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Background Adjuvant therapy decisions in early breast cancer are based on accurate risk assessment. Urokinase plasminogen activator (uPA) and plaminogen activator inhibitor-1 (PAI-1) have been the first biomarkers in hormone receptor (HR) positive breast cancer to reach highest level of evidence. The EndoPredict test (EPclin) combines gene expression information with nodal status and tumor size. The aim of this prospective study was to compare uPA/PAI-1 and EPclin as prognostic biomarkers with regard to feasibility, risk stratification and impact on adjuvant therapy recommendation. Materials and method 395 patients with HR positive, HER2 negative, intermediate risk breast cancer were enrolled. Relations and concordance of histologic grading as well as EPclin and uPA/PAI-1 values were assessed by Spearman’s rank correlation coefficient and Cohen’s Kappa. To compare decision impact of EPclin and uPA/PAI-1 three independent case discussions were held: One with known uPA/PAI-1 and EPclin results, one blinded to EPclin alone and another one blinded to both EPclin and uPA/PAI-1. Results EPclin could be determined in all 395 (100%), uPA/PAI-1 in 190 (48%) of the tumor samples. EPclin allocated 250 patients (63%) to the low-risk group and 145 patients (37%) to the high-risk group, whereas uPA/PAI-1 allocated 88 patients (46%) to the low-risk group and 102 patients (54%) to the high-risk group. In 59% of cases, both tests showed concordant results. EPclin resulted more frequently in a change of therapy recommendation than the uPA/PAI-1 test (46% vs 24%). Recommendation of adjuvant chemotherapy (CTX) was abandoned twice as often by EPclin (45%) compared to uPA/PAI-1 (22%). Conclusion In this first prospective comparison of EPclin and uPA/PAI-1 we found, that EPclin is superior to uPA/PAI-1 with respect to feasibility and decision impact. This leads to substantial avoidance of adjuvant CTX in endocrine-sensitive, HER2-negative breast cancer. Data collection for patients´ clinical outcome is ongoing.

Appendix 1. Topics, number of associated items and relevant literature. (DOCX 87Â kb)

Appendix 2. Questionnaire for the evaluation of the participantsâ self-confidence related to palliative care medicine. (DOCX 88Â kb)

Two nonparametric methods for the identification of subgroups with outstanding outcome values are described and compared to each other in a simulation study and an application to clinical data. The Patient Rule Induction Method (PRIM) searches for box-shaped areas in the given data which exceed a minimal size and average outcome. This is achieved via a combination of iterative peeling and pasting steps, where small fractions of the data are removed or added to the current box. As an alternative, Classification and Regression Trees (CART) prediction models perform sequential binary splits of the data to produce subsets which can be interpreted as subgroups of heterogeneous outcome. PRIM and CART were compared in a simulation study to investigate their strengths and weaknesses under various data settings, taking different performance measures into account. PRIM was shown to be superior in rather complex settings such as those with few observations, a smaller signal-to-noise ratio, and more than one subgroup. CART showed the best performance in simpler situations. A practical application of the two methods was illustrated using a clinical data set. For this application, both methods produced similar results but the higher amount of user involvement of PRIM became apparent. PRIM can be flexibly tuned by the user, whereas CART, although simpler to implement, is rather static.

Appendix 3. Knowledge test. (DOCX 20Â kb)

Context: Oral activated charcoal (AC) for toxin absorption should be applied as soon as possible. Extra-hospital AC-application on site by medical laypersons with pre-emptive obtained AC may save time, but may be inferior to AC-application by medical professionals. Objective: 1) Availability and incidence of pre-emptive stockpiling of AC on site in the German region Bavaria 2) time saved by AC-stockpiling and application on site, 3) quality of AC-application defined by completeness of the applied AC-dose, time needed, incidence of side-effects in lay-care and in professional-care, considering confounding variables: AC-formulation/powder/tablets, recommended AC-dose, patientâs age. Method: telephone-interviews in cases with AC-recommendation by a Poison Information Centre (PIC). Lay-care was suggested according to risk-assessment by PIC. Ingestion sites were classified as either apt for AC-stockpiling or not apt. Results: 1) availability: In Bavaria only 20%â22% of eligible cases had AC on-hand, 2) time-saving was at least 14Â min. 3) Lay-care/professional-care or patientâs age had no significant influence on the completeness of the applied AC-dose, which was higher with AC as powder but negatively correlated with the recommended AC-dose. No significant difference was seen with time needed for application and incidence of side-effects. Conclusion: pre-emptive AC-stocking should be encouraged. Keywords: Activated Charcoal, Poisons Information Centre, Layperson, Extra-hospital, Pre-hospital, pre-emptive stockpiling

Background Non-steroidal anti-inflammatory drugs (NSAIDs) have long been suspected of negatively affecting fracture healing, although numerous disputes still exist and little data are available regarding diclofenac. Glucocorticoids interfere in this process over a similar and even broader mechanism of action. As many previously conducted studies evaluated either morphological changes or biomechanical properties of treated bones, the conjunction of both structural measures is completely missing. Therefore, it was our aim to evaluate the effects of diclofenac and prednisolone on the fracture callus biomechanically, morphologically and by 3-dimensional (3D) microstructural analysis. Methods Femura of diclofenac-, prednisolone- or placebo-treated rats were pinned and a closed transverse fracture was generated. After 21 days, biomechanics, micro-CT (μCT) and histology were examined. Results The diclofenac group showed significantly impaired fracture healing compared with the control group by biomechanics and μCT (e.g. stiffness: 57.31 ± 31.11 N/mm vs. 122.44 ± 81.16 N/mm, p = 0.030; callus volume: 47.05 ± 15.67 mm3 vs. 67.19 ± 14.90 mm3, p = 0.037, trabecular thickness: 0.0937 mm ± 0.003 vs. 0.0983 mm ± 0.003, p = 0.023), as confirmed by histology. Biomechanics of the prednisolone group showed obviously lower absolute values than the control group. These alterations were confirmed in conjunction with μCT and histology. Conclusions The inhibiting effects of both substances were not only mediated by absolute parameters (e.g. breaking load, BV), but we have shown, for the first time, that additional changes occurred in the microstructural bony network. Especially in patients at risk for delayed bone healing (arteriosclerosis, diabetes mellitus, smoking), the administration of these drugs should be weighed carefully. Electronic supplementary material The online version of this article (doi:10.1186/s12891-016-1241-2) contains supplementary material, which is available to authorized users.

Additional file 1: Table S1. Magnitude of background activity measured in unstimulated control wells.

Additional file 3: Table S3. Intra-assay variability of antigen-specific IFNγ, IL2, and IFNγ + IL2 responses ranging between 11-50 SFC/well.

Introduction: Large 3° and deep 2° thermal injuries are life threatening and wound surfaces need quick coverage. Initially, it was assumed that EPO was only a hormone affecting erythropoiesis, it has now been demonstrated in pre-clinical studies, that EPO plays a key role in its reaction to[for full text, please go to the a.m. URL], 46. Jahrestagung der Deutschen Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen (DGPRÄC), 20. Jahrestagung der Vereinigung der Deutschen Ästhetisch-Plastischen Chirurgen (VDÄPC)