@article{SabelFleischhackTippeltetal.2016,
  author    = {Sabel, Magnus and Fleischhack, Gudrun and Tippelt, Stephan and Gustafsson, G{\"o}ran and Doz, Fran{\c{c}}ois and Kortmann, Rolf and Massimino, Maura and Navajas, Aurora and von Hoff, Katja and Rutkowski, Stefan and Warmuth-Metz, Monika and Clifford, Steven C. and Pietsch, Torsten and Pizer, Barry and Linnering, Birgitta},
  title     = {Relapse patterns and outcome after relapse in standard risk medulloblastoma: a report from the HIT-SIOP-PNET4 study},
  series = {Journal of Neurooncology},
  volume    = {129},
  journal   = {Journal of Neurooncology},
  number    = {3},
  organization    = {SIOP-E Brain Tumour Group},
  doi       = {10.1007/s11060-016-2202-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187498},
  pages     = {515-524},
  year      = {2016},
  abstract  = {The HIT-SIOP-PNET4 randomised trial for standard risk medulloblastoma (MB) (2001-2006) included 338 patients and compared hyperfractionated and conventional radiotherapy. We here report the long-term outcome after a median follow up of 7.8 years, including detailed information on relapse and the treatment of relapse. Data were extracted from the HIT Group Relapsed MB database and by way of a specific case report form. The event-free and overall (OS) survival at 10 years were 76 +/- 2 \% and 78 +/- 2 \% respectively with no significant difference between the treatment arms. Seventy-two relapses and three second malignant neoplasms were reported. Thirteen relapses (18 \%) were isolated local relapses in the posterior fossa (PF) and 59 (82 \%) were craniospinal, metastatic relapses (isolated or multiple) with or without concurrent PF disease. Isolated PF relapse vs all other relapses occurred at mean/median of 38/35 and 28/26 months respectively (p = 0.24). Late relapse, i.e. > 5 years from diagnosis, occurred in six patients (8 \%). Relapse treatment consisted of combinations of surgery (25 \%), focal radiotherapy (RT 22 \%), high dose chemotherapy with stem cell rescue (HDSCR 21 \%) and conventional chemotherapy (90 \%). OS at 5 years after relapse was 6.0 +/- 4 \%. In multivariate analysis; isolated relapse in PF, and surgery were significantly associated with prolonged survival whereas RT and HDSCR were not. Survival after relapse was not related to biological factors and was very poor despite several patients receiving intensive treatments. Exploration of new drugs is warranted, preferably based on tumour biology from biopsy of the relapsed tumour.},
  language  = {en}
}
@article{RosenstockPerkovicAlexanderetal.2018,
  author    = {Rosenstock, Julio and Perkovic, Vlado and Alexander, John H. and Cooper, Mark E. and Marx, Nikolaus and Pencina, Michael J. and Toto, Robert D. and Wanner, Christoph and Zinman, Bernard and Baanstra, David and Pfarr, Egon and Mattheus, Michaela and Broedl, Uli C. and Woerle, Hans-J{\"u}rgen and George, Jyothis T. and von Eynatten, Maximilian and McGuire, Darren K.},
  title     = {Rationale, design, and baseline characteristics of the CArdiovascular safety and Renal Microvascular outcomE study with LINAgliptin - (CARMELINA®): a randomized, double-blind, placebo-controlled clinical trial in patients with type 2 diabetes and high cardio-renal risk},
  series = {Cardiovascular Diabetology},
  volume    = {17},
  journal   = {Cardiovascular Diabetology},
  doi       = {10.1186/s12933-018-0682-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226996},
  pages     = {39, 1-15},
  year      = {2018},
  abstract  = {Background: Cardiovascular (CV) outcome trials in type 2 diabetes (T2D) have underrepresented patients with chronic kidney disease (CKD), leading to uncertainty regarding their kidney efficacy and safety. The CARMELINA (R) trial aims to evaluate the effects of linagliptin, a DPP-4 inhibitor, on both CV and kidney outcomes in a study population enriched for cardio-renal risk. Methods: CARMELINA (R) is a randomized, double-blind, placebo-controlled clinical trial conducted in 27 countries in T2D patients at high risk of CV and/or kidney events. Participants with evidence of CKD with or without CV disease and HbA1c 6.5-10.0\% (48-86 mmol/mol) were randomized 1:1 to receive linagliptin once daily or matching placebo, added to standard of care adjusted according to local guidelines. The primary outcome is time to first occurrence of CV death, non-fatal myocardial infarction, or non-fatal stroke. The key secondary outcome is a composite of time to first sustained occurrence of end-stage kidney disease, >= 40\% decrease in estimated glomerular filtration rate (eGFR) from baseline, or renal death. CV and kidney events are prospectively adjudicated by independent, blinded clinical event committees. CARMELINA (R) was designed to continue until at least 611 participants had confirmed primary outcome events. Assuming a hazard ratio of 1.0, this provides 90\% power to demonstrate non-inferiority of linagliptin versus placebo within the pre-specified non-inferiority margin of 1.3 at a one-sided a-level of 2.5\%. If non-inferiority of linagliptin for the primary outcome is demonstrated, then its superiority for both the primary outcome and the key secondary outcome will be investigated with a sequentially rejective multiple test procedure. Results: Between July 2013 and August 2016, 6980 patients were randomized and took >= 1 dose of study drug (40.6, 33.1, 16.9, and 9.4\% from Europe, South America, North America, and Asia, respectively). At baseline, mean +/- SD age was 65.8 +/- 9.1 years, HbA1c 7.9 +/- 1.0\%, BMI 31.3 +/- 5.3 kg/m(2), and eGFR 55 +/- 25 mL/min/1.73 m(2). A total of 5148 patients (73.8\%) had prevalent kidney disease (defined as eGFR < 60 mL/min/1.73 m(2) or macroalbuminuria [albumin-to-creatinine ratio > 300 mg/g]) and 3990 patients (57.2\%) had established CV disease with increased albuminuria; these characteristics were not mutually exclusive. Microalbuminuria (n = 2896 [41.5\%]) and macroalbuminuria (n = 2691 [38.6\%]) were common. Conclusions: CARMELINA (R) will add important information regarding the CV and kidney disease clinical profile of linagliptin by including an understudied, vulnerable cohort of patients with T2D at highest cardio-renal risk.},
  language  = {en}
}