121 results on '"Rupert Oberhuber"'
Search Results
2. Assessment of Mitochondrial Respiration During Hypothermic Storage of Liver Biopsies Following Normothermic Machine Perfusion
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Julia Hofmann, Alexander Kofler, Melanie Schartner, Madita L. Buch, Martin Hermann, Bettina Zelger, Dietmar Öfner, Rupert Oberhuber, Theresa Hautz, Stefan Schneeberger, and Andras T. Meszaros
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liver transplantation ,mitochondria ,normothermic machine perfusion ,high-resolution respirometry ,hypothermic storage ,Specialties of internal medicine ,RC581-951 - Abstract
Organ quality can be assessed prior to transplantation, during normothermic machine perfusion (NMP) of the liver. Evaluation of mitochondrial function by high-resolution respirometry (HRR) may serve as a viability assessment concept in this setting. Freshly collected tissue is considered as optimal sample for HRR, but due to technical and personnel requirements, more flexible and schedulable measurements are needed. However, the impact of cold storage following NMP before processing biopsy samples for mitochondrial analysis remains unknown. We aimed at establishing an appropriate storage protocol of liver biopsies for HRR. Wedge biopsies of 5 human livers during NMP were obtained and assessed by HRR. Analysis was performed after 0, 4, 8, and 12 h of hypothermic storage (HTS) in HTK organ preservation solution at 4°C. With HTS up to 4 h, mitochondrial performance did not decrease in HTS samples compared with 0 h (OXPHOS, 44.62 [34.75–60.15] pmol·s−1·mg wet mass−1 vs. 43.73 [40.69–57.71], median [IQR], p > 0.999). However, at HTS beyond 4 h, mitochondrial respiration decreased. We conclude that HTS can be safely applied for extending the biopsy measurement window for up to 4 h to determine organ quality, but also that human liver respiration degrades beyond 4 h HTS following NMP.
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- 2024
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3. The Predictive Value of Graft Viability and Bioenergetics Testing Towards the Outcome in Liver Transplantation
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Andras T. Meszaros, Annemarie Weissenbacher, Melanie Schartner, Tim Egelseer-Bruendl, Martin Hermann, Jasmin Unterweger, Christa Mittelberger, Beatrix A. Reyer, Julia Hofmann, Bettina G. Zelger, Theresa Hautz, Thomas Resch, Christian Margreiter, Manuel Maglione, Timea Komlódi, Hanno Ulmer, Benno Cardini, Jakob Troppmair, Dietmar Öfner, Erich Gnaiger, Stefan Schneeberger, and Rupert Oberhuber
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liver ,transplantation ,static cold storage ,mitochondria ,high-resolution respirometry ,real-time confocal imaging ,Specialties of internal medicine ,RC581-951 - Abstract
Donor organ biomarkers with sufficient predictive value in liver transplantation (LT) are lacking. We herein evaluate liver viability and mitochondrial bioenergetics for their predictive capacity towards the outcome in LT. We enrolled 43 consecutive patients undergoing LT. Liver biopsy samples taken upon arrival after static cold storage were assessed by histology, real-time confocal imaging analysis (RTCA), and high-resolution respirometry (HRR) for mitochondrial respiration of tissue homogenates. Early allograft dysfunction (EAD) served as primary endpoint. HRR data were analysed with a focus on the efficacy of ATP production or P-L control efficiency, calculated as 1-L/P from the capacity of oxidative phosphorylation P and non-phosphorylating respiration L. Twenty-two recipients experienced EAD. Pre-transplant histology was not predictive of EAD. The mean RTCA score was significantly lower in the EAD cohort (−0.75 ± 2.27) compared to the IF cohort (0.70 ± 2.08; p = 0.01), indicating decreased cell viability. P-L control efficiency was predictive of EAD (0.76 ± 0.06 in IF vs. 0.70 ± 0.08 in EAD-livers; p = 0.02) and correlated with the RTCA score. Both RTCA and P-L control efficiency in biopsy samples taken during cold storage have predictive capacity towards the outcome in LT. Therefore, RTCA and HRR should be considered for risk stratification, viability assessment, and bioenergetic testing in liver transplantation.
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- 2024
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4. Transplant oncology – Current indications and strategies to advance the fieldKey points
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Felix J. Krendl, Ruben Bellotti, Gonzalo Sapisochin, Benedikt Schaefer, Herbert Tilg, Stefan Scheidl, Christian Margreiter, Stefan Schneeberger, Rupert Oberhuber, and Manuel Maglione
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Liver transplantation ,transplant oncology ,HCC ,CCA ,CRLM ,NELM ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Summary: Liver transplantation (LT) was originally described by Starzl as a promising strategy to treat primary malignancies of the liver. Confronted with high recurrence rates, indications drifted towards non-oncologic liver diseases with LT finally evolving from a high-risk surgery to an almost routine surgical procedure. Continuously improving outcomes following LT and evolving oncological treatment strategies have driven renewed interest in transplant oncology. This is not only reflected by constant refinements to the criteria for LT in patients with HCC, but especially by efforts to expand indications to other primary and secondary liver malignancies. With new patient-centred oncological treatments on the rise and new technologies to expand the donor pool, the field has the chance to come full circle. In this review, we focus on the concept of transplant oncology, current indications, as well as technical and ethical aspects in the context of donor organs as precious resources.
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- 2024
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5. The BAR Score Predicts and Stratifies Outcomes Following Liver Retransplantation: Insights From a Retrospective Cohort Study
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Felix J. Krendl, Margot Fodor, Madita L. Buch, Jessica Singh, Hannah Esser, Benno Cardini, Thomas Resch, Manuel Maglione, Christian Margreiter, Lisa Schlosser, Tobias Hell, Benedikt Schaefer, Heinz Zoller, Herbert Tilg, Stefan Schneeberger, and Rupert Oberhuber
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risk factors ,patient survival ,graft survival ,sepsis ,futility ,Specialties of internal medicine ,RC581-951 - Abstract
Liver retransplantation (reLT) yields poorer outcomes than primary liver transplantation, necessitating careful patient selection to avoid futile reLT. We conducted a retrospective analysis to assess reLT outcomes and identify associated risk factors. All adult patients who underwent a first reLT at the Medical University of Innsbruck from 2000 to 2021 (N = 111) were included. Graft- and patient survival were assessed via Kaplan-Meier plots and log-rank tests. Uni- and multivariate analyses were performed to identify independent predictors of graft loss. Five-year graft- and patient survival rates were 64.9% and 67.6%, respectively. The balance of risk (BAR) score was found to correlate with and be predictive of graft loss and patient death. The BAR score also predicted sepsis (AUC 0.676) and major complications (AUC 0.720). Multivariate Cox regression analysis identified sepsis [HR 5.179 (95% CI 2.575–10.417), p < 0.001] as the most significant independent risk factor for graft loss. At a cutoff of 18 points, the 5 year graft survival rate fell below 50%. The BAR score, a simple and easy to use score available at the time of organ acceptance, predicts and stratifies clinically relevant outcomes following reLT and may aid in clinical decision-making.
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- 2024
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6. The Interplay between Perioperative Oxidative Stress and Hepatic Dysfunction after Human Liver Resection: A Prospective Observational Pilot Study
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Florian Primavesi, Thomas Senoner, Sophie Schindler, Aleksandar Nikolajevic, Pietro Di Fazio, Georg Csukovich, Silvia Eller, Bettina Neumayer, Markus Anliker, Eva Braunwarth, Rupert Oberhuber, Thomas Resch, Manuel Maglione, Benno Cardini, Thomas Niederwieser, Silvia Gasteiger, Eckhard Klieser, Herbert Tilg, Stefan Schneeberger, Daniel Neureiter, Dietmar Öfner, Jakob Troppmair, and Stefan Stättner
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oxidative stress ,liver resection ,liver dysfunction ,post-hepatectomy liver failure ,outcome ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Post-hepatectomy liver failure (PHLF) remains the major contributor to death after liver resection. Oxidative stress is associated with postoperative complications, but its impact on liver function is unclear. This first in-human, prospective, single-center, observational pilot study evaluated perioperative oxidative stress and PHLF according to the ISGLS (International Study Group for Liver Surgery). Serum 8-isoprostane, 4-hydroxynonenal (4-HNE), total antioxidative capacity, vitamins A and E, and intraoperative, sequential hepatic tissue 4-HNE and UCP2 (uncoupling protein 2) immunohistochemistry (IHC) were assessed. The interaction with known risk factors for PHLF and the predictive potential of oxidative stress markers were analyzed. Overall, 52 patients were included (69.2% major liver resection). Thirteen patients (25%) experienced PHLF, a major factor for 90-day mortality (23% vs. 0%; p = 0.013). Post-resection, pro-oxidative 8-isoprostane significantly increased (p = 0.038), while 4-HNE declined immediately (p < 0.001). Antioxidative markers showed patterns of consumption starting post-resection (p < 0.001). Liver tissue oxidative stress increased stepwise from biopsies taken after laparotomy to post-resection in situ liver and resection specimens (all p < 0.001). Cholangiocarcinoma patients demonstrated significantly higher serum and tissue oxidative stress levels at various timepoints, with consistently higher preoperative values in advanced tumor stages. Combining intraoperative, post-resection 4-HNE serum levels and in situ IHC early predicted PHLF with an AUC of 0.855 (63.6% vs. 0%; p < 0.001). This was also associated with grade B/C PHLF (36.4% vs. 0%; p = 0.021) and 90-day mortality (18.2% vs. 0%; p = 0.036). In conclusion, distinct patterns of perioperative oxidative stress levels occur in patients with liver dysfunction. Combining intraoperative serum and liver tissue markers predicts subsequent PHLF. Cholangiocarcinoma patients demonstrated pronounced systemic and hepatic oxidative stress, with increasing levels in advanced tumor stages, thus representing a worthwhile target for future exploratory and therapeutic studies.
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- 2024
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7. Mitochondrial respiration during normothermic liver machine perfusion predicts clinical outcomeResearch in context
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Andras T. Meszaros, Julia Hofmann, Madita L. Buch, Benno Cardini, Theresia Dunzendorfer-Matt, Florian Nardin, Michael J. Blumer, Margot Fodor, Martin Hermann, Bettina Zelger, Giorgi Otarashvili, Melanie Schartner, Annemarie Weissenbacher, Rupert Oberhuber, Thomas Resch, Jakob Troppmair, Dietmar ..fner, Heinz Zoller, Herbert Tilg, Erich Gnaiger, Theresa Hautz, and Stefan Schneeberger
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Liver ,Transplantation ,Normothermic machine perfusion ,Mitochondria ,High-resolution respirometry ,Medicine ,Medicine (General) ,R5-920 - Abstract
Summary: Background: Reliable biomarkers for organ quality assessment during normothermic machine perfusion (NMP) are desired. ATP (adenosine triphosphate) production by oxidative phosphorylation plays a crucial role in the bioenergetic homeostasis of the liver. Thus, detailed analysis of the aerobic mitochondrial performance may serve as predictive tool towards the outcome after liver transplantation. Methods: In a prospective clinical trial, 50 livers were subjected to NMP (OrganOx Metra) for up to 24.ßh. Biopsy and perfusate samples were collected at the end of cold storage, at 1.ßh, 6.ßh, end of NMP, and 1.ßh after reperfusion. Mitochondrial function and integrity were characterized by high-resolution respirometry (HRR), AMP, ADP, ATP and glutamate dehydrogenase analysis and correlated with the clinical outcome (L-GrAFT score). Real-time confocal microscopy was performed to assess tissue viability. Structural damage was investigated by histology, immunohistochemistry and transmission electron microscopy. Findings: A considerable variability in tissue viability and mitochondrial respiration between individual livers at the end of cold storage was observed. During NMP, mitochondrial respiration with succinate and tissue viability remained stable. In the multivariate analysis of the 35 transplanted livers (15 were discarded), area under the curve (AUC) of LEAK respiration, cytochrome c control efficiency (mitochondrial outer membrane damage), and efficacy of the mitochondrial ATP production during the first 6.ßh of NMP correlated with L-GrAFT. Interpretations: Bioenergetic competence during NMP plays a pivotal role in addition to tissue injury markers. The AUC for markers of outer mitochondrial membrane damage, ATP synthesis efficiency and dissipative respiration (LEAK) predict the clinical outcome upon liver transplantation. Funding: This study was funded by a Grant from the In Memoriam Dr. Gabriel Salzner Stiftung awarded to SS and the Tiroler Wissenschaftsfond granted to TH.
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- 2022
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8. Bioenergetic and Cytokine Profiling May Help to Rescue More DCD Livers for Transplantation
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Julia Hofmann, Andras T. Meszaros, Madita L. Buch, Florian Nardin, Verena Hackl, Carola J. Strolz, Bettina Zelger, Margot Fodor, Benno Cardini, Rupert Oberhuber, Thomas Resch, Annemarie Weissenbacher, Jakob Troppmair, Stefan Schneeberger, and Theresa Hautz
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liver transplantation ,normothermic machine perfusion ,mitochondria ,high-resolution respirometry ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The majority of organs used for liver transplantation come from brain-dead donors (DBD). In order to overcome the organ shortage, increasingly donation after circulatory death (DCD) organs are also considered. Since normothermic machine perfusion (NMP) restores metabolic activity and allows for in-depth assessment of organ quality and function prior to transplantation, such organs may benefit from NMP. We herein compare the bioenergetic performance through a comprehensive evaluation of mitochondria by high-resolution respirometry in tissue biopsies and the inflammatory response in DBD and DCD livers during NMP. While livers were indistinguishable by perfusate biomarker assessment and histology, our findings revealed a greater impairment of mitochondrial function in DCD livers after static cold storage compared to DBD livers. During subsequent NMPs, DCD organs recovered and eventually showed a similar performance as DBD livers. Cytokine expression analysis showed no differences in the early phase of NMP, while towards the end of NMP, significantly elevated levels of IL-1β, IL-5 and IL-6 were found in the perfusate of DCD livers. Based on our results, we find it worthwhile to reconsider more DCD organs for transplantation to further extend the donor pool. Therefore, donor organ quality criteria must be developed, which may include an assessment of bioenergetic function and cytokine quantification.
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- 2023
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9. Single Center, Propensity Score Matching Analysis of Different Reconstruction Techniques following Pancreatoduodenectomy
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Ruben Bellotti, Benno Cardini, Carola J. Strolz, Stefan Stättner, Rupert Oberhuber, Eva Braunwarth, Thomas Resch, Stefan Scheidl, Christian Margreiter, Stefan Schneeberger, Dietmar Öfner, and Manuel Maglione
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pancreatogastrostomy ,pancreatojejunostomy ,propensity score ,pancreatic fistula ,fistula risk score ,post-pancreatectomy hemorrhage ,Medicine - Abstract
Background: Pancreatoduodenectomy is still hampered by significant morbidity. So far, there is no universally accepted technique aimed at minimizing postoperative complications. Herein, we compare three different reconstruction techniques. Methods: This is a retrospective study of a prospectively maintained database including 283 patients operated between January 2010 and December 2020. Three reconstruction techniques were compared: (1) the Neuhaus-style telescope pancreatojejunostomy, (2) the pancreatogastrostomy, and (3) the modified Blumgart-style, duct-to-mucosa pancreatojejunostomy. The primary endpoint consisted in determining the rates of clinically relevant postoperative pancreatic fistulas (CR-POPF); the secondary endpoints included 90 days morbidity and mortality rates. A propensity score matching analysis was used. Results: Rates of CR-POPF did not differ significantly between the groups (Neuhaus-style pancreatojejunostomy 16%, pancreatogastrostomy 17%, modified Blumgart-style pancreatojejunostomy 15%), neither in the unmatched nor in the matched analysis (p = 0.993 and p = 0.901, respectively). Similarly, no significant differences could be observed with regard to major morbidity (unmatched p = 0.596, matched p = 0.188) and mortality rates (unmatched p = 0.371, matched p = 0.209) within the first 90 days following surgery. Propensity-score matching analyses revealed, however, a higher occurrence of post-pancreatectomy hemorrhage after pancreatogastrostomy (p = 0.015). Conclusion: Similar CR-POPF rates suggest no crucial role of the applied reconstruction technique. Increased incidence of intraluminal post-pancreatectomy hemorrhages following pancreatogastrostomy demands awareness for meticulous hemostasis.
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- 2023
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10. Good Long-term Results Following Simultaneous Pancreas-kidney Transplantation in a 69-y-old Recipient: A Case Report
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Claudia Bösmüller, MD, Felix Krendl, MD, Franka Messner, MD, PhD, Valeria Berchtold, MD, Katrin Kienzl-Wagner, MD, Stefan Scheidl, MD, Rupert Oberhuber, PhD, Dietmar Öfner, MAS, MSc, MD, Stefan Schneeberger, MD, and Christian Margreiter, MD
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Surgery ,RD1-811 - Published
- 2021
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11. Reassessment of Relevance and Predictive Value of Parameters Indicating Early Graft Dysfunction in Liver Transplantation: AST Is a Weak, but Bilirubin and INR Strong Predictors of Mortality
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Margot Fodor, Adriana Woerdehoff, Wolfgang Peter, Hannah Esser, Rupert Oberhuber, Christian Margreiter, Manuel Maglione, Benno Cardini, Thomas Resch, Annemarie Weissenbacher, Robert Sucher, Heinz Zoller, Herbert Tilg, Dietmar Öfner, and Stefan Schneeberger
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liver ,transplantation ,early allograft dysfunction ,outcome ,reassessment ,Surgery ,RD1-811 - Abstract
Introduction: Early graft dysfunction (EAD) complicates liver transplantation (LT). The aim of this analysis was to discriminate between the weight of each variable as for its predictive value toward patient and graft survival.Methods: We reviewed all LT performed at the Medical University of Innsbruck between 2007 and 2018. EAD was recorded when one of the following criteria was present: (i) aspartate aminotransferase (AST) levels >2,000 IU/L within the first 7 days, (ii) bilirubin levels ≥10mg/dL or (iii) international normalized ratio (INR) ≥1.6 on postoperative day 7.Results: Of 616 LT, 30.7% developed EAD. Patient survival did not differ significantly (P = 0.092; log rank-test = 2.87), graft survival was significantly higher in non-EAD patients (P = 0.008; log rank-test = 7.13). Bilirubin and INR on postoperative day 7 were identified as strong mortality predictors (Bilirubin HR = 1.71 [1.34, 2.16]; INR HR = 2.69 [0.51, 14.31]), in contrast to AST (HR = 0.91 [0.75, 1.10]). Similar results were achieved for graft loss estimation. A comparison with the Model for Early Allograft Function (MEAF) and the Liver Graft Assessment Following Transplantation (L-GrAFT) score identified a superior discrimination potential but lower specificity.Conclusion: Contrarily to AST, bilirubin and INR have strong predictive capacity for patient and graft survival. This fits well with the understanding, that bile duct injury and deprivation of synthetic function rather than hepatocyte injury are key factors in LT.
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- 2021
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12. Internal Ileal Diversion as Treatment for Progressive Familial Intrahepatic Cholestasis Type 1-Associated Graft Inflammation and Steatosis after Liver Transplantation
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Anna M. Kavallar, Franka Messner, Stefan Scheidl, Rupert Oberhuber, Stefan Schneeberger, Denise Aldrian, Valeria Berchtold, Murat Sanal, Andreas Entenmann, Simon Straub, Anna Gasser, Andreas R. Janecke, Thomas Müller, and Georg F. Vogel
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PFIC1 ,pediatric liver transplantation ,steatosis ,surgical biliary diversion ,Pediatrics ,RJ1-570 - Abstract
Background: Progressive Familial Intrahepatic cholestasis type I (PFIC1) is a rare congenital hepatopathy causing cholestasis with progressive liver disease. Surgical interruption of the enterohepatic circulation, e.g., surgical biliary diversion (SBD) can slow down development of liver cirrhosis. Eventually, end stage liver disease necessitates liver transplantation (LT). PFIC1 patients might develop diarrhea, graft steatosis and inflammation after LT. SBD after LT was shown to be effective in the alleviation of liver steatosis and graft injury. Case report: Three PFIC1 patients received LT at the ages of two, two and a half and five years. Shortly after LT diarrhea and graft steatosis was recognized, SBD to the terminal ileum was opted to prevent risk for ascending cholangitis. After SBD, inflammation and steatosis was found to be reduced to resolved, as seen by liver biochemistry and ultrasounds. Diarrhea was reported unchanged. Conclusion: We present three PFIC1 cases for whom SBD to the terminal ileum successfully helped to resolve graft inflammation and steatosis.
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- 2022
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13. Liver Transplantation Activity in the Eurotransplant Area Is Recovering Slowly During the COVID-19 Crisis
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Gabriel Putzer, MD, Judith Martini, MD, Lukas Gasteiger, MD, Simon Mathis, MD, Robert Breitkopf, MD, Tobias Hell, PhD, Arjan van Enckevort, MD, Rupert Oberhuber, MD, Dietmar Öfner, MD, and Stefan Schneeberger, MD
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Surgery ,RD1-811 - Published
- 2020
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14. Transplanting Marginal Organs in the Era of Modern Machine Perfusion and Advanced Organ Monitoring
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Thomas Resch, Benno Cardini, Rupert Oberhuber, Annemarie Weissenbacher, Julia Dumfarth, Christoph Krapf, Claudia Boesmueller, Dietmar Oefner, Michael Grimm, and Sefan Schneeberger
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transplantation ,machine perfusion ,marginal ,graft ,immunogenecity ,immunomodulation ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Organ transplantation is undergoing profound changes. Contraindications for donation have been revised in order to better meet the organ demand. The use of lower-quality organs and organs with greater preoperative damage, including those from donation after cardiac death (DCD), has become an established routine but increases the risk of graft malfunction. This risk is further aggravated by ischemia and reperfusion injury (IRI) in the process of transplantation. These circumstances demand a preservation technology that ameliorates IRI and allows for assessment of viability and function prior to transplantation. Oxygenated hypothermic and normothermic machine perfusion (MP) have emerged as valid novel modalities for advanced organ preservation and conditioning. Ex vivo prolonged lung preservation has resulted in successful transplantation of high-risk donor lungs. Normothermic MP of hearts and livers has displayed safe (heart) and superior (liver) preservation in randomized controlled trials (RCT). Normothermic kidney preservation for 24 h was recently established. Early clinical outcomes beyond the market entry trials indicate bioenergetics reconditioning, improved preservation of structures subject to IRI, and significant prolongation of the preservation time. The monitoring of perfusion parameters, the biochemical investigation of preservation fluids, and the assessment of tissue viability and bioenergetics function now offer a comprehensive assessment of organ quality and function ex situ. Gene and protein expression profiling, investigation of passenger leukocytes, and advanced imaging may further enhance the understanding of the condition of an organ during MP. In addition, MP offers a platform for organ reconditioning and regeneration and hence catalyzes the clinical realization of tissue engineering. Organ modification may include immunological modification and the generation of chimeric organs. While these ideas are not conceptually new, MP now offers a platform for clinical realization. Defatting of steatotic livers, modulation of inflammation during preservation in lungs, vasodilatation of livers, and hepatitis C elimination have been successfully demonstrated in experimental and clinical trials. Targeted treatment of lesions and surgical treatment or graft modification have been attempted. In this review, we address the current state of MP and advanced organ monitoring and speculate about logical future steps and how this evolution of a novel technology can result in a medial revolution.
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- 2020
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15. Validation of systems biology derived molecular markers of renal donor organ status associated with long term allograft function
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Paul Perco, Andreas Heinzel, Johannes Leierer, Stefan Schneeberger, Claudia Bösmüller, Rupert Oberhuber, Silvia Wagner, Franziska Engler, and Gert Mayer
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Medicine ,Science - Abstract
Abstract Donor organ quality affects long term outcome after renal transplantation. A variety of prognostic molecular markers is available, yet their validity often remains undetermined. A network-based molecular model reflecting donor kidney status based on transcriptomics data and molecular features reported in scientific literature to be associated with chronic allograft nephropathy was created. Significantly enriched biological processes were identified and representative markers were selected. An independent kidney pre-implantation transcriptomics dataset of 76 organs was used to predict estimated glomerular filtration rate (eGFR) values twelve months after transplantation using available clinical data and marker expression values. The best-performing regression model solely based on the clinical parameters donor age, donor gender, and recipient gender explained 17% of variance in post-transplant eGFR values. The five molecular markers EGF, CD2BP2, RALBP1, SF3B1, and DDX19B representing key molecular processes of the constructed renal donor organ status molecular model in addition to the clinical parameters significantly improved model performance (p-value = 0.0007) explaining around 33% of the variability of eGFR values twelve months after transplantation. Collectively, molecular markers reflecting donor organ status significantly add to prediction of post-transplant renal function when added to the clinical parameters donor age and gender.
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- 2018
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16. Post-Transplant Malignancies following Pancreas Transplantation: Incidence and Implications on Long-Term Outcome from a Single-Center Perspective
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Felix J. Krendl, Franka Messner, Claudia Bösmüller, Stefan Scheidl, Benno Cardini, Thomas Resch, Annemarie Weissenbacher, Rupert Oberhuber, Manuel Maglione, Stefan Schneeberger, Dietmar Öfner, and Christian Margreiter
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graft survival ,immunosuppression ,incidence ,malignancy ,pancreas transplantation ,Medicine - Abstract
Chronic immunosuppression is associated with an increased risk of malignancy. The main objective of this study is to evaluate the incidence and effect of post-transplant malignancies (PTMs) following pancreas transplantation. The 348 first pancreas transplants performed between 1985 and 2015 were retrospectively analyzed in this study. Incidences of PTMs, as well as patient and graft survival, were evaluated. Out of 348 patients, 71 (20.4%) developed a PTM. Median time to diagnosis was 130 months. Thirty-six patients (50.7%) developed skin cancers (four patients with melanoma, 32 with NMSCs). Solid organ malignancy occurred in 25 (35.2%), hematologic malignancy in ten patients (14.1%). Affected patients were transplanted earlier [2000 (IQR 1993−2004) vs. 2003 (IQR 1999−2008); p < 0.001]. No differences in induction therapy were seen, both groups demonstrated comparable patient and graft survival. Pancreas transplant recipients with solid organ and hematologic malignancies had a three- and six-fold increased hazard of death compared to those with skin cancers [aHR 3.04 (IQR 1.17–7.91); p = 0.023; aHR 6.07 (IQR 1.87–19.71); p = 0.003]. PTMs affect every fifth patient following pancreas transplantation. Skin cancers are the most common malignancies accounting for 50% of all PTMs. These results underscore the importance of close dermatologic follow-up.
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- 2021
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17. Perioperative Perfusion of Allografts with Anti-Human T-lymphocyte Globulin Does Not Improve Outcome Post Liver Transplantation—A Randomized Placebo-Controlled Trial
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Paul Viktor Ritschl, Julia Günther, Lena Hofhansel, Stefanie Ernst, Susanne Ebner, Arne Sattler, Sascha Weiß, Annemarie Weissenbacher, Rupert Oberhuber, Benno Cardini, Robert Öllinger, Matthias Biebl, Christian Denecke, Christian Margreiter, Thomas Resch, Stefan Schneeberger, Manuel Maglione, Katja Kotsch, and Johann Pratschke
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liver transplantation ,ATLG ,organ perfusion ,organ pretreatment ,machine perfusion ,polyclonal antibody ,Medicine - Abstract
Due to the lack of suitable organs transplant surgeons have to accept unfavorable extended criteria donor (ECD) organs. Recently, we demonstrated that the perfusion of kidney organs with anti-human T-lymphocyte globulin (ATLG) prior to transplantation ameliorates ischemia-reperfusion injury (IRI). Here, we report on the results of perioperative ATLG perfusion in a randomized, single-blinded, placebo-controlled, feasibility trial (RCT) involving 30 liver recipients (LTx). Organs were randomly assigned for perfusion with ATLG/Grafalon® (AP) (n = 16) or saline only (control perfusion = CP) (n = 14) prior to implantation. The primary endpoint was defined as graft function reflected by aspartate transaminase (AST) values at day 7 post-transplantation (post-tx). With respect to the primary endpoint, no significant differences in AST levels were shown in the intervention group at day 7 (AP: 53.0 ± 21.3 mg/dL, CP: 59.7 ± 59.2 mg/dL, p = 0.686). Similarly, exploratory analysis of secondary clinical outcomes (e.g., patient survival) and treatment-specific adverse events revealed no differences between the study groups. Among liver transplant recipients, pre-operative organ perfusion with ATLG did not improve short-term outcomes, compared to those who received placebo perfusion. However, ATLG perfusion of liver grafts was proven to be a safe procedure without the occurrence of relevant adverse events.
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- 2021
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18. Ex Vivo Mesenchymal Stem Cell Therapy to Regenerate Machine Perfused Organs
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Christina Bogensperger, Julia Hofmann, Franka Messner, Thomas Resch, Andras Meszaros, Benno Cardini, Annemarie Weissenbacher, Rupert Oberhuber, Jakob Troppmair, Dietmar Öfner, Stefan Schneeberger, and Theresa Hautz
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regeneration ,mesenchymal stem cells ,machine perfusion ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Transplantation represents the treatment of choice for many end-stage diseases but is limited by the shortage of healthy donor organs. Ex situ normothermic machine perfusion (NMP) has the potential to extend the donor pool by facilitating the use of marginal quality organs such as those from donors after cardiac death (DCD) and extended criteria donors (ECD). NMP provides a platform for organ quality assessment but also offers the opportunity to treat and eventually regenerate organs during the perfusion process prior to transplantation. Due to their anti-inflammatory, immunomodulatory and regenerative capacity, mesenchymal stem cells (MSCs) are considered as an interesting tool in this model system. Only a limited number of studies have reported on the use of MSCs during ex situ machine perfusion so far with a focus on feasibility and safety aspects. At this point, no clinical benefits have been conclusively demonstrated, and studies with controlled transplantation set-ups are urgently warranted to elucidate favorable effects of MSCs in order to improve organs during ex situ machine perfusion.
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- 2021
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19. A Retrospective Propensity Score Matched Analysis Reveals Superiority of Hypothermic Machine Perfusion over Static Cold Storage in Deceased Donor Kidney Transplantation
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Silvia Gasteiger, Valeria Berchtold, Claudia Bösmüller, Lucie Dostal, Hanno Ulmer, Christina Bogensperger, Thomas Resch, Michael Rudnicki, Hannes Neuwirt, Rupert Oberhuber, Benno Cardini, Stefan Scheidl, Gert Mayer, Dietmar Öfner, Annemarie Weissenbacher, and Stefan Schneeberger
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kidney transplantation ,hypothermic machine perfusion ,delayed graft function ,Medicine - Abstract
Hypothermic machine perfusion (HMP) has been introduced as an alternative to static cold storage (SCS) in kidney transplantation, but its true benefit in the clinical routine remains incompletely understood. The aim of this study was to assess the effect of HMP vs. SCS in kidney transplantation. All kidney transplants performed between 08/2015 and 12/2019 (n = 347) were propensity score (PS) matched for cold ischemia time (CIT), extended criteria donor (ECD), gender mismatch, cytomegalovirus (CMV) mismatch, re-transplantation and Eurotransplant (ET) senior program. A total of 103 HMP and 103 SCS instances fitted the matching criteria. Prior to PS matching, the CIT was longer in the HMP group (17.5 h vs. 13.3 h; p < 0.001), while the delayed graft function (DGF) rates were 29.8% and 32.3% in HMP and SCS, respectively. In the PS matched groups, the DGF rate was 64.1% in SCS vs. 31.1% following HMP: equivalent to a 51.5% reduction of the DGF rate (OR 0.485, 95% CI 0.318–0.740). DGF was associated with decreased 1- and 3-year graft survival (100% and 96.3% vs. 90.8% and 86.7%, p = 0.001 and p = 0.008) or a 4.1-fold increased risk of graft failure (HR = 4.108; 95% CI: 1.336–12.631; p = 0.014). HMP significantly reduces DGF in kidney transplantation. DGF remains a strong predictor of graft survival.
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- 2020
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20. Restoring Mitochondrial Function While Avoiding Redox Stress: The Key to Preventing Ischemia/Reperfusion Injury in Machine Perfused Liver Grafts?
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Julia Hofmann, Giorgi Otarashvili, Andras Meszaros, Susanne Ebner, Annemarie Weissenbacher, Benno Cardini, Rupert Oberhuber, Thomas Resch, Dietmar Öfner, Stefan Schneeberger, Jakob Troppmair, and Theresa Hautz
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ischemia/reperfusion injury ,liver transplantation ,redox stress ,mitochondrial dysfunction ,reactive oxygen species ,machine perfusion ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Mitochondria sense changes resulting from the ischemia and subsequent reperfusion of an organ and mitochondrial reactive oxygen species (ROS) production initiates a series of events, which over time result in the development of full-fledged ischemia-reperfusion injury (IRI), severely affecting graft function and survival after transplantation. ROS activate the innate immune system, regulate cell death, impair mitochondrial and cellular performance and hence organ function. Arresting the development of IRI before the onset of ROS production is currently not feasible and clinicians are faced with limiting the consequences. Ex vivo machine perfusion has opened the possibility to ameliorate or antagonize the development of IRI and may be particularly beneficial for extended criteria donor organs. The molecular events occurring during machine perfusion remain incompletely understood. Accumulation of succinate and depletion of adenosine triphosphate (ATP) have been considered key mechanisms in the initiation; however, a plethora of molecular events contribute to the final tissue damage. Here we discuss how understanding mitochondrial dysfunction linked to IRI may help to develop novel strategies for the prevention of ROS-initiated damage in the evolving era of machine perfusion.
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- 2020
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21. Graft Pre-conditioning by Peri-Operative Perfusion of Kidney Allografts With Rabbit Anti-human T-lymphocyte Globulin Results in Improved Kidney Graft Function in the Early Post-transplantation Period—a Prospective, Randomized Placebo-Controlled Trial
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Paul V. Ritschl, Julia Günther, Lena Hofhansel, Anja A. Kühl, Arne Sattler, Stefanie Ernst, Frank Friedersdorff, Susanne Ebner, Sascha Weiss, Claudia Bösmüller, Annemarie Weissenbacher, Rupert Oberhuber, Benno Cardini, Robert Öllinger, Stefan Schneeberger, Matthias Biebl, Christian Denecke, Christian Margreiter, Thomas Resch, Felix Aigner, Manuel Maglione, Johann Pratschke, and Katja Kotsch
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kidney transplantation ,organ preservation ,ATLG ,ischemia reperfusion injury ,RCT ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Introduction: Although prone to a higher degree of ischemia reperfusion injury (IRI), the use of extended criteria donor (ECD) organs has become reality in transplantation. We therefore postulated that peri-operative perfusion of renal transplants with anti-human T-lymphocyte globulin (ATLG) ameliorates IRI and results in improved graft function.Methods: We performed a randomized, single-blinded, placebo-controlled trial involving 50 kidneys (KTx). Prior to implantation organs were perfused and incubated with ATLG (AP) (n = 24 kidney). Control organs (CP) were perfused with saline only (n = 26 kidney). Primary endpoint was defined as graft function reflected by serum creatinine at day 7 post transplantation (post-tx).Results: AP-KTx recipients illustrated significantly better graft function at day 7 post-tx as reflected by lower creatinine levels, whereas no treatment effect was observed after 12 months surveillance. During the early hospitalization phase, 16 of the 26 CP-KTx patients required dialysis during the first 7 days post-tx, whereas only 10 of the 24 AP-KTx patients underwent dialysis. No treatment-specific differences were detected for various lymphocytes subsets in the peripheral blood of patients. Additionally, mRNA analysis of 0-h biopsies post incubation with ATLG revealed no changes of intragraft inflammatory expression patterns between AP and CP organs.Conclusion: We here present the first clinical study on peri-operative organ perfusion with ATLG illustrating improved graft function in the early period post kidney transplantation.Clinical Trial Registration:www.ClinicalTrials.gov, NCT03377283
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- 2018
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22. Differential depletion of total T cells and regulatory T cells and prolonged allotransplant survival in CD3Ɛ humanized mice treated with polyclonal anti human thymocyte globulin.
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Maja Buszko, Benno Cardini, Rupert Oberhuber, Lukas Oberhuber, Bojana Jakic, Anja Beierfuss, Georg Wick, and Giuseppe Cappellano
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Medicine ,Science - Abstract
Thymoglobulin (ATG) is a polyclonal rabbit antibody against human thymocytes used as a T cell-depleting agent to prevent or treat allotransplant rejection. The aim of the present study was to investigate the effect of low dose ATG treatment exclusively on T cells using a humanized BALB/c human CD3Ɛ transgenic mouse model expressing both human and murine T cell receptors (TCR). Mice received a single intravenous (i.v.) injection of ATG. Blood and peripheral lymphoid organs were obtained after different time points. We found a significant T cell depletion in this mouse model. In addition, regulatory T cells (Tregs) proved to be less sensitive to depletion than the rest of T cells and the Treg:non-Treg ratio was therefore increased. Finally, we also investigated the effect of ATG in a heterotopic allogenic murine model of heart transplantation. Survival and transplant function were significantly prolonged in ATG-treated mice. In conclusion, we showed (a) an immunosuppressive effect of ATG in this humanized mouse model which is exclusively mediated by reactivity against human CD3Ɛ; (b) provided evidence for a relative resistance of Tregs against this regimen; and
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- 2017
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23. Lymphocytes as an Indicator for Initial Kidney Function: A Single Center Analysis of Outcome after Alemtuzumab or Basiliximab Induction
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Annemarie Weissenbacher, Theresa Hautz, Michael Kimelman, Rupert Oberhuber, Hanno Ulmer, Claudia Bösmüller, Manuel Maglione, and Stefan Schneeberger
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Alemtuzumab, an anti-CD52 T-cell and B-cell depleting monoclonal antibody, is established for induction therapy in renal transplantation (KTx). We herein provide a comparative analysis between alemtuzumab and basiliximab induction therapy and correlate lymphocyte depletion and recovery with the clinical course after KTx. This is a single center retrospective analysis of 225 patients/consecutive kidney transplantations treated with alemtuzumab for lymphocyte depletion and 205 recipients treated with basiliximab. Mean lymphocyte counts were 22.8 ± 9.41% before Tx and 2.61 ± 3.11% between week 1 and week 3 in the alemtuzumab group and 23.77 ± 10.42% before Tx and 13.92 ± 8.20% in the basiliximab group. Delayed graft function (DGF), cytomegalovirus (CMV) status, and recipient age showed a significant correlation with lymphocyte counts in the alemtuzumab group only. The outcome was read in reference to the velocity of lymphocyte recovery and in comparison to the control group. Lymphocyte counts early after transplantation, following alemtuzumab treatment, could be identified as a predictive factor for kidney function early after transplantation. A detailed analysis of phenotype and function of lymphocytes after alemtuzumab induction together with a correlation with the clinical course is warranted.
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- 2015
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24. Crucial role for neuronal nitric oxide synthase in early microcirculatory derangement and recipient survival following murine pancreas transplantation.
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Benno Cardini, Katrin Watschinger, Martin Hermann, Peter Obrist, Rupert Oberhuber, Gerald Brandacher, Surawee Chuaiphichai, Keith M Channon, Johann Pratschke, Manuel Maglione, and Ernst R Werner
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Medicine ,Science - Abstract
Aim of this study was to identify the nitric oxide synthase (NOS) isoform involved in early microcirculatory derangements following solid organ transplantation.Tetrahydrobiopterin donor treatment has been shown to specifically attenuate these derangements following pancreas transplantation, and tetrahydrobiopterin-mediated protective effects to rely on its NOS-cofactor activity, rather than on its antioxidant capacity. However, the NOS-isoform mainly involved in this process has still to be defined.Using a murine pancreas transplantation model, grafts lacking one of the three NOS-isoforms were compared to grafts from wild-type controls. Donors were treated with either tetrahydrobiopterin or remained untreated. All grafts were subjected to 16 h cold ischemia time and transplanted into wild-type recipients. Following 4 h graft reperfusion, microcirculation was analysed by confocal intravital fluorescence microscopy. Recipient survival was monitored for 50 days.Transplantation of the pancreas from untreated wild-type donor mice resulted in microcirculatory damage of the transplanted graft and no recipient survived more than 72 h. Transplanting grafts from untreated donor mice lacking either endothelial or inducible NOS led to similar outcomes. In contrast, donor treatment with tetrahydrobiopterin prevented microcirculatory breakdown enabling long-term survival. Sole exception was transplantation of grafts from untreated donor mice lacking neuronal NOS. It resulted in intact microvascular structure and long-term recipient survival, either if donor mice were untreated or treated with tetrahydrobiopterin.We demonstrate for the first time the crucial involvement of neuronal NOS in early microcirculatory derangements following solid organ transplantation. In this model, protective effects of tetrahydrobiopterin are mediated by targeting this isoform.
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- 2014
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25. Liver Transplantation in Recipients With a Positive Crossmatch: A Retrospective Single-Center Match-Pair Analysis
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Felix J. Krendl, Margot Fodor, Franka Messner, Agnes Balog, Anja Vales, Benno Cardini, Thomas Resch, Manuel Maglione, Christian Margreiter, Marina Riedmann, Hanno Ulmer, Dietmar Öfner, Rupert Oberhuber, Stefan Schneeberger, and Annemarie Weissenbacher
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Transplantation - Abstract
A positive crossmatch (XM+) is considered a contraindication to solid abdominal organ transplantation except liver transplantation (LT). Conflicting reports exist regarding the effects of XM+ on post-transplant outcomes. The goal of this retrospective single-center analysis is to evaluate the influence of XM+ on relevant outcome parameters such as survival, graft rejection, biliary and arterial complications. Forty-nine adult patients undergoing LT with a XM+ between 2002 and 2017 were included. XM+ LT recipients were matched 1:2 with crossmatch negative (XM−) LT recipients based on the balance of risk (BAR) score. Patient and graft survival were compared using Kaplan-Meier survival analysis and the log-rank test. Comparative analysis of clinical outcomes in XM+ and XM− groups were conducted. Patient and graft survival were similar in XM+ and XM− patients. Rejection episodes did not differ either. Recipients with a strong XM+ were more likely to develop a PCR+ CMV infection. A XM+ was not associated with a higher incidence of biliary or arterial complications. Donor age, cold ischemia time, PCR+ CMV infection and a rejection episode were associated with the occurrence of ischemic type biliary lesions. A XM+ has no effects on patient and graft survival or other relevant outcome parameters following LT.
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- 2023
26. Liver transplantation after successful downstaging of a locally advanced hepatocellular carcinoma with systemic therapy
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Andreas Schmiderer, Heinz Zoller, Markus Niederreiter, Maria Effenberger, Georg Oberhuber, Felix Julius Krendl, Rupert Oberhuber, Stefan Schneeberger, Herbert Tilg, and Angela Djanani
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Gastroenterology ,General Medicine - Abstract
Introduction: Liver transplantation (LT) is potentially curative for patients with cirrhosis and hepatocellular carcinoma (HCC). However, this procedure is usually reserved for patients with early tumor stages or after successful downstaging with local regional therapies (LRT). In patients with locally advanced HCC current guidelines recommend locoregional and palliative systemic therapies for tumor stages Barcelona Clinic Liver Cancer (BCLC) B and C respectively. Case report: In this article we describe a 63 –year-old male patient with locally advanced hepatocellular carcinoma (BCLC C) and hepatitis C associated cirrhosis. Following systemic treatment with the immune checkpoint inhibitor atezolizumab and the anti-VEGF antibody bevacizumab significant downstaging to a tumor stage within the Milan criteria was achieved after which liver transplantation was successfully performed. Conclusion: As more effective systemic therapies become available, liver transplantation and potential curative treatment could become feasible for selected patients with locally advanced HCC.
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- 2023
27. Intestinal perforation mimicking postoperative gas gangrene: a differential diagnosis of a rare but feared surgical complication
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Magdalena SACHER, Valentin LADENHAUF, Martin C. FREUND, Reinhold KAFKA-RITSCH, Irmgard E. KRONBERGER, Rupert OBERHUBER, Felix KRENDL, Katharina ESSWEIN, Christina BOGENSBERGER, Stefan SCHNEEBERGER, Christoph PROFANTER, Dietmar ÖFNER, and Thomas RESCH
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Surgery - Published
- 2022
28. Normothermic liver machine perfusion as a dynamic platform for assessment and treatment of organs from septic donors
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Felix J. Krendl, Rupert Oberhuber, Robert Breitkopf, Günter Weiss, and Stefan Schneeberger
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Hepatology - Published
- 2023
29. Hyperspectral Imaging as a Tool for Viability Assessment During Normothermic Machine Perfusion of Human Livers: A Proof of Concept Pilot Study
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Margot Fodor, Lukas Lanser, Julia Hofmann, Giorgi Otarashvili, Marlene Pühringer, Benno Cardini, Rupert Oberhuber, Thomas Resch, Annemarie Weissenbacher, Manuel Maglione, Christian Margreiter, Philipp Zelger, Johannes D. Pallua, Dietmar Öfner, Robert Sucher, Theresa Hautz, and Stefan Schneeberger
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Perfusion ,Transplantation ,Hemoglobins ,Liver ,transplantation, perfusion, normothermic, imaging, liver, hyperspectral, machine ,Lactates ,Humans ,Pilot Projects ,ddc:610 ,Hyperspectral Imaging ,Organ Preservation - Abstract
Normothermic machine perfusion (NMP) allows for ex vivo viability and functional assessment prior to liver transplantation (LT). Hyperspectral imaging represents a suitable, non-invasive method to evaluate tissue morphology and organ perfusion during NMP. Liver allografts were subjected to NMP prior to LT. Serial image acquisition of oxygen saturation levels (StO2), organ hemoglobin (THI), near-infrared perfusion (NIR) and tissue water indices (TWI) through hyperspectral imaging was performed during static cold storage, at 1h, 6h, 12h and at the end of NMP. The readouts were correlated with perfusate parameters at equivalent time points. Twenty-one deceased donor livers were included in the study. Seven (33.0%) were discarded due to poor organ function during NMP. StO2 (p < 0.001), THI (p < 0.001) and NIR (p = 0.002) significantly augmented, from static cold storage (pre-NMP) to NMP end, while TWI dropped (p = 0.005) during the observational period. At 12–24h, a significantly higher hemoglobin concentration (THI) in the superficial tissue layers was seen in discarded, compared to transplanted livers (p = 0.036). Lactate values at 12h NMP correlated negatively with NIR perfusion index between 12 and 24h NMP and with the delta NIR perfusion index between 1 and 24h (rs = −0.883, p = 0.008 for both). Furthermore, NIR and TWI correlated with lactate clearance and pH. This study provides first evidence of feasibility of hyperspectral imaging as a potentially helpful contact-free organ viability assessment tool during liver NMP.
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- 2022
30. Perfusate Enzymes and Platelets Indicate Early Allograft Dysfunction After Transplantation of Normothermically Preserved Livers
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Annemarie Weissenbacher, Christian Margreiter, Theresa Hautz, Felix J. Krendl, Jakob Troppmair, Valeria Berchtold, Margot Fodor, Andras T. Meszaros, Manuel Maglione, Andrea Griesmacher, Christian Irsara, Benno Cardini, Thomas Resch, Stefan Schneeberger, Robert Breitkopf, Marc Raynaud, Dietmar Öfner, Rupert Oberhuber, Christina Bogensperger, Hanno Ulmer, Giorgi Otarashvili, Silvia Gasteiger, and Franka Messner
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Blood Platelets ,Transplantation ,Machine perfusion ,business.industry ,medicine.medical_treatment ,Organ Preservation ,Liver transplantation ,Allografts ,Cold Ischemia Time ,Enzymes ,Liver Transplantation ,Perfusion ,Andrology ,Liver ,Humans ,Biomarker (medicine) ,Medicine ,Alkaline phosphatase ,Platelet ,business ,Biomarkers - Abstract
Normothermic machine perfusion (NMP) has become a clinically established tool to preserve livers in a near-physiological environment. However, little is known about the predictive value of perfusate parameters toward the outcomes after transplantation.Fifty-five consecutive NMP livers between 2018 and 2019 were included. All of the livers were perfused on the OrganOx metra device according to an institutional protocol. Transplant and perfusion data were collected prospectively.Forty-five livers were transplanted after NMP. Five livers stem from donors after circulatory death and 31 (68.9%) from extended criteria donors. Mean (SD) cold ischemia time was 6.4 (2.3) h; mean (SD) total preservation time was 21.4 (7.1) h. Early allograft dysfunction (EAD) occurred in 13 of 45 (28.9%) patients. Perfusate aspartate aminotransferase (P = 0.008), alanine aminotransferase (P = 0.006), lactate dehydrogenase (P = 0.007) and their development over time, alkaline phosphatase (P = 0.013), and sodium (P = 0.016) correlated with EAD. Number of perfusate platelets correlated with cold ischemia time duration and were indicative for the occurrence of EAD. Moreover, von Willebrand Factor antigen was significantly higher in perfusates of EAD livers (P 0.001), and Δ von Willebrand factor antigen correlated with EAD. Although perfusate lactate and glucose had no predictive value, EAD was more likely to occur in livers with lower perfusate pH (P = 0.008). ΔPerfusate alkaline phosphatase, Δperfusate aspartate aminotransferase, Δperfusate alanine aminotransferase, and Δperfusate lactate dehydrogenase correlated closely with model for early allograft function but not liver graft assessment following transplantation risk score. Bile parameters correlated with extended criteria donor and donor risk index.Biomarker assessment during NMP may help to predict EAD after liver transplantation. The increase of transaminases and lactate dehydrogenase over time as well as platelets and vWF antigen are important factors indicative for EAD.
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- 2022
31. Clinical Implementation of Prolonged Liver Preservation and Monitoring Through Normothermic Machine Perfusion in Liver Transplantation
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Stefan Schneeberger, Thomas Resch, Manuel Maglione, Christopher J.E. Watson, Alois Obwegeser, Rupert Oberhuber, Benno Cardini, Werner Pajk, Theresa Hautz, Judith Martini, Stefan Scheidl, Christian Margreiter, Herbert Tilg, Marion Frank, Florian Augustin, Annemarie Weissenbacher, Andrea Griesmacher, Claudia Bösmüller, Margot Fodor, Stephan Eschertzhuber, Harald Schennach, Robert Breitkopf, Dietmar Öfner, and Harald Mair
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Adult ,Aged, 80 and over ,Transplantation ,Machine perfusion ,medicine.medical_specialty ,Time Factors ,business.industry ,medicine.medical_treatment ,Graft Survival ,Patient survival ,Organ Preservation ,Middle Aged ,Liver transplantation ,Clinical routine ,Extended criteria ,Liver Transplantation ,Surgery ,Perfusion ,medicine ,Humans ,business ,Liver preservation ,Blood bank ,Aged - Abstract
Background Normothermic machine perfusion (NMP) bears the potential for significant prolongation of liver preservation before transplantation. Although safety and feasibility have been recently published, no data are available describing the significant challenges of establishing NMP programs outside clinical studies. We herein present our experience and propose a multidisciplinary approach for liver NMP in the clinical routine. Methods In February 2018, liver NMP was introduced for routine use in marginal organs, logistic challenges, and complex recipients at our institution. In a multidisciplinary effort among transplant coordinators, perfusionists, transplant surgeons, anesthesia, nurses, blood bank as well as laboratory staff, a clinical routine was established and 34 NMP cases were performed without critical incidents or organ loss. Results Nine livers were discarded due to poor organ quality and function observed during NMP. Twenty-five livers were successfully transplanted after preservation of up to 38 h. The extended criteria donors rate was 100% and 92% in discarded and transplanted livers, respectively. Nighttime procedures and parallel transplantations were eventually omitted. Graft and patient survival was 88% at 20 mo. No cholangiopathy was observed despite the use of extended criteria donor organs in 92% of cases. Conclusions NMP in a multidisciplinary approach enables a safe prolongation of liver preservation and overnight organ care. A first field test of NMP indicates safety and benefit of this approach.
- Published
- 2020
32. Donor cardiac arrest and cardiopulmonary resuscitation: impact on outcomes after simultaneous pancreas–kidney transplantation – a retrospective study
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Rupert Oberhuber, Manuel Maglione, Dietmar Öfner, Stefan Schneeberger, Christian Margreiter, Felix J. Krendl, Franka Messner, Joanna W. Etra, Stefan Scheidl, Gerald Brandacher, Valeria Berchtold, Claudia Bösmüller, and Yifan Yu
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medicine.medical_specialty ,medicine.medical_treatment ,pancreatitis ,kidney transplantation ,cardiac arrest ,030230 surgery ,cardiopulmonary resuscitation ,03 medical and health sciences ,0302 clinical medicine ,Clinical Research ,Humans ,Medicine ,Cardiopulmonary resuscitation ,Pancreas ,Kidney transplantation ,Retrospective Studies ,Transplantation ,business.industry ,Donor selection ,Graft Survival ,simultaneous pancreas ,Retrospective cohort study ,medicine.disease ,Tissue Donors ,Heart Arrest ,Surgery ,Log-rank test ,Relative risk ,Pancreatitis ,Original Article ,030211 gastroenterology & hepatology ,Pancreas Transplantation ,business - Abstract
Summary Donor cardiac arrest and cardiopulmonary resuscitation (CACPR) has been considered critically because of concerns over hypoperfusion and mechanical trauma to the donor organs. We retrospectively analyzed 371 first simultaneous pancreas–kidney transplants performed at the Medical University of Innsbruck between 1997 and 2017. We evaluated short‐ and long‐term outcomes from recipients of organs from donors with and without a history of CACPR. A total of 63 recipients received a pancreas and kidney graft from a CACPR donor. At 1, and 5‐years, patient survival was similar with 98.3%, and 96.5% in the CACPR and 97.0%, and 90.2% in the non‐CACPR group (log rank P = 0.652). Death‐censored pancreas graft survival was superior in the CACPR group with 98.3%, and 91.4% compared to 86.3%, and 77.4% (log rank P = 0.028) in the non‐CACPR group, which remained statistically significant even after adjustment [aHR 0.49 (95% CI 0.24–0.98), P = 0.044]. Similar relative risks for postoperative complications Clavien Dindo > 3a, pancreatitis, abscess, immunologic complications, delayed pancreas graft function, and relative length of stay were observed for both groups. Donors with a history of CACPR are, in the current practice, safe for transplantation. Stringent donor selection and short CPR durations may allow for outcomes surpassing those of donors without CACPR.
- Published
- 2020
33. Preoperative Assessment of Muscle Mass Using Computerized Tomography Scans to Predict Outcomes Following Orthotopic Liver Transplantation
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Herbert Tilg, Mathias Pamminger, Dietmar Öfner, Heinz Zoller, Eva Gassner, Christian Margreiter, Hannah Esser, Armin Finkenstedt, Jakob Troppmair, Marina Riedmann, Thomas Resch, Beatrix Mutschlechner, Benno Cardini, Rupert Oberhuber, Stefan Schneeberger, Annemarie Weissenbacher, Manuel Maglione, and C. Boesmueller
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Male ,Sarcopenia ,medicine.medical_specialty ,medicine.medical_treatment ,Urology ,030230 surgery ,Liver transplantation ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Predictive Value of Tests ,Risk Factors ,Prevalence ,Humans ,Medicine ,Clinical significance ,Risk factor ,Psoas Muscles ,Retrospective Studies ,Transplantation ,business.industry ,Skeletal muscle ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Liver Transplantation ,medicine.anatomical_structure ,Austria ,Predictive value of tests ,Preoperative Period ,Female ,030211 gastroenterology & hepatology ,Tomography, X-Ray Computed ,business ,Follow-Up Studies - Abstract
BACKGROUND Sarcopenia is an established risk factor predicting survival in chronically ill and trauma patients. We herein examine the assessment and clinical implication of sarcopenia in liver transplantation (LT). METHODS Computerized tomography scans from 172 patients waitlisted for LT were analyzed by applying 6 morphometric muscle scores, including 2 density indices (psoas density [PD] and skeletal muscle density [SMD]) and 4 scores based on muscle area (total psoas area, psoas muscle index, skeletal muscle area, and skeletal muscle index). RESULTS The prevalence of sarcopenia in our cohort ranged from 7.0% to 37.8%, depending on the score applied. Only sarcopenia as defined by the density indices PD and SMD (but not total psoas area, psoas muscle index, skeletal muscle area, or skeletal muscle index) revealed clinical relevance since it correlates significantly with postoperative complications (≥Grade III, Clavien-Dindo classification) and sepsis. Furthermore, sarcopenia predicted inferior patient and graft survival, with low muscle density (PD
- Published
- 2019
34. Live Confocal Tissue Assessment With SYTO16/PI and WGA Staining Visualizes Acute Organ Damage and Predicts Delayed Graft Function in Kidney Transplantation
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Raimund Margreiter, Rupert Oberhuber, Jakob Troppmair, Stefan Schneeberger, Martin Hermann, Benno Cardini, Hanno Ulmer, Christian Margreiter, Franka Messner, Afshin Soleiman, Dietmar Öfner, Gert Mayer, Annemarie Weissenbacher, Manuel Maglione, Claudia Bösmüller, and Thomas Resch
- Subjects
Adult ,Graft Rejection ,Male ,Pathology ,medicine.medical_specialty ,Time Factors ,Confocal ,Delayed Graft Function ,Pilot Projects ,Kaplan-Meier Estimate ,Nephrectomy ,Risk Assessment ,Donor Selection ,03 medical and health sciences ,0302 clinical medicine ,Preoperative Care ,Biopsy ,Living Donors ,Humans ,Medicine ,Prospective Studies ,Coloring Agents ,Kidney transplantation ,Aged ,Microscopy, Confocal ,Staining and Labeling ,medicine.diagnostic_test ,business.industry ,Donor selection ,Biopsy, Needle ,Graft Survival ,Middle Aged ,Prognosis ,Tissue Graft ,medicine.disease ,Immunohistochemistry ,Kidney Transplantation ,Staining ,Treatment Outcome ,Liver ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,Surgery ,business - Abstract
The aim of our prospective clinical trial was to test a tissue staining technique (real-time confocal analysis [RTCA]) as a rapid assessment tool for donor kidney quality and function in human kidney transplantation.Tools for objective graft tissue viability assessment before kidney transplantation are lacking. RTCA has recently been established and tested in a pilot study using rodent kidneys.RTCA was performed in kidney biopsies stained with SYTO16/PI and WGA. A score between -3 (100% nonviable) and +3 (100% viable) describes the sum of viable cells divided by the number of nonviable cells per examined area (glomerulus, proximal, and distal tubules). The primary study endpoint was the delayed graft function (DGF).Seventy-one kidney transplant recipients were transplanted. The median recipient and donor age were 58.5 and 57 years, respectively. Cold ischemia time was 13.6 ± 4.7 hours; anastomosis time was 30.8 ± 8.7 minutes (mean ± SD). Overall, 23 (33.8%) patients developed DGF. The RTCA score was significantly lower in kidneys developing DGF -0.43 ± 1.78 versus no DGF 0.91 ± 2.17, P = 0.01. The Remuzzi score did not differ between DGF and no DGF, P = 0.13. Remuzzi score and RTCA score correlate inversely significantly; P = 0.004. In the multivariate analysis, solely RTCA score was revealed as a significant independent factor predicting DGF; P = 0.015, Wald = 5.95, odds ratio = 0.72, 95% confidence interval = 0.55 to 0.94.Our data demonstrate that RTCA is feasible and clinically meaningful. The RTCA score predicts DGF and is a valid option to be applied in renal transplantation.
- Published
- 2019
35. Reassessment of Relevance and Predictive Value of Parameters Indicating Early Graft Dysfunction in Liver Transplantation: AST Is a Weak, but Bilirubin and INR Strong Predictors of Mortality
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Christian Margreiter, Dietmar Öfner, Margot Fodor, Wolfgang Peter, Annemarie Weissenbacher, Benno Cardini, Hannah Esser, Herbert Tilg, Manuel Maglione, Thomas Resch, Stefan Schneeberger, Rupert Oberhuber, Adriana Woerdehoff, Robert Sucher, and Heinz Zoller
- Subjects
medicine.medical_specialty ,Graft dysfunction ,RD1-811 ,Synthetic function ,Bilirubin ,reassessment ,medicine.medical_treatment ,liver, transplantation, early allograft dysfunction, outcome, reassessment ,Liver transplantation ,liver ,Gastroenterology ,chemistry.chemical_compound ,Internal medicine ,medicine ,ddc:610 ,Original Research ,business.industry ,Bile duct ,early allograft dysfunction ,Predictive value ,Transplantation ,medicine.anatomical_structure ,chemistry ,outcome ,Surgery ,Bilirubin levels ,business ,transplantation - Abstract
Introduction: Early graft dysfunction (EAD) complicates liver transplantation (LT). The aim of this analysis was to discriminate between the weight of each variable as for its predictive value toward patient and graft survival.Methods: We reviewed all LT performed at the Medical University of Innsbruck between 2007 and 2018. EAD was recorded when one of the following criteria was present: (i) aspartate aminotransferase (AST) levels >2,000 IU/L within the first 7 days, (ii) bilirubin levels ≥10mg/dL or (iii) international normalized ratio (INR) ≥1.6 on postoperative day 7.Results: Of 616 LT, 30.7% developed EAD. Patient survival did not differ significantly (P = 0.092; log rank-test = 2.87), graft survival was significantly higher in non-EAD patients (P = 0.008; log rank-test = 7.13). Bilirubin and INR on postoperative day 7 were identified as strong mortality predictors (Bilirubin HR = 1.71 [1.34, 2.16]; INR HR = 2.69 [0.51, 14.31]), in contrast to AST (HR = 0.91 [0.75, 1.10]). Similar results were achieved for graft loss estimation. A comparison with the Model for Early Allograft Function (MEAF) and the Liver Graft Assessment Following Transplantation (L-GrAFT) score identified a superior discrimination potential but lower specificity.Conclusion: Contrarily to AST, bilirubin and INR have strong predictive capacity for patient and graft survival. This fits well with the understanding, that bile duct injury and deprivation of synthetic function rather than hepatocyte injury are key factors in LT.
- Published
- 2021
36. The Need to Update Endpoints and Outcome Analysis in the Rapidly Changing Field of Liver Transplantation
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Daniel Seehofer, Stefan Schneeberger, Umberto Cillo, Robert Sucher, Heinz Zoller, Margot Fodor, Pål-Dag Line, Herbert Tilg, and Rupert Oberhuber
- Subjects
Transplantation ,medicine.medical_specialty ,Machine perfusion ,Tissue and Organ Procurement ,Waiting Lists ,business.industry ,Bile duct ,medicine.medical_treatment ,Outcome analysis ,Economic shortage ,Liver transplantation ,Risk profile ,Tissue Donors ,Liver Transplantation ,Perfusion ,medicine.anatomical_structure ,Underlying disease ,Medicine ,Humans ,business ,Intensive care medicine - Abstract
Liver transplantation (LT) survival rates have continued to improve over the last decades, mostly due to the reduction of mortality early after transplantation. The advancement is facilitating a liberalization of access to LT, with more patients with higher risk profiles being added to the waiting list. At the same time, the persisting organ shortage fosters strategies to rescue organs of high-risk donors. This is facilitated by novel technologies such as machine perfusion. Owing to these developments, reconsideration of the current and emerging endpoints for the assessment of the efficacy of existing and new therapies is warranted. While conventional early endpoints in LT have focused on the damage induced to the parenchyma, the fate of the bile duct and the recurrence of the underlying disease have a stronger impact on the long-term outcome. In light of this evolving landscape, we here attempt to reflect on the appropriateness of the currently used endpoints in the field of LT trials.
- Published
- 2021
37. Post-Transplant Malignancies following Pancreas Transplantation: Incidence and Implications on Long-Term Outcome from a Single-Center Perspective
- Author
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Thomas Resch, Franka Messner, Felix J. Krendl, Annemarie Weissenbacher, Dietmar Öfner, Stefan Scheidl, Stefan Schneeberger, Manuel Maglione, Benno Cardini, Christian Margreiter, Claudia Bösmüller, and Rupert Oberhuber
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,graft survival ,Pancreas transplantation ,Malignancy ,Single Center ,Gastroenterology ,Article ,Internal medicine ,medicine ,pancreas transplantation ,immunosuppression ,business.industry ,Melanoma ,Incidence (epidemiology) ,Immunosuppression ,General Medicine ,medicine.disease ,medicine.anatomical_structure ,incidence ,Medicine ,Graft survival ,business ,Pancreas ,malignancy - Abstract
Chronic immunosuppression is associated with an increased risk of malignancy. The main objective of this study is to evaluate the incidence and effect of post-transplant malignancies (PTMs) following pancreas transplantation. The 348 first pancreas transplants performed between 1985 and 2015 were retrospectively analyzed in this study. Incidences of PTMs, as well as patient and graft survival, were evaluated. Out of 348 patients, 71 (20.4%) developed a PTM. Median time to diagnosis was 130 months. Thirty-six patients (50.7%) developed skin cancers (four patients with melanoma, 32 with NMSCs). Solid organ malignancy occurred in 25 (35.2%), hematologic malignancy in ten patients (14.1%). Affected patients were transplanted earlier [2000 (IQR 1993−2004) vs. 2003 (IQR 1999−2008), p <, 0.001]. No differences in induction therapy were seen, both groups demonstrated comparable patient and graft survival. Pancreas transplant recipients with solid organ and hematologic malignancies had a three- and six-fold increased hazard of death compared to those with skin cancers [aHR 3.04 (IQR 1.17–7.91), p = 0.023, aHR 6.07 (IQR 1.87–19.71), p = 0.003]. PTMs affect every fifth patient following pancreas transplantation. Skin cancers are the most common malignancies accounting for 50% of all PTMs. These results underscore the importance of close dermatologic follow-up.
- Published
- 2021
38. Good Long-term Results Following Simultaneous Pancreas-kidney Transplantation in a 69-y-old Recipient: A Case Report
- Author
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Rupert Oberhuber, Dietmar Öfner, Christian Margreiter, Stefan Scheidl, Katrin Kienzl-Wagner, Felix J. Krendl, Claudia Bösmüller, Stefan Schneeberger, Valeria Berchtold, and Franka Messner
- Subjects
Transplantation ,Kidney ,medicine.medical_specialty ,RD1-811 ,business.industry ,Simultaneous pancreas kidney transplantation ,Long term results ,Graft function ,Surgery ,medicine.anatomical_structure ,Older patients ,Renal transplant ,medicine ,Pancreas ,business ,Pancreas and Islet Transplantation - Abstract
In contrast to well-published data with acceptable long-term results in large cohorts of single renal transplant recipients aged >65 y (lit.), combined pancreas-kidney transplantation in recipients >50 y is discussed controversially. Some groups have identified older recipients as a high-risk group, demonstrating decreased patient and graft survival in this population.1-4 Nevertheless, several centers have reported results for pancreatic transplantation in older patients as being comparable to those for younger recipients with the age cutoff ranging from 50 to 60 y.5-10 At our center, we have long-term experience with a total of 655 pancreas transplants performed between 1979 and August 2020, whereby 21 recipients were over 60 y of age; the oldest was age 69 and in remarkably good general condition with good mental adherence and a strong wish to undergo simultaneous kidney-pancreas transplantation (SPK). We retrospectively analyzed patient, pancreas, and kidney graft survival, graft function, and complications at month 38 posttransplant.
- Published
- 2021
39. 313.9: Perfusate IL-6 Levels During Liver NMP Might Be Predictive For Hemodynamic Response and Catecholamine Demand After Reperfusion in the Recipient
- Author
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Annemarie Weissenbacher, Simon Mathis, Benno Cardini, Christina Bogensperger, Gabriel Putzer, Lukas Gasteiger, Thomas Resch, Rupert Oberhuber, Dietmar Öfner, Tobias J Hell, Judith Martini, and Stefan Schneeberger
- Subjects
Transplantation - Published
- 2022
40. Influence of early biliary complications on survival rates after pediatric liver transplantation-A positive outlook
- Author
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Andreas Entenmann, Stefan Schneeberger, Dietmar Öfner, Hanno Ulmer, Christian Margreiter, Franka Messner, Georg F. Vogel, Johanna Krapf, Thomas Müller, Denise Aldrian, Raimund Margreiter, Rupert Oberhuber, Valeria Berchtold, Benno Cardini, Annemarie Weissenbacher, and Hans J. Schlitt
- Subjects
Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Biliary Tract Diseases ,Perforation (oil well) ,030232 urology & nephrology ,030230 surgery ,Liver transplantation ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Postoperative Complications ,Risk Factors ,Internal medicine ,Medicine ,Humans ,Risk factor ,Transplantation ,business.industry ,Graft Survival ,Patient survival ,medicine.disease ,respiratory tract diseases ,Liver Transplantation ,Bowel obstruction ,Survival Rate ,Austria ,Pediatrics, Perinatology and Child Health ,Cohort ,Graft survival ,Female ,business ,Hospital stay - Abstract
BACKGROUND Early biliary complications (EBC) constitute a burden after pediatric liver transplantation frequently requiring immediate therapy. We aimed to assess the impact of EBC on short- and long-term patient and graft survival as well as post-transplant morbidity. METHODS We analyzed 121 pediatric liver transplantations performed between 1984 and 2019 at the Medical University of Innsbruck for the occurrence of early (
- Published
- 2021
41. Interventional management after complicated pancreatic surgery
- Author
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Stefan Schneeberger, Dietmar Öfner, Benno Cardini, Reto Bale, Peter Schullian, Christian Margreiter, Thomas Resch, Daniel Putzer, Werner Jaschke, Margot Fodor, Florian Primavesi, Rupert Oberhuber, Manuel Maglione, Stefan Stättner, and E. Braunwarth
- Subjects
medicine.medical_specialty ,Percutaneous ,medicine.diagnostic_test ,business.industry ,General surgery ,Fistula ,Interventional radiology ,Vascular surgery ,medicine.disease ,Cardiac surgery ,medicine.anatomical_structure ,Radiological weapon ,medicine ,Surgery ,Pancreas ,business ,Abdominal surgery - Abstract
Despite technical advances in surgical resection and postoperative management of the pancreas, surgical procedures of the pancreas are associated with a high rate of complications, resulting in a relevant morbidity and mortality. Early diagnosis and management of complications associated with pancreas surgery is mandatory, favoring a multidisciplinary approach. Interventional radiology offers minimal invasive techniques to manage post-surgical complications. These procedures are highlighted in this review, including percutaneous drainage of fluid collections, percutaneous transhepatic biliary interventions, arterial embolisation and fistula embolisation. Post-surgical complications of pancreatic surgery are effectively managed by radiological procedures, offering a feasible and safe treatment with low morbidity rates. Accurate patient selection is key to an effective management of clinical situations where these interventions represent the first line approach. Radiologic procedures allow for minimal invasive treatment of postoperative complications after pancreatic surgery, reducing the time of hospitalization and the time of recovery.
- Published
- 2019
42. Sodium Sulfite Exacerbates Allograft Vasculopathy and Affects Tryptophan Breakdown in Murine Heterotopic Aortic Transplantation
- Author
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Gerald Brandacher, Maximilian Mackowitz, Christina Maria Steger, Christian Margreiter, Johanna M. Gostner, Stefan Schneeberger, Robert Sucher, Dietmar Fuchs, Elisabeth Mohr, Theresa Hautz, Rupert Oberhuber, Benno Cardini, Vanessa Mellitzer, and Thomas Resch
- Subjects
Aging ,Antioxidant ,Article Subject ,Metabolite ,medicine.medical_treatment ,Vascular Cell Adhesion Molecule-1 ,Pharmacology ,medicine.disease_cause ,Carotid Intima-Media Thickness ,Biochemistry ,Major Histocompatibility Complex ,chemistry.chemical_compound ,Immune system ,medicine ,Animals ,Sulfites ,RNA, Messenger ,Vascular Diseases ,lcsh:QH573-671 ,Aorta ,Kynurenine ,Sodium sulfite ,Mice, Inbred BALB C ,lcsh:Cytology ,Tryptophan ,Cell Biology ,General Medicine ,Allografts ,Mice, Inbred C57BL ,Transplantation ,P-Selectin ,chemistry ,Biomarkers ,Oxidative stress ,Research Article - Abstract
Graft vasculopathy is the main feature of chronic rejection in organ transplantation, with oxidative stress being a major trigger. Inflammation-associated prooxidant processes may be controlled by antioxidants; however, interference with redox-regulated mechanisms is a complex endeavor. An essential feature of the cellular immune response is the acceleration of tryptophan (Trp) breakdown, leading to the formation of several bioactive catabolites. Long-term activation of this immunobiochemical pathway contributes to the establishment of a tolerogenic environment, thereby supporting allograft survival. Herein, the impact of the antioxidant sodium sulfite on the development of graft vasculopathy was assessed in murine aortic transplantation. Allogeneic (BALB/c to C57BL/6) heterotopic murine aortic transplantations were performed. Animals were left untreated or were treated with 10 μl of 0.1 M, of 0.01 M sodium sulfite, or of 0.1 M sodium sulfate, intraperitoneally once/day, until postoperative day (POD) 100. Grafts were assessed by histology, immunohistochemistry, and adhesion molecule gene expression. Serum concentrations of tryptophan and its catabolite kynurenine (Kyn) were measured. On day 100, graft vasculopathy was significantly increased upon treatment with 0.1 M sodium sulfite, compared to allogeneic untreated controls (p=0.004), which correlated with a significant increase ofα-smooth-muscle-actin, Vcam-1, and P-selectin. Serum Kyn concentrations increased in the allogeneic control group over time (p<0.05,POD≥50), while low-dose sodium sulfite treatment (0.01 M) treatment resulted in a decrease in Kyn levels over time (p<0.05,POD≥10), compared to the respective baselines (p<0.05). Longitudinal analysis of serum metabolite concentrations in the different treatment groups further identified an overall effect of sodium sulfite on Kyn concentrations. Antioxidative treatment may result in ambivalent consequences. Our data reveal that an excess of antioxidants like sodium sulfite can aggravate allograft vasculopathy, which further highlights the challenges associated with interventions that interfere with the complex interplay of redox-regulated inflammatory processes.
- Published
- 2019
43. Outcomes following pancreatic resections—results and challenges of an Austrian university hospital compared to nationwide data and international centres
- Author
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Christian Margreiter, Stefan Schneeberger, Manuel Maglione, Thomas Resch, Silvia Gasteiger, Rupert Oberhuber, Stefan Stättner, Julia Oberschmied, Stefanie Kuscher, Benno Cardini, Luisa Guschlbauer, Dietmar Öfner, and Florian Primavesi
- Subjects
medicine.medical_specialty ,Gastric emptying ,business.industry ,General surgery ,Vascular surgery ,medicine.disease ,Pancreatic surgery ,Cardiac surgery ,Pancreatic fistula ,medicine ,Carcinoma ,Surgery ,business ,Body mass index ,Abdominal surgery - Abstract
Despite clear advances in decreasing postoperative mortality below 4% after pancreatic resections in experienced centres, specific morbidity according to standardized definitions still remains high. While some recent multicentre studies have reported on complications after pancreatic surgery in Austria, detailed outcome data from single high-volume centres over longer time-periods are scarce. This study provides an in-depth picture of patient characteristics, indications, morbidity and mortality after pancreatic surgery in an Austrian tertiary referral centre. All patients undergoing curative intent resection between 2010 and 2017 at the Medical University of Innsbruck were evaluated. Patient characteristics and procedural details, overall and specific complications including postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE) and post-pancreatectomy haemorrhage (PPH) rates according to accepted definitions are reported. Outcomes after pancreatic head resections, distal pancreatectomy and other types of resections are compared. Factors associated with severe and overall morbidity are evaluated by logistic regression modelling. A total of 343 patients underwent pancreatic resection, at a median of 64 years (53% males). Most common indications were pancreatic or bile-duct carcinoma (52%), benign/precursor lesions (22%) and neuroendocrine tumours (11%). The 90-day mortality was 2%; 90-day overall/severe morbidity was 66.2%/22.4%. POPF grade B/C occurred in 19.3%, PPH in 17.5% and DGE in 14.3%. Male gender was associated with severe morbidity, body mass index and procedures other than distal resections with overall morbidity. POPF and PPH were major causes for relaparotomy. Pancreatic resections in our centre are performed with low mortality, although morbidity still represents a relevant clinical problem, especially POPF and PPH.
- Published
- 2019
44. Good Results with Individually Adapted Long-Term Immunosuppression Following Alemtuzumab Versus ATG Induction Therapy in Combined Kidney-Pancreas Transplantation: A Single-Center Report
- Author
-
Franka Messner, Stefan Scheidl, Manuel Maglione, Rupert Oberhuber, Stefan Schneeberger, Dietmar Öfner, Raimund Margreiter, Robert Öllinger, Claudia Bösmüller, Christian Margreiter, and Hannes Neuwirt
- Subjects
Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Urology ,030230 surgery ,Pancreas transplantation ,Single Center ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Humans ,Survival rate ,Alemtuzumab ,Kidney transplantation ,Letter To Editor ,Antilymphocyte Serum ,Immunosuppression Therapy ,Transplantation ,Creatinine ,business.industry ,Graft Survival ,Immunosuppression ,General Medicine ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Survival Rate ,Diabetes Mellitus, Type 1 ,Treatment Outcome ,chemistry ,030211 gastroenterology & hepatology ,Female ,Pancreas Transplantation ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Retrospective analysis of the long-term results of a randomized controlled trial comparing alemtuzumab (ALEM) and antithymocyte globulin (ATG) as induction therapy in simultaneous pancreas-kidney transplantation (SPK) to address individualized long-term immunosuppression. Between 2006 and 2010 a total of 30 SPKs were randomized to treatment with ALEM plus tacrolimus (TAC) monotherapy (Group A, n=14) versus ATG induction plus TAC, mycophenolate mofetil (MMF) and steroids (Group B, n=16), followed by individualized long-term immunosuppression. We here present the long-term results for graft survival, graft function, and major complications. The 9-year patient survival rates in Groups A and Group B were 92.9% and 86.7% respectively; pancreas graft survival was 75.0% and 65.0% respectively; renal graft survival was 83.1% and 93.8% respectively. Long-term graft function was excellent with a creatinine of 1.5 mg/dL and 1.4 mg/dL, fasting glycemia of 104 mg/dL and 102 mg/dL, hemoglobin (Hb) A1c of 5.4 g% and 5.6 g% in Group A and Group B, respectively. Major complications were comparable in both groups. Good long-term results for patient, pancreas graft and kidney graft survival were achieved in both groups with individually adapted maintenance immunosuppression. ALEM is a valid induction therapy.
- Published
- 2019
45. Successful management of recurrent focal segmental glomerulosclerosis
- Author
-
Stefan Schneeberger, Alejandra Rosales, Michael A. Rudnicki, Christian Margreiter, Siegfried Waldegger, Rupert Oberhuber, Katrin Kienzl-Wagner, Thomas Giner, Afschin Soleiman, Stefan Scheidl, Dietmar Öfner, and Claudia Bösmüller
- Subjects
medicine.medical_specialty ,domino transplantation ,kidney disease ,medicine.medical_treatment ,030232 urology & nephrology ,Case Report ,Case Reports ,urologic and male genital diseases ,Ofatumumab ,Nephropathy ,retransplantation ,03 medical and health sciences ,chemistry.chemical_compound ,recurrent ,0302 clinical medicine ,Focal segmental glomerulosclerosis ,medicine ,Immunology and Allergy ,Pharmacology (medical) ,030212 general & internal medicine ,Kidney transplantation ,disease ,disease pathogenesis ,Transplantation ,urogenital system ,business.industry ,Primary Focal Segmental Glomerulosclerosis ,medicine.disease ,female genital diseases and pregnancy complications ,Surgery ,surgical procedures, operative ,chemistry ,Hemodialysis ,business ,Kidney disease - Abstract
Primary focal segmental glomerulosclerosis (FSGS) recurs in up to 55% of patients after kidney transplantation. Herein we report the successful management of recurrent FSGS. A 5‐year‐old boy with primary FSGS received a deceased donor renal transplant. Immediate and fulminant recurrence of FSGS caused anuric graft failure that was resistant to plasmapheresis and rituximab. After exclusion of structural or immunologic damage to the kidney by repeated biopsies, the allograft was retrieved from the first recipient on day 27 and transplanted into a 52‐year‐old second recipient who had vascular nephropathy. Immediately after retransplantation, the allograft regained function with excellent graft function persistent now at 3 years after transplant. After 2 years on hemodialysis, the boy was listed for kidney retransplantation. To prevent FSGS recurrence, pretreatment with ofatumumab was performed. Nephrotic range proteinuria still occurred after the second transplantation, which responded, however, to daily plasma exchange in combination with ofatumumab. At 8 months after kidney retransplantation graft function is good. The clinical course supports the hypothesis of a circulating permeability factor in the pathogenesis of FSGS. Successful ofatumumab pretreatment implicates a key role of B cells. Herein we provide a description of successful management of kidney failure by FSGS, carefully avoiding waste of organs., Successful management of recurrent primary focal segmental glomerulosclerosis after kidney transplantation includes retransplantation of an allograft that failed in the first recipient due to disease recurrence into a second recipient and ofatumumab pretreatment before kidney retransplantation in the patient with fulminant recurrence of focal segmental glomerulosclerosis in the first graft.
- Published
- 2018
46. High alpha-fetoprotein levels after liver transplantation in hepatoblastoma: Does it matter?
- Author
-
Benjamin Hetzer, Rupert Oberhuber, Stefan Schneeberger, Roman Crazzolara, and Andreas Entenmann
- Subjects
Gynecology ,Hepatoblastoma ,medicine.medical_specialty ,Alpha fetoprotein levels ,Cardiothoracic surgery ,business.industry ,medicine.medical_treatment ,medicine ,Liver transplantation ,medicine.disease ,business - Abstract
High alpha-fetoprotein levels after liver transplantation in hepatoblastoma: Does it matter?Hetzer Benjamin, M.D.1, Oberhuber Rupert, M.D.2, Entenmann Andreas, M.D.1, Schneeberger Stefan, M.D.2, Crazzolara Roman, M.D.1,*1Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria2Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria*Correspondence to:Roman Crazzolara, M.D., Department of Pediatrics, Anichstrasse 35, 6020 Innsbruck, Austria; Tel.: 0043-512-504-23600; Fax: 0043-512-504-24934; Email: roman.crazzolara@i-med.ac.at
- Published
- 2020
47. Live Confocal Imaging as a Novel Tool to Assess Liver Quality: Insights From a Murine Model
- Author
-
Stefan Schneeberger, Benno Cardini, Thomas Resch, Christian Margreiter, Margot Fodor, Bettina Zelger, Rupert Oberhuber, Dietmar Öfner, H. G. Schwelberger, Annemarie Weißenbacher, Martin Hermann, Verena Wieser, Manuel Maglione, Vanessa Mellitzer, Jakob Troppmair, Herbert Tilg, and Theresa Hautz
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Time Factors ,Biopsy ,Cold storage ,030230 surgery ,law.invention ,Proinflammatory cytokine ,03 medical and health sciences ,0302 clinical medicine ,Methionine ,Confocal microscopy ,law ,Non-alcoholic Fatty Liver Disease ,Predictive Value of Tests ,Nonalcoholic fatty liver disease ,medicine ,Animals ,Warm Ischemia ,Survival analysis ,Liver injury ,Tissue Survival ,Transplantation ,Microscopy, Confocal ,Warm Ischemia Time ,business.industry ,Cold Ischemia ,medicine.disease ,Choline Deficiency ,Mice, Inbred C57BL ,Disease Models, Animal ,Liver ,Murine model ,Reperfusion Injury ,Reperfusion ,030211 gastroenterology & hepatology ,business ,Fatty Liver, Alcoholic - Abstract
BACKGROUND In an experimental murine liver clamping model, we aimed to investigate the efficacy of real-time confocal microscopy (RCM) in assessing viability of steatotic livers in comparison to standard assessment tools, including histopathological evaluation. METHODS C57Bl/6 mice were subjected to a methionine-choline-deficient diet causing nonalcoholic fatty liver disease or to Lieber DeCarli diet causing ethanol-induced liver injury. Untreated animals served as controls. Liver biopsies were analyzed following challenge with 45 min of warm ischemia time and either 4 h of reperfusion or 24 h of cold storage. Organ quality assessment was performed at defined time points by RCM, histological staining, measurement of serum alanine aminotransferase activity, and expression analyses of proinflammatory cytokines. Additionally, survival analysis was performed. RESULTS Cold as well as warm ischemia time resulted in a significant decrease in cell viability when compared with naive livers as well as nonischemic-challenged steatotic livers (P
- Published
- 2020
48. Liver Transplantation Activity in the Eurotransplant Area Is Recovering Slowly During the COVID-19 Crisis
- Author
-
Dietmar Öfner, Gabriel Putzer, Robert Breitkopf, Tobias Hell, Rupert Oberhuber, Simon Mathis, Arjan van Enckevort, Lukas Gasteiger, Stefan Schneeberger, and Judith Martini
- Subjects
2019-20 coronavirus outbreak ,Transplantation ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,medicine.medical_treatment ,MEDLINE ,lcsh:Surgery ,lcsh:RD1-811 ,Liver transplantation ,Virology ,medicine ,business ,Letter to the Editor - Published
- 2020
49. Dealing With Liver Transplantation during Coronavirus Disease 2019 Pandemic: Normothermic Machine Perfusion Enables for Donor, Organ, and Recipient Assessment: A Case Report
- Author
-
Annemarie Weissenbacher, Dietmar Öfner, Benno Cardini, Christina Bogensperger, Stefan Schneeberger, Rupert Oberhuber, Giorgi Otarashvili, Silvia Gasteiger, and Valeria Berchtold
- Subjects
medicine.medical_treatment ,AST, aspartate aminotransferase ,030230 surgery ,Liver transplantation ,RT-PCR, real-time polymerase chain reaction ,law.invention ,NMP, normothermic machine preservation ,ECD, expanded criteria donor ,0302 clinical medicine ,COVID-19 Testing ,law ,Pandemic ,MELD, Model for End-stage Liver Disease ,Liver preservation ,SOTR, solid organ transplant recipients ,LDH, lactate dehydrogenase ,Reverse Transcriptase Polymerase Chain Reaction ,Organ Preservation ,SCS, static cold storage ,DRI, donor risk index ,ICU, intensive care unit ,Intensive care unit ,Tissue Donors ,Perfusion ,DBD, donor after brain death ,IL-6, interleukin 6 ,030211 gastroenterology & hepatology ,Female ,Coronavirus Infections ,Adult ,medicine.medical_specialty ,CIT, cold ischemia time ,Coronavirus disease 2019 (COVID-19) ,ALT, alanine transaminase ,Pneumonia, Viral ,Ischemia ,SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 ,Article ,WHO, World Health Organization ,03 medical and health sciences ,Betacoronavirus ,OR, operating room ,medicine ,Humans ,Intensive care medicine ,Pandemics ,ARDS, acute respiratory distress syndrome ,Transplantation ,Machine perfusion ,business.industry ,Clinical Laboratory Techniques ,SARS-CoV-2 ,AIH, autoimmune hepatitis ,CT, computer tomography ,COVID-19 ,COVID-19, Coronavirus Disease ,INR, International normalized ratio (INR) ,medicine.disease ,Liver Transplantation ,Surgery ,PBC, primary biliary cholangitis ,BMI, Body Mass Index ,business - Abstract
The coronavirus disease 2019 (COVID-19) pandemic has changed life on a global scale. The numbers of transplantations have plummeted as a result of fear of disease transmission, recipient coronavirus disease 2019 infection, priority shift, and resource limitations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complicates transplantation because donor testing, (re)allocation of limited resources, and recipient testing may exceed permissible ischemia times. Normothermic machine perfusion (NMP) helps safely prolong liver preservation up to 38 hours. Additional time is essential under the current circumstances. Here we present the case of a 29-year-old liver transplant recipient in whom prolonged liver preservation required for SARS-CoV-2 screening was accomplished through NMP. Donor and recipient test results for SARS-CoV-2 were negative, and intensive care unit capacity was eventually available. The surgical procedure and postoperative course were uneventful. NMP can extend preservation times in liver transplantation while awaiting SARS-CoV-2 test results and available intensive care unit capacity.
- Published
- 2020
50. A Retrospective Propensity Score Matched Analysis Reveals Superiority of Hypothermic Machine Perfusion over Static Cold Storage in Deceased Donor Kidney Transplantation
- Author
-
Rupert Oberhuber, Michael A. Rudnicki, Valeria Berchtold, Annemarie Weissenbacher, Gert Mayer, Stefan Scheidl, Silvia Gasteiger, Hanno Ulmer, Benno Cardini, Dietmar Öfner, Christina Bogensperger, Stefan Schneeberger, Lucie Dostal, Claudia Bösmüller, Thomas Resch, and Hannes Neuwirt
- Subjects
medicine.medical_specialty ,animal structures ,Urology ,Cold storage ,kidney transplantation ,lcsh:Medicine ,030230 surgery ,Cold Ischemia Time ,Article ,03 medical and health sciences ,0302 clinical medicine ,hypothermic machine perfusion ,delayed graft function ,Medicine ,Kidney transplantation ,Machine perfusion ,Kidney ,business.industry ,lcsh:R ,General Medicine ,medicine.disease ,Delayed Graft Function ,Transplantation ,medicine.anatomical_structure ,Propensity score matching ,030211 gastroenterology & hepatology ,business - Abstract
Hypothermic machine perfusion (HMP) has been introduced as an alternative to static cold storage (SCS) in kidney transplantation, but its true benefit in the clinical routine remains incompletely understood. The aim of this study was to assess the effect of HMP vs. SCS in kidney transplantation. All kidney transplants performed between 08/2015 and 12/2019 (n = 347) were propensity score (PS) matched for cold ischemia time (CIT), extended criteria donor (ECD), gender mismatch, cytomegalovirus (CMV) mismatch, re-transplantation and Eurotransplant (ET) senior program. A total of 103 HMP and 103 SCS instances fitted the matching criteria. Prior to PS matching, the CIT was longer in the HMP group (17.5 h vs. 13.3 h, p <, 0.001), while the delayed graft function (DGF) rates were 29.8% and 32.3% in HMP and SCS, respectively. In the PS matched groups, the DGF rate was 64.1% in SCS vs. 31.1% following HMP: equivalent to a 51.5% reduction of the DGF rate (OR 0.485, 95% CI 0.318&ndash, 0.740). DGF was associated with decreased 1- and 3-year graft survival (100% and 96.3% vs. 90.8% and 86.7%, p = 0.001 and p = 0.008) or a 4.1-fold increased risk of graft failure (HR = 4.108, 95% CI: 1.336&ndash, 12.631, p = 0.014). HMP significantly reduces DGF in kidney transplantation. DGF remains a strong predictor of graft survival.
- Published
- 2020
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