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Clinical Transplantation May 2024Individual events during donation after circulatory death (DCD) procurement, such as hypotensive or hypoxic warm ischemia, or circulatory arrest are all a part of donor...
BACKGROUND
Individual events during donation after circulatory death (DCD) procurement, such as hypotensive or hypoxic warm ischemia, or circulatory arrest are all a part of donor warm ischemia time (dWIT), and may have differing effects on the outcome of the liver graft. This study aimed to identify risk factors for postreperfusion syndrome (PRS), a state of severe hemodynamic derangement following graft reperfusion, and its impact on DCD liver transplantation (LT) outcomes.
METHODS
This was a retrospective analysis using 106 DCD LT. Detailed information for events during procurement (withdrawal of life support; systolic blood pressure < 80 mmHg; oxygen saturation < 80%; circulatory arrest; aortic cold perfusion) and their association with the development of PRS were examined using logistic regression.
RESULTS
The overall incidence of PRS was 26.4%, occurring in 28 patients. Independent risk factors for PRS were asystolic dWIT (odds ratio (OR) 3.65, 95% confidence interval (CI) 1.38-9.66) and MELD score (OR 1.06, 95% CI 1.01-1.10). Total bilirubin was significantly higher in the PRS group at postoperative day (POD) 1 (p = .02; 5.2 mg/dL vs. 3.4 mg/dL), POD 3 (p = .049; 4.5 mg/dL vs. 2.8 mg/dL), and POD 7 (p = .04; 3.1 mg/dL vs. 1.9 mg/dL). Renal replacement therapy after LT was more likely to be required in the PRS group (p = .01; 48.2% vs. 23.1%).
CONCLUSION
Asystolic dWIT is a risk factor for the development of PRS in DCD LT. Our results suggest that asystolic dWIT should be considered when selecting DCD liver donors.
Topics: Humans; Liver Transplantation; Male; Female; Retrospective Studies; Warm Ischemia; Middle Aged; Risk Factors; Tissue Donors; Prognosis; Follow-Up Studies; Graft Survival; Adult; Tissue and Organ Procurement; Postoperative Complications; Reperfusion Injury; Reperfusion; Syndrome; Tissue and Organ Harvesting
PubMed: 38762783
DOI: 10.1111/ctr.15336 -
Minerva Urology and Nephrology Jun 2024Robot-assisted partial nephrectomy (RAPN) has emerged as the preferred approach for T1 renal-cell-carcinoma. As new robotic platforms like Hugo RAS emerge, we seek to... (Comparative Study)
Comparative Study
BACKGROUND
Robot-assisted partial nephrectomy (RAPN) has emerged as the preferred approach for T1 renal-cell-carcinoma. As new robotic platforms like Hugo RAS emerge, we seek to understand their potential in achieving similar RAPN outcomes as the established Da Vinci system.
METHODS
A prospective single-center comparative study was conducted, and 50 patients selected for RAPN were enrolled (25 Da Vinci Xi; 25 Hugo RAS). The choice of robotic system was based solely on hospital logistics criteria. Surgeries were performed by expert surgeons. Demographic data, tumor characteristics, operative details and postoperative outcomes were collected. SPSS version 22.0 was used for statistical analyses.
RESULTS
The average age of patients was 62.52±9.47 years, with no significant differences in median age, sex, and nephrometry scores between groups. Da Vinci group showed a significantly shorter docking time (12.56 vs. 20.08 min; P<0.01), while other intraoperative measures like console time and warm ischemia time were similar. The Hugo RAS group had a shorter renorraphy time (14.33 vs. 18.84 min; P=0.024). Postoperative outcomes and surgical margin positivity showed no significant differences. Each group had one patient (4%) who developed major surgical complications (Clavien IIIa). Trifecta rates were comparable between both groups (Da Vinci 88% vs. Hugo RAS 84%; P=0.93).
CONCLUSIONS
Initial findings suggest similar perioperative outcomes for RAPN when using Hugo RAS compared to the Da Vinci system. Further research with long-term follow-up is necessary to evaluate oncological and functional outcomes.
Topics: Humans; Robotic Surgical Procedures; Nephrectomy; Female; Middle Aged; Prospective Studies; Male; Kidney Neoplasms; Treatment Outcome; Carcinoma, Renal Cell; Aged; Operative Time
PubMed: 38757775
DOI: 10.23736/S2724-6051.24.05623-4 -
Transplantation Jun 2024Split liver transplantation is a valuable means of mitigating organ scarcity but requires significant surgical and logistical effort. Ex vivo splitting is associated...
BACKGROUND
Split liver transplantation is a valuable means of mitigating organ scarcity but requires significant surgical and logistical effort. Ex vivo splitting is associated with prolonged cold ischemia, with potentially negative effects on organ viability. Machine perfusion can mitigate the effects of ischemia-reperfusion injury by restoring cellular energy and improving outcomes.
METHODS
We describe a novel technique of full-left/full-right liver splitting, with splitting and reconstruction of the vena cava and middle hepatic vein, with dual arterial and portal hypothermic oxygenated machine perfusion. The accompanying video depicts the main surgical passages, notably the splitting of the vena cava and middle hepatic vein, the parenchymal transection, and the venous reconstruction.
RESULTS
The left graft was allocated to a pediatric patient having methylmalonic aciduria, whereas the right graft was allocated to an adult patient affected by hepatocellular carcinoma and cirrhosis.
CONCLUSIONS
This technique allows ex situ splitting, counterbalancing prolonged ischemia with the positive effects of hypothermic oxygenated machine perfusion on graft viability. The venous outflow is preserved, safeguarding both grafts from venous congestion; all reconstructions can be performed ex situ, minimizing warm ischemia. Moreover, there is no need for highly skilled surgeons to reach the donor hospital, thereby simplifying logistical aspects.
Topics: Humans; Hepatic Veins; Liver Transplantation; Perfusion; Liver Neoplasms; Liver; Organ Preservation; Carcinoma, Hepatocellular; Male; Treatment Outcome; Cold Ischemia; Reperfusion Injury; Adult; Liver Cirrhosis; Hypothermia, Induced
PubMed: 38755751
DOI: 10.1097/TP.0000000000005039 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Feb 2024The mouse kidney transplantation model presents challenges in terms of surgical difficulty and low success rate, making it difficult to master. This study aims to...
OBJECTIVES
The mouse kidney transplantation model presents challenges in terms of surgical difficulty and low success rate, making it difficult to master. This study aims to provide a crucial model for transplantation immunology research by modifying and developing novel techniques for mouse kidney transplantation.
METHODS
A total of 57 pairs of mice were used to establish and compare the modified and innovative surgical techniques for mouse kidney transplantation. Three different surgical models were established, including the abdominal suture technique for orthotopic kidney transplantation, the abdominal cuff technique for orthotopic kidney transplantation, and the cervical cuff technique for ectopic kidney transplantation. BALB/c or C57BL/6 male mice, aged 8 to 12 weeks and weighed 20 to 25 g with specified pathogen free-grade were served as the donor mice or the recipient mice. The surgical technique characteristics, key surgical times, complications, and pathological examination in the early postoperative period were summarized and compared.
RESULTS
Three different surgical models of mouse kidney transplantation were successfully established. The comparison of warm ischemic time for the 3 groups of mice showed no statistical significance (=0.510 4). The abdominal suture group had the shortest total operation time of the donor compared with the abdominal cuff group and the cervical cuff group [(18.3±3.6) min vs (26.2±4.7) min and (22.8±2.5) min; both <0.000 1]. There was a significant difference in cold ischemia time among the 3 groups (all <0.000 1), with (60.8±4.1) min in the cervical cuff group, (43.3±5.0) min in the abdominal suture group, and (88.8±6.7) min in the abdominal cuff group. Due to different anastomosis methods, the cervical cuff group had the shortest time [(17.6±2.7) min], whereas the abdominal cuff group had the longest time [(38.8±5.4) min]. The total operation time for the recipients showed significant differences (<0.000 1), with the abdominal suture group having the shortest time [(44.0±6.9) min], followed by the cervical cuff group [(64.1±5.2) min], and the abdominal cuff group [(80.0±6.0) min] being the longest. In the 32 mice of the abdominal suture group, there were 6 with intraoperative bleeding, including 1 arterial intimal injury bleeding and 5 with bleeding after vessel opening. Six mice had ureteral complications, including ureteral bladder anastomotic stenosis, necrosis, and renal pelvis dilation. Two mice had postoperative abdominal infections. In the abdominal cuff group, there was no intraoperative bleeding, but 6 mice showed mild arterial stenosis and 5 showed venous stenosis, 4 arterial injury, 4 arterial thrombosis, and 2 ureteral complications. No postoperative infections occurred in the mice. In the cervical cuff group, no intraoperative bleeding, arterial intimal injury, arterial/venous stenosis, or thrombosis were found in 13 mice. Five mice had ureteral complications, including ureteral necrosis and infection, which were the main complications in the cervical cuff group. The renal function in mice of the 3 groups remained stable 7 days after surgery. Hematoxylin and eosin staining and periodic acid-Schiff staining showed no significant differences in terms of acute rejection among the 3 surgical methods (all >0.05).
CONCLUSIONS
All 3 surgical methods are able to successfully establish mouse kidney transplantation models, with no significant differences observed in the short-term graft survival and acute rejection. The modified abdominal suture technique and abdominal cuff technique have their respective advantages in research applications. The novel cervical cuff technique for ectopic kidney transplantation model is relatively simple to be prepared and causes less trauma to the mice, providing more options for studies involving xenotransplantation, secondary transplantation, and local lymphatic drainage. However, the difficulty in harvesting the donor kidney and the high incidence of ureteral infections need further validation in long-term survival. This study holds important reference value for choosing the type of mouse kidney transplantation model for different research needs.
Topics: Animals; Mice; Kidney Transplantation; Male; Mice, Inbred C57BL; Mice, Inbred BALB C; Models, Animal
PubMed: 38755718
DOI: 10.11817/j.issn.1672-7347.2024.230599 -
Transplantation Jul 2024Withdrawal of life-sustaining therapy (WLST) performed in the circulatory determination of death (DCD) donors leads to cardiac arrest, challenging the utilization of the...
BACKGROUND
Withdrawal of life-sustaining therapy (WLST) performed in the circulatory determination of death (DCD) donors leads to cardiac arrest, challenging the utilization of the myocardium for transplantation. The rapid initiation of normothermic regional perfusion or extracorporeal membrane oxygenation after death helps to optimize organs before implantation. However, additional strategies to mitigate the effects of stress response during WLST, hypoxic/ischemic injury, and reperfusion injury are required to allow myocardium recovery.
METHODS
To this aim, our team routinely used a preconditioning protocol for each DCD donation before and during the WLST and after normothermic regional perfusion/extracorporeal membrane oxygenation. The protocol includes pharmacological treatments combined to reduce oxidative stress (melatonin, N -acetylcysteine, and ascorbic acid), improve microcirculation (statins), and mitigate organ's ischemic injury (steroids) and organ ischemia/reperfusion injury (remifentanil and sevoflurane when the heart is available for transplantation).
RESULTS
This report presents the first case of recovery of cardiac function, with the only support of normothermic regional reperfusion, following 20 min of a no-touch period and 41 min of functional warm ischemic time in a DCD donor after the preconditioning protocol.
CONCLUSIONS
Our protocol seems to be effective in abolishing the stress response during WLST and, on the other hand, particularly organ protective (and heart protective), giving a chance to donate organs less impaired from ischemia/reperfusion injury.
Topics: Humans; Extracorporeal Membrane Oxygenation; Recovery of Function; Male; Tissue Donors; Heart Transplantation; Time Factors; Perfusion; Treatment Outcome; Oxidative Stress; Death; Middle Aged; Adult; Warm Ischemia
PubMed: 38750639
DOI: 10.1097/TP.0000000000004940 -
PloS One 2024Hepatic ischemia-reperfusion injury causes liver damage during surgery. In hepatic ischemia-reperfusion injury, the blood coagulation cascade is activated, causing...
Hepatic ischemia-reperfusion injury causes liver damage during surgery. In hepatic ischemia-reperfusion injury, the blood coagulation cascade is activated, causing microcirculatory incompetence and cellular injury. Coagulation factor Xa (FXa)- protease-activated receptor (PAR)-2 signaling activates inflammatory reactions and the cytoprotective effect of FXa inhibitor in several organs. However, no studies have elucidated the significance of FXa inhibition on hepatic ischemia-reperfusion injury. The present study elucidated the treatment effect of an FXa inhibitor, edoxaban, on hepatic ischemia-reperfusion injury, focusing on FXa-PAR-2 signaling. A 60 min hepatic partial-warm ischemia-reperfusion injury mouse model and a hypoxia-reoxygenation model of hepatic sinusoidal endothelial cells were used. Ischemia-reperfusion injury mice and hepatic sinusoidal endothelial cells were treated and pretreated, respectively with or without edoxaban. They were incubated during hypoxia/reoxygenation in vitro. Cell signaling was evaluated using the PAR-2 knockdown model. In ischemia-reperfusion injury mice, edoxaban treatment significantly attenuated fibrin deposition in the sinusoids and liver histological damage and resulted in both anti-inflammatory and antiapoptotic effects. Hepatic ischemia-reperfusion injury upregulated PAR-2 generation and enhanced extracellular signal-regulated kinase 1/2 (ERK 1/2) activation; however, edoxaban treatment reduced PAR-2 generation and suppressed ERK 1/2 activation in vivo. In the hypoxia/reoxygenation model of sinusoidal endothelial cells, hypoxia/reoxygenation stress increased FXa generation and induced cytotoxic effects. Edoxaban protected sinusoidal endothelial cells from hypoxia/reoxygenation stress and reduced ERK 1/2 activation. PAR-2 knockdown in the sinusoidal endothelial cells ameliorated hypoxia/reoxygenation stress-induced cytotoxicity and suppressed ERK 1/2 phosphorylation. Thus, edoxaban ameliorated hepatic ischemia-reperfusion injury in mice by protecting against micro-thrombosis in sinusoids and suppressing FXa-PAR-2-induced inflammation in the sinusoidal endothelial cells.
Topics: Animals; Reperfusion Injury; Factor Xa Inhibitors; Receptor, PAR-2; Pyridines; Thiazoles; Mice; Liver; MAP Kinase Signaling System; Male; Endothelial Cells; Mice, Inbred C57BL; Disease Models, Animal; Mitogen-Activated Protein Kinase 3
PubMed: 38748746
DOI: 10.1371/journal.pone.0292628 -
Indian Journal of Urology : IJU :... 2024There is an unmet need for high-quality data for Robot-assisted partial nephrectomy (RAPN) in the Indian population. Indian study group on partial nephrectomy (ISGPN) is...
INTRODUCTION
There is an unmet need for high-quality data for Robot-assisted partial nephrectomy (RAPN) in the Indian population. Indian study group on partial nephrectomy (ISGPN) is a consortium of Indian centers contributing to the partial nephrectomy (PN) database. The current study is a descriptive analysis of perioperative and functional outcomes following RAPN.
METHODS
For this study, the retrospective ISGPN database was reviewed, which included patients who underwent RAPN for renal masses at 14 centers across India from September 2010 to September 2022. Demographic, clinical, radiological, perioperative, and functional data were collected and analyzed. Ethics approval was obtained from each of the participating centers.
RESULTS
In this study, 782 patients were included, and 69.7% were male. The median age was 53 years (interquartile range [IQR 44-62]), median operative time was 180 min (IQR 133-240), median estimated blood loss was 100 mL (IQR 50-200), mean warm ischemia time was 22.7 min and positive surgical margin rates were 2.5%. The complication rate was 16.2%, and most of them were of minor grade. Trifecta and pentafecta outcomes were attained in 61.4% and 60% of patients, respectively.
CONCLUSIONS
This is the largest Indian multi-centric study using the Indian Robotic PN Collaborative database to evaluate the outcomes of robot-assisted PN, and has proven its safety and efficacy in the management of renal masses.
PubMed: 38725898
DOI: 10.4103/iju.iju_443_23 -
Annals of Plastic Surgery Jun 2024A common consideration for replantation success is the ischemia time following injury and the preservation temperature. A classic principle within the hand surgery... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
A common consideration for replantation success is the ischemia time following injury and the preservation temperature. A classic principle within the hand surgery community describes 12 hours of warm ischemia and 24 hours of cold ischemia as the upper limits for digit replantation; however, these limits are largely anecdotal and based on older studies. We aimed to compare survival data from the large body of literature to aid surgeons and all those involved in the replantation process in hopes of optimizing success rates.
METHODS
The PubMed database was queried on April 4th, 2023, for articles that included data on digit replantation survival in terms of temperature of preservation and ischemia time. All primary outcomes were analyzed with the Mantel-Haenszel method within a random effects model. Secondary outcomes were pooled and analyzed using the chi-square statistic. Statistical analysis and forest plot generation were completed with RevMan 5.4 software with odds ratios calculated within a 95% confidence interval.
RESULTS
Our meta-analysis identified that digits preserved in cold ischemia for over 12 hours had significantly higher odds of replantation success than the amputated digits replanted with 0-12 hours of warm ischemia time ( P ≤ 0.05). The odds of survival in the early (0-6 hours) replantation group were around 40% greater than the later (6-12 hours) replantation group ( P ≤ 0.05). Secondary outcomes that were associated with higher survival rates included a clean-cut amputation, increased venous and arterial anastomosis, a repair that did not require a vein graft, and replants performed in nonsmokers ( P ≤ 0.05).
DISCUSSION
Overall, these findings suggest that when predicting digit replantation success, time is of the essence when the digit has yet to be preserved in a cold environment. This benefit, however, is almost completely diminished when the amputated digit is appropriately maintained in a cold environment soon after injury. In conclusion, our results suggest that there is potential for broadening the ischemia time limits for digit replant survival outlined in the literature, particularly for digits that have been stored correctly in cold ischemia.
Topics: Humans; Replantation; Amputation, Traumatic; Finger Injuries; Time Factors; Fingers; Warm Ischemia; Cold Ischemia; Ischemia; Temperature
PubMed: 38725110
DOI: 10.1097/SAP.0000000000003944 -
Transplantation May 2024Hepatic ischemia/reperfusion (I/R) injury is a major cause of complications in clinical liver surgery. AXL receptor tyrosine kinase (AXL) is a member of the TAM receptor...
BACKGROUND
Hepatic ischemia/reperfusion (I/R) injury is a major cause of complications in clinical liver surgery. AXL receptor tyrosine kinase (AXL) is a member of the TAM receptor tyrosine kinase family (TYRO3, AXL, and MERTK). Our previous study has shown that AXL expression was markedly upregulated in liver transplantation patients. However, the underlying mechanism of AXL in hepatic I/R injury remains unclear.
METHODS
A mouse liver warm I/R model and a primary hepatocyte hypoxia/reoxygenation model were established to investigate the role of AXL activation and ferroptosis in hepatic I/R injury by pretreating with recombinant mouse growth arrest-specific protein 6 (AXL activator) or R428 (AXL inhibitor). Moreover, we used LY294002 (phosphatidylinositol 3-kinase [PI3K] inhibitor) to evaluate the relationship between the PI3K/AKT (the Ser and Thr kinase AKT) pathway and ferroptosis in hepatic I/R injury.
RESULTS
Hepatic I/R injury decreased phosphorylation AXL expression and enhanced ferroptosis in liver transplantation patients and hepatic I/R-subjected mice. AXL activation attenuated lipid peroxidation and ferroptosis in hepatic I/R injury in vivo and in vitro. Inhibition of AXL activation exacerbated liver pathological damage and liver dysfunction, as well as iron accumulation and lipid peroxidation in hepatic I/R injury. Mechanistically, activated growth arrest-specific protein 6/AXL and its downstream PI3K/AKT signaling pathway inhibited ferroptosis during hepatic I/R injury.
CONCLUSIONS
AXL activation protects against hepatic I/R injury by preventing ferroptosis through the PI3K/AKT pathway. This study is the first investigation on the AXL receptor and ferroptosis, and activating AXL to mitigate ferroptosis may be an innovative therapeutic strategy to combat hepatic I/R injury.
PubMed: 38725107
DOI: 10.1097/TP.0000000000005036 -
Transplantation May 2024Warm ischemia time (WIT) and ischemia-reperfusion injury are limiting factors for vascularized composite allograft (VCA) transplantation. Subnormothermic machine...
BACKGROUND
Warm ischemia time (WIT) and ischemia-reperfusion injury are limiting factors for vascularized composite allograft (VCA) transplantation. Subnormothermic machine perfusion (SNMP) has demonstrated the potential to extend WIT in organ transplantation. This study evaluates the effect of SNMP on VCA viability after prolonged WIT.
METHODS
Rat hindlimbs underwent WIT for 30, 45, 60, 120, 150, or 210 min, followed by 3-h SNMP. Monitoring of perfusion parameters and outflow determined the maximum WIT compatible with limb viability after SNMP. Thereafter, 2 groups were assessed: a control group with inbred transplantation (Txp) after 120 min of WIT and an experimental group that underwent WIT + SNMP + Txp. Graft appearance, blood gas, cytokine levels, and histology were assessed for 21 d.
RESULTS
Based on potassium levels, the limit of WIT compatible with limb viability after SNMP is 120 min. Before this limit, SNMP reduces potassium and lactate levels of WIT grafts to the same level as fresh grafts. In vivo, the control group presented 80% graft necrosis, whereas the experimental group showed no necrosis, had better healing (P = 0.0004), and reduced histological muscle injury (P = 0.012). Results of blood analysis revealed lower lactate, potassium levels, and calcium levels (P = 0.048) in the experimental group. Both groups presented an increase in interleukin (IL)-10 and IL-1b/IL-1F2 with a return to baseline after 7 to 14 d.
CONCLUSIONS
Our study establishes the limit of WIT compatible with VCA viability and demonstrates the effectiveness of SNMP in restoring a graft after WIT ex vivo and in vivo, locally and systemically.
PubMed: 38722685
DOI: 10.1097/TP.0000000000005035