TY - JOUR A1 - Wischnewsky, Manfred A1 - Schwentner, Lukas A1 - Diessner, Joachim A1 - De Gregorio, Amelie A1 - Joukhadar, Ralf A1 - Davut, Dayan A1 - Salmen, Jessica A1 - Bekes, Inga A1 - Kiesel, Matthias A1 - Müller-Reiter, Max A1 - Blettner, Maria A1 - Wolters, Regine A1 - Janni, Wolfgang A1 - Kreienberg, Rolf A1 - Wöckel, Achim A1 - Ebner, Florian T1 - BRENDA-Score, a hghly significant, internally and externally validated prognostic marker for metastatic recurrence: analysis of 10,449 primary breast cancer patients JF - Cancers N2 - Background Current research in breast cancer focuses on individualization of local and systemic therapies with adequate escalation or de-escalation strategies. As a result, about two-thirds of breast cancer patients can be cured, but up to one-third eventually develop metastatic disease, which is considered incurable with currently available treatment options. This underscores the importance to develop a metastatic recurrence score to escalate or de-escalate treatment strategies. Patients and methods Data from 10,499 patients were available from 17 clinical cancer registries (BRENDA-project. In total, 8566 were used to develop the BRENDA-Index. This index was calculated from the regression coefficients of a Cox regression model for metastasis-free survival (MFS). Based on this index, patients were categorized into very high, high, intermediate, low, and very low risk groups forming the BRENDA-Score. Bootstrapping was used for internal validation and an independent dataset of 1883 patients for external validation. The predictive accuracy was checked by Harrell's c-index. In addition, the BRENDA-Score was analyzed as a marker for overall survival (OS) and compared to the Nottingham prognostic score (NPS). Results: Intrinsic subtypes, tumour size, grading, and nodal status were identified as statistically significant prognostic factors in the multivariate analysis. The five prognostic groups of the BRENDA-Score showed highly significant (p < 0.001) differences regarding MFS:low risk: hazard ratio (HR) = 2.4, 95%CI (1.7–3.3); intermediate risk: HR = 5.0, 95%CI.(3.6–6.9); high risk: HR = 10.3, 95%CI (7.4–14.3) and very high risk: HR = 18.1, 95%CI (13.2–24.9). The external validation showed congruent results. A multivariate Cox regression model for OS with BRENDA-Score and NPS as covariates showed that of these two scores only the BRENDA-Score is significant (BRENDA-Score p < 0.001; NPS p = 0.447). Therefore, the BRENDA-Score is also a good prognostic marker for OS. Conclusion: The BRENDA-Score is an internally and externally validated robust predictive tool for metastatic recurrence in breast cancer patients. It is based on routine parameters easily accessible in daily clinical care. In addition, the BRENDA-Score is a good prognostic marker for overall survival. Highlights: The BRENDA-Score is a highly significant predictive tool for metastatic recurrence of breast cancer patients. The BRENDA-Score is stable for at least the first five years after primary diagnosis, i.e., the sensitivities and specificities of this predicting system is rather similar to the NPI with AUCs between 0.76 and 0.81 the BRENDA-Score is a good prognostic marker for overall survival. KW - breast cancer KW - risk KW - prediction KW - BRENDA KW - score KW - follow up Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-241064 SN - 2072-6694 VL - 13 IS - 13 ER - TY - JOUR A1 - Meyer, Ursina A1 - Schindler, Christian A1 - Zahner, Lukas A1 - Ernst, Dominique A1 - Hebestreit, Helge A1 - van Mechelen, Willem A1 - Brunner-La Rocca, Hans-Peter A1 - Probst-Hensch, Nicole A1 - Puder, Jardena J. A1 - Kriemler, Susi T1 - Long-Term Effect of a School-Based Physical Activity Program (KISS) on Fitness and Adiposity in Children: A Cluster-Randomized Controlled Trial JF - PLOS ONE N2 - Background: School-based intervention studies promoting a healthy lifestyle have shown favorable immediate health effects. However, there is a striking paucity on long-term follow-ups. The aim of this study was therefore to assess the 3 yr-follow-up of a cluster-randomized controlled school-based physical activity program over nine month with beneficial immediate effects on body fat, aerobic fitness and physical activity. Methods and Findings: Initially, 28 classes from 15 elementary schools in Switzerland were grouped into an intervention (16 classes from 9 schools, n = 297 children) and a control arm (12 classes from 6 schools, n = 205 children) after stratification for grade (1st and 5th graders). Three years after the end of the multi-component physical activity program of nine months including daily physical education (i.e. two additional lessons per week on top of three regular lessons), short physical activity breaks during academic lessons, and daily physical activity homework, 289 (58%) participated in the follow-up. Primary outcome measures included body fat (sum of four skinfolds), aerobic fitness (shuttle run test), physical activity (accelerometry), and quality of life (questionnaires). After adjustment for grade, gender, baseline value and clustering within classes, children in the intervention arm compared with controls had a significantly higher average level of aerobic fitness at follow-up (0.373 z-score units [95%-CI: 0.157 to 0.59, p = 0.001] corresponding to a shift from the 50th to the 65th percentile between baseline and follow-up), while the immediate beneficial effects on the other primary outcomes were not sustained. Conclusions: Apart from aerobic fitness, beneficial effects seen after one year were not maintained when the intervention was stopped. A continuous intervention seems necessary to maintain overall beneficial health effects as reached at the end of the intervention. KW - re-aim framework KW - shuttle run test KW - follow up KW - risk factors KW - prevention program KW - metabolic syndrome KW - primary schoolchildren KW - nutrition education KW - cardiovascular risk KW - health Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117436 SN - 1932-6203 VL - 9 IS - 2 ER - TY - JOUR A1 - Otto, Wolfgang A1 - Rubenwolf, Peter C. A1 - Burger, Maximilian A1 - Fritsche, Hans-Martin A1 - Rößler, Wolfgang A1 - May, Matthias A1 - Hartmann, Arndt A1 - Hofstädter, Ferdinand A1 - Wieland, Wolf F. A1 - Denzinger, Stefan T1 - Loss of aquaporin 3 protein expression constitutes an independent prognostic factor for progression-free survival: an immunohistochemical study on stage pT1 urothelial bladder cancer JF - BMC Cancer N2 - Background: Treatment of patients with stage pT1 urothelial bladder cancer (UBC) continues to be a challenge due to its unpredictable clinical course. Reliable molecular markers that help to determine appropriate individual treatment are still lacking. Loss of aquaporin (AQP) 3 protein expression has previously been shown in muscle-invasive UBC. The aim of the present study was to investigate the prognostic value of AQP3 protein expression with regard to the prognosis of stage pT1 UBC. Method: AQP 3 protein expression was investigated by immunohistochemistry in specimens of 87 stage T1 UBC patients, who were diagnosed by transurethral resection of the bladder (TURB) and subsequent second resection at a high-volume urological centre between 2002 and 2009. Patients underwent adjuvant instillation therapy with Bacillus Calmette-Guerin (BCG). Loss of AQP3 protein expression was defined as complete absence of the protein within the whole tumour. Expression status was correlated retrospectively with clinicopathological and follow-up data (median: 31 months). Multivariate Cox regression analysis was used to assess the value of AQP3 tumour expression with regard to recurrence-free (RFS), progression-free (PFS) and cancer-specific survival (CSS). RFS, PFS and CSS were calculated by Kaplan-Meier analysis and Log rank test. Results: 59% of patients were shown to exhibit AQP3-positive tumours, whereas 41% of tumours did not express the marker. Loss of AQP3 protein expression was associated with a statistically significantly worse PFS (20% vs. 72%, p=0.020). This finding was confirmed by multivariate Cox regression analysis (HR 7.58, CI 1.29 - 44.68; p=0.025). Conclusions: Loss of AQP3 protein expression in pT1 UBC appears to play a key role in disease progression and is associated with worse PFS. Considering its potential prognostic value, assessment of AQP3 protein expression could be used to help stratify the behavior of patients with pT1 UBC. KW - urothelial bladder carcinoma KW - progression KW - transitional cell carcinoma KW - bacillus calmette guerin KW - water channels KW - follow up KW - in vitro KW - recurrence KW - growth KW - T1 KW - tumor KW - proliferation KW - stage pT1 KW - aquaporin 3 protein KW - immunohistochemistry Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135679 VL - 12 IS - 459 ER - TY - JOUR A1 - Prugger, Christof A1 - Heidrich, Jan A1 - Wellmann, Jürgen A1 - Dittrich, Ralf A1 - Brand, Stefan-Martin A1 - Telgmann, Ralph A1 - Breithardt, Günter A1 - Reinecke, Holger A1 - Scheld, Hans A1 - Kleine-Katthöfer, Peter A1 - Heuschmann, Peter U. A1 - Keil, Ulrich T1 - Trends in Cardiovascular Risk Factors Among Patients With Coronary Heart Disease : Results From the EUROASPIRE I, II, and III Surveys in the Münster Region JF - Deutsches Ärzteblatt International N2 - Background: Target values for cardiovascular risk factors in patients with coronary heart disease (CHD) are stated in guidelines for the prevention of cardiovascular disease. We studied secular trends in risk factors over a 12-year period among CHD patients in the region of Munster, Germany. Methods: The cross-sectional EUROASPIRE I, II and III surveys were performed in multiple centers across Europe. For all three, the Munster region was the participating German region. In the three periods 1995/96, 1999/2000, and 2006/07, the surveys included (respectively) 392, 402 and 457 <= 70-year-old patients with CHD in Munster who had sustained a coronary event at least 6 months earlier. Results: The prevalence of smoking remained unchanged, with 16.8% in EUROASPIRE I and II and 18.4% in EUROASPIRE III (p=0.898). On the other hand, high blood pressure and high cholesterol both became less common across the three EUROASPIRE studies (60.7% to 69.4% to 55.3%, and 94.3% to 83.4% to 48.1%, respectively; p<0.001 for both). Obesity became more common (23.0% to 30.6% to 43.1%, p<0.001), as did treatment with antihypertensive and lipid-lowering drugs (80.4% to 88.6% to 94.3%, and 35.0% to 67.4% to 87.0%, respectively; p<0.001 for both). Conclusion: The observed trends in cardiovascular risk factors under-score the vital need for better preventive strategies in patients with CHD. KW - smoking-cessation KW - follow up KW - primary-care physicians KW - myocardial infarction KW - secondary prevention KW - clinical practice KW - European countries KW - drug therapies KW - life style KW - task force Y1 - 2012 U6 - https://doi.org/10.3238/arztebl.2012.0303 VL - 109 IS - 17 ER -