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Heliyon Apr 2024Liver donation after cardiac death (DCD) makes up a small percentage of the organs used in transplantation and poses a higher risk of graft loss compared to donation...
BACKGROUND
Liver donation after cardiac death (DCD) makes up a small percentage of the organs used in transplantation and poses a higher risk of graft loss compared to donation after brain death (DBD); this is a result of ischemia reperfusion for which the exact injury mechanisms are currently not fully understood. However, reperfusion injury has been shown to lead to necrosis as well as apoptosis through oxidative stress and mitochondrial dysfunction. In this work, we propose that use of the pro-survival, anti-apoptotic CEPT cocktail in post-ischemia normothermic machine perfusion (NMP) may improve recovery in rat livers subjected to extended durations of warm ischemia.
MATERIALS AND METHODS
Livers procured from male Lewis rats were subjected to 90 min of warm ischemia, followed by 6 h of NMP where they were treated either with the survival-enhancing anti-apoptotic cocktail (CEPT), the vehicle (DMSO) or the base media with no additives.
RESULTS
The CEPT-treated group exhibited lower expression of hepatic injury biomarkers, and improvement in a range of hepatocellular symptoms associated with the hepatic parenchyma, biliary epithelium and the sinusoidal endothelium, including recovery of bile secretion and lowered vascular resistance.
CONCLUSIONS
This study's findings suggest apoptosis plays a more significant role in ischemia-reperfusion injury than previously understood, and provide useful insight for further investigation of the specific underlying mechanisms and development of novel treatment methods.
PubMed: 38660283
DOI: 10.1016/j.heliyon.2024.e29519 -
Central European Journal of Urology 2024The aim of this review was to assess the outcomes of partial nephrectomy using indocyanine green (ICG) regarding ischemia time, positive surgical margins (PSM),... (Review)
Review
INTRODUCTION
The aim of this review was to assess the outcomes of partial nephrectomy using indocyanine green (ICG) regarding ischemia time, positive surgical margins (PSM), estimated blood loss (EBL) and estimated GFR reduction while also suggesting the optimal dosage scheme.
MATERIAL AND METHODS
A systematic review was performed using Medline (PubMed), ClinicalTrials.gov, and Cochrane Library (CENTRAL) databases, in concordance with the PRISMA statement. Studies in English regarding the use of indocyanine green in partial nephrectomy were reviewed. Reviews and meta-analyses, editorials, perspectives, and letters to the editors were excluded.
RESULTS
Individual ICG dose was 5 mg in most of the studies. The mean warm ischemia time (WIT) on each study ranged from 11.6 minutes to 27.2 minutes. The reported eGFR reduction ranged from 0% to 15.47%. Lowest mean EBL rate was 48.2 ml and the highest was 347 ml. Positive surgical margin rates were between 0.3% to 11%.
CONCLUSIONS
Indocyanine green seems to be a useful tool in partial nephrectomy as it can assist surgeons in identifying tumor and its related vasculature. Thereby, warm ischemia time can be reduced and, in some cases, selective ischemia can be implemented leading to better renal functional preservation.
PubMed: 38645804
DOI: 10.5173/ceju.2023.155 -
American Journal of Transplantation :... Apr 2024Normothermic machine perfusion (NMP) is increasingly considered for pretransplant kidney quality assessment. However, fundamental questions about differences between in...
Magnetic resonance imaging as a noninvasive adjunct to conventional assessment of functional differences between kidneys in vivo and during ex vivo normothermic machine perfusion.
Normothermic machine perfusion (NMP) is increasingly considered for pretransplant kidney quality assessment. However, fundamental questions about differences between in vivo and ex vivo renal function, as well as the impact of ischemic injury on ex vivo physiology, remain unanswered. This study utilized magnetic resonance imaging (MRI), alongside conventional parameters to explore differences between in vivo and ex vivo renal function and the impact of warm ischemia on a kidney's behavior ex vivo. Renal MRI scans and samples were obtained from living pigs (n = 30) in vivo. Next, kidney pairs were procured and exposed to minimal, or 75 minutes of warm ischemia, followed by 6 hours of hypothermic machine perfusion. Both kidneys simultaneously underwent 6-hour ex vivo perfusion in MRI-compatible NMP circuits to obtain multiparametric MRI data. Ischemically injured ex vivo kidneys showed a significantly altered regional blood flow distribution compared to in vivo and minimally damaged organs. Both ex vivo groups showed diffusion restriction relative to in vivo. Our findings underscore the differences between in vivo and ex vivo MRI-based renal characteristics. Therefore, when assessing organ viability during NMP, it should be considered to incorporate parameters beyond the conventional functional markers that are common in vivo.
PubMed: 38615901
DOI: 10.1016/j.ajt.2024.04.001 -
Canadian Urological Association Journal... Apr 2024In 2019, our center attempted to transition all partial nephrectomies (PNs) to robotic-assisted laparoscopic PN (RALPN). The purpose of this study was to compare RALPN...
INTRODUCTION
In 2019, our center attempted to transition all partial nephrectomies (PNs) to robotic-assisted laparoscopic PN (RALPN). The purpose of this study was to compare RALPN outcomes to laparoscopic PN (LPN) and open PN (OPN) at our institution, as there is limited literature from Canadian centers.
METHODS
In this single-center, two-surgeon, retrospective cohort study, we compared RALPN outcomes during the early phase of our robotics program to OPN and LPN performed just before the introduction of RALPN.
RESULTS
A total of 106 patients underwent OPN, 83 LPN, and 82 RALPN during the study period. Median RALPN RENAL score was 7 vs. 6 for LPN (p<0.05) and 8 for OPN (p=0.10). Median RALPN length of stay (LOS) was two days vs. three and four days for LPN and OPN (p<0.05), respectively. OPN median procedure time was 104 minutes vs. 94 and 82 minutes for LPN and RALPN (p<0.05), respectively. Median OPN operating room (OR) time was 160 minutes vs. 150 and 146 minutes for LPN and RALPN (p<0.05), respectively. There were no significant differences in intraoperative (p=0.92) or postoperative complications rates (p=0.47). RALPN warm ischemia time (WIT) was 17 minutes vs 14.5 and 15 minutes for OPN and LPN (p<0.05), respectively. Median RALPN estimated blood loss (EBL) was 165 ml vs. 250 ml for OPN (p<0.05) and 125 ml for LPN (p=0.15).
CONCLUSIONS
Although patients who underwent RALPN had longer WIT, they had similar rates of complications, required less total OR time, and had shorter procedure time and LOS compared with OPN and LPN despite similar RENAL score compared to OPN and greater score than LPN.
PubMed: 38587976
DOI: 10.5489/cuaj.8585 -
BioRxiv : the Preprint Server For... Mar 2024Precision oncology is driven by molecular biomarkers. For glioblastoma multiforme (GBM), the most common malignant adult primary brain tumor, O6-methylguanine-DNA...
Precision oncology is driven by molecular biomarkers. For glioblastoma multiforme (GBM), the most common malignant adult primary brain tumor, O6-methylguanine-DNA methyltransferase ( ) gene DNA promoter methylation is an important prognostic and treatment clinical biomarker. Time consuming pre-analytical steps such as biospecimen storage before fixing, sampling, and processing are major sources of errors and batch effects, that are further confounded by intra-tumor heterogeneity of promoter methylation. To assess the effect of pre-analytical variables on GBM DNA methylation, tissue storage/sampling (CryoGrid), sample preparation multi-sonicator (PIXUL) and 5-methylcytosine (5mC) DNA immunoprecipitation (Matrix MeDIP-qPCR/seq) platforms were used. promoter CpG methylation was examined in 173 surgical samples from 90 individuals, 50 of these were used for intra-tumor heterogeneity studies. promoter methylation levels in paired frozen and formalin fixed paraffin embedded (FFPE) samples were very close, confirming suitability of FFPE for promoter methylation analysis in clinical settings. Matrix MeDIP-qPCR yielded similar results to methylation specific PCR (MS-PCR). Warm ex-vivo ischemia (37°C up to 4hrs) and 3 cycles of repeated sample thawing and freezing did not alter 5mC levels at promoter, exon and upstream enhancer regions, demonstrating the resistance of DNA methylation to the most common variations in sample processing conditions that might be encountered in research and clinical settings. 20-30% of specimens exhibited intratumor heterogeneity in the DNA promoter methylation. Collectively these data demonstrate that variations in sample fixation, ischemia duration and temperature, and DNA methylation assay technique do not have significant impact on assessment of promoter methylation status. However, intratumor methylation heterogeneity underscores the need for histologic verification and value of multiple biopsies at different GBM geographic tumor sites in assessment of promoter methylation. Matrix-MeDIP-seq analysis revealed that promoter methylation status clustered with other differentially methylated genomic loci (e.g. HOXA and lncRNAs), that are likewise resilient to variation in above post-resection pre-analytical conditions. These -associated global DNA methylation patterns offer new opportunities to validate more granular data-based epigenetic GBM clinical biomarkers where the CryoGrid-PIXUL-Matrix toolbox could prove to be useful.
PubMed: 38586048
DOI: 10.1101/2024.03.26.586350 -
World Journal of Transplantation Mar 2024Prolonged donor hepatectomy time may be implicated in early and late complications of liver transplantation.
BACKGROUND
Prolonged donor hepatectomy time may be implicated in early and late complications of liver transplantation.
AIM
To evaluate the impact of donor hepatectomy time on outcomes of liver transplant recipients, mainly early allograft dysfunction.
METHODS
This multicenter retrospective study included brain-dead donors and adult liver graft recipients. Donor-recipient matching was obtained through a crossover list. Clinical and laboratory data were recorded for both donors and recipients. Donor hepatectomy, cold ischemia, and warm ischemia times were recorded. Primary outcome was early allograft dysfunction. Secondary outcomes included need for retransplantation, length of intensive care unit and hospital stay, and patient and graft survival at 12 months.
RESULTS
From January 2019 to December 2021, a total of 243 patients underwent a liver transplant from a brain-dead donor. Of these, 57 (25%) developed early allograft dysfunction. The median donor hepatectomy time was 29 (23-40) min. Patients with early allograft dysfunction had a median hepatectomy time of 25 (22-38) min, whereas those without it had a median time of 30 (24-40) min ( = 0.126).
CONCLUSION
Donor hepatectomy time was not associated with early allograft dysfunction, graft survival, or patient survival following liver transplantation.
PubMed: 38576765
DOI: 10.5500/wjt.v14.i1.89702 -
Indian Journal of Critical Care... Jan 2024Acute kidney injury (AKI) significantly contributes to the mortality and morbidity rates among pediatric liver transplant (LT) recipients.
BACKGROUND
Acute kidney injury (AKI) significantly contributes to the mortality and morbidity rates among pediatric liver transplant (LT) recipients.
OBJECTIVE
Our study aimed to assess the potential factors contributing to AKI in pediatric LT patients and to analyze the impact of AKI on postoperative mortality and hospitalization duration.
MATERIALS AND METHODS
About 235 pediatric LT patients under the age of 18 between the years 2015 and 2021 were evaluated retrospectively. The relationship between preoperative and intraoperative variables of the patients and AKI developed when the early postoperatıve period was assessed.
RESULTS
A correlation was found between the patients' preoperative age, albumin levels, and AKI. AKI was found to be associated with the duration of surgery and intraoperative blood transfusion.
CONCLUSION
Our findings revealed that the severity of AKI in pediatric LT patients is linked to extended surgical durations and increased blood transfusions resulting from hemodynamically compromised blood loss. Furthermore, independent risk factors for AKI were identified as prolonged warm ischemia and the overall duration of the operation.
HOW TO CITE THIS ARTICLE
Demiroz D, Colak YZ, Ozdes OO, Ucar M, Ali Erdogan M, Toprak HI, . Incidence and Risk Factors of Acute Kidney İnjury in Pediatric Liver Transplant Patients: A Retrospective Study. Indian J Crit Care Med 2024;28(1):75-79.
PubMed: 38510757
DOI: 10.5005/jp-journals-10071-24616 -
World Journal of Urology Mar 2024Accurate surgical reconstruction of arterial vascular supply is a crucial part of living kidney transplantation (LDKT). The presence of multiple renal arteries (MRA) in...
Retrospective analysis of the perioperative outcome in living donor kidney transplantation with multiple renal arteries: does accessory vessel ligation affect the outcome?
PURPOSE
Accurate surgical reconstruction of arterial vascular supply is a crucial part of living kidney transplantation (LDKT). The presence of multiple renal arteries (MRA) in grafts can be challenging. In the present study, we investigated the impact of ligation versus anastomosis of small accessory graft arteries on the perioperative outcome.
METHODS
Clinical and radiological outcomes of 51 patients with MRA out of a total of 308 patients who underwent LDKT with MRA between 2011 and 2020 were stratified in two groups and analyzed. In group 1 (20 patients), ligation of accessory arteries (ARAs) and group 2 (31 patients) anastomosis of ARAs was performed.
RESULTS
Significant differences were observed in the anastomosis-, surgery-, and warm ischemia time (WIT) in favor of group 1. Students t-test showed comparable serum creatinine levels of 2.33 (± 1.75) to 1.68 (± 0.83) mg/dL in group 1 and 2.63 (± 2.47) to 1.50 (± 0.41) mg/dL in group 2, were seen from 1 week to 1 year after transplant. No increased rates of Delayed graft function (DGF), primary transplant dysfunction and transplant rejection were seen, but graft loss and revision rates were slightly higher when the ARAs were ligated. Analysis of Doppler sonography revealed that segmental perfusion deficits tend to regenerate during the clinical course.
CONCLUSION
Ligation of smaller accessory renal arteries may not affect the outcome of living kidney transplantation, except for a minor increase in the reoperation rate. Segmental perfusion deficits of the graft seem to regenerate in most cases as seen in Doppler sonography.
Topics: Humans; Kidney Transplantation; Renal Artery; Living Donors; Retrospective Studies; Graft Survival; Kidney; Treatment Outcome
PubMed: 38488940
DOI: 10.1007/s00345-024-04883-9 -
Transplantation Direct Apr 2024Intragraft microthrombi prevent complete organ perfusion, thereby compromising the viability maintained by preservation solutions or machine perfusion. Herein, we...
BACKGROUND
Intragraft microthrombi prevent complete organ perfusion, thereby compromising the viability maintained by preservation solutions or machine perfusion. Herein, we developed and evaluated a hypobaric perfusion method for flushing microthrombi from kidney grafts with prolonged circulatory arrest in a porcine model.
METHODS
Porcine renal grafts with 1-h warm ischemia were flushed with heparin-containing perfusate in a normobaric environment (control group) or a hypobaric environment of -20 to -30 mm Hg (hypobaric perfusion group) for 10 min using a gravity drip from a 1-m height. Perfusion parameters, histological findings in ex vivo blood perfusion experiments (2 control and 4 hypobaric perfusion kidneys), and safety in allogeneic porcine transplantation experiments (1 donor to 2 recipients) were evaluated.
RESULTS
The -20 mm Hg hypobaric perfusion group exhibited greater maximal flow than the control group (20.4 versus 6.9 mL/min; = 0.028). Histological evaluation following 3 h of static cold storage and 10 min ex vivo porcine whole-blood perfusion revealed statistically significant reductions in congestion and edema (1.5 versus 3, and 0.5 versus 4 on a 5-point scale, from 0 to 4; = 0.014 and 0.006, respectively) in the medulla along with improved ischemia-reperfusion injury scores (4.0 versus 4.7 on a 6-point scale, from 0 to 5; = 0.004) in the -20 mm Hg hypobaric perfusion group. Kidney grafts perfused under -30 mm Hg hypobaric environment followed by 3 h of static cold storage could be used for porcine allogeneic transplantation without any macroscopic damage to the graft, effect on intraoperative handling, or perioperative adverse events. Thus, the hypobaric perfusion method was considered safe.
CONCLUSIONS
Perfusion in a hypobaric environment may prevent graft congestion, edema, and further reperfusion injury by flushing out erythrocytes occluding the medullary capillaries, improving marginal renal graft quality, and reducing the number of discarded grafts.
PubMed: 38481962
DOI: 10.1097/TXD.0000000000001611 -
JAMA Network Open Mar 2024The use of ex vivo normothermic organ perfusion has enabled the use of deceased after circulatory death (DCD) donors for heart transplants. However, compared with...
IMPORTANCE
The use of ex vivo normothermic organ perfusion has enabled the use of deceased after circulatory death (DCD) donors for heart transplants. However, compared with conventional brain death donation, DCD heart transplantation performed with ex vivo organ perfusion involves an additional period of warm and cold ischemia, exposing the allograft to multiple bouts of ischemia reperfusion injury and may contribute to the high rates of extracorporeal membrane oxygenation usage after DCD heart transplantation.
OBJECTIVE
To assess whether the beating heart method of DCD heart transplantation is safe and whether it has an acceptable rate of extracorporeal membrane oxygenation use postoperatively.
DESIGN, SETTING, AND PARTICIPANTS
This case series includes 10 patients with end-stage heart failure undergoing DCD heart transplantation at a single academic medical center from October 1, 2022, to August 3, 2023. Data were analyzed from October 2022 to August 2023.
INTERVENTIONS
Using a beating heart method of implantation of the donor allograft.
MAIN OUTCOMES AND MEASURES
The main outcome was primary graft dysfunction necessitating postoperative initiation of mechanical circulatory support. Survival and initiation of mechanical circulatory support were secondary outcomes.
RESULTS
In this case series, 10 consecutive patients underwent DCD heart transplantation via the beating heart method. Ten of 10 recipients were male (100%), the mean (SD) age was 51.2 (13.8) years, and 7 (70%) had idiopathic dilated cardiomyopathy. Ten patients (100%) survived, and 0 patients had initiation of extracorporeal membrane oxygenation postoperatively. No other mechanical circulatory support, including intra-aortic balloon pump, was initiated postoperatively. Graft survival was 100% (10 of 10 patients), and, at the time of publication, no patients have been listed for retransplantation.
CONCLUSIONS AND RELEVANCE
In this study of 10 patients undergoing heart transplantation, the beating heart implantation method for DCD heart transplantation was safe and may mitigate ischemia reperfusion injury, which may lead to lower rates of primary graft dysfunction necessitating extracorporeal membrane oxygenation. These results are relevant to institutions using DCD donors for heart transplantation.
Topics: Humans; Male; Middle Aged; Female; Primary Graft Dysfunction; Cardiovascular System; Heart Transplantation; Heart; Tissue Donors
PubMed: 38466306
DOI: 10.1001/jamanetworkopen.2024.1828