1,721,099 research outputs found
Renal resistance during hypothermic machine perfusion: A scoping review of variability and determinants, with a meta-analysis of predictive value for transplant outcomes
No full textBackground: Renal resistance (RR) measured during hypothermic machine perfusion (HMP) is used to assess donor kidney quality and guide transplantation decisions. However, its clinical reliability and relationship with donor factors remain unclear. Methods: This scoping review and meta-analysis evaluate the variability, determinants, and predictive value of RR during HMP. A systematic search of PubMed, Embase, Web of Science, and Cochrane Library (July 2024) identified 49 primary studies reporting RR in perfused human kidneys. The risk of bias was assessed using the ROBINS-I tool. Meta-analyses for the predictive value of RR were performed when >= 3 studies reported univariable associations for the same time point and outcome. Results: Most studies had moderate to serious risk of bias. RR typically declined rapidly, stabilizing within 5 h (range: 0.30-3.50 to 0.17-1.50 mmHg/mL/min), but patterns varied widely. Determinants included histology, donor characteristics, and perfusion additives, though evidence was inconsistent. A meta-analysis showed terminal RR was significantly associated with delayed graft function (odds ratio 2.49, 95 % CI 1.49-4.18, I2 = 58 %). While several studies proposed RR-thresholds, none were consistently validated, and heterogeneity in measurement timings and device settings limits comparability. Conclusion: RR shows potential as a functional assessment parameter during HMP but is influenced by multiple technical and biological factors. Current evidence does not support the use of isolated RR-thresholds for organ acceptance. Standardized HMP protocols, trajectory modeling, and prospective studies are needed to clarify RR's role in clinical decision-making.Funding
This study was funded by a grant from the KU Leuven Research Council (C2M/23/051) and was preregistered
We thank Veerle Heedfeld and Tine Wylin for their help with data extraction, quality assessment, and table preparation. We also thank Thomas Vandendriessche, Chayenne Van Meel, and Krizia Tuand, biomedical reference librarians of the KU Leuven Libraries—2Bergen—Learning Centre D´esir´e Collen (Leuven, Belgium) for their help in conducting the systematic literature search
Effect of a Combined Drug Approach on the Severity of Ischemia-Reperfusion Injury During Liver Transplant A Randomized Clinical Trial
No full textIMPORTANCE: In a porcine model of liver transplant, a combined drug approach that targeted the donor graft and graft recipient reduced ischemia-reperfusion injury, a major hurdle to the success of liver transplant. OBJECTIVE: To assess the effect of a clinical form of a perioperative combined drug approach delivered immediately before implantation to the procured liver and to the liver recipient on the degree of ischemia-reperfusion injury. DESIGN, SETTING, AND PARTICIPANTS: This unicentric, investigator-driven, open-label randomized clinical trial with 2 parallel arms was conducted in Belgium from September 2013 through February 2018, with 1-year follow-up. Adults wait-listed for a first solitary full-size liver transplant were screened for eligibility. Exclusion criteria were acute liver failure, kidney failure, contraindication to treatment, participation in another trial, refusal, technical issues, and death while awaiting transplant. Included patients were enrolled and randomized at the time of liver offer. Data were analyzed from May 20, 2019, to May 27, 2020. INTERVENTIONS: Participants were randomized to a combined drug approach with standard of care (static cold storage) or standard of care only (control group). In the combined drug approach group, following static cold preservation, donor livers were infused with epoprostenol (ex situ, portal vein); recipients were given oral α-tocopherol and melatonin prior to anesthesia and intravenous antithrombin III, infliximab, apotransferrin, recombinant erythropoietin-β, C1-inhibitor, and glutathione during the anhepatic and reperfusion phase. MAIN OUTCOMES AND MEASURES: The primary outcome was the posttransplant peak serum aspartate aminotransferase (AST) level within the first 72 hours. Secondary end points were the frequencies of postreperfusion syndrome, ischemia-reperfusion injury score, early allograft dysfunction, surgical complications, ischemic cholangiopathy, acute kidney injury, acute cellular rejection, and graft and patient survival. RESULTS: Of 93 randomized patients, 21 were excluded, resulting in 72 patients (36 per study arm) in the per protocol analysis (median recipient age, 60 years [IQR, 51.7-66.2 years]; 52 [72.2%] men). Peak AST serum levels were not different in the combined drug approach and control groups (geometric mean, 1262.9 U/L [95% CI, 946.3-1685.4 U/L] vs 1451.2 U/L [95% CI, 1087.4-1936.7 U/L]; geometric mean ratio, 0.87 [95% CI, 0.58-1.31]; P = .49) (to convert AST to μkat/L, multiply by 0.0167). There also were no significant differences in the secondary end points between the groups. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the combined drug approach targeting the post-cold storage graft and the recipient did not decrease ischemic-reperfusion injury. The findings suggest that in addition to a downstream strategy that targets the preimplantation liver graft and the graft recipient, a clinically effective combined drug approach may need to include an upstream strategy that targets the donor graft during preservation. Dynamic preservation strategies may provide an appropriate delivery platform. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02251041.sponsorship: This research was funded by IWT grant 100790 from the Research Foundation Flanders (Dr Monbaliu), which allowed for payment of the research nurse and research costs. (IWT grant from the Research Foundation Flanders|100790)status: Publishe
The Impact of Hepatectomy Time of the Liver Graft on Post-transplant Outcome
No full textObjective: Assessing the effect of donor hepatectomy time on outcome after transplantation. Summary of Background Data: When blood supply in a deceased organ donor stops, ischemic injury starts. Livers are cooled to reduce cellular metabolism and minimize ischemic injury. This cooling is slow and livers are lukewarm during hepatectomy, potentially affecting outcome. Methods: We used the Eurotransplant Registry to investigate the relationship between donor hepatectomy time and post-transplant outcome in 12,974 recipients of deceased-donor livers (January 1, 2004, to December 31, 2013). Cox regression analyses for patient and graft survival (censored and uncensored for death with a functioning graft) were corrected for donor, preservation, and recipient variables. Donor hepatectomy time was defined as time between start of aortic cold flush and placement of the liver in the ice-bowl. Results: Median donor hepatectomy time was 41 minutes [interquartile range (IQR) 32 to 52]. Livers donated after circulatory death had longer hepatectomy times than those from brain-dead donors [50 minutes (35 to 68) vs 40 minutes (32 to 51), P < 0.001]. Donor hepatectomy time was independently associated with graft loss [adjusted hazard ratio (HR) 1.03 for every 10-minute increase, 95% confidence interval (95% CI) 1.02-1.05; P < 0.001]. The magnitude of this effect was comparable to the effect of each hour of additional cold ischemia time (adjusted HR 1.04, 95% CI 1.02-1.05; P < 0.001). Donor hepatectomy time had a similar effect on death-censored graft survival and patient survival. Livers donated after circulatory death and those with a higher donor risk index were more susceptible to the effect of donor hepatectomy time on death-censored graft survival. Conclusion: Donor hepatectomy time impairs liver transplant outcome. Keeping this time short together with efficient cooling during hepatectomy might improve outcome.We thank all centers within Eurotransplant for providing data to the Eurotransplant Registry and Erwin de Vries from Eurotransplant for compilation of the data. We also thank the Eurotransplant Liver and Intestinal Advisory Committee and the Eurotransplant Organ Procurement Committee for their support
Effects of Cyclodextrin Curcumin Formulation on Ischemia-Reperfusion Injury in Porcine DCD Liver Transplantation
No full textBackground.Curcumin is a pleiotropic antioxidant polyphenol, which has proven to be highly protective in various models of liver injury and inflammation. We hypothesized that adding a stable aqueous curcumin formulation which comprises a water-soluble cyclodextrin curcumin formulation (CDC) complex of the water-insoluble curcumin molecule (Novobion, Espoo, Finland) to preservation solution during liver procurement may reduce ischemia-reperfusion injury and improve graft function after liver transplantation using donation after circulatory death (DCD). Methods.In a preclinical pig model of DCD-liver transplantation, livers exposed to 15' of warm ischemia were either modulated (N = 6) with a flush of preservation solution (histidine-tryptophan-ketoglutarate) containing CDC (60 mu mol/L) through the vena porta and the aorta, or not (controls, N = 6) before 4 h of cold storage. Area under the curve of log serum aspartate aminotransferase, markers of graft function (lactate, glycemia, prothrombin time, and bile production), inflammation (tumor necrosis factor-alpha), and survival were monitored. Results.Area under the curve of log serum aspartate aminotransferase were similar between curcumin and control groups (22.12 [20.87-24.88] versus 25.08 [22.1-26.55]; P = 0.28). No difference in the liver function markers were observed between groups except a lower serum lactate level 3-h post-reperfusion in the curcumin group (3 [1.95-6.07] versus 8.2 [4.85-13.45] mmol/L; P = 0.05). Serum tumor necrosis factor-alpha levels were similar in each group. Recipient survival rates were found similar. Conclusions.CDC added to the preservation solution in DCD liver pig model did not improve ischemia-reperfusion injury severity, liver function, or survival. Further efforts are needed to explore this strategy, particularly with dynamic preservation, which finds its way into clinical practice.This research was funded by IWT grant 100790 from the Research Foundation Flanders (Dr Monbaliu), which allowed for payment of the research nurse and research costs
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
De aanpak van "delayed graft function" na niertransplantatie
No full textDelayed graft function is a scarcely studied but major complication of kidney transplantation. Up to 25% of standard brain dead kidney grafts develop delayed graft function and this incidence is likely to increase because of the increased use of "higher-risk" kidneys, i.e. kidneys from expanded criteria donors and kidneys donated after circulatory death. Indeed, delayed graft function can be attributed largely to ischaemia-reperfusion injury of the graft and higher-risk kidney grafts are particularly vulnerable to ischaemia-reperfusion injury with incidences of delayed graft function between 40% and 80%. Nevertheless, they still provide a better outcome compared to continued dialysis.Preventing and predicting delayed graft function and quantifying initial graft injury, the focus of this doctoral thesis, is essential to improve results after transplantation of higher-risk kidney grafts and safely increase the overall deceased donor transpant activity. In a series of clinical and experimental studies, this thesis shows that - until a better preservation method is fully clinically applicable - hypothermic machine perfusion should be the gold standard to preserve higher-risk kidney grafts because it reduces the chance for developing delayed graft function. Furthermore, it shows that machine perfusion characteristics such as renal vascular resistance and perfusate injury markers are independent predictor of delayed graft function, however, they should no longer be used as stand-alone tools to discard kidney grafts. Nevertheless, they can provide additional information to tailor peri- and postoperative care. And finally, plasma injury markers have the potential to quantify ischaemia-reperfusion injury and might lead to a more accurate and objective definition of short-term graft outcome and could potentially be used to assess the effect of emerging treatment strategies.status: Publishe
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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