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El-Helou, Sabine M. ; Biegner, Anika-Kerstin ; Bode, Sebastian ; Ehl, Stephan ; Heeg, Maximilian ; Maccari, Maria E. ; Ritterbusch, Henrike ; Speckmann, Carsten ; Rusch, Stephan ; Scheible, Raphael ; Warnatz, Klaus ; Atschekzei, Faranaz ; Beider, Renata ; Ernst, Diana ; Gerschmann, Stev ; Jablonka, Alexandra ; Mielke, Gudrun ; Schmidt, Reinhold E. ; Schürmann, Gesine ; Sogkas, Georgios ; Baumann, Ulrich ; Klemann, Christian ; Viemann, Dorothee ; Bernuth, Horst von ; Krüger, Renate ; Hanitsch, Leif Gunnar ; Scheibenbogen, Carmen ; Wittke, Kirsten ; Albert, Michael H. ; Eichinger, Anna ; Hauck, Fabian ; Klein, Christoph ; Rack-Hoch, Anita ; Sollinger, Franz ; Avila, Anne ; Borte, Michael ; Borte, Stephan ; Fasshauer, Maria ; Hauenherm, Anja ; Kellner, Nils ; Müller, Anna H. ; Ülzen, Anett ; Bader, Peter ; Bakhtiar, Shahrzad ; Lee, Jae-Yun ; Heß, Ursula ; Schubert, Ralf ; Wölke, Sandra ; Zielen, Stefan ; Ghosh, Sujal ; Laws, Hans-Jürgen ; Neubert, Jennifer ; Oommen, Prasad Thomas ; Hönig, Manfred ; Schulz, Ansgar ; Steinmann, Sandra ; Schwarz, Klaus ; Dückers, Gregor ; Lamers, Beate ; Langemeyer, Vanessa ; Niehues, Tim ; Shai, Sonu ; Graf, Dagmar ; Müglich, Carmen ; Schmalzing, Marc ; Schwaneck, Eva C. ; Tony, Hans-Peter ; Dirks, Johannes ; Haase, Gabriele ; Liese, Johannes G. ; Morbach, Henner ; Föll, Dirk ; Hellige, Antje ; Wittkowski, Helmut ; Masjosthusmann, Katja ; Mohr, Michael ; Geberzahn, Linda ; Hedrich, Christian Michael ; Müller, Christiane ; Rösen-Wolff, Angela ; Roesler, Joachim ; Zimmermann, Antje ; Behrends, Uta ; Rieber, Nikolaus ; Schauer, Uwe ; Handgretinger, Rupert ; Holzer, Ursula ; Henes, Jörg Christoph ; Kanz, Lothar ; Boesecke, Christoph ; Rockstroh, Jürgen ; Schwarze-Zander, Carolynne ; Wasmuth, Jan-Christian ; Dilloo, Dagmar ; Hülsmann, Brigitte ; Schönberger, Stefan ; Schreiber, Stefan ; Zeuner, Rainald ; Ankermann, Tobias ; Bismarck, Philipp von ; Huppertz, Hans-Iko ; Kaiser-Labusch, Petra ; Greil, Johann ; Jakoby, Donate ; Kulozik, Andreas ; Metzler, Markus ; Naumann-Bartsch, Nora ; Sobik, Bettina ; Graf, Norbert ; Heine, Sabine ; Kobbe, Robin ; Lehmberg, Kai ; Müller, Ingo ; Herrmann, Friedrich ; Horneff, Gerd ; Klein, Ariane ; Peitz, Joachim ; Schmidt, Nadine ; Bielack, Stefan S. ; Groß-Wieltsch, Ute ; Classen, Carl Friedrich ; Klasen, Jessica ; Deutz, Peter ; Kamitz, Dirk ; Lassay, Lisa ; Tenbrock, Klaus ; Wagner, Norbert ; Bernbeck, Benedikt ; Brummel, Bastian ; Lara-Villacanas, Eusebia ; Münstermann, Esther ; Schneider, Dominik T. ; Tietsch, Nadine ; Westkemper, Marco ; Weiß, Michael ; Kramm, Christof M. ; Kühnle, Ingrid ; Kullman, Silke ; Girschick, Hermann ; Specker, Christof ; Vinnemeier-Laubenthal, Elisabeth ; Haenicke, Henriette ; Schulz, Claudia ; Schweigerer, Lothar ; Müller, Thomas G. ; Stiefel, Martina ; Belohradsky, Bernd H. ; Soetedjo, Veronika ; Kindle, Gerhard ; Grimbacher, Bodo
Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs.
Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel.
Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy.
Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.
Schmidt-Horlohé, Kay ; Wilde, Philipp ; Becker, Lars ; Reimertz, Christoph ; Bonk, Andreas ; Hoffmann, Reinhard
Meeting Abstract : Deutscher Kongress für Orthopädie und Unfallchirurgie ; 73. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie ; 95. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie ; 50. Tagung des Berufsverbandes der Fachärzte für Orthopädie und Unfallchirurgie ; 21. - 24.10.2009, Berlin Fragestellung: Ziel war die Evaluierung der funktionellen und radiologischen Ergebnisse nach osteosynthestischer Versorgung von Olecranonfrakturen mit einer zur Hakenplatte modifizierten Drittelrohrplatte. Methodik: In einem Zeitraum von 12 Monaten wurden 29 Patienten mit Olecranonfrakturen prospektiv erfasst und eine Osteosynthese mit einer zur Hakenplatte modifizierten Kleinfragment-Drittelrohrplatte durchgeführt. Eine additive Verschraubung von zusätzlichen Fragmenten erfolgte bei 6 Patienten (20%). Das mittlere Patientenalter zum Unfallzeitpunkt betrug 50 Jahre (Min 29/ Max 83). Unter Verwendung der Frakturklassifikation nach Schatzker stellte sich in 8 Fällen (28%) eine Querfraktur vom Typ A, in 6 Fällen (20%) eine Querfraktur mit Impaktion vom Typ B und in 15 Fällen (52%) eine Mehrfragmentfraktur vom Typ D dar. Bei 4 Patienten (14%) lag eine offene Fraktursituation vor. Nach im Mittel 7,2 Monaten (Min 6/ Max 8) wurde das funktionelle Outcome anhand des Mayo Elbow Performence Scores (MEPS), der visuellen Analogskala (VAS) und des Disabilities of the Arm, Shoulder and Hand Scores (DASH) bewertet sowie die radiologischen Befunde erhoben. Ergebnisse und Schlussfolgerungen: Das Ziel einer primär übungsstabilen Osteosynthese konnte bei allen Patienten erreicht werden. Unter Verwendung des MEPS wurden annähernd ausschließlich sehr gute (12 Fälle/41%) und gute (16 Fälle/55%) Ergebnisse erzielt. Lediglich bei einem Patienten ergab sich ein nur befriedigendes Ergebnis. Der mittlere Punktwert für den MEPS betrug 91,4 (Min 65/Max 100). In der VAS konnte ein Mittelwert von 8,2 Punkten (Min 7/Max 10) erzielt werden (0=keine Zufriedenheit, 10=volle Zufriedenheit). Der mittlere DASH-Wert betrug 16,2 Punkte (Min 0/Max 39). Der mittlere Bewegungsumfang betrug für Extension/Flexion bei einem durchschnittlichen Streckdefizit von 8° (Min 0°/Max 25°) und einer Beugung von 135° (Min 105°/Max 155°) 125° (Min 90°/Max 155°). Die Unterarmumwendbewegungen waren mit 175° (Min 165°/Max 180°) kaum eingeschränkt. Bei keinem Patienten gab es postoperative Komplikationen. Eine zur Hakenplatte modifizierte Drittelrohrplatte stellt im Gegensatz zu präformierten, winkelstabilen Implantaten eine kostengünstige Alternative zur Osteosynthese bei Olecranonfrakturen dar. Auch bei komplexen mehrfragmentären Frakturtypen und osteoporotischer Knochenqualität konnte so im nachuntersuchten Kollektiv eine sichere Frakturretention erzielt werden. Hinsichtlich des funktionellen Ergebnisses profitieren die Patienten von einer dadurch unmittelbar postoperativ möglichen, physiotherapeutischen Nachbehandlung. Das für die Hakenplatte benötigte Osteosynthesematerial (Kleinfragment-Drittelrohrplatte) ist nahezu überall verfügbar und lässt sich in kurzer Zeit der individuellen Anatomie und Frakturmorphologie anpassen. Eine Drahtmigration, wie bei der weit verbreiteten Zuggurtungsosteosynthese häufig beobachtet, ist ausgeschlossen.
Meeting Abstract : Deutscher Kongress für Orthopädie und Unfallchirurgie ; 73. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie ; 95. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie ; 50. Tagung des Berufsverbandes der Fachärzte für Orthopädie und Unfallchirurgie ; 21. - 24.10.2009, Berlin Fragestellung: Evaluierung der intraoperativen Bildgebung mit einem motorgesteuerten 3D-Bildwandlersystem hinsichtlich des klinischen Zusatznutzens sowie der Praktikabilität bei der Versorgung intraartikulärer Frakturen im Bereich des OSG und USG. Methodik: In einer prospektiven klinischen Studie wurde bei 36 Patienten mit intraartikulärer Fraktur im Bereich von OSG und USG die intraoperative Bildgebung mit einem 3D-Bildwandler der neuesten Generation (Siemens® Arcadis Orbic 3D) im Rahmen der indizierten operativen Versorgung durchgeführt. Die Frakturen wurden unfallchirurgisch durch erfahrene Operateure mit Hilfe konventioneller 2D-Bildgebung reponiert und osteosynthetisch versorgt. Anschließend erfolgte vor Wundverschluss die Generierung des hochauflösenden multiplanaren 3D-Bilddatensatzes aus 100 Einzeldurchleuchtungen, welche im Rahmen einer einminütigen Rotation um das Untersuchungsgebiet akquiriert wurden. Die Bildanalyse hinsichtlich Reposition und Implantatlage erfolgte durch den Operateur. Sofern aufgrund der gewonnenen Informationen die Revisionsindikation bestand, erfolgte diese unmittelbar im Anschluss. Neben der Korrekturrate wurde die subjektive Wertigkeit der 3D-Bildgebung durch den Operateur ferner anhand des benötigten Zeitbedarfs, der Beurteilung des klinischen Nutzens (VAS 1–10) und der Benutzerfreundlichkeit (VAS 1–10) beurteilt. Ergebnisse und Schlussfolgerungen: Insgesamt wurde die 3D-Bildgebung bei der operativen Versorgung von 36 Frakturen eingesetzt (Pilon tibiale: n=10, bi-/trimalleoläre OSG-Luxationsfrakturen: n=8, Talus: n=4, Calcaneus: n=14). In 9 von 36 Fällen (25%) wurde auf Basis der Bildgebungsinformationen durch den Operateur die Indikation zur Revision der Reposition oder Implantatlage gestellt. Weitere osteosynthesebedingte Revisionen waren im postoperativen Verlauf nicht indiziert. Mit einer Ausnahme zeigte sich das Bildwandlersystem stets stabil und ohne technische Probleme. Die zusätzliche OP-Zeit lag im Mittel bei 9 Minuten (6,5–15 Minuten). Die erforderliche Untersuchungszeit sank tendenziell mit zunehmender Anwendung, eine entsprechend steile Lernkurve war ableitbar. Die 3D-Bilgebung wurde bei allen Eingriffen als sehr hilfreich betrachtet, der Mittelwert auf der VAS bezüglich des klinischen Zusatznutzens lag bei 8,3 (6–10), bezüglich der Benutzerfreundlichkeit bei 8,7 (7–10). Die 3D-Bildgebung stellt ein sicheres und zuverlässiges Verfahren zur intraoperativen Evaluierung der osteosynthetischen Versorgung im Bereich des OSG und USG dar und kann ein etwaig indiziertes strahlenintensiveres CT postoperativ ersetzen. Die sichere Identifikation von Fehlstellungen und Implantatfehllagen ermöglicht noch im OP die sofortige Revision. Die Anwendung ist einfach zu erlernen und verlängert die OP-Dauer lediglich in überschaubarem Umfang. Den hohen Investitionskosten steht somit bei regelmäßiger Anwendung ein bedeutsames Kosteneinsparpotenzial gegenüber.
Kebir, Sied ; Schmidt, Teresa ; Weber, Matthias ; Lazaridis, Lazaros ; Galldiks, Norbert ; Langen, Karl-Josef ; Kleinschnitz, Christoph ; Hattingen, Elke ; Herrlinger, Ulrich ; Lohmann, Philipp ; Glas, Martin
Simple Summary: Pseudoprogression detection in glioblastoma patients remains a challenging task. Although pseudoprogression has only a moderate prevalence of 10–30% following first-line treatment of glioblastoma patients, it bears critical implications for affected patients. Non-invasive techniques, such as amino acid PET imaging using the tracer O-(2-[18F]-fluoroethyl)-L-tyrosine (FET), expose features that have been shown to provide useful information to distinguish tumor progression from pseudoprogression. The usefulness of FET-PET in IDH-wildtype glioblastoma exclusively, however, has not been investigated so far. Recently, machine learning (ML) algorithms have been shown to offer great potential particularly when multiparametric data is available. In this preliminary study, a Linear Discriminant Analysis-based ML algorithm was deployed in a cohort of newly diagnosed IDH-wildtype glioblastoma patients (n = 44) and demonstrated a significantly better diagnostic performance than conventional ROC analysis. This preliminary study is the first to assess the performance of ML in FET-PET for diagnosing pseudoprogression exclusively in IDH-wildtype glioblastoma and demonstrates its potential.
Abstract: Pseudoprogression (PSP) detection in glioblastoma remains challenging and has important clinical implications. We investigated the potential of machine learning (ML) in improving the performance of PET using O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) for differentiation of tumor progression from PSP in IDH-wildtype glioblastoma. We retrospectively evaluated the PET data of patients with newly diagnosed IDH-wildtype glioblastoma following chemoradiation. Contrast-enhanced MRI suspected PSP/TP and all patients underwent subsequently an additional dynamic FET-PET scan. The modified Response Assessment in Neuro-Oncology (RANO) criteria served to diagnose PSP. We trained a Linear Discriminant Analysis (LDA)-based classifier using FET-PET derived features on a hold-out validation set. The results of the ML model were compared with a conventional FET-PET analysis using the receiver-operating-characteristic (ROC) curve. Of the 44 patients included in this preliminary study, 14 patients were diagnosed with PSP. The mean (TBRmean) and maximum tumor-to-brain ratios (TBRmax) were significantly higher in the TP group as compared to the PSP group (p = 0.014 and p = 0.033, respectively). The area under the ROC curve (AUC) for TBRmax and TBRmean was 0.68 and 0.74, respectively. Using the LDA-based algorithm, the AUC (0.93) was significantly higher than the AUC for TBRmax. This preliminary study shows that in IDH-wildtype glioblastoma, ML-based PSP detection leads to better diagnostic performance.
High-throughput metabarcoding studies on fungi and other eukaryotic microorganisms are rapidly becoming more frequent and more complex, requiring researchers to handle ever increasing amounts of raw sequence data. Here, we provide a flexible pipeline for pruning and analyzing fungal barcode (ITS rDNA) data generated as paired-end reads on Illumina MiSeq sequencers. The pipeline presented includes specific steps fine-tuned for ITS, that are mostly missing from pipelines developed for prokaryotes. It (1) employs state of the art programs and follows best practices in fungal high-throughput metabarcoding; (2) consists of modules and scripts easily modifiable by the user to ensure maximum flexibility with regard to specific needs of a project or future methodological developments; and (3) is straightforward to use, also in classroom settings. We provide detailed descriptions and revision techniques for each step, thus giving the user maximum control over data treatment and avoiding a black-box approach. Employing this pipeline will improve and speed up the tedious and error-prone process of cleaning fungal Illumina metabarcoding data.
We investigate the role of competition on the outcome of Austrian Treasury auctions. Austria's EU accession led to an increase in the number of banks participating in treasury auctions. We use structural estimates of bidders' private values to examine the effect of increased competition on auction performance: We find that increased competition reduced bidder surplus substantially, but less than reduced form estimates would suggest. A significant component of the surplus reduction is due to more aggressive bidding. Counterfactuals establish that as competition increases, concerns regarding auction format play a smaller role.
Soil fungal communities are an essential element in the terrestrial ecosystem, however their response to ongoing anthropogenic climate change is currently poorly understood. Fungi are one of the most abundant groups of microbes in soil, they are mainly responsible for the decomposition of organic matter (Baldrian et al., 2012; Buée et al., 2009). By binding carbon in soil, fungi thus maintain an important role in the global carbon cycle (Bardgett et al., 2008). Future climates are likely to influence the communities of belowground microbial organisms (Castro et al., 2010; Deacon et al., 2006). However, how these communities are affected in their diversity, composition, and function after environmental perturbation is insufficiently known.
Molecular techniques using high-throughput sequencing are presently revolutionizing the analysis of complex communities, such as soil fungi. High-throughput metabarcoding enables the recovery of DNA sequence data directly from environmental samples, and DNA sequences from entire communities present in these samples can be simultaneously recovered through massively parallel sequencing reactions (Bik et al., 2012; Taberlet et al., 2012b). This results in more accurate estimation of diversity and community composition and thus provides unprecedented insight into cryptic communities (Lindahl and Kuske, 2014). Yet, challenges associated with these novel techniques include the bioinformatic processing, and the ecological analyses of the large amount of sequence data generated. Most biologists without explicit training in bioinformatics spend a fair amount of time learning how to filter raw sequence data, and customize bioinformatics pipelines specific to their project. To improve the quality of data treatment, and decrease the time needed for the analyses, it is desirable to have bioinformatics pipelines that are easy to use, well explained to researchers not trained in bioinformatics, and adaptable to individual research needs...
Eckert, Joachim Philipp ; Schmidt, Marco ; Magedanz, Annett ; Voigtländer, Thomas ; Schmermund, Axel
Invasive coronary angiography (ICA) was the only method to image coronary arteries for a long time and is still the gold-standard. Technology of noninvasive imaging by coronary computed-tomography angiography (CCTA) has experienced remarkable progress during the last two decades. It is possible to visualize atherosclerotic lesions in the vessel wall in contrast to "lumenography" performed by ICA. Coronary artery disease can be ruled out by CCTA with excellent accuracy. The degree of stenoses is, however, often overestimated which impairs specificity. Atherosclerotic lesions can be characterized as calcified, non-calcified and partially calcified. Calcified plaques are usually quantified using the Agatston-Score. Higher scores are correlated with worse cardiovascular outcome and increased risk of cardiac events. For non-calcified or partially calcified plaques different angiographic findings like positive remodelling, a large necrotic core or spotty calcification more frequently lead to myocardial infarctions. CCTA is an important tool with increasing clinical value for ruling out coronary artery disease or relevant stenoses as well as for advanced risk stratification.
Hartke, Juliane ; Schell, Tilman ; Jongepier, Evelien ; Schmidt, Hanno ; Sprenger, Philipp P. ; Paule, Juraj ; Bornberg-Bauer, Erich ; Schmitt, Thomas ; Menzel, Florian ; Pfenninger, Markus ; Feldmeyer, Barbara
The success of social insects is largely intertwined with their highly advanced chemical communication system that facilitates recognition and discrimination of species and nest-mates, recruitment, and division of labor. Hydrocarbons, which cover the cuticle of insects, not only serve as waterproofing agents but also constitute a major component of this communication system. Two cryptic Crematogaster species, which share their nest with Camponotus ants, show striking diversity in their cuticular hydrocarbon (CHC) profile. This mutualistic system therefore offers a great opportunity to study the genetic basis of CHC divergence between sister species. As a basis for further genome-wide studies high-quality genomes are needed. Here, we present the annotated draft genome for Crematogaster levior A. By combining the three most commonly used sequencing techniques—Illumina, PacBio, and Oxford Nanopore—we constructed a high-quality de novo ant genome. We show that even low coverage of long reads can add significantly to overall genome contiguity. Annotation of desaturase and elongase genes, which play a role in CHC biosynthesis revealed one of the largest repertoires in ants and a higher number of desaturases in general than in other Hymenoptera. This may provide a mechanistic explanation for the high diversity observed in C. levior CHC profiles.
Schnitzbauer, Andreas ; Zuelke, Carl ; Graeb, Christian ; Rochon, Justine ; Bilbao, Itxarone ; Burra, Patrizia ; de Jong, Koert P. ; Duvoux, Christophe ; Kneteman, Norman M. ; Adam, Rene ; Bechstein, Wolf Otto ; Becker, Thomas ; Beckebaum, Susanne ; Chazouilleres, Olivier ; Cillo, Umberto ; Colledan, Michele ; Fandrich, Fred ; Gugenheim, Jean ; Hauss, Johann P. ; Heise, Michael ; Hidalgo, Ernest ; Jamieson, Neville ; Königsrainer, Alfred ; Lamby, Philipp E. ; Lerut, Jan P. ; Makisalo, Heikki ; Margreiter, Raimund ; Mazzaferro, Vincenzo ; Mutzbauer, Ingrid ; Otto, Gerd ; Pageaux, Georges-Philippe ; Pinna, Antonio D. ; Pirenne, Jacques ; Rizell, Magnus ; Rossi, Giorgio ; Rostaing, Lionel ; Roy, Andre ; Turrion, Victor Sanchez ; Schmidt, Jan ; Troisi, Roberto I. ; Hoek, Bart van ; Valente, Umberto ; Wolf, Philippe ; Wolters, Heiner ; Mirza, Darius F. ; Scholz, Tim ; Steininger, Rudolf ; Soderdahl, Gunnar ; Strasser, Simone I. ; Jauch, Karl-Walter ; Neuhaus, Peter ; Schlitt, Hans J. ; Geissler, Edward K.
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)