Ethics Committee of the Medical Faculty of the Ludwig-Maximilians-University of Munich / Bayerische Landesärztekammer; Nr. 13023) and all other local Ethics Committees of the study centres. Written informed consent was obtained from all individual participants included in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide. Although the risk of developing CRC increases with age, approximately 10% of newly diagnosed cases occur in individuals under the age of 50. Significant changes in dietary habits in young adults since industrialization create a favorable microenvironment for colorectal carcinogenesis. We aim here to shed light on the complex interplay between diet and gut microbiome in the pathogenesis and prevention of early-onset CRC (EO-CRC). We provide an overview of dietary risk factors associated with EO-CRC and contrast them with the general trends for CRC. We delve into gut bacteria, fungi, and phages with potential benefits against CRC and discuss the underlying molecular mechanisms. Furthermore, based on recent findings from human studies, we offer insights into how dietary modifications could potentially enhance gut microbiome composition to mitigate CRC risk. All together, we outline the current research landscape in this area and propose directions for future investigations that could pave the way for novel preventive and therapeutic strategies., Competing Interests: Disclosure and competing interests statement. The authors declare no competing interests., (© 2024. The Author(s).)

Background: The COVID-19 pandemic prompted a range of studies on mental health, with mixed results. While numerous studies reported worsened conditions in individuals with pre-existing mental disorders, others showed resilience and stability in mental health. However, longitudinal data focusing on the German population are sparse, especially regarding effects of age and pre-existing mental disorders during the early stages of the pandemic., Objectives: To assess the interplay between psychiatric history, age, and the timing of the pandemic, with a focus on understanding how these factors relate to the severity of depression and anxiety symptoms., Methods: Exploratory analyses were based on 135,445 individuals aged 20-72 years from the German National Cohort (NAKO). Depressive and anxiety symptoms were assessed before and after the first wave of the pandemic. Inferential statistical analyses and negative binomial regression models were calculated., Results: Persons with a self-reported psychiatric history exhibited comparable levels of depression and anxiety symptom severity after the first wave of the pandemic compared to the time before. In contrast, individuals without a psychiatric history, particularly those in their 20s to 40s, experienced an increase in mental health symptom severity during the first wave of the pandemic., Limitations: Analyses focuses on the first wave of the pandemic, leaving the long-term mental health effects unexplored., Conclusion: Future research should consider age-specific and mental-health-related factors when addressing global health crises. Additionally, it is important to explore factors influencing resilience and adaptation, aiming to develop targeted interventions and informed policies for effective mental health management during pandemics., Competing Interests: HG has received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm, Servier and Janssen Cilag as well as research funding from Fresenius Medical Care. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Stein, Pabst, Berger, Karch, Teismann, Streit, Grabe, Mikolajczyk, Massag, Lieb, Castell, Heise, Schulze, Gastell, Harth, Obi, Peters, Huemer, Bohmann, Leitzmann, Schipf, Meinke-Franze, Hebestreit, Fuhr, Michels, Jaskulski, Stocker, Koch-Gallenkamp, Willich, Keil, Löffler, Wirkner and Riedel-Heller.)

Objective: To compare health service use (HSU) between migrants and non-migrants in Germany. Methods: Using data from the population-based German National Cohort (NAKO), we compared the HSU of general practitioners, medical specialists, and psychologists/psychiatrists between six migrant groups of different origins with the utilization of non-migrants. A latent profile analysis (LPA) with a subsequent multinomial regression analysis was conducted to characterize the HSU of different groups. Additionally, separate regression models were calculated. Both analyses aimed to estimate the direct effect of migration background on HSU. Results: In the LPA, the migrant groups showed no relevant differences compared to non-migrants regarding HSU. In separate analyses, general practitioners and medical specialists were used comparably to slightly more often by first-generation migrants from Eastern Europe, Turkey, and resettlers. In contrast, the use of psychologists/psychiatrists was substantially lower among those groups. Second-generation migrants and migrants from Western countries showed no differences in their HSU compared to non-migrants. Conclusion: We observed a low mental HSU among specific migrant groups in Germany. This indicates the existence of barriers among those groups that need to be addressed., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2024 Wiessner, Licaj, Klein, Bohn, Brand, Castell, Führer, Harth, Heier, Heise, Holleczek, Jaskulski, Jochem, Koch-Gallenkamp, Krist, Leitzmann, Lieb, Meinke-Franze, Mikolajczyk, Moreno Velásquez, Obi, Pischon, Schipf, Thierry, Willich, Zeeb and Becher.)

Effective preventive strategies are urgently needed to address the rising burden of non-communicable diseases such as cardiovascular disease and cancer. To date, most prevention efforts to reduce disease incidence have primarily targeted populations using "one size fits all" public health recommendations and strategies. However, the risk for complex heterogeneous diseases is based on a multitude of clinical, genetic, and environmental factors, which translate into individual sets of component causes for every person. Recent advances in genetics and multi-omics enable the use of new technologies to stratify disease risks at an individual level fostering personalized prevention. In this article, we review the main components of personalized prevention, provide examples, and discuss both emerging opportunities and remaining challenges for its implementation. We encourage physicians, health policy makers, and public health professionals to consider and apply the key elements and examples of personalized prevention laid out in this article while overcoming challenges and potential barriers to their implementation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer HP declared a shared affiliation with the author(s) KM to the handling editor at the time of review., (Copyright © 2023 Jaskulski, Nuszbaum and Michels.)

Adipokines including leptin, adiponectin and resistin have been linked to risk of obesity-related cancers potentially through low-grade chronic inflammation pathways. We aimed to assess the role of post-diagnosis circulating adipokines on long-term prognosis in a prospective breast cancer cohort. Adipokines were measured in blood collected at baseline shortly after diagnosis (2002-2005) and at follow-up (2009) from 3112 breast cancer patients enrolled in the population-based MARIE study. Half of the patients had measurements at both time-points. All-cause mortality, breast cancer specific mortality and recurrences were ascertained up to June 2015 (11 years median follow-up). Associations with time-varying adipokine concentrations overall and stratified by estrogen and progesterone receptor (ERPR) were evaluated using adjusted proportional hazard regression. At baseline (n = 2700) and follow-up (n = 2027), median concentrations for leptin, adiponectin and resistin were 4.6 and 2.7 ng/ml, 24.4 and 30.0 mg/l, 15.4 and 26.2 ng/ml, respectively. After adjustment, there was no evidence for associations between adipokines and any outcome overall. In ERPR negative tumors, highest vs. lowest quintile of adiponectin was significantly associated with increased breast cancer specific mortality (HR 2.51, 95%CI 1.07-5.92). Overall, post-diagnosis adipokines were not associated with long-term outcomes after breast cancer. In patients with ERPR negative tumors, higher concentrations of adiponectin may be associated with increased breast cancer specific mortality and warrant further investigation., (© 2021. The Author(s).)

Lignans are associated with improved postmenopausal breast cancer (BC) survival, but whether these associations, particularly with enterolactone (major lignan metabolite), persist over time is unclear. Little is known about other phytoestrogens on prognosis in long-term survivors. The study examines associations of prognosis with 1) circulating postdiagnosis enterolactone, 2) eight circulating phytoestrogen metabolites, and 3) changes in enterolactone and genistein. In a German cohort of 2,105 postmenopausal BC patients with blood samples collected at recruitment 2002-2005 (baseline) and re-interview in 2009 (follow-up), delay-entry Cox proportional hazards regression was used. Landmark analysis showed that circulating enterolactone (log2) associations with 5-year survival changed over time, with strongest hazard ratios of 0.89 (95% CI, 0.80-0.99) at blood draw (BD) and 0.86 (0.77-0.97) at 2 years post-BD for BC mortality, and 0.87 (0.80-0.95) at BD and 0.84 (0.76-0.92) at 3 years post-BD for all-cause mortality, which attenuated thereafter. In long-term survivors, increasing concentrations of genistein (1.17, 1.01-1.36), resveratrol (1.19, 1.02-1.40), and luteolin (1.96, 1.07-3.58) measured in follow-up blood samples were associated with poorer subsequent prognosis. Neither enterolactone at follow-up nor changes in enterolactone/genistein were associated with prognosis. Large long-term longitudinal studies with multiple phytoestrogen measurements are required to understand long-term effects of phytoestrogens after BC.

Background: There is a paucity of information on the prevalence of dietary supplement use in breast cancer survivors. Only a few studies have examined the impact of dietary supplements, particularly antioxidants, on breast cancer prognosis and the results are inconclusive., Objective: We examined pre- and postdiagnosis use of supplements in postmenopausal breast cancer survivors in Germany and investigated associations between postdiagnosis use of antioxidants and other supplements, and prognosis (total and breast cancer mortality, and recurrence-free survival) both overall and in women who received chemotherapy and radiation therapy., Design: Data from 2223 postmenopausal women diagnosed with nonmetastatic breast cancer from the population-based Mamma Carcinoma Risk Factor Investigation (MARIE) study were used. Women were interviewed at recruitment in 2002-2005 and again in 2009 and followed-up until 30 June 2015. Multivariate Cox regression analysis was used to estimate HRs and corresponding 95% CIs., Results: Pre- and postdiagnosis supplement use was reported by 36% and 45% of the women, respectively. There were 240 deaths (134 from breast cancer) and 200 breast cancer recurrences after a median follow-up time of 6.0 y after the 2009 re-interview. After adjusting for relevant confounders, concurrent antioxidant use with chemotherapy or radiation therapy among 1940 women was associated with increased risk of total mortality (HR: 1.64; 95% CI: 1.01, 2.66) and worsened recurrence-free survival (HR: 1.84; 95% CI: 1.26, 2.68). Overall postdiagnosis supplement use was not associated with breast cancer prognosis., Conclusions: Antioxidant use during chemotherapy or radiation therapy was associated with worsened breast cancer prognosis in postmenopausal women. There was no overall association between postdiagnosis supplement use and breast cancer prognosis. Results from our study align with the current recommendation to possibly avoid the use of antioxidants during chemotherapy or radiation therapy.

Higher lignan exposure has been associated with lower all-cause mortality (ACM) and breast cancer-specific mortality (BCSM) for postmenopausal breast cancer patients. However, the biological mechanisms underpinning these associations are still unclear. We investigated for the first time whether and to what extent the association between enterolactone (ENL), the major lignan metabolite, and postmenopausal breast cancer prognosis is mediated by inflammatory biomarkers. Circulating concentrations of ENL and inflammatory markers were measured in a population-based prospective cohort of 1,743 breast cancer patients recruited between 2002 and 2005 and followed-up until 2009. Hazard ratios (HR) and 95% CIs were estimated using multivariable Cox regression. Mediation analysis was performed to estimate the percentage association between ENL (log2) and ACM, BCSM and distant disease-free survival (DDFS), which is mediated by C-reactive protein (CRP) (log2), as the strongest potential mediator, and also interleukin (IL)-10. Median serum/plasma ENL and CRP concentrations for all patients, including 180 deceased patients, were 23.2 and 17.5 nmol/L, and 3.2 and 6.5 mg/l, respectively. ENL concentrations were significantly inversely associated with ACM, BCSM and DDFS (per doubling of ENL concentrations: HRs 0.93 [0.87, 0.99], 0.91 [0.84, 0.99] and 0.92 [0.87, 0.99]), after adjusting for prognostic factors and BMI. Estimated 18, 14 and 12% of the effects of ENL on ACM, BCSM and DDFS, respectively, were mediated through CRP. No mediational effect of IL-10 was found. We provide first evidence that the proinflammatory marker CRP may partially mediate the association of ENL with postmenopausal breast cancer survival, which supports hormone-independent mechanisms., (© 2018 UICC.)

Scope: Phytoestrogens (PE) may improve breast cancer prognosis by modifying tumor prognostic markers, such as cell proliferation marker Ki-67 and human epidermal growth factor receptor 2 (HER2). Epidemiological evidence linking lignans and isoflavones to Ki-67 and HER2 is limited. We examined associations between the major metabolites of lignans and isoflavones - enterolactone (ENL) and genistein (GEN) - respectively, and Ki-67 expression and HER2 in tumor tissue of breast cancer patients., Methods and Results: Data from 1060 invasive breast cancer patients from the population-based MARIE study were used. Multivariate-adjusted linear (Ki-67 log-transformed) and quantile regression, and logistic regression analyses (HER2, Ki-67 dichotomized) were performed to calculate β estimates and ORs, respectively. Median post-diagnostic ENL and GEN concentrations were 19.5 and 4.8 nmol/L, respectively. Median Ki-67 was 12.0%, and 21.2% of the tumors were HER2+. After adjustment, there was an inverse association between GEN and Ki-67 at high expression levels (OR for Ki-67 ≥20% versus <20% of 0.93 (95%CI [0.87;0.99]) per 10 nmol/L GEN increment)., Conclusion: Our findings indicate an inverse association between GEN and Ki-67 at high levels of Ki-67 expression. Additional investigations are recommended to confirm our findings and to further elucidate mechanisms linking PE metabolites to breast cancer survival., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Artifacts on mammographic images detract from the overall quality of the images and often present clinical and technical troubleshooting difficulties for the interpreting radiologist, technologist, and medical physicist and for the equipment and processor service personnel. This presentation demonstrates several types of mammographic artifacts that may pose a clinical challenge. They are arranged in the following categories: (1) particularly dangerous artifacts, (2) masses, (3) calcifications, (4) density variations, and (5) miscellaneous artifacts. Examples of such findings as summation shadows, normal anatomic variations, and incorrect positioning are also demonstrated as artifacts in this guide, because they may affect image quality or patient radiation dose. Under the Mammography Quality Standards Act, the lead interpreting physician has the responsibility for ensuring that the facility meets quality assurance requirements and is required to follow up with the technologist on poor-quality images. It is vital to recognize and correct for artifacts, whether they simulate non-existent lesions or obscure real pathology, because misinterpretation can lead to undesirable consequences.