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Critical Care for Potential Liver Transplant Candidates
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The book Critical Care for Potential Liver Transplant Candidates
(D. Bezinover and F. Saner [Eds.]) focuses on patients with end-stage-liver disease (ESLD) who could possibly qualify for liver transplant. This patient cohort raises many problems: who should be treated and also, when is it too late for transplant? The authors are all dedicated experts in the field of ESLD/liver transplantation, but from different disciplines with different views of the problem.
In the past 15 years many things have changed in the treatment for these patients: cardiac assessment, treatment of porto-pulmonary hypertension, hemodynamics, coagulation assessment and management, diagnosis of kidney failure, and the timing of dialysis. These issues are comprehensively discussed in this book, in order to provide physicians starting in the field of transplantation an overview of different areas of concern.
This book is aimed at specialists and trainees in critical care, hepatology, anesthesia, surgery, and nephrology.

N. Raschzok, K.H. Hillebrandt and I.M. Sauer contributed with the chapter "Liver Assist Systems for Bridging to Transplantation: Devices and Concepts".

Mor information via this link.
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Composite tissue allotransplantation: opportunities and challenges
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"Composite tissue allotransplantation: opportunities and challenges" is available in Cellular & Molecular Immunology (Cell Mol Immunol. 2019 Mar 6. doi: 10.1038/s41423-019-0215-3. [Epub ahead of print]). Authors are J. Iske, Y. Nian, R. Maenosono, M. Maurer, I.M. Sauer & S.G. Tullius.

Vascularized composite allotransplants (VCAs) have unique properties because of diverse tissue components transplanted en mass as a single unit. In addition to surgery, this type of transplant also faces enormous immunological challenges that demand a detailed analysis of all aspects of alloimmune responses, organ preservation, and injury, as well as the immunogenicity of various tissues within the VCA grafts to further improve graft and patient outcomes. Moreover, the side effects of long-term immunosuppression for VCA patients need to be carefully balanced with the potential benefit of a non-life-saving procedure. In this review article, we provide a comprehensive update on limb and face transplantation, with a specific emphasis on the alloimmune responses to VCA, established and novel immunosuppressive treatments, and patient outcomes.
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Human stem cells promote liver regeneration after partial hepatectomy
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"Human Stem Cells Promote Liver Regeneration After Partial Hepatectomy in BALB/C Nude Mice" will be published in J Surg Res. 2019 (Mar 4;239:191-200. doi: 10.1016/j.jss.2019.02.010. [Epub ahead of print]).
Authors are S. Wabitsch, Ch. Benzing, F. Krenzien, K. Splith, P.K. Haber, A. Arnold, M. Nösser, C. Kamalia, F. Hermann, Ch. Günther, D. Hirsch, I.M. Sauer, J. Pratschke, and M. Schmelzle.

Mesenchymal stem cells (MSCs) have been suggested to augment liver regeneration after surgically and pharmacologically induced liver failure. To further investigate this we processed human bone marrow-derived MSC according to good manufacturing practice (GMP) and tested those cells for their modulatory capacities of metabolic alterations and liver regeneration after partial hepatectomy in BALB/c nude mice.

Human bone marrow-derived MSC attenuate metabolic alterations and improve liver regeneration after partial hepatectomy in BALB/c nude mice. Obtained results using GMP-processed human MSC suggest functional links between fat accumulation and hepatocyte proliferation, without any evidence for cellular homing. This study using GMP-proceeded MSC has important regulatory implications for an urgently needed translation into a clinical trial.
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Diffusion-weighted magnetic resonance imaging using a preclinical 1 T PET/MRI
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"Diffusion-weighted magnetic resonance imaging using a preclinical 1 T PET/MRI in healthy and tumor-bearing rats" was published in EJNMMI Res. 2019 Feb 22;9(1):21. doi: 10.1186/s13550-019-0489-6.
Authors are J. Albrecht, D. Polenz, A.A. Kühl, J.M.M. Rogasch, A. Leder, I.M. Sauer, M. Babos, G. Mócsai, N. Beindorff, I.G. Steffen, W. Brenner, and E.J. Koziolek.

Hybrid positron emission tomography and magnetic resonance imaging (PET/MRI) scanners are increasingly used for both clinical and preclinical imaging. Especially functional MRI sequences such as diffusion-weighted imaging (DWI) are of great interest as they provide information on a molecular level, thus, can be used as surrogate biomarkers. Due to technical restrictions, MR sequences need to be adapted for each system to perform reliable imaging. There is, to our knowledge, no suitable DWI protocol for 1 Tesla PET/MRI scanners.
We established a respiratory-gated DWI protocol for a preclinical 1 T PET/MRI scanner allowing to monitor growth-related changes in ADC values of orthotopic HCC liver tumors. By monitoring the changes in tumor ADCs over time, different cellular stages were described. However, each study needs to adapt the protocol further according to their question to generate best possible results.
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Comparison of AR HMDs in Visceral Surgery
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"Real World Usability Analysis of two Augmented Reality Headsets in Visceral Surgery" was accepted for publication in Artificial Organs. Authors are S. Moosburner, C. Remde, P. Tang, M. Queisner, N. Haep, J. Pratschke, and I.M. Sauer.

Recent developments in the field of augmented reality (AR) have enabled new use cases in surgery. Initial set-up of an appropriate infrastructure for maintaining an AR surgical workflow requires investment in appropriate hardware. We compared the usability of the Microsoft HoloLens and Meta 2 head mounted displays (HMDs). Fifteen medicine students tested each device and were questioned with a variant of the System Usability Scale (SUS). Two surgeons independently tested the devices in an intraoperative setting.
In our adapted SUS, ergonomics, ease of use and visual clarity of the display did not differ significantly between HMD groups. The field of view (FOV) was smaller in the Microsoft HoloLens than the Meta 2 and significantly more study subjects (80% vs. 13.3%; p < 0.001) felt limited through the FOV. Intraoperatively, decreased mobility due to the necessity of an AC adapter and additional computing device for the Meta 2 proved to be limiting. Object stability was rated superior in the Microsoft HoloLens than the Meta 2 by our surgeons and lead to increased use.
We examined the Meta 2 and the Microsoft HoloLens and found key advantages in the Microsoft HoloLens which provided palpable benefits in a surgical setting.
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Nanomolar sensing of NAD
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"The nanomolar sensing of nicotinamide adenine dinucleotide in human plasma using a cycling assay in albumin modified simulated body fluids." was published in Nature Scientific Reports.
Authors are P. Brunnbauer, A. Leder, C. Kamali, K. Kamali, E. Keshi, K. Splith, S. Wabitsch, P. Haber, G. Atanasov, L. Feldbrügge, I.M. Sauer, J. Pratschke, M. Schmelzle, and F. Krenzien.

Nicotinamide adenine dinucleotide (NAD), a prominent member of the pyridine nucleotide family, plays a pivotal role in cell-oxidation protection, DNA repair, cell signalling and central metabolic pathways, such as beta oxidation, glycolysis and the citric acid cycle. In particular, extracellular NAD+ has recently been demonstrated to moderate pathogenesis of multiple systemic diseases as well as aging. Herein we present an assaying method, that serves to quantify extracellular NAD+ in human heparinised plasma and exhibits a sensitivity ranging from the low micromolar into the low nanomolar domain. The assay achieves the quantification of extracellular NAD+ by means of a two-step enzymatic cycling reaction, based on alcohol dehydrogenase. An albumin modified revised simulated body fluid was employed as standard matrix in order to optimise enzymatic activity and enhance the linear behaviour and sensitivity of the method. In addition, we evaluated assay linearity, reproducibility and confirmed long-term storage stability of extracellular NAD+ in frozen human heparinised plasma. In summary, our findings pose a novel standardised method suitable for high throughput screenings of extracellular NAD+ levels in human heparinised plasma, paving the way for new clinical discovery studies.
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Normothermic ex vivo machine perfusion
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"Improvement of normothermic ex vivo machine perfusion of rat liver grafts by dialysis and Kupffer Cell inhibition with glycine" was accepted for publication in Liver Transplantation.
Authors are J. Gassner, M. Nösser, S. Moosburner, R. Horner, P. Tang, L. Wegener, D. Wyrwal, F. Claussen, R. Arsenic, J. Pratschke, I.M. Sauer, and N. Raschzok.

Normothermic ex vivo liver machine perfusion might be a superior preservation strategy for liver grafts from extended criteria donors. However, standardized small animal models are not available for basic research on machine perfusion of liver grafts. A laboratory-scaled perfusion system was developed consisting of a custom-made perfusion chamber, a pressure-controlled roller pump, and an oxygenator. Male Wistar rat livers were perfused via the portal vein for 6 hours using oxygenated culture medium supplemented with rat erythrocytes. A separate circuit was connected via a dialysis membrane to the main circuit for plasma volume expansion. Glycine was added to the flush solution, the perfusate, and the perfusion circuit. Portal pressure and transaminase release were stable over the perfusion period. Dialysis significantly decreased the potassium concentration of the perfusate and led to significantly higher bile and total urea production. Hematoxylin and eosin staining and immunostaining for ssDNA and activated caspase 3 showed less sinusoidal dilatation and tissue damage in livers treated with dialysis and glycine. While Kupffer cells were preserved, tumor necrosis factor α mRNA levels were significantly decreased by both treatments. For proof of concept, the optimized perfusion protocol was tested with DCD grafts, resulting in significantly lower transaminase release into the perfusate and preserved liver architecture compared to baseline perfusion.
Our laboratory-scale normothermic portovenous ex vivo liver perfusion system enables rat liver preservation for 6 hours. Both dialysis and glycine treatment were shown to be synergistic for preservation of the integrity of normal and DCD liver grafts.
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