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Thi Phuong Thao Hoang,1 Philipp Schindler,2 Nikolaus Börner,3 Max Masthoff,2 Mirjam Gerwing,2 Philippa von Beauvais,2 Enrico N De Toni,4 Christian M Lange,4 Jonel Trebicka,5 Haluk Morgül,6 Max Seidensticker,1 Jens Ricke,1 Andreas Pascher,6 Markus Guba,3 Michael Ingrisch,1 Moritz Wildgruber,1,* Osman Öcal1,* 1Department of Radiology, University Hospital, LMU Munich, Munich, Germany; 2Clinic for Radiology, University Hospital Muenster, Muenster, Germany; 3Department of General, Visceral and Transplantation Surgery, University Hospital, LMU Munich, Munich, Germany; 4Department for Internal Medicine II, University Hospital, LMU Munich, Munich, Germany; 5Department for Internal Medicine B, Universitätsklinikum Münster, Münster, Germany; 6Department of General, Visceral and Transplant Surgery, Universitätsklinikum Münster, Münster, Germany*These authors contributed equally to this workCorrespondence: Osman Öcal, Department of Radiology, University Hospital – LMU Munich, Marchioninistrasse 15, D-81377, München, Germany, Email osman.oecal@med.uni-muenchen.dePurpose: To investigate the prognostic value of computed tomography (CT) derived imaging biomarkers in hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) and develop a predictive nomogram model.Patients and Methods: This retrospective study included 178 patients with histopathologically confirmed HCC who underwent liver transplantation between 2007 and 2021 at the two academic liver centers. We evaluated dedicated imaging features from baseline multiphase contrast-enhanced CT supplemented by several clinical findings and laboratory parameters. Time-to-recurrence was estimated by Kaplan–Meier analysis. Univariable Cox proportional hazard regression and multivariable Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to assess independent prognostic factors for recurrence. A nomogram model was then built based on the independent factors selected through LASSO regression, to predict the probabilities of HCC recurrence at one, three, and five years.Results: The rate of HCC recurrence after LT was 17.4% (31 of 178). The LASSO analysis revealed six independent predictors associated with an elevated risk of tumor recurrence. These predictors included the presence of peritumoral enhancement, the presence of over three tumor lesions, the largest tumor diameter greater than 3 cm, serum alpha-fetoprotein (AFP) levels exceeding 400 ng/mL, and the presence of a tumor capsule. Conversely, a history of bridging therapies was found to be correlated with a reduced risk of HCC recurrence. In addition, Kaplan-Meier curves showed patients with irregular margin, satellite nodules, or small lesions displayed shorter time-to-recurrence. Our nomogram demonstrated good performance, yielding a C-index of 0.835 and AUC values of 0.86, 0.88, and 0.85 for the predictions of 1-year, 3-year, and 5-year TTR, respectively.Conclusion: Imaging parameters derived from baseline contrast-enhanced CT showing malignant behavior and aggressive growth patterns, along with serum AFP and history of bridging therapies, show potential as biomarkers for predicting HCC recurrence after transplantation.Keywords: hepatocellular carcinoma, transplantation, imaging, recurrence

Competing Interests: Die Übersicht über die Interessenkonflikte der Autorinnen und Autoren sind im Leitlinienreport veröffentlicht.

Background: With the increasing efficacy of systemic therapy, liver transplantation plays an important role not only for hepatocellular carcinoma (HCC) but also for nonresectable intrahepatic cholangiocellular carcinoma (iCC), perihilar cholangiocellular carcinoma (phCC) and colorectal liver metastases (CRLM)., Aim: To review the current state of knowledge regarding the indications, patient selection and expected outcomes of liver transplantation for HCC, iCC, phCC and CRLM., Results: When combined with neoadjuvant locoregional therapy (LRT) and/or systemic therapy, patients with nonresectable HCC, iCC, pCC and CRLM confined to the liver can be successfully transplanted with 5‑year survival rates exceeding 65%. The key to success is strict patient selection, which includes oncogenetic (e.g., BRAFV600E mutation status) and clinical criteria indicative of individual tumor biology (tumor markers: alpha-fetoprotein, AFP/carbohydrate antigen 19‑9, CA19-9/carcinoembryonic antigen, CEA, stable response to neoadjuvant therapy) in addition to morphometric criteria., Conclusion: Liver transplantation offers the possibility of curative treatment even for nonresectable hepatic malignancies. A major limitation of this treatment is the lack of donor organs. Crucial for success is patient selection based on individual tumor biology., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Here, we present a detailed computational study of the stability and the electronic structure of nitrogen-doped graphene (N 4 V 2 ) supported Cu n ( n = 1-5) clusters, which are promising carbon-dioxide electroreduction catalysts. The binding of the clusters to the nitrogen-doped graphene and the electronic structure of these systems were investigated under vacuum and electrochemical conditions. The stability analysis showed that among the systems, the nitrogen-doped graphene bound Cu 4 is the most stable in vacuum, while in an electrolyte, and at a negative potential, the N 4 V 2 -Cu 3 is energetically more favorable. The ground state electronic structure of the nitrogen-doped graphene substrate undergoes topological phase transition, from a semimetallic state, and we observed a metallic and topologically trivial state after the clusters are deposited. The electrode potential adjusts the type and density of the charge carriers in the semimetallic models, while the structures containing copper exhibit bands which are deformed and relaxed by the modified number of electrons., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: While 4 randomized controlled clinical trials confirmed the early benefits of hypothermic oxygenated machine perfusion (HOPE), high-level evidence regarding long-term clinical outcomes is lacking. The aim of this follow-up study from the HOPE-ECD-DBD trial was to compare long-term outcomes in patients who underwent liver transplantation using extended criteria donor allografts from donation after brain death (ECD-DBD), randomized to either HOPE or static cold storage (SCS)., Methods: Between September 2017 and September 2020, recipients of liver transplantation from 4 European centers receiving extended criteria donor-donation after brain death allografts were randomly assigned to HOPE or SCS (1:1). Follow-up data were available for all patients. Analyzed endpoints included the incidence of late-onset complications (occurring later than 6 months and graded according to the Clavien-Dindo Classification and the Comprehensive Complication Index) and long-term graft survival and patient survival., Results: A total of 46 patients were randomized, 23 in both arms. The median follow-up was 48 months (95% CI: 41-55). After excluding early perioperative morbidity, a significant reduction in late-onset morbidity was observed in the HOPE group (median reduction of 23 Comprehensive Complication Index-points [p=0.003] and lower incidence of major complications [Clavien-Dindo ≥3, 43% vs. 85%, p=0.009]). Primary graft loss occurred in 13 patients (HOPE n=3 vs. SCS n=10), resulting in a significantly lower overall graft survival (p=0.029) and adverse 1-, 3-, and 5-year survival probabilities in the SCS group, which did not reach the level of significance (HOPE 0.913, 0.869, 0.869 vs. SCS 0.783, 0.606, 0.519, respectively)., Conclusions: Our exploratory findings indicate that HOPE reduces late-onset morbidity and improves long-term graft survival providing clinical evidence to further support the broad implementation of HOPE in human liver transplantation., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Background: Climate change may well be the "largest threat" to humankind. Changes to our climate system lead to a decrease in global health. The healthcare sector presents one of the largest carbon footprints across all industries. Since surgical departments have one of the largest carbon footprints within the healthcare sector, they represent an area with vast opportunities for improvement. To drive change, it is vital to create awareness of these issues and encourage engagement in changes among people working in the healthcare industry., Methods: We conducted an anonymous cross-sectional survey study to assess awareness among surgeons regarding the impact of healthcare systems on climate change. The questions were designed to investigate surgeons' willingness to accept and promote changes to reduce carbon footprints. Participants included surgical professionals of all ages and levels of expertise., Results: A total of 210 participants completed the survey in full and were included in the evaluation. Sixty percent emphasized a lack of information and the need for personal education. Over 90 % expressed concern for the environment and a strong desire to gain new insights. Provided that clinical performance remains the same, more than 70 % are willing to embrace carbon-friendly alternatives. In this context, all participants accepted the additional time required for training and initially increased personal efforts to achieve equal performance., Conclusion: Limited awareness and information about carbon footprints were observed in surgical departments in German hospitals. Nevertheless, the vast majority of surgeons across all age groups are more than willing to acquire new insights and adapt to changes in order to reduce energy consumption and carbon dioxide production., Competing Interests: This work has not been published or accepted for publication, nor is it under consideration at another journal. Moreover, I would like to declare on behalf of the authors that there are no ethical, financial nor other conflicts of interests and that all authors have seen and approved the manuscript., (© 2024 The Authors.)

The purpose of this study is to evaluate the technical and clinical outcome of percutaneous transhepatic biliary drainage (PTBD) in patients with biliary leakage. All patients who underwent ultrasound-assisted PTBD between January 2017 and December 2021 due to biliary leakage with nondilated biliary systems were retrospectively evaluated for periprocedural characteristics, medical indications, technical success (successful placement of drainage catheter), clinical success (resolved leak without additional procedures), fluoroscopy time, procedure duration, and clinical outcomes. 74 patients with a mean age of 64.1 ± 15.1 years were identified. Surgery was the most common etiology of biliary leak with 93.2% of the cases. PTBD had a 91.8% (68/74) technical success rate and an 80.8% clinical success rate. The mean procedure and fluoroscopy duration were 43.5 and 18.6 minutes. Age > 65 years (P = .027) and left-sided drainage (P = .034) were significant risk factors of clinical failure. Procedure-related major complications were 2 bleedings from the liver and 1 bleeding from an intercostal artery (major complication rate 4%). PTBD is a feasible, safe, and effective treatment option in patients with biliary leakage with low complication rates., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

This observational study focuses on the characteristics and survival of patients taken off of the liver transplant waiting list. Assessment of post-delisting survival and a frequent follow-up of patients after delisting are important keys to improve the survival rate of patients with liver failure after being delisted. Within this study, delisted liver transplant candidates were divided into the following groups: (1) "too good" (54%) or (2) "too sick" (22%) for transplantation, (3) adherence issues (12%) or (4) therapy goal changed (11%). The 5-year survival after delisting within these groups was 84%, 9%, 50%, and 68%, respectively. Less than 3% of the delisted patients had to be relisted again. The clinical expert decision of the multidisciplinary transplant team was sufficiently accurate to differentiate between patients requiring liver transplantation and those who were delisted after a stable recovery of liver function. The assessment of post-delisting survival may serve as a complementary metric to assess differences in center practices and to estimate cumulative post-delisting mortality risk.

Adipose-derived mesenchymal stem cells are increasingly being used in regenerative medicine as cell therapy targets, including in the treatment of burns and ulcers. The regenerative potential of AD-MSCs and some of their immunological properties are known from in vitro studies; however, in clinical applications, cells are used in non-ideal conditions and can behave differently in inflammatory environments, affecting the efficacy and outcome of therapy. Our aim was to investigate and map the pathways that the inflammatory microenvironment can induce in these cells. High-throughput gene expression assays were performed on AD-MSCs activated with LPS and TNFα. Analysis of RNA-Seq data showed that control, LPS-treated and TNFα-treated samples exhibited distinct gene expression patterns. LPS treatment increased the expression of 926 genes and decreased the expression of 770 genes involved in cell division, DNA repair, the cell cycle, and several metabolic processes. TNFα treatment increased the expression of 174 genes and decreased the expression of 383 genes, which are related to cell division, the immune response, cell proliferation, and differentiation. We also map the biological pathways by further investigating the most altered genes using the Gene Ontology and KEGG databases. Secreted cytokines, which are important in the immunological response, were also examined at the protein level, and a functional assay was performed to assess wound healing. Activated AD-MSC increased the secretion of IL-6, IL-8 and CXCL-10, and also the closure of wounds. AD-MSCs presented accelerated wound healing under inflammation conditions, suggesting that we could use this cell in clinical application.

The proper functioning of mesenchymal stem cells (MSCs) is of paramount importance for the homeostasis of the body. Inflammation and infection can alter the function of MSCs, which can also affect the regenerative potential and immunological status of tissues. It is not known whether human herpes simplex viruses 1 and 2 (HSV1 and HSV2), well-known human pathogens that can cause lifelong infections, can induce changes in MSCs. In non-healing ulcers, HSV infection is known to affect deeper tissue layers. In addition, HSV infection can recur after initially successful cell therapies. Our aim was to study the response of adipose-derived MSCs (ADMSCs) to HSV infection in vitro. After confirming the phenotype and differentiation capacity of the isolated cells, we infected the cells in vitro with HSV1-KOS, HSV1-532 and HSV2 virus strains. Twenty-four hours after infection, we examined the gene expression of the cells via RNA-seq and RT-PCR; detected secreted cytokines via protein array; and determined autophagy via Western blot, transmission electron microscopy (TEM) and fluorescence microscopy. Infection with different HSV strains resulted in different gene-expression patterns. In addition to the activation of pathways characteristic of viral infections, distinct non-immunological pathways (autophagy, tissue regeneration and differentiation) were also activated according to analyses with QIAGEN Ingenuity Pathway Analysis, Kyoto Encyclopedia of Genes and Genome and Genome Ontology Enrichment. Viral infections increased autophagy, as confirmed via TEM image analysis, and also increased levels of the microtubule-associated protein light chain 3 (LC3B) II protein. We identified significantly altered accumulation for 16 cytokines involved in tissue regeneration and inflammation. Our studies demonstrated that HSV infection can alter the viability and immunological status of ADMSCs, which may have implications for ADMSC-based cell therapies. Alterations in autophagy can affect numerous processes in MSCs, including the inhibition of tissue regeneration as well as pathological differentiation.

Purpose: The objective of this work was to uncover inequalities in access to liver transplantation in Bavaria, Germany., Methods: For this purpose, the annual transplantation rate per 1 million inhabitants for the respective districts was determined from the aggregated postal codes of the place of residence of transplanted patients. The variables examined were proximity and travel time to the nearest transplant center, as well as the care category of the regional hospital. In addition, we assessed whether the head of gastroenterology at the regional hospital through which liver transplant candidates are referred was trained at a liver transplant center., Results: We could not demonstrate a direct relationship between proximity or travel time to the nearest transplant center and access to liver transplantation. Multivariate regression analysis shows that liver transplant training (p < 0.0001) of the chief physician (gastroenterologist) of the regional hospital was the most decisive independent factor for access to liver transplantation within a district., Conclusion: We show that the transplant training experience of the head of gastroenterology at a regional hospital is an independent factor for the regional transplantation rate. Therefore, it appears important to maintain some liver transplant expertise outside the transplant centers in order to properly identify and assign potential transplant candidates for transplantation., (© 2023. The Author(s).)

Background: The formation of neutrophil extracellular traps (NETs) was initially discovered as a novel immune response against pathogens. Recent studies have also suggested that NETs play an important role in tumor progression. This review summarizes the cellular mechanisms by which NETs promote distant metastasis and discusses the possible clinical applications targeting NETs., Method: The relevant literature from PubMed and Google Scholar (2001-2021) have been reviewed for this article., Results: The presence of NETs has been detected in various primary tumors and metastatic sites. NET-associated interactions have been observed throughout the different stages of metastasis, including initial tumor cell detachment, intravasation and extravasation, the survival of circulating tumor cells, the settlement and the growth of metastatic tumor cells. Several in vitro and in vivo studies proved that inhibiting NET formation resulted in anti-cancer effects. The biosafety and efficacy of some NET inhibitors have also been demonstrated in early phase clinical trials., Conclusions: Considering the role of NETs in tumor progression, NETs could be a promising diagnostic and therapeutic target for cancer management. However, current evidence is mostly derived from experimental models and as such more clinical studies are still needed to verify the clinical significance of NETs in oncological settings., (© 2022. The Author(s).)

In times of an unprecedented energy crisis, sustainability is becoming increasingly important. This development does not stop at medicine and especially at the operating room, where a considerable amount of greenhouse gases is produced. Due to this development, the question arises whether sterility, safety and service can be reconciled with a resource-saving use of medical devices. One goal here must be to replace disposables, which offer a high degree of sterility, with safely reprocessable reusables. Due to rising energy costs as well as supply bottlenecks, reprocessing of products offers increasing independence for the hospital. Furthermore, the move towards renewable energy for reusable products is visibly improving the carbon footprint. The independence gained by clinics also offers greater safety for patients, as the risk of unavailable materials is reduced. In addition to the goal of increasing the use of reusable items, the recycling of disposable products will also play an increasing role. Life cycle assessments will increasingly guide the optimal choice of products in this regard. In summary, these options offer the possibility of implementing the increasing need for sustainability in the OR., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Liver transplantation as a treatment option for end-stage liver diseases is associated with a relevant risk for complications. On the one hand, immunological factors and associated chronic graft rejection are major causes of morbidity and carry an increased risk of mortality due to liver graft failure. On the other hand, infectious complications have a major impact on patient outcomes. In addition, abdominal or pulmonary infections, and biliary complications, including cholangitis, are common complications in patients after liver transplantation and can also be associated with a risk for mortality. Thereby, these patients already suffer from gut dysbiosis at the time of liver transplantation due to their severe underlying disease, causing end-stage liver failure. Despite an impaired gut-liver axis, repeated antibiotic therapies can cause major changes in the gut microbiome. Due to repeated biliary interventions, the biliary tract is often colonized by several bacteria with a high risk for multi-drug resistant germs causing local and systemic infections before and after liver transplantation. Growing evidence about the role of gut microbiota in the perioperative course and their impact on patient outcomes in liver transplantation is available. However, data about biliary microbiota and their impact on infectious and biliary complications are still sparse. In this comprehensive review, we compile the current evidence for the role of microbiome research in liver transplantation with a focus on biliary complications and infections due to multi-drug resistant germs.

Background: Climate neutrality is the major aim of our generation. In order to be able to achieve this a net zero emission should be strived for in operating theaters., Objective: What does zero emission implicate for the operative sector? Which structural approaches already exist? Can zero emission surgery be achieved?, Material and Methods: Evaluation of published studies, discussion of fundamental research and expert recommendations., Results: Studies in England and Germany show that by structural alterations and strict sustainability structures net zero emission surgery seems to be feasible. In Germany the attention and awareness of the topic are greatly increasing and the first projects and studies have been launched., Conclusion: To achieve the aim of net zero emission by 2050 we must rapidly and significantly increase our efforts., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objective: To present technical details and short-term experiences of liver transplantation as a 2-stage procedure using small for size grafts in a multicenter cohort study., Background: Two-stage liver transplantation using small for size grafts should be a feasible procedure with lower morbidity and mortality rates. Retrospective cohort study between 2015 and 2022 with multicenter experience. Twenty-three resection and partial liver transplantation with delayed total hepatectomy procedures for noncirrhotic indications were performed in 6 European centers (20 with grafts from living donors and 3 after deceased donation). Procedure's feasibility, graft volumetric changes, morbidity, and mortality of donor and recipient were explored., Results: There was a low donor morbidity (4.3%) in our cohort. Hypertrophy of the graft was rapid (mean graft volume increases 107% between both stages) and offered the opportunity for remnant hepatectomy after a median of 14 days. In all cases, portomesenteric flow was routed to the graft by right remnant portal vein ligation. Portal vein inflow modulation to alleviate transient harmful portal hypertension was not needed in any case. Early postoperative mortality (4.3%) of the recipients were low. Ten patients suffered from complications ≥IIIb according to the Clavien-Dindo classification., Conclusions: Two-stage liver transplantation is a feasible option for noncirrhotic patients allowing the safe use of small for size grafts and could possibly be extended with caution to liver diseases with portal hypertension and cirrhosis. The resection and partial liver transplantation with delayed total hepatectomy technique might be a viable option for expanding the donor pool given the current organ shortage especially for low-model of end stage liver disease patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disease, ranging from simple steatosis to hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Liver fibrosis, which portends a poor prognosis in NAFLD, is characterized by the excessive accumulation of extracellular matrix (ECM) proteins resulting from abnormal wound repair response and metabolic disorders. Various metabolic factors play crucial roles in the progression of NAFLD, including abnormal lipid, bile acid, and endotoxin metabolism, leading to chronic inflammation and hepatic stellate cell (HSC) activation. Autophagy is a conserved process within cells that removes unnecessary or dysfunctional components through a lysosome-dependent regulated mechanism. Accumulating evidence has shown the importance of autophagy in NAFLD and its close relation to NAFLD progression. Thus, regulation of autophagy appears to be beneficial in treating NAFLD and could become an important therapeutic target.

The importance of three-dimensional (3D) models in pharmacological tests and personalized therapies is significant. These models allow us to gain insight into the cell response during drug absorption, distribution, metabolism, and elimination in an organ-like system and are suitable for toxicological testing. In personalized and regenerative medicine, the precise characterization of artificial tissues or drug metabolism processes is more than crucial to gain the safest and the most effective treatment for the patients. Using these 3D cell cultures derived directly from patient, such as spheroids, organoids, and bioprinted structures, allows for testing drugs before administration to the patient. These methods allow us to select the most appropriate drug for the patient. Moreover, they provide chance for better recovery of patients, since time is not wasted during therapy switching. These models could be used in applied and basic research as well, because their response to treatments is quite similar to that of the native tissue. Furthermore, they may replace animal models in the future because these methods are cheaper and can avoid interspecies differences. This review puts a spotlight on this dynamically evolving area and its application in toxicological testing., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Author(s).)

Background: The "digital era" in the field of medicine is the new "here and now". Artificial intelligence has entered many fields of medicine and is recently emerging in the field of organ transplantation. Solid organs remain a scarce resource. Being able to predict the outcome after liver transplantation promises to solve one of the long-standing problems within organ transplantation. What is the perfect donor recipient match? Within this work we developed and validated a novel deep-learning-based donor-recipient allocation system for liver transplantation., Method: In this study we used data collected from all liver transplant patients between 2004 and 2019 at the university transplantation centre in Munich. We aimed to design a transparent and interpretable deep learning framework to predict the outcome after liver transplantation. An individually designed neural network was developed to meet the unique requirements of transplantation data. The metrics used to determine the model quality and its level of performance are accuracy, cross-entropy loss, and F1 score as well as AUC score., Results: A total of 529 transplantations with a total of 1058 matching donor and recipient observations were added into the database. The combined prediction of all outcome parameters was 95.8% accurate (cross-entropy loss of 0.042). The prediction of death within the hospital was 94.3% accurate (cross-entropy loss of 0.057). The overall F1 score was 0.899 on average, whereas the overall AUC score was 0.940., Conclusion: With the achieved results, the network serves as a reliable tool to predict survival. It adds new insight into the potential of deep learning to assist medical decisions. Especially in the field of transplantation, an AUC Score of 94% is very valuable. This neuronal network is unique as it utilizes transparent and easily interpretable data to predict the outcome after liver transplantation. Further validation must be performed prior to utilization in a clinical context.

Hepatic ischemia-reperfusion injury (IRI) represents a major challenge during liver surgery, liver preservation for transplantation, and can cause hemorrhagic shock with severe hypoxemia and trauma. The reduction of blood supply with a concomitant deficit in oxygen delivery initiates various molecular mechanisms involving the innate and adaptive immune response, alterations in gene transcription, induction of cell death programs, and changes in metabolic state and vascular function. Hepatic IRI is a major cause of morbidity and mortality, and is associated with an increased risk for tumor growth and recurrence after oncologic surgery for primary and secondary hepatobiliary malignancies. Therapeutic strategies to prevent or treat hepatic IRI have been investigated in animal models but, for the most part, have failed to provide a protective effect in a clinical setting. This review focuses on the molecular mechanisms underlying hepatic IRI and regeneration, as well as its clinical implications. A better understanding of this complex and highly dynamic process may allow for the development of innovative therapeutic approaches and optimize patient outcomes.

The adsorption and desorption kinetics of molecules is of significant fundamental and applied interest. In this paper, we present a new method to quantify the energy barriers for the adsorption and desorption of gas molecules on few-atom clusters, by exploiting reaction induced changes of the doping level of a graphene substrate. The method is illustrated for oxygen adsorption on Au 3 clusters. The gold clusters were deposited on a graphene field effect transistor and exposed to O 2 . From the change in graphene's electronic properties during adsorption, the energy barrier for the adsorption of O 2 on Au 3 is estimated to be 0.45 eV. Electric current pulses increase the temperature of the graphene strip in a controlled way and provide the required thermal energy for oxygen desorption. The oxygen binding energy on Au 3 /graphene is found to be 1.03 eV and the activation entropy is 1.4 meV K -1 . The experimental values are compared and interpreted on the basis of density functional theory calculations of the adsorption barrier, the binding energy and the activation entropy. The large value of the activation entropy is explained by the hindering effect that the adsorbed O 2 has on the fluxional motion of the Au 3 cluster.

Background: Kidney transplantation is the best treatment option for patients with end-stage kidney disease (ESKD) with a superiority of graft survival after living kidney donation (LKD) compared to deceased donation. However, a large part of potential donors and recipients are ineligible for LKD. Here, we analyze the leading causes for disqualification of potential living donor-recipient pairs from the LKD program and the health-related consequences for ESKD patients excluded from the LKD program in a German transplant center., Methods: In this single-center retrospective cohort study we evaluated all candidates (potential donors and recipients) presenting for assessment of LKD from 2012 to 2020 at our transplant center. Thereby we focused on candidates excluded from the LKD program. Main reasons for disqualification were categorized as medical (donor-related), psychosocial, immunological, recipient-related, and unknown., Results: Overall, 601 donor-recipient pairs were referred to our transplant center for LKD assessment during the observation time. Out of those, 326 (54.2%) discontinued the program with 52 (8.7%) dropouts and 274 (45.6%) donor-recipient pairs being ineligible for LKD. Donor-related medical contraindications were the main reason for disqualification [139 out of 274 (50.7%) potential donors] followed by recipient-related contraindications [60 out of 274 (21.9%) of potential donor-recipient pairs]. Only 77 out of 257 (29.9%) potential recipients excluded from the LKD program received a kidney transplant afterward with a median waiting time of 2 (IQR: 1.0-4.0) years. Overall, 18 (7.0%) ESKD patients initially declined for LKD died in this period., Conclusion: A large percentage of donor-recipient pairs are disqualified from the German LKD program, mostly due to medical reasons related to the donor and with partly severe consequences for the potential recipients. For these, alternative solutions that promptly enable kidney transplantation are essential for improving patient quality of life and survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Grigorescu, Kemmner, Schönermarck, Sajin, Guenther, Cerqueira, Illigens, Siepmann, Meiser, Guba, Fischereder and Stang.)

Background: The effect of bacterobilia on morbidity after pancreatoduodenectomy remains unclear. The aim of this study was to examine the influence of positive intraoperative bile cultures and perioperative antibiotic prophylaxis on morbidity measured using the Comprehensive Complication Index, a weighted composite of postoperative complications., Methods: Intraoperative bile cultures of 182 patients who underwent pancreatoduodenectomy were obtained. We examined the effect of intraoperative bile cultures and perioperative antibiotic prophylaxis on the Comprehensive Complication Index and the occurrence of postoperative complications. To this aim, we performed general linear models controlling for relevant demographic and perioperative factors., Results: Positive (versus negative) intraoperative bile cultures were associated with a higher mean Comprehensive Complication Index (25.34 vs 16.81, P = .025). The mean Comprehensive Complication Index differed significantly between individuals with positive intraoperative bile cultures and bacterial strains not covered by perioperative antibiotic prophylaxis (26.2) versus positive intraoperative bile cultures and bacterial strains sensitive to perioperative antibiotic prophylaxis (22.7) (P = .045). Positive (versus negative) intraoperative bile cultures were associated with 4.75 times (95% confidence interval: 1.74-13.00, P = .002) greater odds of wound infections. The odds of wound infection were 1.93 times (95% confidence interval: .47-8.04) greater in those with positive intraoperative bile cultures and adequate perioperative antibiotic prophylaxis and 6.14 times (95% confidence interval: 2.17-17.35) greater in those with positive intraoperative bile cultures and inadequate perioperative antibiotic prophylaxis (versus negative intraoperative bile cultures) (P = .001)., Conclusion: Bacterobilia is associated with a significant increase in Comprehensive Complication Index and wound infections after pancreatoduodenectomy, which may be reduced by administration of a specific perioperative antibiotic prophylaxis. Acquisition of bile cultures sampled through the external conduit of patients with preoperative biliary drainage could help in selecting a specific perioperative antibiotic prophylaxis and patients with bile duct stents might benefit from broad spectrum perioperative antibiotic prophylaxis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Összefoglaló. A bőrpótlóknak mind a klinikumban, mind a gyógyszerkutatásokban kiemelt szerepük van. Ezek a kezdetleges mesterséges bőrszövetek segíthetik a bőr regenerálódását, modellezhetik a főbb funkciókat, de megvannak a korlátaik is, mechanikailag sérülékenyek, és nem tartósak. A legtöbb bőrpótló vagy acelluláris, vagy csak egy-két sejttípust tartalmaz. Az eredeti bőrrel megegyező szerkezetű, teljesen funkcionális mesterséges bőrszövet a mai napig nem létezik. A háromdimenziós szövetnyomtatás megoldást kínálhat erre a problémára is, hiszen a bőrszövet minden sejtes eleme felhasználható, megfelelő hidrogélek és biotinták segítségével pedig olyan komplex struktúrák hozhatók létre, amelyek képesek a bőr teljes funkcionális repertoárját biztosítani. Ez nemcsak klinikai szempontból kiemelt jelentőségű, hanem a preklinikai kísérletek esetében kiválthatja az állatmodelleket és számos toxikológiai vizsgálatot is. Orv Hetil. 2022; 163(10): 375-385. Summary. Skin substitutes have a prominent role in therapeutic applications and drug research. These simple artificial skin tissues can support skin regeneration, in vitro they can model the main functions of the skin but they also have limitations such as being mechanically vulnerable and not durable enough. Most skin substitutes are either acellular or contain only one or two cell types. Fully functional artificial skin substitute with the same structure as the original skin has not been produced to this day. Three-dimensional tissue bioprinting can also offer a solution to this problem, as all cellular elements of skin tissue can be used, and with the help of appropriate hydrogels and bioinks, complex structures can be created that can provide a complete functional repertoire of the skin. It is important not just in the clinical therapeutic use, but it can also trigger the replacement of animal models and a number of toxicological studies in preclinical trials. Orv Hetil. 2022; 163(10): 375-385.

Background: Gastric cancer (GC) is a very heterogenous disease necessitating further stratification for prognostic and therapeutic aspects. Based on the recommendation of The Asisan Cancer Research Group (ACRG) recently established four molecular subtypes (MSI, MSS/EMT, MSS/TP53+, MSS/TP53-) which require molecular expression analysis. The technology required for comprehensive molecular analysis is expensive and not applicable for routine diagnostics. Thus, in this study we established a classification system utilizing immunohistochemistry and morphology-based analyses as surrogate markers in order to reproduce the ACRG molecular subtypes of gastric cancer. To clarify the clinical relevance of the novel classification system, we performed a correlation with established clinical parameters., Methods: The study cohort consisted of 189 patients with GC (UICC III and IV). Using immunohistochemistry, the following markers were analysed: MLH1, MSH2, MSH6, PMS2 (as a surrogate for microsatellite status), p53, SOX9. We assessed tumor budding as a surrogate for EMT to distinguish between MSS/EMT and MSS/non-EMT groups., Results: Immunohistochemical and morphologic subtyping classified cases as follows: 10% MSI, 35% MSS/EMT, 16% MSS/TP53 + and 39% MSS/TP53-. Subtypes significantly correlated with the Lauren classification, tumor stage, venous invasion and SOX9 expression (p < .05). There was no significant correlation between molecular subtype and lymph node growth pattern., Conclusion: We propose a simple algorithm for molecular subtyping of GC using universally available immunohistochemistry, which correlates with clinical parameters and is cost-effective and applicable in diagnostic routine. This classification might prospectively help to determine patient prognosis, optimize patient care and homogenize patient cohorts for clinical trials., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Background: Hepatosteatosis is the earliest stage in the pathogenesis of nonalcoholic fatty (NAFLD) and alcoholic liver disease (ALD). As NAFLD is affecting 10-24% of the general population and approximately 70% of obese patients, it carries a large economic burden and is becoming a major reason for liver transplantation worldwide. ALD is a major cause of morbidity and mortality causing 50% of liver cirrhosis and 10% of liver cancer related death. Increasing evidence has accumulated that gut-derived factors play a crucial role in the development and progression of chronic liver diseases., Methods: A selective literature search was conducted in Medline and PubMed, using the terms "nonalcoholic fatty liver disease," "alcoholic liver disease," "lipopolysaccharide," "gut barrier," and "microbiome.", Results: Gut dysbiosis and gut barrier dysfunction both contribute to chronic liver disease by abnormal regulation of the gut-liver axis. Thereby, gut-derived lipopolysaccharides (LPS) are a key factor in inducing the inflammatory response of liver tissue. The review further underlines that endotoxemia is observed in both NAFLD and ALD patients. LPS plays an important role in conducting liver damage through the LPS-TLR4 signaling pathway. Treatments targeting the gut microbiome and the gut barrier such as fecal microbiota transplantation (FMT), probiotics, prebiotics, synbiotics, and intestinal alkaline phosphatase (IAP) represent potential treatment modalities for NAFLD and ALD., Conclusions: The gut-liver axis plays an important role in the development of liver disease. Treatments targeting the gut microbiome and the gut barrier have shown beneficial effects in attenuating liver inflammation and need to be further investigated., (© 2021. The Author(s).)

Background: In gastric cancer (GC), extracapsular growth (ECG) pattern of lymph node metastases is associated with decreased overall survival rates compared to intracapsular lymph node metastases (ICG). Epithelial-to-mesenchymal transition (EMT) plays a pivotal role in hematogenous metastatic spread. Aim of the present study was to analyze if EMT related genes are involved in the growth pattern of lymph node metastases in GC., Methods: Out of our prospective database with 529 patients who underwent surgical resection for GC between 2002 and 2014 forty lymph node positive patients were identified (20 ECG, 20 ICG). The expression of 84 EMT-associated genes were analyzed by RT2 Profiler PCR Array (n = 20). Results were validated by Real-Time PCR (n = 20)., Results: GC with ECG showed differently expressed EMT related genes. GC leading to ECG showed an upregulation of three and downregulation of eleven genes. Those differences, however, could not be confirmed in PCR analysis., Conclusions: This study demonstrates that EMT related genes are not responsible for the different growth patterns of lymph node metastases in GC. Further studies are required to evaluate the underlying mechanisms of ECG in GC as it might provide a potential therapeutic target for this subgroup of more aggressive tumors in the future., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Objective: The aim of this study was to evaluate peak serum alanine aminotransferase (ALT) and postoperative clinical outcomes after hypothermic oxygenated machine perfusion (HOPE) versus static cold storage (SCS) in extended criteria donation (ECD) liver transplantation (LT) from donation after brain death (DBD)., Background: HOPE might improve outcomes in LT, particularly in high-risk settings such as ECD organs after DBD, but this hypothesis has not yet been tested in a randomized controlled clinical trial (RCT)., Methods: Between September 2017 and September 2020, 46 patients undergoing ECD-DBD LT from four centers were randomly assigned to HOPE (n = 23) or SCS (n = 23). Peak-ALT levels within 7 days following LT constituted the primary endpoint. Secondary endpoints included incidence of postoperative complications [Clavien-Dindo classification (CD), Comprehensive Complication Index (CCI)], length of intensive care- (ICU) and hospital-stay, and incidence of early allograft dysfunction (EAD)., Results: Demographics were equally distributed between both groups [donor age: 72 (IQR: 59-78) years, recipient age: 62 (IQR: 55-65) years, labMELD: 15 (IQR: 9-25), 38 male and 8 female recipients]. HOPE resulted in a 47% decrease in serum peak ALT [418 (IQR: 221-828) vs 796 (IQR: 477-1195) IU/L, P = 0.030], a significant reduction in 90-day complications [44% vs 74% CD grade ≥3, P = 0.036; 32 (IQR: 12-56) vs 52 (IQR: 35-98) CCI, P = 0.021], and shorter ICU- and hospital-stays [5 (IQR: 4-8) vs 8 (IQR: 5-18) days, P = 0.045; 20 (IQR: 16-27) vs 36 (IQR: 23-62) days, P = 0.002] compared to SCS. A trend toward reduced EAD was observed for HOPE (17% vs 35%; P = 0.314)., Conclusion: This multicenter RCT demonstrates that HOPE, in comparison to SCS, significantly reduces early allograft injury and improves post-transplant outcomes in ECD-DBD liver transplantation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The utilization of liver allografts could be optimized if nonacceptance is predicted. This study aimed to evaluate the prognostic ability of an updated Discard Risk Index in Eurotransplant., Materials and Methods: Potential deceased donors from January 2010 to December 2015 who had been reported to Eurotransplant were included in our analyses. Liver utilization was defined by transplant status as the primary outcome to evaluate the performance of the Eurotransplant-developed Discard Risk Index., Results: Of 11670 potential livers, 9565 (81%) were actually transplanted. Donor sex, age, history of diabetes, drug abuse, use of vasopressors, body mass index category, serum sodium, cause of death, donor type, and levels of C-reactive protein, bilirubin, aspartate and alanine aminotransferases, international normalized ratio, and gamma-glutamyltranspeptidase were associated with discard and combined in the Eurotransplant-developed Discard Risk Index. Correlation between the two Discard Risk Indexes was high (r = 0.86), and both achieved high C statistics of 0.72 and 0.75 (P < .001), respectively. Despite strong calibration, discard rates of 0.8% for overall donors and 6% of donors after circulatory death could be predicted with 80% accuracy., Conclusions: The Eurotransplant-developed Discard Risk Index showed a high prognostic ability to predict liver utilization in a European setting. The model could therefore be valuable for identifying livers at high risk of not being transplanted in an early stage. These organs might profit the most from modified allocation strategies or advanced preservation techniques.

The extension of liver transplantation to new oncologic indications might exacerbate the shortage of grafts. Living donor liver transplantation (LDLT) may emerge as a viable resource, although its diffusion in the Western world is still very limited. Several groups have advocated for minimizing the impact on donors by reducing the extent of donor hepatectomy, i.e., shifting from right-lobe to left-lobe or left-lateral segment donation ("shift-to-left"). This is particularly relevant when dealing with non-established indications and could make it more acceptable both for potential donors and for the recipients. Left grafts can be transplanted straightforward, despite a higher risk of small-for-size syndrome, or they can be used in the setting of dual-graft LDLT or RAPID procedures, despite technical complexity. This review will expose the most relevant features of each technique, highlighting their strengths and pitfalls and focusing on outcomes. This wide set of tools should be available at high-volume transplant centers, to propose the best technique to adapt to donor-recipient matching., (© 2024. Italian Society of Surgery (SIC).)

Background: Ischemia-reperfusion Injury (IRI) is a complex pathophysiological process with severe consequences, including irreversible loss of renal function. Various intraoperative prevention methods have been proposed to mitigate the harmful effects of warm ischemia and kidney reperfusion., Aim: This comprehensive analysis provides an overview of pharmacological agents and intraoperative methods for preventing and treating renal IRI., Methods: Our analysis revealed that eplerenone exhibited the highest binding affinity to crucial targets, including Aldehyde Dehydrogenase (AD), Estrogen Receptor (ER), Klotho protein, Mineralocorticoid Receptor (MR), and Toll-like Receptor 4 (TLR4). This finding indicates eplerenone's potential as a potent preventive agent against IRI, surpassing other available therapeutics like Benzodioxole, Hydrocortisone, Indoles, Nicotinamide adenine dinucleotide, and Niacinamide. In preventing kidney IRI, our comprehensive analysis emphasizes the significance of eplerenone due to its strong binding affinity to key targets involved in the pathogenesis of IRI., Results: This finding positions eplerenone as a promising candidate for further clinical investigation and consideration for future clinical practice., Conclusion: The insights provided in this analysis will assist clinicians and researchers in selecting effective preventive approaches for renal IRI in surgical settings, potentially improving patient outcomes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

De novo or viral reactivation cancers are a major cause of morbidity and mortality in the solid organ transplant (SOT) population. Primary sclerosing cholangitis (PSC) is an aggressive disease which can lead to cholestatic liver damage and cirrhosis. PSC often cooccurs with inflammatory bowel disease (IBD). Here, we describe the case of a 28‐year‐old male with PSC along with poorly controlled IBD who underwent a liver transplant and developed colonic Kaposi sarcoma (KS). Our case highlights the importance of adequate pretransplant screening for endemic viruses, high clinical suspicion for KS in the setting of difficult‐to‐control colitis, and early multidisciplinary involvement. [ABSTRACT FROM AUTHOR]

Background: We have recently constructed a DNA methylation classifier that can discriminate between pancreatic ductal adenocarcinoma (PAAD) liver metastasis and intrahepatic cholangiocarcinoma (iCCA) with high accuracy (PAAD-iCCA-Classifier). PAAD is one of the leading causes of cancer of unknown primary and diagnosis is based on exclusion of other malignancies. Therefore, our focus was to investigate whether the PAAD-iCCA-Classifier can be used to diagnose PAAD metastases from other sites. Methods: For this scope, the anomaly detection filter of the initial classifier was expanded by 8 additional mimicker carcinomas, amounting to a total of 10 carcinomas in the negative class. We validated the updated version of the classifier on a validation set, which consisted of a biological cohort (n = 3579) and a technical one (n = 15). We then assessed the performance of the classifier on a test set, which included a positive control cohort of 16 PAAD metastases from various sites and a cohort of 124 negative control samples consisting of 96 breast cancer metastases from 18 anatomical sites and 28 carcinoma metastases to the brain. Results: The updated PAAD-iCCA-Classifier achieved 98.21% accuracy on the biological validation samples, and on the technical validation ones it reached 100%. The classifier also correctly identified 15/16 (93.75%) metastases of the positive control as PAAD, and on the negative control, it correctly classified 122/124 samples (98.39%) for a 97.85% overall accuracy on the test set. We used this DNA methylation dataset to explore the organotropism of PAAD metastases and observed that PAAD liver metastases are distinct from PAAD peritoneal carcinomatosis and primary PAAD, and are characterized by specific copy number alterations and hypomethylation of enhancers involved in epithelial-mesenchymal-transition. Conclusions: The updated PAAD-iCCA-Classifier (available at https://classifier.tgc-research.de/) can accurately classify PAAD samples from various metastatic sites and it can serve as a diagnostic aid. [ABSTRACT FROM AUTHOR]

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Liver transplantation has evolved into a mature clinical field, but scarcity of usable organs poses a unique challenge. Expanding the donor pool requires novel approaches for protecting hepatic physiology and cellular homeostasis. Here we define hepatocellular injury during transplantation, with an emphasis on modifiable cell death pathways as future therapeutics. [ABSTRACT FROM AUTHOR]

Nanomedicine holds great potential for revolutionizing medical treatment. Ongoing research and advancements in nanotechnology are continuously expanding the possibilities, promising significant advancements in healthcare. To fully harness the potential of nanotechnology in medical applications, it is crucial to conduct safety evaluations for the nanomedicines that offer effective benefits in the preclinical stage. Our recent efficacy studies indicated that rapamycin perfluorocarbon (PFC) nanoparticles showed promise in mitigating cisplatin-induced acute kidney injury (AKI). As cisplatin is routinely administered to ovarian cancer patients as their first-line chemotherapy, in this study, we focused on evaluating the safety of rapamycin PFC nanoparticles in mice bearing ovarian tumor xenografts. Specifically, this study evaluated the effects of repeat-dose rapamycin PFC nanoparticle treatment on vital organs, the immune system, and tumor growth and assessed pharmacokinetics and biodistribution. Our results indicated that rapamycin PFC nanoparticle treatment did not cause any detectable adverse effects on cardiac, renal, or hepatic functions or on splenocyte populations, but it reduced the splenocyte secretion of IL-10, TNFα, and IL12p70 upon IgM stimulation. The pharmacokinetics and biodistribution results revealed a significant enhancement in the delivery of rapamycin to tumors by rapamycin PFC nanoparticles, which, in turn, led to a significant reduction in ovarian tumor growth. Therefore, rapamycin PFC nanoparticles have the potential to be clinically beneficial in cisplatin-treated ovarian cancer patients. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is known to be the most lethal cancer. Fewer new treatments are being developed for pancreatic cancer as compared to other cancers. The bioactive lipid S1P, which is mainly regulated by sphingosine kinase 1 (SK1) and sphingosine kinase 2 (SK2) enzymes, plays significant roles in pancreatic cancer initiation and exacerbation. S1P controls many signaling pathways to modulate the progression of pancreatic cancer through the G-coupled receptor S1PR1-5. Several papers reporting amelioration of pancreatic cancer via modulation of S1P levels or downstream signaling pathways have previously been published. In this paper, for the first time, we have reviewed the results of previous studies to understand how S1P and its receptors contribute to the development of pancreatic cancer, and whether S1P can be a therapeutic target. In addition, we have also reviewed papers dealing with the effects of SK1 and SK2, which are kinases that regulate the level of S1P, on the pathogenesis of pancreatic cancer. We have also listed available drugs that particularly focus on S1P, S1PRs, SK1, and SK2 for the treatment of pancreatic cancer. Through this review, we would like to suggest that the SK/S1P/S1PR signaling system can be an important target for treating pancreatic cancer, where a new treatment target is desperately warranted. [ABSTRACT FROM AUTHOR]

Background: Surgeries represent a mainstay of medical care globally. Patterns of complications are frequently recognized late and place a considerable burden on health care systems. The aim was to develop and test the first deep learning-adjusted CUSUM program (DL-CUSUM) to predict and monitor in-hospital mortality in real time after liver transplantation. Methods: Data from 1066 individuals with 66,092 preoperatively available data point variables from 2004 to 2019 were included. DL-CUSUM is an application to predict in-hospital mortality. The area under the curve for risk adjustment with Model of End-stage Liver Disease (D-MELD), Balance of Risk (BAR) score, and deep learning (DL), as well as the ARL (average run length) and control limit (CL) for an in-control process over 5 years, were calculated. Results: D-MELD AUC was 0.618, BAR AUC was 0.648 and DL model AUC was 0.857. CL with BAR adjustment was 2.3 with an ARL of 326.31. D-MELD reached an ARL of 303.29 with a CL of 2.4. DL prediction resulted in a CL of 1.8 to reach an ARL of 332.67. Conclusions: This work introduces the first use of an automated DL-CUSUM system to monitor postoperative in-hospital mortality after liver transplantation. It allows for the real-time risk-adjusted monitoring of process quality. [ABSTRACT FROM AUTHOR]

The use of marginal grafts is very challenging and is associated with post-reperfusion syndrome and early allograft dysfunction. The outcomes of machine perfusion for the preservation of marginal grafts have been compared with that of static cold storage, with studies reporting a reduced risk of ischemic cholangiopathy and graft loss. We performed this systematic review and meta-analysis of randomized controlled trials (RCTs) comparing outcomes of machine perfusion of liver grafts to static cold storage (SCS) of liver grafts during liver transplantation. Two independent researchers thoroughly searched for literature in the following databases: PubMed (Medline), Cochrane Central Register of Controlled Studies (CENTRAL), clinical trial registry, ResearchGate, Google Scholar, and Scopus (ELSEVIER) databases (last search: November 2023). The search terms used were: "dynamic perfusion," "normothermic perfusion," "hypothermic perfusion," "liver transplantation," "static cold storage," "NMP," "HOPE," "extended criteria grafts," "marginal grafts," "RCTs," "randomized controlled trials," "warm ischemia," and "cold ischemia." Eight RCTs published between 2019 and 2023 were included in the data synthesis and meta-analysis. The primary outcome considered was the overall incidence of early allograft dysfunction (EAD) between the two methods of graft perfusion after liver transplantation. The secondary outcome considered was the rate of retransplantation. Our meta-analysis revealed that SCS is associated with more EAD when compared with machine perfusion, with a p-value of <0.00001. We also found that the rate of retransplantation is higher among patients who received a liver preserved by SCS, with a p-value of 0.02. The use of machine perfusion in the preservation of liver grafts showed a significant reduction in early allograft dysfunction and retransplantation [ABSTRACT FROM AUTHOR]

Ritonavir is a protease inhibitor initially developed for HIV treatment that is now used as a pharmacokinetic booster for other antiretrovirals due to it being a cytochrome P450 3A4 enzyme and P-glycoprotein inhibitor. Consequently, ritonavir is of special interest for repurposing in other diseases. It had an important role in battling the COVID-19 pandemic as a part of the developed drug Paxlovid® in association with nirmatrelvir and has shown effects in hepatitis and other pathogenic diseases. Ritonavir has also shown promising results in overcoming drug resistance and enhancing the efficacy of existing chemotherapeutic agents in oncology. Evidence of cancer repurposing potential was demonstrated in cancers such as ovarian, prostate, lung, myeloma, breast, and bladder cancer, with several mechanisms of action presented. In vitro studies indicate that ritonavir alone can inhibit key pathways involved in cancer cell survival and proliferation, causing apoptosis, cell cycle arrest, endoplasmic reticulum stress, and metabolic stress due to the inhibition of molecules like heat shock protein 90 and cyclin-dependent kinases. Ritonavir also causes resistant cells to become sensitized to anticancer drugs like gemcitabine or docetaxel. These findings indicate that repurposing ritonavir, either on its own or in combination with other medications, could be a promising approach for treating various diseases. This is particularly relevant in cancer therapy, where ritonavir repurposing is the central focus of this review. [ABSTRACT FROM AUTHOR]

The Arabic diphthongs have two sounds, which are /aɪ/ and /aʊ/, each in its nouns and weak verbs. This study aims to analyse phonological rules related to Arabic diphthongs and syllable segmentation among Arabic diphthongs. Qualitative methods are applied in this research wherein content analysis is conducted using Chomsky and Halle’s phonological rules (1968) and Crowley (1987) theory to analyse all data. The data are collected from the Arabic dictionary called Mu’jam Taşrīf al-`af’āl al-‘arabiyyah and the data are then divided into two categories, namely sound /w/ and /y/. The study observes that the Arabic diphthong sounds are found in in the forms of nouns and defective verbs with suffixes other than /a/, /t/ and /w/. The study finds that in Arabic, diphthong sounds are deleted in defective verbs when the suffix consists of two phonemes, and these sounds transform into long vowel sounds upon the addition of /a/, indicating the third-person singular male in the past tense. The suffixes /t/ and /w/ similarly convert the diphthong to a basic vowel. This study concludes that phonological changes occur more frequently in Arabic defective verbs than in nouns, following certain rules. Additionally, syllable segments change as well when the glide sounds forming diphthongs are deleted. [ABSTRACT FROM AUTHOR]