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- A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma (2010)
- Background: The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC. Methods: The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 3-year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating. Discussion: If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC. (trial registered at www.clinicaltrials.gov: NCT00355862) (EudraCT Number: 2005-005362-36)
- Extended pancreas donor program – the EXPAND study rationale and study protocol (2013)
- Background: Simultaneous pancreas kidney transplantation (SPK), pancreas transplantation alone (PTA) or pancreas transplantation after kidney (PAK) are the only curative treatment options for patients with type 1 (juvenile) diabetes mellitus with or without impaired renal function. Unfortunately, transplant waiting lists for this indication are increasing because the current organ acceptability criteria are restrictive; morbidity and mortality significantly increase with time on the waitlist. Currently, only pancreas organs from donors younger than 50 years of age and with a body mass index (BMI) less than 30 are allocated for transplantation in the Eurotransplant (ET) area. To address this issue we designed a study to increase the available donor pool for these patients. Methods/Design: This study is a prospective, multicenter (20 German centers), single blinded, non-randomized, two armed trial comparing outcome after SPK, PTA or PAK between organs with the currently allowed donor criteria versus selected organs from donors with extended criteria. Extended donor criteria are defined as organs procured from donors with a BMI of 30 to 34 or a donor age between 50 and 60 years. Immunosuppression is generally standardized using induction therapy with Myfortic, tacrolimus and low dose steroids. In principle, all patients on the waitlist for primary SPK, PTA or PAK are eligible for the clinical trial when they consent to possibly receiving an extended donor criteria organ. Patients receiving an organ meeting the current standard criteria for pancreas allocation (control arm) are compared to those receiving extended criteria organ (study arm); patients are blinded for a follow-up period of one year. The combined primary endpoint is survival of the pancreas allograft and pancreas allograft function after three months, as an early relevant outcome parameter for pancreas transplantation. Discussion: The EXPAND Study has been initiated to investigate the hypothesis that locally allocated extended criteria organs can be transplanted with similar results compared to the currently allowed standard ET organ allocation. If our study shows a favorable comparison to standard organ allocation criteria, the morbidity and mortality for patients waiting for transplantation could be reduced in the future. Trial registered at: NCT01384006
- Successful transplantation of a hart’s tongue fern population (Asplenium scolopendrium L.) with ten years of monitoring (2010)
- At the edge of the Harz Mountains in Lower Saxony a population of the hart’s tongue fern (Asplenium scolopendrium) threatened by destruction by a gypsum quarry were transplanted into a dolina which was not populated by the species at that time, and the new population was followed over ten years. 90% of the 59 transplanted plants survived this period and grew larger during the first six years after transplantation. Progenies appeared in the third year after transplantation. Nowadays, in the tenth year after transplantation, there are 1110 progenies, 171 of which are reproducing. Overall, the population increased by 1781% in the ten years. Plants that were planted on a rocky slope or a boulder heap in the new habitat, where soil was available, grew better than plants in rock faces without soil. In contrast, in the rock faces, where substrate was not covered with autumn foliage, more juveniles established. The distance between juveniles and mother plants rarely exceeded three meters, which indicates a limited dispersal potential of the hart’s tongue fern and may explain together with low diaspore pressure as a result of local rarity of the species that the dolina had not been colonized spontaneously. We conclude that transplantations of adult plants or introduction of spores are a suitable measure for preserving hart’s tongue fern populations that are endangered by destruction. In the long run, however, such measures cannot compensate for ongoing destruction of natural habitats by mining activities in the gypsum karst region at the southern edge of the Harz Mountains.
- Dry grasslands: species interactions and distribution – Editorial to the Special Feature with contributions from the 6th European Dry Grassland Meeting 2009 in Halle (Saale) (2010)
- In our contribution, we report on the 6th European Dry Grassland Meeting held from 31 August to 1 September 2009 in Halle (Saale), Germany. The meeting was attended by 40 participants, who gave 15 oral and 17 poster presentations. The rapid positive development of the European Dry Grassland Group (EDGG), the organiser of this conference, is mentioned: the inclusion of the EDGG in the International Association for Vegetation Science (IAVS) as a working group, the establishment of two new subgroups focussing on Mediterranean and South-East European dry grasslands, respectively, and the organisation of the first EDGG research expedition in 2010 belong to the most important events. In the last part of our contribution, we give a short introduction to the six articles of this Special Feature. Two of them deal with phytosociological classification of semi-natural grassland communities, one with vegetation- environment relationships. Two papers are concerned with conservational topics, one focussing on the population structure of endangered Pulsatilla patens, the other dealing with conservation of xeric grasslands in Transylvania. The last paper examines temporal changes in calcareous grasslands with regard to species diversity.