Addition of a liver to the normothermic perfusion circuit reduces renal pro-inflammatory factors.

BACKGROUND: Normothermic machine perfusion (NMP) provides a novel platform to preserve isolated organs in an artificial condition. Our study aimed to explore the interaction between the liver and kidney at an ex vivo organ level by adding a liver to the kidney NMP circuit. METHODS: Porcine kidney and liver obtained from abattoir were subjected to 9 h NMP after suffering 30-min warm ischemia time and 90-min cold ischemia time. The liver-kidney NMP group (n = 5) and the single-kidney NMP group (n = 5) were designed. During the NMP, perfusion parameters, blood gas analysis, and tissue samples were compared. RESULTS: The perfusate of both groups remained stable, and continuous urine production was observed during NMP. In the liver-kidney NMP group, the lactate level was low, while blood urea nitrogen increased and glucose levels decreased. After the NMP, the renal tissue in the liver-kidney group exhibited fewer histological changes such as tubular epithelium vacuolization, along with reduced expression of IL-6, IL-8, IL-1ß, NLRP3, and GSDMD. CONCLUSIONS: Our results indicated that the expression of renal pro-inflammatory factors was reduced in the liver-kidney NMP system.

Limited non-linear impact of warm ischemia time on renal functional decline after partial nephrectomy: a propensity score-matched study.

OBJECTIVE: To quantificationally illustrate the impact of ischemia time (IT) on renal function decline after partial nephrectomy (PN), especially for patients with compromised baseline renal function (estimated glomerular filtration rate [eGFR] < 90 mL/min/1.73 m2). METHODS: Patients undergoing PN during 2014-2021 from a prospectively maintained database were reviewed. Propensity score matching (PSM) was employed to balance the possible covariates between patients with or without baseline compromised renal function. Specifically, the relationship of IT with postoperative renal function was illustrated. Two machine learning methods (logistic least absolute shrinkage and selection operator [LASSO] logistic regression and random forest) were applied to quantify the relative impact of each covariables. RESULTS: The average drop percent of eGFR was -10.9% (- 12.2%, - 9.0%). Multivariable Cox proportional regression and linear regression analyses identified five risk factors for renal function decline, namely RENAL Nephrometry Score (RNS), age, baseline eGFR, diabetes and IT (all p < 0.05). Specifically, the relationship of IT with postoperative functional decline emerged as non-linear, with an increase from 10-30 min and a plateau afterwards among patients with normal function (eGFR ≥ 90 mL/min/1.73 m2), whereas with an increase from 10 to 20 min and a plateau afterwards among patients with compromised function (eGFR < 90 mL/min/1.73 m2). Furthermore, the coefficient's path and random forest analysis revealed that the top two most important features were RNS and age. CONCLUSION: IT exhibits the secondarily non-linear relationship with postoperative renal function decline. Patients with compromised baseline renal function are less tolerant to ischemia damage. The use of a single cut-off interval of IT in the setting of PN is flawed.

Functional recovery after partial nephrectomy: next generation analysis.

OBJECTIVES: To provide a more rigorous assessment of factors affecting functional recovery after partial nephrectomy (PN) using novel tools that allow for analysis of more patients and improved accuracy for assessment of parenchymal volume loss, thereby revealing the potential impact of secondary factors such as ischaemia. PATIENTS AND METHODS: Of 1140 patients managed with PN (2012-2014), 670 (59%) had imaging and serum creatinine levels measured before and after PN necessary for inclusion. Recovery from ischaemia was defined as the ipsilateral glomerular filtration rate (GFR) saved normalised by parenchymal volume saved. Acute kidney injury was assessed through Spectrum Score, which quantifies the degree of acute ipsilateral renal dysfunction due to exposure to ischaemia that would otherwise be masked by the contralateral kidney. Multivariable regression was used to identify predictors of Spectrum Score and Recovery from Ischaemia. RESULTS: In all, 409/189/72 patients had warm/cold/zero ischaemia, respectively, with median (interquartile range [IQR]) ischaemia times for cold and warm ischaemia of 30 (25-42) and 22 (18-28) min, respectively. The median (IQR) global preoperative GFR and new baseline GFR (NBGFR) were 78 (63-92) and 69 (54-81) mL/min/1.73 m2 , respectively. The median (IQR) ipsilateral preoperative GFR and NBGFR were 40 (33-47) and 31 (24-38) mL/min/1.73 m2 , respectively. Functional recovery correlated strongly with parenchymal volume preserved (r = 0.83, P < 0.01). The median (IQR) decline in ipsilateral GFR associated with PN was 7.8 (4.5-12) mL/min/1.73 m2 with loss of parenchyma accounting for 81% of this loss. The median (IQR) recovery from ischaemia was similar across the cold/warm/zero ischaemia groups at 96% (90%-102%), 95% (89%-101%), and 97% (91%-102%), respectively. Independent predictors of Spectrum Score were ischaemia time, tumour complexity, and preoperative global GFR. Independent predictors of recovery from ischaemia were insulin-dependent diabetes mellitus, refractory hypertension, warm ischaemia, and Spectrum Score. CONCLUSIONS: The main determinant of functional recovery after PN is parenchymal volume preservation. A more robust and rigorous evaluation allowed us to identify secondary factors including comorbidities, increased tumour complexity, and ischaemia-related factors that are also independently associated with impaired recovery, although altogether these were much less impactful.

Long-Term Renal Function Following Renal Cancer Surgery: Historical Perspectives, Current Status, and Future Considerations.

Knowledge of functional recovery after partial (PN) and radical nephrectomy for renal cancer has advanced considerably, with PN now established as the reference standard for most localized renal masses. However, it is still unclear whether PN provides an overall survival benefit in patients with a normal contralateral kidney. While early studies seemingly demonstrated the importance of minimizing warm-ischemia time during PN, multiple new investigations over the last 10 years have proven that parenchymal mass lost is the most important predictor of new baseline renal function. Minimizing loss of parenchymal mass during resection and reconstruction is the most important controllable aspect of long-term post-operative renal function preservation.

Safe heart flush technique during recovery from donors after circulatory death.

BACKGROUND: Donation after circulatory death is the donation after cardiac arrest. This technique has been employed and adopted by clinicians to overcome the shortage of available hearts for transplant. Warm ischemia time plays a pivotal role in the survival outcome of the heart recipients. AIM OF THE STUDY: To assess the efficacy of using the Foley catheter to flush the heart during procurement from donation after circulatory death donors. METHODS: We utilized a 2-WAY Foley catheter to flush the heart during procurement. The catheter was prepared and modified on the back table. RESULTS: We were successfully able to flush the heart within 3 minutes from skin incision with a good recipient outcome. CONCLUSIONS: Using the Foley catheter to flush the heart during recovery from donation after circulatory death donors was both efficient and fast.

Liquid Ventilation Reconditions Isolated Rat Lungs Following Ischemia-Reperfusion Injury.

Lung transplantation remains the only curative treatment for end-stage pulmonary disease. Lung ischemia-reperfusion injury (IRI) is a major contributor to primary allograft dysfunction and donor organ nonutilization. The alveolar macrophage is a key inflammatory mediator in IRI. Ex vivo lung perfusion (EVLP) has been investigated to rehabilitate lungs before transplant but has failed to provide significant improvements after IRI. We hypothesized that liquid ventilation (LV) could be utilized for ex vivo lung reconditioning in a rat IRI model. We compared EVLP with LV in an isolated ex vivo rat lung with an aqueous ventilant using quantitative physiological and immunological parameters. We observed improved physiological parameters and mechanical clearance of alveolar macrophages and cytokines halting the propagation of the inflammatory response in IRI. While the wide applicability to large animal or human transplantation have yet to be explored, these findings represent a method for lung reconditioning in the setting of significant IRI that could widen the lung organ donation pool and limit morbidity and mortality associated with ischemia-induced primary graft dysfunction.

[Evaluation of the results of sodium fumarate, furosemide, and mannitol on the initiation and outcome of renal warm ischemia in an experimental study].

While performing surgical treatment of the localized form of renal cell cancer by means of open or laparoscopic partial nephrectomy, renal warm ischemia is an important issue. Using renal warm ischemia allows to prevent parenchymal bleeding, to optimize conditions for resection of the tumor and to increase significantly the efficiency of hemostasis. However, an important problem is the probability of ischemic hypoxic damage of the remaining part of the kidney tissue during renal warm ischemia and renal functional impairment in the postoperative period. AIM: To compare nephroprotective activity of sodium fumarate, mannitol and furosemide using experimental model of 30- and 60-minute renal warm ischemia in rabbits. MATERIALS AND METHODS: The experiments were carried out on 360 conventional male-rabbits of the "Chinchilla" breed weighed 2,6+/-0,3 kg which were allocated into 10 groups. The control group No1 included intact animals, the control group No2 included the rabbits in which renal artery was not clamped. For the animals from the trial groups (No3-No10) the experimental model of 30- and 60-minute renal warm ischemia was used. In groups No3 and No4 no drugs were provided. Other rabbits undergone renal warm ischemia with a protection by sodium fumarate (groups No5 and No6 - 1,5 ml/kg IV), lasix (groups No7 and No8 - 3,0 mg/kg IV) and mannitol (No9 and No10 - 1,0 g/kg IV). The influence of renal warm ischemia on the renal tissue ultrastructure and the levels of NGAL, Cystatin-C and creatinine in blood and urine were studied. RESULTS: During experimental pharmacologically uncorrected 30-minute renal warm ischemia in animals, edema of the terminal part of microvilli of the proximal tubules epithelium, an increase of lysosome number in the hyaloplasm of epithelial cells, appearance of flaky content of medium electronic density in the lumens of distal tubules and collecting tubules, as well as sharp peak-like increase of NGAL and cystatin-C in blood and urine were observed. Increasing the time of ischemia up to 60 minutes was accompanied by more severe disturbances. In groups where sodium fumarate, lasix and mannitol were used the observed ultrastructural disturbances were expressed to lesser extent, whereas sodium fumarate demonstrated the best nephroprotective activity. After using mannitol the severity of disturbances was less than in the groups where mannitol, lasix or sodium fumarate were not given. Lasix and sodium salt of fumaric acid showed a higher nephroprotective activity. The best results were received in the animals received sodium fumarate. CONCLUSIONS: The studied drugs provided a nephroprotective effect regarding ischemia of rabbit kidney. The effect of sodium fumarate was the most pronounced, followed by furosemide and, to a lesser extent, mannitol. Use of sodium fumarate allows to protect and stimulate the kidney tissue effectively during oxygen deprivation under ischemic state.

Tolerable Duration of Warm Ischaemia After Circulatory Death Is Safe For At Least One Hour in Porcine Lungs: Functional Assessment with Ex Vivo Lung Perfusion.

BACKGROUND: Lungs from donation after circulatory death (DCD) may be an underused resource for transplantation. The aim was to investigate, with a DCD pig model, if it was possible to recondition lungs exposed for up to 2 h of warm ischaemia with ex vivo lung perfusion (EVLP). METHODS: Danish domestic pigs (N = 17) were randomized into three groups. In the two study groups, lungs were exposed to either 1 or 2 h of warm ischaemia. All lungs were reconditioned and evaluated after 83 ± 38 minutes of perfusion at FiO2 1.0 and 0.21 with EVLP. Outcome measures were gas exchange, pulmonary physiology, inflammatory markers, and histopathologic assessment score. RESULTS: Lungs exposed for 2 h of warm ischaemia did not meet the criteria: PaO2 > 13 kPa required for donation compared with lungs subjected to 0 and 1 h of warm ischaemia (11.0 kPa vs. 14.2 kPa, P < 0.001). These lungs also developed an increased amount of foam and fluid in the airways. No differences in PaCO2, compliance, or pulmonary vascular resistance were observed. CONCLUSION: Results show that while lungs subjected to 0 or 1 h of warm ischaemia meet the criteria for transplantation based on EVLP evaluation, lungs subjected to 2 h of warm ischaemia did not.

Novel heat shock protein 90 inhibitor improves cardiac recovery in a rodent model of donation after circulatory death.

OBJECTIVE: Organ donation after circulatory death (DCD) is a potential solution for the shortage of suitable organs for transplant. Heart transplantation using DCD donors is not frequently performed due to the potential myocardial damage following warm ischemia. Heat shock protein (HSP) 90 has recently been investigated as a novel target to reduce ischemia/reperfusion injury. The objective of this study is to evaluate an innovative HSP90 inhibitor (HSP90i) as a cardioprotective agent in a model of DCD heart. METHODS: A DCD protocol was initiated in anesthetized Lewis rats by discontinuation of ventilation and confirmation of circulatory death by invasive monitoring. Following 15 minutes of warm ischemia, cardioplegia was perfused for 5 minutes at physiological pressure. DCD hearts were mounted on a Langendorff ex vivo heart perfusion system for reconditioning and functional assessment (60 minutes). HSP90i (0.01 µmol/L) or vehicle was perfused in the cardioplegia and during the first 10 minutes of ex vivo heart perfusion reperfusion. Following assessment, pro-survival pathway signaling was evaluated by western blot or polymerase chain reaction. RESULTS: Treatment with HSP90i preserved left ventricular contractility (maximum + dP/dt, 2385 ± 249 vs 1745 ± 150 mm Hg/s), relaxation (minimum -dP/dt, -1437 ± 97 vs 1125 ± 85 mm Hg/s), and developed pressure (60.7 ± 5.6 vs 43.9 ± 4.0 mm Hg), when compared with control DCD hearts (All P = .001). Treatment abrogates ischemic injury as demonstrated by a significant reduction of infarct size (2,3,5-triphenyl-tetrazolium chloride staining) of 7 ± 3% versus 19 ± 4% (P = .03), troponin T release, and mRNA expression of Bax/Bcl-2 (P < .05). CONCLUSIONS: The cardioprotective effects of HSP90i when used following circulatory death might improve transplant organ availability by expanding the use of DCD hearts.

Ex Vivo Lung Perfusion with K(ATP) Channel Modulators Antagonize Ischemia Reperfusion Injury.

Ex vivo lung perfusion (EVLP) has been implemented to increase the number of donor lungs available for transplantation. The use of K(ATP) channel modulators during EVLP experiments may protect against lung ischemia-reperfusion injury and may inhibit the formation of reactive oxygen species. In a rat model of donation after circulatory death with 2 h warm ischemic time, we evaluated rat lungs for a 4-hour time in EVLP containing either mitochondrial-specific or plasma membrane and/or sarcolemmal-specific forms of K(ATP) channel modulators. Lung physiological data were recorded, and metabolic parameters were assessed. When compared to the control group, in the EVLP performed with diazoxide or 5-hydroxydecanoic acid (5-HD) we recorded significantly lower pulmonary vascular resistance and only in the diazoxide group recorded significant lung weight loss. In the perfusate of the 5-HD group, interleukin-1ß and interleukin-1α were significantly lower when compared to the control group. Perfusate levels of calcium ions were significantly higher in both 5-HD and cromakalim groups, whereas the levels of calcium, potassium, chlorine and lactate were reduced in the diazoxide group, although not significantly when compared to the control. The use of a diazoxide mitochondrial-specific K(ATP) channel opener during EVLP improved lung physiological and metabolic parameters and reduced edema.

Reconditioning of circulatory death hearts by ex-vivo machine perfusion with a novel HTK-N preservation solution.

BACKGROUND: Warm ischemia followed by blood reperfusion is associated with reduced myocardial contractility. Circulatory death (CD) hearts are maintained by machine perfusion (MP) with blood. However, the impact of MP with histidine-tryptophane-ketoglutarate (HTK) or novel HTK-N solution on reconditioning of CD-heart contractility is unknown. METHODS: In a porcine model, native hearts were directly harvested (control), or CD was induced before harvesting, followed by left ventricular (LV) contractile assessment. In MP-groups, CD-hearts were maintained for 4 h by MP with blood (CD-B), cold oxygenated HTK (CD-HTK) or HTK-N (CD-HTK-N) before contractile evaluation (all groups n = 8). We performed immunohistochemistry of LV myocardial samples. We profiled myocardial expression of 84 oxidative stress-related genes and correlated the findings with myocardial contractility via a machine learning algorithm. RESULTS: HTK-N improved end-systolic pressure (ESP=172±10 vs 132±5 mmHg, p = 0.02) and maximal slope of pressure increment (dp/dtmax=2161±214 vs 1240±167 mmHg/s, p = 0.005) compared to CD, whereas CD-B failed to improve contractility. Dp/dtmax (2161±214 vs 1177±156, p = 0.08) and maximal rate of pressure decrement (dp/dtmin=-1501±228 vs -637±79, p = 0.005) were also superior in CD-HTK-N compared to CD-B. In CD-HTK-N, myocardial 4-hydroxynonenal (marker for oxidative stress; p<0.001), nitrotyrosine (marker for nitrosative stress; p = 0.004), poly(adenosine diphosphate-ribose)polymerase (marker for necrosis; p = 0.028) immunoreactivity and cell swelling (p = 0.008) were decreased compared to CD-B. Strong correlation of gene expression with ESP was identified for oxidative stress defense genes in CD-HTK-N. CONCLUSION: During harvesting procedure, MP with HTK-N reconditions CD-heart systolic and diastolic function by reducing oxidative and nitrosative stress and preventing cardiomyocytes from cell swelling and necrosis.

Can remote ischemic preconditioning counteract the renal functional deterioration attributable to partial nephrectomy under warm ischemia? Results of an animal study.

BACKGROUND: To investigate if remote ischemic preconditioning (RIPC) can offer any renoprotective value by counteracting the deleterious effect of partial nephrectomy (PN) under warm ischemia on renal function. METHODS: Four groups, each with 5 Wistar albino rats, were constructed; RIPC + PN, PN, RIPC and sham. Right nephrectomy was performed to constitute a solitary kidney model. RIPC denoted sequential clamping/declamping of the femoral artery/vein complex. PN was performed under warm-ischemia following RIPC. Blood samples were collected on multiple occasions until euthanasia on day 7. Immunoassays were conducted to measure the serum and tissues levels of kidney injury markers. Kidneys were examined histologically and morphometric analyzes were performed using digital scanning. RESULTS: IL-33 levels did not differ significantly between the groups. Serum levels of KIM-1, NGAL, and aldose reductase in RIPC + PN, PN and RIPC groups were significantly lower than that of sham group. Tissue biomarker levels were similar across groups. The observed trend in mean necrosis area of PN group was higher than that of RIPC + PN group (p > 0.05). The transitional zone between necrosis and healthy tissue showed a trend towards increasing width in the rats subjected to RIPC before PN vs. those who underwent PN without RIPC (p > 0.05). CONCLUSION: RIPC failed to counteract the renal functional consequences of PN under warm ischemia in a solitary kidney animal model. The supportive but marginal histological findings in favor of RIPC's renoprotective potential were not supplemented with the changes in serum and tissue biomarker levels.

Rapid postmortem ventilation improves donor lung viability by extending the tolerable warm ischemic time after cardiac death in mice.

Uncontrolled donation after cardiac death (uDCD) contributes little to ameliorating donor lung shortage due to rapidly progressive warm ischemia after circulatory arrest. Here, we demonstrated that nonhypoxia improves donor lung viability in a novel uDCD lung transplant model undergoing rapid ventilation after cardiac death and compared the evolution of ischemia-reperfusion injury to mice that underwent pulmonary artery ligation (PAL). The tolerable warm ischemia time at 37°C was initially determined in mice using a modified PAL model. The donor lung following PAL was also transplanted into syngeneic mice and compared with those that underwent rapid ventilation or no ventilation at 37°C before transplantation. Twenty-four hours following reperfusion, lung histology, [Formula: see text]/[Formula: see text] ratio, and inflammatory mediators were measured. Four hours of PAL had little impact on [Formula: see text]/[Formula: see text] ratio and acute lung injury score in contrast to significant injury induced by 5 h of PAL. Four-hour PAL lungs showed an early myeloid-dominant inflammatory signature when compared with naïve lungs and substantially injured 5 h PAL lungs. In the context of transplantation, unventilated donor lungs showed severe injury after reperfusion, whereas ventilated donor lungs showed minimal changes in [Formula: see text]/[Formula: see text] ratio, histologic score, and expression of inflammatory markers. Taken together, the tolerable warm ischemia time of murine lungs at 37°C can be extended by maintaining alveolar ventilation for up to 4 h. Nonhypoxic lung undergoing warm ischemia-reperfusion injury shows an early transcriptional signature of myeloid cell recruitment and extracellular matrix proteolysis before blood-gas barrier dysfunction and significant tissue damage.

Effects of cold or warm ischemia and ex-vivo lung perfusion on the release of damage associated molecular patterns and inflammatory cytokines in experimental lung transplantation.

BACKGROUND: Lung transplantation (LTx) is associated with sterile inflammation, possibly related to the release of damage associated molecular patterns (DAMPs) by injured allograft cells. We have measured cellular damage and the release of DAMPs and cytokines in an experimental model of LTx after cold or warm ischemia and examined the effect of pretreatment with ex-vivo lung perfusion (EVLP). METHODS: Rat lungs were exposed to cold ischemia alone (CI group) or with 3h EVLP (CI-E group), warm ischemia alone (WI group) or with 3 hour EVLP (WI-E group), followed by LTx (2 hour). Bronchoalveolar lavage (BAL) was performed before (right lung) or after (left lung) LTx to measure LDH (marker of cellular injury), the DAMPs HMGB1, IL-33, HSP-70 and S100A8, and the cytokines IL-1ß, IL-6, TNFα, and CXCL-1. Graft oxygenation capacity and static compliance after LTx were also determined. RESULTS: Compared to CI, WI displayed cellular damage and inflammation without any increase of DAMPs after ischemia alone, but with a significant increase of HMGB1 and functional impairment after LTx. EVLP promoted significant inflammation in both cold (CI-E) and warm (WI-E) groups, which was not associated with cell death or DAMP release at the end of EVLP, but with the release of S100A8 after LTx. EVLP reduced graft damage and dysfunction in warm ischemic, but not cold ischemic, lungs. CONCLUSIONS: The pathomechanisms of sterile lung inflammation during LTx are significantly dependent on the conditions. The release of HMGB1 (in the absence of EVLP) and S100A8 (following EVLP) may be important factors in the pathogenesis of LTx.

Inflammatory responses in lungs from donation after brain death: Mechanisms and potential therapeutic targets.

The vast majority of lungs used in clinical transplantation are donated after brain death (DBD). The utilization of DBD lungs is low due to brain death-induced lung injury. Moreover, inflammatory responses in DBD lungs used for transplantation contribute to ischemia-reperfusion injury and primary graft dysfunction. Work from human observational studies has demonstrated overexpression of cytokines, activation of endothelial cells, and cell death in DBD lungs, are associated with the activation of signaling pathways. Animal models have characterized the pulmonary injury induced by brain death and identified potential strategies to improve donor management. Interestingly, transcriptomic studies comparing DBD and donated after circulatory death (DCD) lungs have found that inflammatory responses are elevated in DBD lungs, while cell death pathways are elevated in DCD lungs. Development of the ex vivo lung perfusion technique, has made it possible to assess donor lungs using inflammation and cell death biomarkers. In the future, identification of potential therapeutic targets and development of novel treatments strategies may allow for lung repair during EVLP prior to transplantation.

Lower beta cell yield from donor pancreases after controlled circulatory death prevented by shortening acirculatory warm ischemia time and by using IGL-1 cold preservation solution.

Organs from donors after controlled circulatory death (DCD III) exhibit a higher risk for graft dysfunction due to an initial period of warm ischemia. This procurement condition can also affect the yield of beta cells in islet isolates from donor pancreases, and hence their use for transplantation. The present study uses data collected and generated by our Beta Cell Bank to compare the number of beta cells in isolates from DCD III (n = 141) with that from donors after brain death (DBD, n = 609), before and after culture, and examines the influence of donor and procurement variables. Beta cell number per DCD III-organ was significantly lower (58 x 106 versus 84 x 106 beta cells per DBD-organ; p < 0.001) but their purity (24% insulin positive cells) and insulin content (17 µg / 106 beta cells in DCD III-organs versus 19 µg / 106 beta cells in DBD-organs) were similar. Beta cell number correlated negatively with duration of acirculatory warm ischemia time above 10 min; for shorter acirculatory warm ischemia time, DCD III-organs did not exhibit a lower beta cell yield (74 x 106 beta cells). Use of Institut Georges Lopez-1 cold preservation solution instead of University of Wisconsin solution or histidine-tryptophan-ketoglutarate also protected against the loss in beta cell yield from DCD III-organs (86 x 106 for IGL-1 versus 54 x 106 and 65 x 106 beta cells respectively, p = 0.042). Multivariate analysis indicates that both limitation of acirculatory warm ischemia time and use of IGL-1 prevent the reduced beta cell yield in islet cell isolates from DCD III-organs.

Retroperitoneal or transperitoneal approach in robot-assisted partial nephrectomy, which one is better?

PURPOSE: To systematically assess the perioperative outcomes of retroperitoneal (RP) and transperitoneal (TP) approaches in robot-assisted partial nephrectomy (RAPN), we conducted an updated meta-analysis. METHODS: A literature retrieval of multi-database including PubMed, Web of Science, Embase, Cochrane Library, and CNKI was performed to identify eligible comparative studies from the inception dates to January 2021. Perioperative outcomes included operative time (OT), estimated blood loss (EBL), warm ischemia time (WIT), postoperative length of stay (PLOS), positive surgical margin (PSM), and complications (major complications and overall complications). Outcomes of data were pooled and analyzed with Review Manager 5.4.1. RESULTS: Twenty-one studies involving a total of 2482 RP and 3423 TP approach RAPN patients met the inclusion criteria. Operating time (OT) (weighted mean difference [WMD] -16.60; 95% confidence interval [CI] -23.08, -10.12; p < 0.01) and PLOS (WMD -0.46 days; 95% CI -0.69, -0.23; p < 0.01) were shorter in RP-RAPN. Besides, lower EBL (WMD -21.67; 95% CI -29.74, -13.60; p < 0.05) was also found in RP-RAPN. Meanwhile, no significant differences were found in other outcomes. CONCLUSIONS: RP-RARN was superior to TP-RAPN in patients undergoing RAPN in terms of OT, PLOS, and estimated blood loss. Besides these two approaches have no significant differences in PSMs or perioperative complications.

Static cold storage compared with normothermic machine perfusion of the liver and effect on ischaemic-type biliary lesions after transplantation: a propensity score-matched study.

BACKGROUND: Given the susceptibility of organs to ischaemic injury, alternative preservation methods to static cold storage (SCS), such as normothermic machine perfusion (NMP) are emerging. The aim of this study was to perform a comparison between NMP and SCS in liver transplantation with particular attention to bile duct lesions. METHODS: The outcomes of 59 consecutive NMP-preserved donor livers were compared in a 1 : 1 propensity score-matched fashion to SCS control livers. Postoperative complications, patient survival, graft survival and bile duct lesions were analysed. RESULTS: While patients were matched for cold ischaemia time, the total preservation time was significantly longer in the NMP group (21 h versus 7 h, P < 0.001). Patient and graft survival rates at 1 year were 81 versus 82 per cent (P = 0.347) and 81 versus 79 per cent (P = 0.784) in the NMP and SCS groups, respectively. The postoperative complication rate was comparable (P = 0.086); 37 per cent NMP versus 34 per cent SCS patients had a Clavien-Dindo grade IIIb or above complication. There was no difference in early (30 days or less) (NMP 22 versus SCS 19 per cent, P = 0.647) and late (more than 30 days) (NMP 27 versus SCS 36 per cent, P = 0.321) biliary complications. However, NMP-preserved livers developed significantly fewer ischaemic-type bile duct lesions (NMP 3 versus SCS 14 per cent, P = 0.047). CONCLUSION: The use of NMP allowed for a significantly prolonged organ preservation with a lower rate of observed ischaemic-type bile duct lesions.

Evaluation of the ex vivo liver viability using a nuclear magnetic resonance relaxation time-based assay in a porcine machine perfusion model.

There is a dearth of effective parameters for selecting potentially transplantable liver grafts from expanded-criteria donors. In this study, we used a nuclear magnetic resonance (NMR) relaxation analyzer-based assay to assess the viability of ex vivo livers obtained via porcine donation after circulatory death (DCD). Ex situ normothermic machine perfusion (NMP) was utilized as a platform for viability test of porcine DCD donor livers. A liver-targeted contrast agent, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), was injected into the perfusate during NMP, and the dynamic biliary excretion of the Gd-EOB-DTPA was monitored by measuring the longitudinal relaxation time (T1). The longitudinal relaxation rate (R1) of the bile was served as a parameter. The delay of increase in biliary R1 during early stage of NMP indicated the impaired function of liver grafts in both warm and cold ischemia injury, which was correlated with the change of alanine aminotransferase. The preservative superiority in cold ischemia of dual hypothermic oxygenated machine perfusion could also be verified by assessing biliary R1 and other biochemical parameters. This study allows for the dynamic assessment of the viability of porcine DCD donor livers by combined usage of ex situ NMP and NMR relaxation time based assay, which lays a foundation for further clinical application.

A Mouse Model of Acute Liver Injury by Warm, Partial Ischemia-Reperfusion for Testing the Efficacy of Virus-Derived Therapeutics.

Ischemia-reperfusion injury (IRI) drives early and long-term damage to organs as well as compounding damage from acute transplant rejection and surgical trauma. IRI initiates an aggressive and prolonged inflammation leading to tissue injury, organ failure, and death. However, there are few effective therapeutic interventions for IRI. The destructive inflammatory cell activity in IRI is part of an aberrant innate immune response that triggers multiple pathways. Hence, immune-modulating treatments to control pathways triggered by IRI hold great therapeutic potential. Viruses, especially large DNA viruses, have evolved highly effective immune-modulating proteins for the purpose of immune evasion and to protect the virus from the host immune defenses. A number of these immune-modulating proteins have proven therapeutically effective in preclinical models, many with function targeting pathways known to be involved in IRI. The use of virus-derived immune-modulating proteins thus represents a promising source for new treatments to target ischemia-reperfusion injury. Laboratory small animal models of IRI are well established and are able to reproduce many aspects of ischemia-reperfusion injury seen in humans. This chapter will discuss the methods used to perform the IRI procedure in mice, as well as clinically relevant diagnostic tests to evaluate liver injury and approaches for assessing histological damage while testing novel immune modulating protein treatments.