@article{ProetelPletschLausekeretal.2014, author = {Proetel, Ulrike and Pletsch, Nadine and Lauseker, Michael and M{\"u}ller, Martin C. and Hanfstein, Benjamin and Krause, Stefan W. and Kalmanti, Lida and Schreiber, Annette and Heim, Dominik and Baerlocher, Gabriela M. and Hofmann, Wolf-Karsten and Lange, Elisabeth and Einsele, Hermann and Wernli, Martin and Kremers, Stephan and Schlag, Rudolf and M{\"u}ller, Lothar and H{\"a}nel, Mathias and Link, Hartmut and Hertenstein, Bernd and Pfirrmann, Markus and Hochhaus, Andreas and Hasford, Joerg and Hehlmann, R{\"u}diger and Saußele, Susanne}, title = {Older patients with chronic myeloid leukemia (≥65 years) profit more from higher imatinib doses than younger patients: a subanalysis of the randomized CML-Study IV}, series = {Annals of Hematology}, volume = {93}, journal = {Annals of Hematology}, number = {7}, issn = {0939-5555}, doi = {10.1007/s00277-014-2041-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121574}, pages = {1167-76}, year = {2014}, abstract = {The impact of imatinib dose on response rates and survival in older patients with chronic myeloid leukemia in chronic phase has not been studied well. We analyzed data from the German CML-Study IV, a randomized five-arm treatment optimization study in newly diagnosed BCR-ABL-positive chronic myeloid leukemia in chronic phase. Patients randomized to imatinib 400 mg/day (IM400) or imatinib 800 mg/day (IM800) and stratified according to age (≥65 years vs. <65 years) were compared regarding dose, response, adverse events, rates of progression, and survival. The full 800 mg dose was given after a 6-week run-in period with imatinib 400 mg/day. The dose could then be reduced according to tolerability. A total of 828 patients were randomized to IM400 or IM800. Seven hundred eighty-four patients were evaluable (IM400, 382; IM800, 402). One hundred ten patients (29 \%) on IM400 and 83 (21 \%) on IM800 were ≥65 years. The median dose per day was lower for patients ≥65 years on IM800, with the highest median dose in the first year (466 mg/day for patients ≥65 years vs. 630 mg/day for patients <65 years). Older patients on IM800 achieved major molecular remission and deep molecular remission as fast as younger patients, in contrast to standard dose imatinib with which older patients achieved remissions much later than younger patients. Grades 3 and 4 adverse events were similar in both age groups. Five-year relative survival for older patients was comparable to that of younger patients. We suggest that the optimal dose for older patients is higher than 400 mg/day. ClinicalTrials.gov identifier: NCT00055874}, language = {en} } @article{GroteNoeldekeBlauthetal.2013, author = {Grote, Stefan and Noeldeke, Tatjana and Blauth, Michael and Mutschler, Wolf and B{\"u}rklein, Dominik}, title = {Mechanical torque measurement in the proximal femur correlates to failure load and bone mineral density ex vivo}, series = {Orthopedic Reviews (Pavia)}, volume = {5}, journal = {Orthopedic Reviews (Pavia)}, number = {e16}, doi = {10.4081/or.2013.e16}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132358}, year = {2013}, abstract = {Knowledge of local bone quality is essential for surgeons to determine operation techniques. A device for intraoperative measurement of local bone quality has been developed by the AO-Research Foundation (DensiProbe®). We used this device to experimentally measure peak breakaway torque of trabecular bone in the proximal femur and correlated this with local bone mineral density (BMD) and failure load. Bone mineral density of 160 cadaver femurs was measured by ex situ dual-energy X-ray absorptiometry. The failure load of all femurs was analyzed by side-impact analysis. Femur fractures were fixed and mechanical peak torque was measured with the DensiProbe® device. Correlation was calculated whereas correlation coefficient and significance was calculated by Fisher's Z-transformation. Moreover, linear regression analysis was carried out. The unpaired Student's t-test was used to assess the significance of differences. The Ward triangle region had the lowest BMD with 0.511 g/cm2 (±0.17 g/cm2), followed by the upper neck region with 0.546 g/cm2 (±0.16 g/cm2), trochanteric region with 0.685 g/cm2 (±0.19 g/cm2) and the femoral neck with 0.813 g/cm2 (±0.2 g/cm2). Peak torque of DensiProbe® in the femoral head was 3.48 Nm (±2.34 Nm). Load to failure was 4050.2 N (±1586.7 N). The highest correlation of peak torque measured by Densi Probe® and load to failure was found in the femoral neck (r=0.64, P<0.001). The overall correlation of mechanical peak torque with T-score was r=0.60 (P<0.001). A correlation was found between mechanical peak torque, load to failure of bone and BMD in vitro. Trabecular strength of bone and bone mineral density are different aspects of bone strength, but a correlation was found between them. Mechanical peak torque as measured may contribute additional information about bone strength, especially in the perioperative testing.}, language = {en} } @article{KurotschkaTiedemannWolfetal.2021, author = {Kurotschka, Peter Konstantin and Tiedemann, Elena and Wolf, Dominik and Thier, Nicola and Forster, Johannes and Liese, Johannes G. and Gagyor, Ildiko}, title = {Management of common infections in German primary care: a cross-sectional survey of knowledge and confidence among General Practitioners and outpatient pediatricians}, series = {Antibiotics}, volume = {10}, journal = {Antibiotics}, number = {9}, issn = {2079-6382}, doi = {10.3390/antibiotics10091131}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246272}, year = {2021}, abstract = {Outpatient antibiotic use is closely related to antimicrobial resistance and in Germany, almost 70\% of antibiotic prescriptions in human health are issued by primary care physicians (PCPs). The aim of this study was to explore PCPs, namely General Practitioners' (GPs) and outpatient pediatricians' (PDs) knowledge of guideline recommendations on rational antimicrobial treatment, the determinants of confidence in treatment decisions and the perceived need for training in this topic in a large sample of PCPs from southern Germany. Out of 3753 reachable PCPs, 1311 completed the survey (overall response rate = 34.9\%). Knowledge of guideline recommendations and perceived confidence in making treatment decisions were high in both GPs and PDs. The two highest rated influencing factors on prescribing decisions were reported to be guideline recommendations and own clinical experiences, hence patients' demands and expectations were judged as not influencing treatment decisions. The majority of physicians declared to have attended at least one specific training course on antibiotic use, yet almost all the participating PCPs declared to need more training on this topic. More studies are needed to explore how consultation-related and context-specific factors could influence antibiotic prescriptions in general and pediatric primary care in Germany beyond knowledge. Moreover, efforts should be undertaken to explore the training needs of PCPs in Germany, as this would serve the development of evidence-based educational interventions targeted to the improvement of antibiotic prescribing decisions rather than being focused solely on knowledge of guidelines.}, language = {en} } @article{SausseleHehlmannFabariusetal.2018, author = {Saussele, Susanne and Hehlmann, Ruediger and Fabarius, Alice and Jeromin, Sabine and Proetel, Ulrike and Rinaldetti, Sebastien and Kohlbrenner, Katharina and Einsele, Hermann and Falge, Christine and Kanz, Lothar and Neubauer, Andreas and Kneba, Michael and Stegelmann, Frank and Pfreundschuh, Michael and Waller, Cornelius F. and Oppliger Leibundgut, Elisabeth and Heim, Dominik and Krause, Stefan W. and Hofmann, Wolf-Karsten and Hasford, Joerg and Pfirrmann, Markus and M{\"u}ller, Martin C. and Hochhaus, Andreas and Lauseker, Michael}, title = {Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV}, series = {Leukemia}, volume = {32}, journal = {Leukemia}, number = {5}, doi = {10.1038/s41375-018-0055-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227528}, pages = {1222-1228}, year = {2018}, abstract = {Major molecular remission (MMR) is an important therapy goal in chronic myeloid leukemia (CML). So far, MMR is not a failure criterion according to ELN management recommendation leading to uncertainties when to change therapy in CML patients not reaching MMR after 12 months. At monthly landmarks, for different molecular remission status Hazard ratios (HR) were estimated for patients registered to CML study IV who were divided in a learning and a validation sample. The minimum HR for MMR was found at 2.5 years with 0.28 (compared to patients without remission). In the validation sample, a significant advantage for progression-free survival (PFS) for patients in MMR could be detected (p-value 0.007). The optimal time to predict PFS in patients with MMR could be validated in an independent sample at 2.5 years. With our model we provide a suggestion when to define lack of MMR as therapy failure and thus treatment change should be considered. The optimal response time for 1\% BCR-ABL at about 12-15 months was confirmed and for deep molecular remission no specific time point was detected. Nevertheless, it was demonstrated that the earlier the MMR is achieved the higher is the chance to attain deep molecular response later.}, language = {en} } @article{GroebnerWorstWeischenfeldtetal.2018, author = {Gr{\"o}bner, Susanne N. and Worst, Barbara C. and Weischenfeldt, Joachim and Buchhalter, Ivo and Kleinheinz, Kortine and Rudneva, Vasilisa A. and Johann, Pascal D. and Balasubramanian, Gnana Prakash and Segura-Wang, Maia and Brabetz, Sebastian and Bender, Sebastian and Hutter, Barbara and Sturm, Dominik and Pfaff, Elke and H{\"u}bschmann, Daniel and Zipprich, Gideon and Heinold, Michael and Eils, J{\"u}rgen and Lawerenz, Christian and Erkek, Serap and Lambo, Sander and Waszak, Sebastian and Blattmann, Claudia and Borkhardt, Arndt and Kuhlen, Michaela and Eggert, Angelika and Fulda, Simone and Gessler, Manfred and Wegert, Jenny and Kappler, Roland and Baumhoer, Daniel and Stefan, Burdach and Kirschner-Schwabe, Renate and Kontny, Udo and Kulozik, Andreas E. and Lohmann, Dietmar and Hettmer, Simone and Eckert, Cornelia and Bielack, Stefan and Nathrath, Michaela and Niemeyer, Charlotte and Richter, G{\"u}nther H. and Schulte, Johannes and Siebert, Reiner and Westermann, Frank and Molenaar, Jan J. and Vassal, Gilles and Witt, Hendrik and Burkhardt, Birgit and Kratz, Christian P. and Witt, Olaf and van Tilburg, Cornelis M. and Kramm, Christof M. and Fleischhack, Gudrun and Dirksen, Uta and Rutkowski, Stefan and Fr{\"u}hwald, Michael and Hoff, Katja von and Wolf, Stephan and Klingebeil, Thomas and Koscielniak, Ewa and Landgraf, Pablo and Koster, Jan and Resnick, Adam C. and Zhang, Jinghui and Liu, Yanling and Zhou, Xin and Waanders, Angela J. and Zwijnenburg, Danny A. and Raman, Pichai and Brors, Benedikt and Weber, Ursula D. and Northcott, Paul A. and Pajtler, Kristian W. and Kool, Marcel and Piro, Rosario M. and Korbel, Jan O. and Schlesner, Matthias and Eils, Roland and Jones, David T. W. and Lichter, Peter and Chavez, Lukas and Zapatka, Marc and Pfister, Stefan M.}, title = {The landscape of genomic alterations across childhood cancers}, series = {Nature}, volume = {555}, journal = {Nature}, organization = {ICGC PedBrain-Seq Project, ICGC MMML-Seq Project,}, doi = {10.1038/nature25480}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229579}, pages = {321-327}, year = {2018}, abstract = {Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7-8\% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50\% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.}, language = {en} }