BACKGROUND: Efforts to address the shortage of donor organs include increasing the use of renal allografts from donors after circulatory death (DCD). While warm ischemia time (WIT) is thought to be an important factor in DCD kidney evaluation, few studies have compared the relationship between WIT and DCD kidney outcomes, and WIT acceptance practices remain variable.
METHODS: We conducted a single-center retrospective review of all adult patients who underwent deceased donor kidney transplantation from 2000 to 2021. We evaluated the impact of varied functional warm ischemia time (fWIT) in controlled DCD donors by comparing donor and recipient characteristics and posttransplant outcomes between high fWIT (>60 min), low fWIT (≤60 min), and kidneys transplanted from donors after brain death (DBD).
RESULTS: Two thousand eight hundred eleven patients were identified, 638 received low fWIT DCD, 93 received high fWIT DCD, and 2080 received DBD kidneys. There was no significant difference in 5-year graft survival between the DCD low fWIT, high fWIT, and DBD groups, with 84%, 83%, and 83% of grafts functioning, respectively. Five-year patient survival was 91% in the low fWIT group, 92% in the high fWIT group, and 90% in the DBD group. An increase in kidney donor risk index (KDRI) (HR 3.37, 95% CI = 2.1-5.7) and high CIT compared to low CIT (HR 2.12, 95% CI = 1.4-3.1) have higher hazard ratios for 1-year graft failure.
CONCLUSIONS: Increased acceptance of kidneys from selected DCD donors with prolonged fWIT may present an opportunity to increase kidney utilization while preserving outcomes. Our group specifically prioritizes the use of kidneys from younger donors, with lower KDPI, and without acute kidney injury, or risk factors for underlying chronic kidney disease.

The safety and efficacy of single-port and multi-port robot-assisted partial nephrectomy (SP-RAPN and MP-RAPN, respectively) were assessed for treating partial nephrectomy in this study. A systematic review of PubMed, Cochrane Library, and Web of Science databases was conducted up to June 2024 to compare studies on SP-RAPN and MP-RAPN. Primary outcomes included perioperative results, complications, and oncological outcomes. Eight studies involving 1014 patients were analyzed. For binary outcomes, comparisons were performed using odds ratios (OR), and for continuous variables, weighted mean differences (WMD) with 95% confidence intervals (CI). The search failed to discover significant meaningful variations in operating times (p = 0.54), off-clamp procedure (P = 0.36), blood loss (p = 0.31), positive surgical margins (PSMs) (p = 0.78), or major complications (Clavien-Dindo grade ≥ 3) (p = 0.68) between SP-RAPN and MP-RAPN. However, shorter hospital stays (WMD - 0.26 days, 95% CI - 0.36 to - 0.15; p < 0.00001) and longer warm ischemia times (WIT) (WMD 3.13 min, 95% CI 0.81-5.46; p = 0.008) were related to SP-RAPN, and higher transfusion rate (OR 2.99, 95% CI 1.31-6.80; p = 0.009) compared to MP-RAPN. SP-RAPN performed better in terms of hospital stay but had slightly higher rates of transfusion, off-clamp procedures, and warm ischemia time (WIT) compared to MP-RAPN. As an emerging technology, preliminary research suggests that SP-RAPN is a feasible and safe method for carrying out a nephrectomy partial. However, compared to MP-RAPN, it shows inferior outcomes regarding (WIT) and transfusion rates.

BACKGROUND: In free flap reconstruction, improving flap tolerance to warm ischemia (WI) is fundamental. WI is the result of a venous or arterial thrombosis, which can only be addressed through surgical revision. No additional treatments have shown superior efficacy at salvaging free flaps after or during WI. Custom perfusion machines (PM), used to reduce the intensity of lesions of the flap stored in cold ischemia, have not been evaluated for WI flap salvage. This proof-of-concept study assessed whether the Lifeport® perfusion machine could improve the salvage procedure\'s success rates after one hour of venous WI.
METHODS: Five different groups were evaluated with four porcine latissimus dorsi free flaps included in each group. Depending on the group, the flaps were subjected to one hour of WI followed by revascularization, static hypothermic submersion, or dynamic Lifeport® perfusion. Additionally, two flap perfusion liquids were evaluated: KPS-1® and IGL-1®. Biopsies were performed before in vivo warm ischemia of the flap, after in vivo warm ischemia of the flap, and after one and two hours of preservation. Interstitial edema, muscular cell size and muscular diffuse necrosis were quantified by histological assessment.
RESULTS: Static submersion did not demonstrate any efficacy for venous flap salvage. Dynamic perfusion on Lifeport® machine showed a significant improvement in tissue parameters. Thrombi and fibrine, present during the WI period, were no longer visible inside vessels and the perfusion machine flow evacuated the inflammatory cells and their substrates from the flap. The flap weights did not increase during perfusion time, confirming the benefits of the Lifeport® perfusion machine.
CONCLUSIONS: Evaluating Lifeport® advantages on human free flap salvage is necessary to confirm the benefits for the tissue and to increase post-operative results after congestive free flap revision surgery.

BACKGROUND: Simultaneous liver-kidney transplantation is indicated for patients with concomitant end-stage liver disease and end-stage renal disease. The traditional technique involves separate implantations of the liver and the kidney. In the en bloc approach, the liver is recovered en bloc with the right kidney and the donor renal artery is anastomosed to the donor splenic artery. We aimed to compare the outcomes of the traditional and en bloc techniques for simultaneous liver-kidney transplantation in a single center.
METHODS: This single-center retrospective study involved all adult patients who underwent simultaneous liver-kidney transplantation from brain-dead donors from January 2017 to December 2022.
RESULTS: A total of 15 patients were included: 10 transplanted with the traditional technique and 5 with the en bloc approach. Patients in the en bloc group presented higher body mass index, shorter kidney cold and total ischemia times, shorter overall surgical time and longer kidney warm ischemia time (29.07 kg/m2vs 23.20 kg/m2 [P = .048]; 560 minutes vs 880 minutes [P = .026]; 615 minutes vs 908 minutes [P = 0.025]; 405 minutes vs 485 minutes [P = .046]; 46 minutes vs 33.5 minutes [P = 0.027], respectively). Ureteroneocystostomy was performed in 2 patients of the en bloc group and ureteroureterostomy in the remaining 3 patients. One patient in the en bloc group presented stenosis of renal artery anastomosis and underwent percutaneous angioplasty. This same patient eventually developed late urinary fistula. In the traditional technique group, there were 2 cases of renal vein thrombosis and 1 of ureteral stenosis.
CONCLUSIONS: Compared with the traditional technique, the en bloc approach is feasible and safe, reducing kidney total ischemia time and overall surgical time.

Glucagon-like peptide-1 (GLP-1) has proven to be protective in animal models of lung disease but the underlying mechanisms are unclear. Atrial natriuretic peptide (ANP) is mainly produced in the heart. As ANP possesses potent vaso- and bronchodilatory effects in pulmonary disease, we hypothesised that the protective functions of GLP-1 could involve potentiation of local ANP secretion from the lung. We examined whether the GLP-1 receptor agonist liraglutide was able to improve oxygenation in lungs exposed to 2 h of warm ischemia and if liraglutide stimulated ANP secretion from the lungs in the porcine ex vivo lung perfusion (EVLP) model. Pigs were given a bolus of 40 µg/kg liraglutide or saline 1 h prior to sacrifice. The lungs were then left in vivo for 2 h, removed en bloc and placed in the EVLP machinery. Lungs from the liraglutide treated group were further exposed to liraglutide in the perfusion buffer (1.125 mg). Main endpoints were oxygenation capacity, and plasma and perfusate concentrations of proANP and inflammatory markers. Lung oxygenation capacity, plasma concentrations of proANP or concentrations of inflammatory markers were not different between groups. ProANP secretion from the isolated perfused lungs were markedly higher in the liraglutide treated group (area under curve for the first 30 min in the liraglutide group: 635 ± 237 vs. 38 ± 38 pmol/L x min in the saline group) (p < 0.05). From these results, we concluded that liraglutide potentiated local ANP secretion from the lungs.

To assess the robotic-assisted partial nephrectomy (RAPN) trifecta rate within a fellowship program. Patients undergoing RAPN 01/01/2010-01/07/2023 were enrolled from a prospectively maintained database. All cases were performed jointly with surgical fellows, except when privately insured. Patients were excluded if they were converted to open or radical nephrectomy. The primary outcome was achieving the \'trifecta\' of negative surgical margins, no complications < 30 days post-operatively and warm ischaemia time (WIT) < 25 min. The secondary outcomes were factors associated with trifecta success. Ethics approval was obtained. In the enrolment period, 355 patients underwent intended RAPN, of whom seven were excluded due to conversion to conversion to radical nephrectomy (6 patients) or conversion to open (one). Amongst the 348 eligible patients, median age was 60 years, 115 (33%) were female and 19 were private patients. WIT was < 25 min for 324/337 patients (96%), surgical margins were negative in 325 (93%), 294 (84%) were complication-free at 30 days and 301/320 (94%) had a < 30% decline in estimated glomerular filtration rate at 3-6 months postoperatively. Subsequently, trifecta outcomes were achieved in 253/337 (75%) patients. Comparing with patients without those with trifecta success were similar in all thirteen measured patients and tumour factors. In a teaching hospital, with a fellowship training programme, trifecta outcome is achievable for most RAPN patients, and at a rate comparable to international standards. Fellowship centres should monitor their outcomes to ensure high patient outcomes are maintained alongside training requirements.

UNASSIGNED: During donation after circulatory death (DCD), cardiac grafts are exposed to potentially damaging conditions that can impact their quality and post-transplantation outcomes. In a clinical DCD setting, patients have closed chests in most cases, while many experimental models have used open-chest conditions. We therefore aimed to investigate and characterize differences in open- vs. closed-chest porcine models.
UNASSIGNED: Withdrawal of life-sustaining therapy (WLST) was simulated in anesthetized juvenile male pigs by stopping mechanical ventilation following the administration of a neuromuscular block. Functional warm ischemic time (fWIT) was defined to start when systolic arterial pressure was <50 mmHg. Hemodynamic changes and blood chemistry were analyzed. Two experimental groups were compared: (i) an open-chest group with sternotomy prior to WLST and (ii) a closed-chest group with sternotomy after fWIT.
UNASSIGNED: Hemodynamic changes during the progression from WLST to fWIT were initiated by a rapid decline in blood oxygen saturation and a subsequent cardiovascular hyperdynamic (HD) period characterized by temporary elevations in heart rates and arterial pressures in both groups. Subsequently, heart rate and systolic arterial pressure decreased until fWIT was reached. Pigs in the open-chest group displayed a more rapid transition to the HD phase after WLST, with peak heart rate and peak rate-pressure product occurring significantly earlier. Furthermore, the HD phase duration tended to be shorter and less intense (lower peak rate-pressure product) in the open-chest group than in the closed-chest group.
UNASSIGNED: Progression from WLST to fWIT was more rapid, and the hemodynamic changes tended to be less pronounced in the open-chest group than in the closed-chest group. Our findings support clear differences between open- and closed-chest models of DCD. Therefore, recommendations for clinical DCD protocols based on findings in open-chest models must be interpreted with care.

Ischemia-reperfusion injury (IRI) is an intrinsic risk associated with liver transplantation. Ex vivo hepatic machine perfusion (MP) is an emerging organ preservation technique that can mitigate IRI, especially in livers subjected to prolonged warm ischemia time (WIT). However, a method to quantify the biological response to WIT during MP has not been established. Previous studies used physiologically based pharmacokinetic (PBPK) modeling to demonstrate that a decrease in hepatic transport and biliary excretion of the tracer molecule sodium fluorescein (SF) could correlate with increasing WIT in situ. Furthermore, these studies proposed intracellular sequestration of the hepatocyte canalicular membrane transporter multidrug resistance-associated protein 2 (MRP2) leading to decreased MRP2 activity (maximal transport velocity; Vmax) as the potential mechanism for decreased biliary SF excretion. We adapted an extant PBPK model to account for ex vivo hepatic MP and fit a six-parameter version of this model to control time-course measurements of SF in MP perfusate and bile. We then identified parameters whose values were likely insensitive to changes in WIT and fixed them to generate a reduced model with only three unknown parameters. Finally, we fit the reduced model to each individual biological replicate SF time course with differing WIT, found the mean estimated value for each parameter, and compared them using a one-way ANOVA. We demonstrated that there was a significant decrease in the estimated value of Vmax for MRP2 at the 30-min WIT. These studies provide the foundation for future studies investigating real-time assessment of liver viability during ex vivo MP.NEW & NOTEWORTHY We developed a computational model of sodium fluorescein (SF) biliary excretion in ex vivo machine perfusion and used this model to assess changes in model parameters associated with the activity of MRP2, a hepatocyte membrane transporter, in response to increasing warm ischemia time. We found a significant decrease in the parameter value describing MRP2 activity, consistent with a role of decreased MRP2 function in ischemia-reperfusion injury leading to decreased secretion of SF into bile.

BACKGROUND: Surgical video review is an emerging tool for assessing patient outcomes, especially in complex surgeries such as robot-assisted partial nephrectomy (RAPN). Assessing and measuring warm ischaemia time (WIT) during RAPN by dividing it into the time used for tumour excision time (ExcT), time used for kidney reconstruction time (RecT) and intermediate time (IntT) has not been performed before. This study aimed to analyse the factors that can influence all surgical times and assess their impact on positive surgical margins (PSMs) and complication rates.
METHODS: We evaluated 32 surgical video recordings from patients undergoing RAPN and measured WIT, ExcT, RecT and IntT with a stopwatch. Factors such as tumour characteristics and surgeon experience were also recorded. SPSS software was used to identify the predictors for all surgical times and to correlate ExcT with PSM and RecT with complication rate.
RESULTS: We recorded a median WIT of 1,048 s (17 min and 28 s). The median of ExcT, RecT and IntT was 398 s (37.1% of WIT), 518 s (46.7% of WIT) and 180 s (16.2% of WIT), respectively. We found a significant correlation (P < 0.001) between R.E.N.A.L. score and all surgical times. No correlation was found between ExcT and PSM (P = 0.488) and between RecT and the probability of developing complications (P = 0.544).
CONCLUSIONS: Tumour morphology influences all surgical times, and surgeon experience influences only ExcT. We observed a short RecT during RAPN though at the cost of increased ExcT, and we believe that improving surgical experience, especially for the excision of more complex tumours, can reduce WIT during RAPN.

Current graft evaluation during normothermic ex situ liver perfusion lacks real-time parameters for predicting posttransplant hepatocyte and biliary function. Indocyanine green (ICG) imaging has been widely used in liver surgery, enabling the visualization of hepatic uptake and excretion through bile using near-infrared light. In this research, porcine livers under various ischemic conditions were examined during a 5-hour normothermic ex situ liver perfusion procedure, introducing ICG at 1 hour through the hepatic artery. These conditions included livers from heart-beating donors, donation after circulatory death (DCD) with warm ischemic durations of 60 minutes (DCD60) and 120 minutes (DCD120), as well as interventions utilizing tissue plasminogen activator in DCD120 cases (each n = 5). Distinct hepatic fluorescence patterns correlated with different degrees of ischemic injury ( p = 0.01). Low ICG uptake in the parenchyma (less than 40% of maximum intensity) was more prevalent in DCD120 (21.4%) compared to heart-beating donors (6.2%, p = 0.06) and DCD60 (3.0%, p = 0.02). Moreover, ICG clearance from 60 minutes to 240 minutes was significantly higher in heart-beating donors (69.3%) than in DCD60 (17.5%, p < 0.001) and DCD120 (32.1%, p = 0.01). Furthermore, thrombolytic intervention using tissue plasminogen activator in DCD120 resulted in noteworthy outcomes, including significantly reduced ALP levels ( p = 0.04) and improved ICG clearance ( p = 0.02) with a trend toward mitigating fibrin deposition similar to DCD60, as well as enhancements in bile production ( p = 0.09). In conclusion, ICG fluorescence imaging during normothermic ex situ liver perfusion provides real-time classification of hepatic vascular and biliary injuries, offering valuable insights for the more accurate selection and postintervention evaluation of marginal livers in transplantation.