BIH Charité Clinician Scientist Symposium in Honor and Memory of Duška Dragun
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28 May 2021 - 29 May 2021
BIH Charité Clinician Scientist Symposium in Honor and Memory of Duška Dragun

The symposium is composed of several components: First and foremost, it will commemorate Prof. Duška Dragun, the former Director of the BIH Biomedical Innovation Academy (BIA) and Director of the BIH Charité Clinician Scientist Program, who passed away in December 2020, and will be joined by stakeholders from academia and science policy. In addition, there will be scientific sessions, which will form tandems of program fellows and invited speaker. During a digital certificate ceremony on the evening of 28 May 2021, some 50 alumni will be bid farewell. The event language is English.

When
28 and 29 May 2021
10:00 - 6:30 pm

How
Online Event (semi-digital)

Registration
To receive the login link please register here.
Advanced Clinician Scientists
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Priv.-Doz. Dr. Nathanael Raschzok and Priv.-Doz. Dr. Felix Krenzien successfully applied for the BIH Charité Advanced Clinician Scientist Pilot Programme (AdCSP) in a highly competitive process.

The BIH Charité AdCSP is designed as a career-phase-specific, sustainable funding programme that aims to closely interlink individual and institutional funding. The primary goal of the programme is to simultaneously incentivise the fellows and recognise the permissive academic culture of the respective clinics or institutes. Like the BIH Charité Clinician Scientist Programme (CSP) and the "Digital Clinician Scientist Programme" (DCSP), which has been additionally funded by the DFG since 2019, it is intended to be open to all clinical disciplines and to offer multiple networking opportunities for the funded fellows and participating clinics and institutes.

Congratulations!
Grant provided by the Berliner Krebsgesellschaft e.V.
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Dr. med. M. Felsenstein receives a grant provided by the Berliner Krebsgesellschaft e.V. for his project "Deciphering the molecular determinants of pancreatic duct dysplasia by analysis of single-cell transcriptomics (RNAseq) in precursor lesions".

Besides great advances in the molecular and genetic understanding of pancreatic duct adenocarcinoma (PDAC), this tumor entity remains particularly aggressive with dismal prognosis. Recent single-cell sequencing studies underline the eminent urgency to understand tumor heterogeneity in the setting of PDAC. More detailed knowledge about the molecular mechanisms of pancreatic cancer evolution, carcinogenesis and heterogeneity could direct ideas for earlier detection and more effective targeted therapies, also preventing disease recurrence. Future therapeutic approaches in precision medicine will likely focus on the disease relevant sub-populations, specifically driving cancer progression, dissemination and exerting tumor escape mechanisms. In-depth transcriptomic data of single carcinoma environmental cells and respective cell clusters may help to discover novel biomarkers, which can be clinically instrumented for earlier detection and putatively increase the fraction of patients, amenable to curatively intended therapies. This study aims to analyze sorted single cells of macro-dissected precursor and cancerous lesions of the pancreas by single nuclei RNA sequencing (snRNAseq). In this feasibility study, we will include 10 patients, who will undergo resection of the pancreas due to “worrisome” or malignant lesions. We will perform in-depth transcriptomic analysis of pancreatic dysplasia in order to broaden our understanding of the molecular mechanisms of pancreatic carcinogenesis.

Congratulations!
Recellularization of decellularized bovine carotid arteries
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"In vitro recellularization of decellularized bovine carotid arteries using human endothelial colony forming cells" was published in the latest issue of Journal of Biological Engineering.
Many patients suffering from peripheral arterial disease (PAD) are dependent on bypass surgery. However, in some patients no suitable replacements (i.e. autologous or prosthetic bypass grafts) are available. Advances have been made to develop autologous tissue engineered vascular grafts (TEVG) using endothelial colony forming cells (ECFC) obtained by peripheral blood draw in large animal trials. Clinical translation of this technique, however, still requires additional data for usability of isolated ECFC from high cardiovascular risk patients.
Bovine carotid arteries (BCA) were decellularized using a combined SDS (sodium dodecyl sulfate) -free mechanical-osmotic-enzymatic-detergent approach to show the feasibility of xenogenous vessel decellularization. Decellularized BCA chips were seeded with human ECFC, isolated from a high cardiovascular risk patient group, suffering from diabetes, hypertension and/or chronic renal failure. ECFC were cultured alone or in coculture with rat or human mesenchymal stromal cells (rMSC/hMSC). Decellularized BCA chips were evaluated for biochemical, histological and mechanical properties. Successful isolation of ECFC and recellularization capabilities were analyzed by histology.

Decellularized BCA showed retained extracellular matrix (ECM) composition and mechanical properties upon cell removal. Isolation of ECFC from the intended target group was successfully performed (80% isolation efficiency). Isolated cells showed a typical ECFC-phenotype. Upon recellularization, co-seeding of patient-isolated ECFC with rMSC/hMSC and further incubation was successful for 14 (n = 9) and 23 (n = 5) days. Reendothelialization (rMSC) and partial reendothelialization (hMSC) was achieved. Seeded cells were CD31 and vWF positive, however, human cells were detectable for up to 14 days in xenogenic cell-culture only. Seeding of ECFC without rMSC was not successful.

Using our refined decellularization process we generated easily obtainable TEVG with retained ECM- and mechanical quality, serving as a platform to develop small-diameter (< 6 mm) TEVG. ECFC isolation from the cardiovascular risk target group is possible and sufficient. Survival of diabetic ECFC appears to be highly dependent on perivascular support by rMSC/hMSC under static conditions. ECFC survival was limited to 14 days post seeding.
Authors are N. Seiffert, P. Tang, E. Keshi, A. Reutzel-Selke, S. Moosburner, H. Everwien, D. Wulsten, H. Napierala, J. Pratschke, I.M. Sauer, K. Hillebrandt, and B. Struecker.
J Biol Eng 15, 15 (2021). https://doi.org/10.1186/s13036-021-00266-5
Position for Research Associate / Research Fellow
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Priv.-Doz. Dr. Nathanael Raschzok and his team are working on strategies for (re-) conditioning of marginal liver grafts by ex vivo liver machine perfusion. The aim for the proposed job offer, which is funded by grants of the Else Kröner-Fresenius-Stiftung, is to make steatotic liver grafts, which are usually discarded from transplantation due to the high risk for the recipient, acceptable for transplantation. We have already established a small animal model of ex vivo liver machine perfusion as well as transplantation. Aim of this project is to test a clinically approved drug in dose-response studies (based on preliminary data), followed by in vivo studies in the rat liver transplantation model.

Your responsibility will be:
  • Organ perfusion of murine livers in our established small animal modell for ex vivo liver machine perfusion
  • Support of in rat liver transplantation experiments
  • Organ recovery and transplantation (not mandatory)
  • Biochemical analysis of the perfusat and the lipid metabolism (ELISA), tissue analysis (qRT-PCR, Wester Blot, immunochemistry, immunofluorescence)
  • We fully support the application and submission of a doctoral thesis (e.g. Dr. rer.medic or MD/PhD)
Require­ments
  • Degree in biology, biochemistry, biotechnology or medicine
  • Pevious experience in molecular cell biology and/or proteinbiochemistry, or surgical research
  • Proficiency in standard methods, especially histology, immunhistochemistry, qPCR, FACS, microscopy, cell culture/cell isolation
  • Excellent english language skills
Personal characteristics
  • innovative spirit and extraordinary motivation, interest in purposeful work
  • team work orientated
  • organized, ability for analytic and independent work ethic

If you're the right person: please send all application documents, e.g. cover letter, curriculum vitae, certificates, attestations, etc. to the following address, quoting the reference number by e-mail to
Charité – Universitätsmedizin Berlin
Chirurgische Klinik, Exp. Chirurgie
z.Hd. PD Dr. Nathanael Raschzok
Augustenburger Platz 1
D-13353 Berlin
nathanael.raschzok@charite.de
Notch Signaling Pathway in Pancreatobiliary Tumors
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The Notch signaling pathway plays an important role both in the development of the ductal systems of the pancreas and the bile ducts as well as in cancer development and progression. The aim of this study was to examine the expression of central proteins of the Notch signaling pathway in pancreatobiliary tumors and its influence on patient survival.

Materials and Methods: We compared the receptors (Notch1, Notch4), activating splicing factors (ADAM17), and target genes (HES1) of the Notch pathway and progenitor cell markers with relevance for the Notch signaling pathway (CD44, MSI1) between pancreatic adenocarcinomas (PDAC, n = 14), intrahepatic cholangiocarcinoma (iCC, n = 24), and extrahepatic cholangiocarcinoma (eCC, n = 22) cholangiocarcinomas.

A significant overexpression of almost all studied components of the Notch signaling pathway can be found in the tumor tissue, however, without a significant influence on patient survival. Therefore, further studies are warranted to draw conclusions on Notch pathway's relevance for patient survival.

The paper "Notch Signaling Pathway in Pancreatobiliary Tumors" is available via Medicina, 2021;57(2):105. Authors are Francesca Borlak, Anja Reutzel-Selke, Anja Schirmeier, Julia Gogolok, Ellen von Hoerschelmann, Igor M Sauer, Johann Pratschke, Marcus Bahra, and Rosa B Schmuck.
Extended liver resection in mice: state of the art and pitfalls
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"Extended liver resection in mice: state of the art and pitfalls – a systematic review" is available in ur J Med Res. 2021; 26(1):6.
Rodent models of liver resection have been used to investigate and evaluate the liver's complex physiology and pathology since 1931. First documented by Higgins and Anderson, such models were created to understand liver regeneration mechanisms to improve outcomes in patients undergoing extensive liver resection for liver cancer or other underlying liver diseases. A systematic search was conducted using Pubmed, gathering publications up to January 2019, which engaged with the mouse model of extended liver resection as a method itself. The results of this search were filtered according to their language, novelty, and relevancy.
Through the overview, laid out in the selected publications, this paper reviews the shift of the extended liver resection model from rat to the mouse, describes the state of the art in the experimental setting, and discusses the possible limitations and pitfalls. Clearly, the extended liver resection in mice is a reproducible, practical and easy to learn method.
Authors are Can Kamali, Kaan Kamali, Philipp Brunnbauer, Katrin Splith, Johann Pratschke, Moritz Schmelzle, and Felix Krenzien.
Duška Dragun
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We have received the sad news that Professor Duška Dragun, Director of the Biomedical Innovation Academy (BIA) of the Berlin Institute of Health (BIH) and Head of the Charité BIH Clinician Scientist Program, succumbed to her long, severe, bravely endured illness on December 28, 2020 at the age of 51.
 
Her tireless efforts were devoted to her life's work: the Charité BIH Clinician Scientist Program. Ten years ago, she launched the first Clinician Scientist Program in Berlin and over the decade established and continuously expanded it as "best practice" for the German-speaking region. She has played a key role in developing and shaping the various programs for scientifically active physicians: from the Clinician Scientist Program, which enables aspiring specialists to spend up to 50 percent of their working time on research, to the Junior Clinician Scientist Program with 20 percent working time on research, which begins in the first year of specialist training, to the Advanced Clinician Scientist Program for specialists with postdoctoral qualifications. Two years ago, she successfully applied to the German Research Foundation (DFG) for the first and only Digital Clinician Scientist Program in Germany. This enables young physicians and scientists to conduct research and work in the field of digitalization in medicine and healthcare. Thus, within a few years, Duška Dragun made a significant contribution to building a new generation of young professionals for medicine – the impact of her programs will last for a long time, via promising individual careers as well as via the programmatic strengthening of a patient-oriented science.  
 
As a physician herself, Professor Duška Dragun has always been committed to research: As acting senior physician and deputy to the acting director of the Department of Nephrology and Intensive Care Medicine at the Charité Campus Virchow-Klinikum, as well as head of the nephrology research laboratory, she made highly regarded, internationally distinguished contributions to transplantation research with the goal of improving graft approach and long-term survival, preventing cardiovascular comorbidity, and thus improving the quality of life and life expectancy of transplanted patients.  She pursued her great goals with tremendous energy and passion, impressive perseverance and clear determination. She devoted her full attention to her employees, colleagues, and students, being equally attentive, understanding, and demanding.
 
The death of Duška Dragun is a great and painful loss. We will miss her greatly as director of the Charité BIH Clinician Scientist Program, as a physician, university professor and scientist. To us she was an inspiration, a mentor and an ever driving force.

Above all, however, we will greatly miss Duška as a friend.  
Karl Hillebrandt | Charité 3R Tandem project for early career researchers
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Together with Dr. Björn Papke (Molecular tumour pathology), Dr. Karl Hillebrandt was able to acquire funding for a "Tandem project for early career researchers" from the Charité 3R. The project is entitled "A personalised therapy approach implementing individually matched matrix-based in vitro colorectal liver metastases to reduce metastatic mouse models".
Although modern multimodal therapy strategies have improved the clinical outcome of patients with colorectal liver metastases (CRLM), the overall prognosis is still poor. To further improve treatment options for patients, it is necessary to develop and test new targeted therapeutic approaches. To date, mouse models have often been used to study metastatic colorectal cancer. However, the rate of successful translation of animal models into clinical trials is less than 8%, highlighting the urgent need for alternative models to study the biology of metastatic cancer. This project aims to develop a novel personalised extracellular matrix-based in vitro model of human CRLM. This model will be validated against existing data from patient-derived organoids and xenografts (histology, single cell RNA sequencing and targeted gene sequencing). After internal comparison of our in vitro CRLM with the original CRLM, we will translate it into a personalised drug screening platform to test drug response from standard therapy to novel inhibitor combinations.
Dr. Moritz Queisner
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Dr. rer. medic. Moritz Queisner received his doctorate certificate today (magna cum laude)! This is in recognition of his work in the field of extended reality technology in visceral surgery. His thesis is entitled XR in surgery – spatial end embodied computing in digital surgery: technology, application, design.

CONGRATULATIONS !
CLOUZ | spinoff from the Charité
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Dr. Panagiotis Fikatas invented a surgical device using a knot technology for minimally invasive surgery. Early prototyping and development work was significantly supported by the SPARK-BIH program with the Validation Fund and funds from the Stiftung Charité.

The startup Clouz GmbH, a spinoff from the Charité – Universitätsmedizin Berlin, has developed a novel surgical knot-tying device for use in restrictive access surgery. Clouz GmbH has signed a purchasing agreement for the knot patent with the Charité Technology Transfer Office. The medical device startup was founded by Dr. Panagiotis Fikatas, Marco Climaco and Anne-Mette Jensen.

The novel surgical closure device allows surgical knots to be tied easily, quickly, and most importantly, safely, even in surgeries with severely limited access (e.g. minimally invasive procedures). The products are based on a patented knotting technology that can be used in a range of device types: from manual application by the surgeon to devices for robotic surgery. CLOUZ OneKnot ensures consistent closure for the surgeon and saves valuable time in the operating room.

Two new (Junior) Clinician Scientitsts
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Dr. Simon Moosburner and Dr. Tomasz Dziodzio successfully applied for the BIH Charité (Junior) Clinician Scientist Program.

Dr. Dziodzio is studying pathomechanisms of obesity in the context of kidney transplantation and investigates the impact of obesity on the immune response in the kidney transplant recipient. In addition, a clinical trial will investigate whether surgical weight reduction in obese patients prior to kidney transplantation leads to improved graft function.

Dr. Moosburner is working on the extracorporeal evaluation of liver grafts from older donors. The aim is to characterise old liver grafts during normothermic machine perfusion. For this purpose, a model for normothermic ex vivo machine perfusion of small animal livers as well as liver transplantation in the rat model was established.

CASSANDRA | Clinical ASSist AND aleRt Algorithms
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The Innovationsausschuss beim Gemeinsamen Bundesausschuss (G-BA) is funding 33 new projects in healthcare research. A total of 186 project applications were received in response to the funding announcements of December 2019. Nine project proposals from the open topic area and 24 project proposals from the topic-specific area received a positive funding decision.

Our project CASSANDRA (Clinical ASSist AND aleRt Algorithms – Early detection of postoperative complications with machine learning algorithms) is one of the projects funded for three years.

The aim of the project is to evaluate Machine Learning (ML) in the detection of postoperative complications after major abdominal surgery. By means of digital records and ML-driven analysis of perioperative risk factors, postoperative parameters as well as telemedical vital parameter monitoring, it is to be examined whether complications requiring treatment – in particular infections of the abdominal cavity after liver, pancreas, stomach and intestinal surgery – can be automatically detected and predicted, in order to develop the basis for an autonomous real-time monitoring system on normal wards.
CASSANDRA is a collaboration of Axel Winter, Dr. Max Maurer, Prof. Dr. Igor M. Sauer (Charité – Universitätsmedizin Berlin) and Prof. Dr. Bert Arnrich, Head of the Chair, Professor for Digital Health - Connected Healthcare, Hasso Plattner Institut.
DICOM_XR | XR4ALL 2nd Open Call: Project Selected for Phase 1
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XR4ALL is an initiative by the European Commission to strengthen the European XR industry.

After 140 applications, 18 projects have been selected for Phase 1 of the 2nd Cut-off date of the XR4ALL Open Call. In this phase, projects need to expand upon and validate their concept from a business and a technical perspective during two months.
Based on an evaluation at the end of the first phase, only the best-rated projects will be admitted to Phase 2 and therefore be able to develop the proposed solution.

Our project DICOM_XR (PI: Christoph Rüger) is one of them (and one of three from Germany)!

One of the most common use-cases for XR in medicine is the visualization of medical imaging data like computed tomography (CT) scans. The well-established standard for storing and transferring such data is DICOM (Digital Imaging and Communications in Medicine). It is used in all major hospitals in the European Union – XR applications that involve medical images need to be built upon this standard. Existing open-source DICOM frameworks offer data interoperability and are compatible with 3D engines, like Unity. However, while DICOM is well-established and very feature rich, it is also a complex standard to work with as a developer. In addition to data interoperability provided by DICOM, most medical XR applications also require: 1) Data transfer from a machine with access to the hospital’s image network to mobile XR devices such as HMDs, 2) performant visualization, particularly for stereographic displays, and 3) view manipulation with 3D input (e.g. hand tracking) instead of mouse input. These requirements are, at best, additional workloads for technically skilled teams and, at worst, insurmountable hurdles for projects lacking programmers.
DICOM_XR is a framework aiming to solve all three of these requirements: data transfer, performant visualization and utilization of three-dimensional input. Building upon an existing open-source DICOM solution, DICOM_XR will offer a ‘plug and play’ solution for XR developers. It will significantly decrease technical hurdles for e.g. medical studies evaluating XR, which are still sorely needed. It can also streamline the development of commercial XR applications: Medical open-source projects such as SlicerIGT have been successfully used as a foundation for certified medical products. In short, DICOM_XR will allow medical XR developers to focus on features that their users want, rather than technical infrastructure.
Engineering an endothelialized, endocrine NeoPancreas
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Acta Biomaterialia accepted our latest paper on "Engineering an endothelialized, endocrine Neo-Pancreas: evaluation of islet functionality in an ex vivo model".

Islet-based recellularization of decellularized, repurposed rat livers may form a transplantable Neo-Pancreas. The aim of this study is the establishment of the necessary protocols, the evaluation of the organ structure and the analysis of the islet functionality ex vivo.
After perfusion-based decellularization of rat livers, matrices were repopulated with endothelial cells and mesenchymal stromal cells, incubated for 8 days in a perfusion chamber and finally repopulated on day 9 with intact rodent islets. Integrity and quality of re-endothelialization was assessed by histology and FITC-dextran perfusion assay. Functionality of the islets of Langerhans was determined on day 10 and day 12 via glucose stimulated insulin secretion.
Blood gas analysis variables confirmed the stability of the perfusion cultivation. Histological staining showed that cells formed a monolayer inside the intact vascular structure. These findings were confirmed by electron microscopy. Islets infused via the bile duct could histologically be found in the parenchymal space. Adequate insulin secretion after glucose stimulation after 1-day and 3-day cultivation verified islet viability and functionality after the repopulation process.
We provide the first proof-of-concept for the functionality of islets of Langerhans engrafted in a decellularized rat liver. Furthermore, a re-endothelialization step was implemented to provide implantability. This technique can serve as a bioengineered platform to generate implantable and functional endocrine Neo-Pancreases.

Authors are Hannah Everwien, Eriselda Keshi, Karl H. Hillebrandt, Barbara Ludwig, Marie Weinhart, Peter Tang, Anika S. Beierle, Hendrik Napierala, Joseph MGV Gassner, Nicolai Seiffert, Simon Moosburner, Dominik Geisel, Anja Reutzel-Selke, Benjamin Strücker, Johann Pratschke, Nils Haep, and Igor M. Sauer.
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Best Poster prize for Anna Pfefferkorn
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Anna Pfefferkorn won the Best Poster prize for our work on "Molecular and cellular mechanisms of Lipocalin-2 mediated renoprotection in kidney transplantation" at the Kongress für Nephrologie 2020, held in Berlin 1.-4. October, 2020!

Lipocalin-2 (Lcn2) is distinctly upregulated in kidney transplants and serves as an early marker of AKI, DGF and acute rejection. However, the functional role and mechanisms underlying Lcn2 upregulation remain largely unknown. Using a mouse model of kidney transplantation we recently demonstrated a renoprotective role of recombinant Lcn2:Siderophore:Fe (rLcn2). However, the molecular and cellular events underlying the renoprotective effects of rLcn2 in kidney allografts remain unclear. Elucidating these events forms the primary focus of the current study.
rLcn2 significantly lowered CD8+ T cells in the allograft, LN and blood at POD 7, whereas their number remained unaffected in spleen. Nevertheless, the number of CD4+ T Lymphocytes was reduced only in lymph nodes. NKG2D+CD8+T cells and CD27+CD11b+NKp46+NK cells were the most prominent subpopulations of the cytotoxic lymphocytes whose frequencies were significantly reduced in graft, spleen and blood with the treatment of rLcn2. Besides, a significantly reduced infiltration of monocytes/macrophages was also observed at POD-7 with the said treatment. Importantly, degranulation capacity and IFNg production of intragraft and splenic CD4+ and CD8+ T cells were impaired in the treated animals. Besides, rLcn2 lowered hypoxia and reoxygenation induced cytotoxicity of the primary RTECs, associated with reduced caspase-3 cleavage and activation of Erk and AKt signaling.

rLcn2 treatments differentially affects the relative frequencies and activation of various immune cell. Besides, rLcn2 depicts cytoprotective effect on murine primary RTECs during H/R, possibly via activation of Erk and Akt signaling.

CONGRATULATIONS !
Declined Liver Grafts – Analysis of the German Donor Population from 2010 to 2018
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"Declined Liver Grafts – Analysis of the German Donor Population from 2010 to 2018" was published in the Zeitschrift für Gastroenterologie.
The lack of suitable allografts limits the availability of liver transplantation in Germany. The quality of potentially available German donor livers has to date not been analyzed.
Analysis of all donors for potential liver transplantations reported to the Eurotransplant by the German Organ Transplantation Foundation from 2010 to 2018. Categorization of transplanted and discarded organs utilizing available histopathological reports and predefined extended criteria for organ donation.
A total of 8594 livers were offered for transplantation, of which 15.2 % were discarded. During the analysis period the proportion of donor livers from extended criteria donors increased from 65 % to 70 % (p = 0.005). In 2018, 21.3 % of offered donor livers were discarded, more than half (56.4 %) of these organs came from donors meeting multiple extended criteria. Livers were significantly more likely to be not transplanted, when from donors of older age (> 65 years; 41 vs. 28 %), BMI > 30 kg/m2 (29 vs. 14 %) or elevated transaminase levels (all p < 0.001).
Despite the consistent organ scarcity in Germany, a relevant amount of livers cannot be transplanted due to a multitude of organ quality limitations. This should stimulate the search for concepts such as normothermic ex vivo machine perfusion to evaluate, protect and potentially improve organ quality.

Authors are Simon Moosburner, Nathanael Raschzok, Christina Schleicher, Detlef Bösebeck, Joseph M.G.V. Gaßner, Paul V. Ritschl, Axel Rahmel, Igor M. Sauer, and Johann Pratschke.
Z Gastroenterol. 2020 Aug 24. doi: 10.1055/a-1199-7432. Online ahead of print.
Felix Krenzien received Ferdinand-Sauerbruch Prize 2020
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Priv.-Doz. Dr. Felix Krenzien received the Ferdinand-Sauerbruch Prize 2020 for his project and publication „The ILLS Laparoscopic Liver Surgery Fellow Skills Curriculum“ published in Annals of Surgery (online ahead of print).

Congratulations!

Laparoscopy is becoming the standard approach in liver surgery. As the degree of difficulty varies greatly from core skills to advanced procedures, strategies for teaching young surgeons need to be reconsidered. We here aimed to design a skills curriculum for LLR. Using the nominal group technique, 22 substeps of LLR were identified by 61 hepatobiliary surgeons. The raters were asked to rate (1) the difficulty of substeps and (2) the minimum number of times that the substep must be performed for mastery of the technique. According to the frequency of defined substeps, being estimated on the basis of high volume center experiences (n = 222 LLR; 1/2017-12/2018), the center's training capacity and defined goals for a 2-year fellowship were calculated.
Ten surgical substeps (45%) are routinely performed and can thus be taught sufficiently at centers carrying out ≥50 LLR in 2 years. As the mobilization of the right liver lobe and the dissection of the hepatic artery or portal vein is performed in only 27% and 28% of all LLR, respectively, sufficient training can only be provided at centers with ≥100 LLRs in 2 years. Mastery of complex parenchymal dissection (19%) and hilar lymphadenectomy (8%) can only be achieved in center performing ≥200 LLR in 2 years.
The authors suggest a stepwise approach for training of hepatobiliary fellows in LLR. Based on the estimated complexity of the substeps and the size of the center, not every substep can be learned within 2 years.

Authors are Felix Krenzien, Wenzel Schöning, Philipp Brunnbauer, Christian Benzing, Robert Öllinger, Matthias Biebl, Marcus Bahra, Nathanael Raschzok, Daniel Cherqui, David Geller, Ho-Seong Han, Go Wakabayashi, Moritz Schmelzle, Johann Pratschke, and the study group of the International Laparoscopic Liver Society (ILLS).
EKFS grant | Metabolic reconditioning of steatotic rat liver grafts by normothermic ex vivo machine perfusion
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The Else Kröner Fresenius Stiftung will fund the project "Metabolic reconditioning of steatotic rat liver grafts by normothermic ex vivo machine perfusion" (PI: Priv.-Doz. Dr. Nathanael Raschzok) for two years.

Liver transplantation is the treatment of choice for end-stage liver disease, yet the number of transplant candidates constantly exceeds the organ supply. The imbalance between demand and supply of liver grafts is dramatically exacerbated by the rising prevalence of obesity and the metabolic syndrome, which both show a strong correlation with steatosis hepatis. Liver grafts with macrovesicular steatosis above 30% are associated with delayed graft function and lower graft and patient survival, and livers with >60% steatosis are generally discarded from transplantation. Within the next 10 years, the overall liver graft utilization could potentially be halved due to the rising prevalence of steatosis, emphasizing the urgent clinical need to find solutions to make steatotic livers acceptable for transplantation.

In this project the hypothesis is tested whether metabolic reprogramming of steatotic liver grafts will 1) restore hepatocyte function, 2) activate lipid catabolism, 3) increase resistance to ischemia reperfusion damage, and 4) alleviate overwhelming inflammatory processes in the early phase of post-transplant regeneration with beneficial long-term impact for graft function and recipient survival.
The Human Liver Matrisome
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Biomaterials accepted our latest paper on „The Human Liver Matrisome – Proteomic Analysis of Native and Fibrotic Human Liver Extracellular Matrices for Organ Engineering Approaches“.

The production of biomaterials that endow significant morphogenic and microenvironmental cues for the constitution of cell integration and regeneration remains a key challenge in the successful implementation of functional organ replacements. Despite the vast development in the production of biological and architecturally native matrices, the complex compositions and pivotal figures by which the human matrisome mediates many of its essential functions are yet to be defined. Here we present a thorough analysis of the native human liver proteomic landscape using decellularization and defatting protocols to extract create extracellular matrix scaffolds of natural origin that can further be used in both bottom-up and top-down approaches in tissue engineering based organ replacements. Furthermore, by analyzing human liver extracellular matrices in different stages of fibrosis and cirrhosis, we have identified distinct attributes of these tissues that could potentially be exploited therapeutically and thus require further investigation. The general experimental pipeline presented in this study is applicable to any type of tissue and can be widely used for different approaches in regenerative medicine and in the construction of novel biomaterials for organ engineering approaches.

Authors are A. Daneshgar, O. Klein, G. Nebrich, M. Weinhart, P. Tang, A. Arnold, I. Ullah, J. Pohl, S. Moosburner, N. Raschzok, B. Strücker, M. Bahra, J. Pratschke, I.M. Sauer, and K.H. Hillebrandt. The authors acknowledge the support of the Cluster of Excellence Matters of Activity. Image Space Material funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany´s Excellence Strategy – EXC 2025.
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Ex vivo machine perfusion: current applications and future directions in liver transplantation
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Langenbeck's Archives of Surgery accepted the manuscript „Ex vivo machine perfusion: current applications and future directions in liver transplantation“ for publication.

Liver transplantation is the only curative treatment option for end-stage liver disease, however, its use remains limited due to a shortage of suitable organs. In recent years, ex vivo liver machine perfusion has been introduced to liver transplantation, as a means to expand the donor organ pool.
To present a narrative review of prospective clinical studies on ex vivo liver machine perfusion, in order to assess current applications and highlight future directions.
Methods: A systematic literature search of both PubMed and ISI web of science databases as well as the ClinicalTrials.gov registry was performed.
Twenty articles on prospective clinical trials on ex vivo liver machine perfusion were identified. Out of these, eight reported on hypothermic, nine on normothermic, and two on sequential perfusion. These trials have demonstrated the safety and feasibility of ex vivo liver machine perfusion in both standard and expanded criteria donors. Currently, there are 12 studies enrolled in the clinicaltrials.gov registrar, and these focus on use of ex vivo perfusion in extended criteria donors as well as declined organs.
Ex vivo liver machine perfusion seems to be a suitable strategy to expand the donor pool for liver transplantation and holds promise as a platform for reconditioning diseased organs.

Authors are Julian Michelotto, Joseph MGV Gaßner, Simon Moosburner, Vanessa Muth, Madhukar S Patel, Markus Selzner, Johann Pratschke, Igor M. Sauer, and Nathanael Raschzok.
SiM | Der Simulierte Mensch
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„Der Simulierte Mensch“ ("The Simulated Human", Si-M) is a new research building which is currently under construction and is expected to be finished in 2023. The building site is directly adjacent to the Charité Campus Virchow-Klinikum of the Charité - Universitätsmedizin in Berlin-Wedding and is also the birthplace of biotechnology at the TU Berlin.

The initiators of Si-M are Roland Lauster (Head of the Department of Medical Biotechnology at TU Berlin) and Andreas Thiel (Head of the research group Regenerative Immunology and Aging at Charité – Universitätsmedizin Berlin). They applied for the research building in 2018 (GG §91b) and successfully defended it before the German Science Council.

In the building, scientists from both institutions will work together to simulate the functions of human cells and tissues with new technologies of 3D cultivation, multi-organ chips or 3D bioprinting. In contrast to already existing collaborative projects, the building will be used to practice the joint development of models "side by side" in the same laboratory environment. In this way, both the development of organ models and technological developments can be adapted and optimized at the same time.

More information via https://www.si-m.org .

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Ultrasound in augmented reality: a mixed-methods evaluation of head-mounted displays in image-guided interventions
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The International Journal of Computer Assisted Radiology and Surgery accepted Christoph Rüger's paper on "Ultrasound in augmented reality: a mixed-methods evaluation of head-mounted displays in image-guided interventions" for publication.

Augmented reality (AR) and head-mounted displays (HMD) are current subjects of investigation in medical practice. A commonly proposed use-case of AR-HMDs is to display data in image-guided interventions. Although technical feasibility has been thoroughly shown, effects of AR-HMDs on interventions are not yet well researched, hampering clinical applicability. Therefore, the goal of this study is to better understand the benefits and limitations of this technology in ultrasound-guided interventions.
We used an AR-HMD system (based on Hololens, Microsoft Corp.) which overlays live ultrasound images spatially correctly at the location of the ultrasound transducer. We chose ultrasound-guided needle placements as a representative task for image-guided interventions. To examine the effects of the AR-HMD, we used mixed methods and conducted two studies in a lab setting: (1) in an experimental study, we asked participants to place needles into a training model and evaluated task duration and accuracy with the AR- HMD as compared to the standard procedure without visual overlay and (2) in a qualitative study, we analysed the user experience with AR-HMD using think-aloud protocols during ultrasound examinations and semi-structured interviews after the task.
Participants (n=20) placed needles more accurately (mean error of 7.4 mm vs. 4.9 mm, p=0.022) but not significantly faster (mean task duration of 74.4 s vs. 66.4 s, p=0.211) with the AR-HMD. All participants in the qualitative study (n=6) reported limitations of and unfamiliarity with the AR-HMD, yet all but one also clearly noted benefits and/or that they would like to test the technology in practice.
We present additional, though still preliminary, evidence that AR-HMDs provide benefits in image-guided procedures. Our data also contribute insights into potential causes underlying the benefits, such as improved spatial perception. Still, more comprehensive studies are needed to ascertain benefits for clinical applications and to clarify underlying mechanisms.

Authors are Christoph Rüger, Markus A. Feufel, Simon Moosburner, Christopher Özbek, Johann Pratschke, and Igor M. Sauer.
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