The increasing use of extended kidney grafts to bridge organ shortage has led to delayed and impaired graft function, warranting the development of new preservation strategies. In addition to hypothermic machine perfusion, the addition of pharmacological agents to preservation solutions has been primarily investigated, with a few promising agents making their way into clinical trials. This review aimed to identify and summarize current literature studies on pharmacological treatment additives for hypothermic kidney graft preservation. A scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. A comprehensive literature search was performed using Medline and Cochrane Library databases until 1 December 2023. All studies published in English reporting on pharmacological supplementation of preservation solutions to improve hypothermic kidney graft preservation were included. A total of 67 records were retrieved, all of which were preclinical except one. Of these, 8 were conducted on cellular models, 21 on ex vivo kidneys, and 38 on animal kidney transplantations. A total of 40 pharmacological agents were evaluated based on the key markers of ischemia–reperfusion injury (IRI) pathophysiology, most of them showing promise in kidney preservation. Although promising, with numerous preclinical studies identifying various effective additives, the pharmacological treatment additive strategy to improve hypothermic kidney preservation has still not been translated into clinical practice. Clinical investigations should be promoted to support few ongoing trials offering encouraging outcomes.

To describe the clinical and tumor characteristics of bladder leiomyoma (BL) and to explore potential etiological factors and prognostic factors to guide management strategies. Patients with histologically confirmed BL treated at 14 hospitals between 1995 and 2025 were included. Associations between tumor characteristics, symptoms, management, and outcomes were evaluated using appropriate statistical tests and logistic regression. A p-value < 0.05 was considered significant. Among 74 patients (55.4

BACKGROUND:Early graft function after pediatric kidney transplantation (KT) may be influenced by perioperative hemodynamic and fluid management variables. However, previous studies have yielded conflicting results. This study aimed to evaluate the impact of perioperative factors on early graft function in pediatric KT recipients. METHODS:This retrospective multicenter study included pediatric KT recipients from four academic centers in Turkiye and France. Early graft function was assessed using estimated glomerular filtration rate (eGFR) at postoperative day 7 and day 30. Delayed graft function (DGF) was defined as the need for dialysis within the first 7 days post-transplant. Mean arterial pressure (MAP) was calculated where reperfusion blood pressure data were available, and a sensitivity analysis accounting for transplant center was performed. Associations between perioperative variables and outcomes were evaluated using univariate and multivariate regression analyses. RESULTS:Ninety-seven patients were included (median age 154 months; 45.4% female). DGF occurred in 11.3% of recipients. In multivariate analysis, no perioperative variable was independently associated with DGF. Longer cold ischemia time was independently associated with lower 7-day eGFR (B = -0.05; 95% CI -0.10 to -0.01; p = 0.014). At 30 days, preemptive transplantation (B = -15.99; 95% CI -27.02 to -4.96; p = 0.005) and DGF (B = -36.94; 95% CI -58.39 to -15.50; p = 0.001) were independently associated with lower eGFR; the preemptive association was attenuated after accounting for transplant center. CONCLUSION:Intraoperative hemodynamic parameters were not independently associated with DGF or early graft function. At day 7, early graft function was primarily associated with cold ischemia time, whereas at day 30 it was mainly associated with preemptive transplantation status and DGF.

Long-term allograft survival is limited by the occurrence of chronic allograft dysfunction, mainly due to antibody mediated rejection and aspecific fibrosis. The latter is favored by ischemia-reperfusion injury (IRI), particularly in organs from extended criteria donors and from donors after cardiocirculatory arrest. The graft endothelium is highly sensitive to IRI that causes chronic damages and increases its immunogenicity. Thus, improvement of preservation methods and the treatment of organs prior to implantation (so called “graft preconditioning”) constitute a major clinical challenge to improve graft survival. Among the mechanisms implicated in the reactivity of endothelial cells, neddylation has emerged as a potential candidate of interest. To study the potential of neddylation blockade as a preconditioning strategy, we used an in vitro model of microvascular endothelial cells (ECs) treated in conditions close to those of organ transplant preservation. ECs were subjected to hypothermic preservation (4 °C) in the presence of the neddylation inhibitor MLN4924, and following rewarming (37 °C), stimulated with TNAα and IFNγ to mimic sterile inflammation at reperfusion. We found that preconditioning of ECs with MLN4924 had potent anti-inflammatory effects by blocking the induction of adhesion molecules (ICAM1, VCAM1, E-Selectin), of HLA class I and II, and of the pro-inflammatory cytokines and chemokines IL6, RANTES and Fractalkine. Functionally, this translated into inhibition of EC-mediated T lymphocyte activation and of T cell adhesion to ECs. MLN4924 preconditioning also blocked the induction of prothrombotic molecules (Tissue Factor and PAI-1), and platelet adhesion to ECs. Finally, MLN4924 enhanced the expression of the complement inhibitor CD55 and of the antioxidant molecule HO-1, and protected ECs from hypothermia and hypoxia induced cell death. Our results identify the neddylation inhibitor MLN4924 as a powerful protective molecule for endothelial cells and a promising candidate for graft preconditioning and protection of organs against IRI.

To compare early and late complications rates after robot-assisted radical cystectomy for muscle invasive bladder tumors and certain high-risk non-muscle-invasive tumors according to the type of reconstruction. We conducted a single-center retrospective study including 109 patients who underwent robot-assisted radical cystectomy between 2008 and 2022. Patients were divided into two groups based on urinary diversion: extracorporeal Bricker ileal conduit (n = 74) or orthotopic neobladder (n = 35). Complications were graded by the Clavien-Dindo classification. Multivariate analysis identified independent risk factors for morbidity and mortality. Operative time was significantly longer for neobladder reconstruction (320 vs. 291 min, p = 0.047), as was hospital stay (14 vs. 10 days, p < 0.001). Early complications (< 30 days) occurred in 59.6% of patients, with a higher rate of minor complications in the neobladder group (57.1% vs. 28.4%, p = 0.006). There was no significant difference in major complications (Clavien III-V) or late complications (> 30 days), which affected 47.7% of patients. Operative time was an independent risk factor for major complications (OR = 1.15 per additional 15 min). Neobladder reconstruction was associated with increased early morbidity, mainly minor, without impact on late morbidity or mortality. Urinary diversion choice should be guided by patient profile and expected functional benefits.

Autoantibodies targeting the angiotensin II receptor type 1 (AT1R) have been identified as drivers of allograft vascular inflammation in kidney transplantation. We investigated the role of AT1R autoantibodies (AT1R-AA) in pancreas transplantation with a focus on rejection and thrombosis. We included all pancreas transplant recipients followed in our center with available pretransplant sera (day 0). AT1R-AA levels were assessed, and a multivariable cause-specific Cox model was used to examine their association with pancreas rejection and survival. Additionally, pancreatic tissues were analyzed for AT1R expression at the molecular and protein levels. Among 305 patients, 34 experienced pancreatic rejection and 50 allografts were lost at 1 year. In multivariable analysis, AT1R-AA titer at transplantation was significantly associated with pancreas survival (adjusted hazard ratio = 1.04, 95% confidence interval [1.00; 1.08], P = .0427) and pancreas rejection (adjusted hazard ratio = 1.07, 95% confidence interval [1.03; 1.12], P = .0015). AT1R-AA levels were significantly higher in patients with early thrombosis compared with others (10.1 U/mL vs 6.3 U/mL, P < .0001). Analysis of tissues from deceased donors and follow-up biopsies revealed wide variation in pancreatic AT1R expression. In conclusion, AT1R-AA were significantly associated with a higher risk of pancreatic rejection and allograft failure from complete thrombosis. Variations in pancreatic AT1R expression may contribute to different outcomes among patients with pretransplant AT1R-AA.

INTRODUCTION:Non-obstructive azoospermia (NOA), which accounts for 10% of male infertility cases, is managed by microdissection testicular sperm extraction (mTESE), currently consider the gold standard technique. While mTESE improves sperm retrieval rates (SRR) and minimizes testicular damage, this is only the first step in the assisted reproductive technology (ART) pathway, whose goal is live birth. Advanced sperm preparation techniques, including SpermVD® vitrification and synchronous oocyte retrieval, may further optimize outcomes. However, live birth and ongoing pregnancy rates (LBR) after mTESE remain poorly reported. This study aimed to evaluate reproductive outcomes following mTESE combined with advanced sperm preparation techniques in NOA. MATERIALS & METHODS:This retrospective study included 55 patients with NOA who underwent mTESE between July 2019 and March 2023. The primary outcomes included LBR, while the secondary outcome concerned SRR. Univariate analyses were performed to identify risk factors associated with unsuccessful sperm retrieval. RESULTS:Mean age was 36.6years, mean FSH level of 20.9IU/L and mean testicular volume was 7.4mL. SRR was 47.3% (95% CI: 34.2% - 60.4%) and increased to 53.2% after excluding Klinefelter patients. Live birth and ongoing pregnancies were achieved in 27.3% of couples (95% CI: 15.5% - 39.1%) and 57,7% of positive biopsies (95%. CI: 38,5% - 76,9%). Karyotype abnormalities (P=0.025), elevated FSH (P=0.029), and familial infertility (P=0.003) were associated with unsuccessful sperm retrieval. CONCLUSION:In our cohort, mTESE enabled 27.3% of couples to achieve a live birth or ongoing pregnancy without requiring sperm donation.

Background. Static cold storage (SCS) remains the standard method for organ preservation. The development of parenchymal edema during prolonged hypothermic machine perfusion (HMP) was a major barrier to the introduction of this technique for the preservation of pancreases. A short period of HMP could optimize the pancreas for reperfusion while minimizing the side effects related to perfusion. Our objective is to evaluate the impact of short-term HMP on the pancreatic reperfusion. Methods. A preclinical study using a controlled donation after circulatory death porcine model was conducted. After procurement, the pancreases were preserved under hypothermic conditions for 2 h either by SCS (n = 4) or HMP (n = 4). After these 2 h of preservation, the pancreases were reperfused using a normothermic machine perfusion (NMP) for 2 h. During NMP, oxygenation, perfusion parameters, biochemical analyses, a glucose stimulation insulin secretion test, and an evaluation of ischemia/reperfusion injury by photoacoustic tomography were assessed. Results. During NMP, resistance indices were significantly lower in the HMP group compared with the SCS group, even after 2 h of reperfusion. The tissue oxygen partial pressure was higher throughout NMP after HMP preservation. Lactate and amylase levels were equal between the 2 groups. Lipase levels were higher in the HMP group. The glucose stimulation test showed no difference between the 2 groups. Photoacoustic tomography assessment showed no endothelial damage in either group. Conclusions. Our study suggests that a short-term HMP applied to pancreases for 2 h is effective in reducing resistance indexes and improving oxygenation.

The pancreases used were derived from a preliminary feasibility study and were employed following the principle of reuse. Animal euthanasia was performed in accordance with the law governing the protection of animals for scientific purposes (conditions of killing: Articles R214-98 to R214-98-1). The research protocol was approved by the French Ministry of Research (APAFiS nos 31507). All experiments adhered to the ARRIVE 2.0 recommendations and the European Directive 2010/63/EU on animal experimentation. In organ transplantation, ex vivo normothermic perfusion (EVNP) is increasingly being developed and used before transplantation, both to evaluate grafts and to recondition them. The assessment of grafts during EVNP is based on macroscopic evaluation of the organ, perfusion parameters, biochemical markers, and sometimes histology or organ function recovery (eg, urine output in kidney transplantation). To date, no strategy includes a morphological evaluation of vascularization or the integrity of the endothelial barrier. Photoacoustic tomography (PT) is an innovative modality for assessing organ vascularization, particularly microvascularization. This noninvasive imaging technique visualizes hemoglobin distribution, indirect assessing graft vascularization, both on the surface and deep within the parenchyma. An optical probe directly applied to the parenchyma emits a laser into the tissue with a wavelength corresponding to the excitation wavelength of hemoglobin. The absorption of this light by hemoglobin induces rapid thermal expansion, leading to the localized generation of ultrasound waves triggered by this excitation.1,2 The resulting acoustic signal is then recorded and, after reconstruction, allows visualization of hemoglobin and, indirectly, blood vessels, as well as hemorrhagic suffusions that may occur during ischemia/reperfusion injury (IRI).3 Here, we present the first images of the evaluation of pancreatic grafts by PT during EVNP (porcine model, use of pancreatic grafts due to their high sensitivity to IRI4). After 2 or 24 h of cold ischemia (static cold storage or hypothermic machine perfusion), pancreatic grafts were reperfused. The imaging platform for PT was provided by Deepcolor Imaging SAS (Nantes, France; http://www.deepcolorimaging.com). During reperfusion, PT was performed every 5 min during the first 30 min of reperfusion. A volumetric image of 1 × 1 × 1 cm was obtained during each analysis. The resolution is on the order of 100 µm. The perfusion fluid during EVNP consisted of autologous whole blood without additives. The reperfusion of 5 pancreatic grafts was evaluated (Figure 1). After 2 h of cold preservation, PT revealed the presence of hemoglobin along vessel-like structures during reperfusion according to EVNP. The signal appears at 5 min in structures approximately 3–4 mm in size as well as in those <1 mm. This supports the idea of revascularization in both medium-sized and small vessels at 5 min. The signal remains constant over the course of the following 30 min. The mesh-like structures of small vessels corresponded to pancreatic gland tissue, whereas larger vessels corresponded to duodenal parenchyma. No hemoglobin extravasation outside the vessels was observed during the first 30 min of reperfusion. After 24 h of preservation, the signal seems to appear progressively, which may correspond to a slower revascularization of the pancreas. We observed the appearance of additional imaging near the vessels, which may correspond to hemoglobin outside the vessels. In our opinion, this may reflect hemoglobin extravasation, secondary to endothelial barrier rupture and IRI.FIGURE 1.: Photoacoustic tomography evaluation of pancreatic transplants preserved for 2 or 24 h (SCS or HMP) before reperfusion according to ex vivo normothermic perfusion. The amount of hemoglobin is represented by the intensity of the photoacoustic signal. The colors represent the depth of the measurement and help to understand the 3D structure: (1) pancreatic parenchyma and (2) duodenal parenchyma. 3D, 3-dimensional; HMP, hypothermic machine perfusion; SCS, statical cold storage.PT may provide evidence of endothelial barrier function loss. Thus, PT could become a major marker of interest for graft evaluation during EVNP. It allows for in-depth vascularization evaluation while remaining noninvasive, nonionizing, and free of contrast agents, which is particularly valuable in EVNP. In contrast, PT has several technical limitations: although the acquisition time is <10 s, it does not allow for real-time assessment. Furthermore, light penetration into the parenchyma depends on the organ and is less effective in pigmented organs (eg, liver), impacting both image depth and the quality of the assessment obtained. Additionally, PT does not allow for determining whether the blood delivered to the graft is oxygenated or not. Finally, the future integration of PT technology into EVNP will first require a detailed description of the normal vascularization of organs and IRI as visualized by PT. ACKNOWLEDGMENTS The authors express their gratitude to Deepcolor Imaging SAS (Nantes, France, http://www.deepcolorimaging.com) for providing the platform, the time dedicated by their technical teams, and their scientific expertise. The authors thank the Center for Research in Transplantation and Translational Immunology for their scientific expertise (S. Le Bas-Bernardet, D. Minault, J. Herouvet, and G. Blancho), the French National Agency (Agence de la biomedicine) for grant funding, the French Urological Association (Association Française d'Urologie) for grant funding, the Nantes University Hospital for grant funding, the biochemical analysis laboratory of the Nantes University Hospital for logistical support, and the Institut Georges Lopez for grant funding and technical support.

Background. Uterus transplantation from deceased donors offers a promising solution to the organ shortage, but optimal preservation methods are crucial for successful outcomes. Our primary objective is to conduct an initial assessment of the contribution of oxygenated hypothermic perfusion in uterine transplantation. Methods. We performed a preclinical study on a porcine model of controlled donation after circulatory death (60 min warm ischemia). Ten uterus grafts were preserved for 12 h using static cold storage or hypothermic machine perfusion (VitaSmart device, perfusion pressure at 15 mm Hg). Subsequently, they were reperfused using ex vivo normothermic machine perfusion (Liverassist, perfusion pressure at 30 mm Hg) with oxygenated autologous blood to assess early ischemia/reperfusion injury. Not only resistance index assessment and oxygenation evaluation but also immunochemistry and gene expression analysis were performed. Results. This study demonstrates the feasibility of using hypothermic machine perfusion for uterine graft preservation, showing improvements in reperfusion capacity (decrease of resistance indexes; P < 0.0001) and tissue oxygenation (higher oxygen level) compared with static cold storage. Conclusions. These findings provide valuable insights for further research and refinement of uterine transplantation procedures.

The rate of early pancreas allograft failure remains high due to thrombosis but also to severity of rejection episodes. We investigated if adjunct anti-TNFα therapy was safe and could improve outcomes after pancreas transplantation. We investigated all pancreas transplants performed in our institution between 2010 and 2022. Etanercept, an anti TNFα therapy, was added to our standard immunosuppressive regimen since 2017 after approval from our institutional human ethics committee. Pancreas survival, rejection episodes, as well as infectious complications were analyzed. A total of 236 pancreas transplants were included, among whom 87 received Etanercept for induction. In multivariable analysis, after adjustment on confounding variables, pancreas survival did not differ between groups (HR = 0.92, CI 95% = 0.48; 1.73, p = 0.79). However, patients receiving Etanercept presented a significantly lower occurrence of pancreas rejection in multivariate analysis (HR = 0.36, CI 95% = 0.14; 0.95, p = 0.04). Patients receiving Etanercept did not experienced a higher risk of bacterial, fungal, CMV nor BK virus infections compared to the non-treated group. The use of anti-TNFα after pancreas transplantation was safe and did not increase infectious complications. Despite a similar rate of thrombosis, anti-TNFα significantly reduced pancreatic rejection, thus supporting its use among pancreas transplant recipients.

To evaluate in vivo a fully integrated photoacoustic tomography imaging system based on Fabry–Pérot ultrasound sensing method applied on porcine abdominal organs. This approach could be used by surgeons during intraoperative clinical procedures. The photoacoustic imaging system was fully integrated into a single structure, and the detection technology was based on a Fabry–Pérot interferometer. The detection probe connected to the imaging system was applied directly to the organs of a male “large white” Sus scrofa pig weighing 80 kg, either manually or using a stand, with or without a gel interface. All experiments were performed in compliance with EU Directive 2010/63/EU on animal experimentation (APAFiS #31507). All intraperitoneal and retroperitoneal organs were evaluated using photoacoustic imaging. The evaluation of both hollow and solid organs was successfully conducted with consistent three-dimensional image quality. We demonstrate the system’s ability to image blood vessels with diameters ranging from several millimeters down to less than 100 µm. Macroscopic evaluation of the organs using photoacoustic tomography imaging did not reveal any damage or burns caused by the excitation laser. To our knowledge, this is the first reported imaging session of abdominal organs in an in vivo porcine model, performed using a photoacoustic tomography system with Fabry–Pérot interferometer detection. We present a high-resolution photoacoustic tomography system that is closer to routine clinical translation, thanks to a fully integrated system. Photoacoustic evaluation of organs using a fully integrated system could become a valuable tool for surgical teams for intraprocedural assessment of vascularization.

OBJECTIVES:To externally validate the tetrafecta and pentafecta frameworks for assessing the quality of radical nephroureterectomy (RNU) and their correlation with oncological outcomes in patients with localised upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS:This retrospective study included 545 patients who underwent RNU for localised UTUC between 2012 and 2023 at eight French university hospitals and one Lebanese university hospital. Achievement of tetrafecta required four criteria to be met: negative surgical margins, complete bladder cuff excision, lymph node dissection (if indicated), and absence of recurrence within 12 months. Pentafecta consisted of the same criteria, plus no major complications or haematological events. Oncological outcomes assessed included intravesical recurrence-free survival (IVRFS), recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier analyses, Cox regression, and calibration plots were used to evaluate the predictive performance of the frameworks for 3-year outcomes. RESULTS:A total of 29.5% of our cohort achieved tetrafecta and 34.5% achieved pentafecta. Patients meeting either of these quality care metrics demonstrated significantly improved oncological outcomes, with higher 3-year OS rates (tetrafecta: 90.1% vs 74.2%, P < 0.001; pentafecta: 89.4% vs 73.4%, P < 0.001) and RFS rates (tetrafecta: 84.5% vs 57.6%, P < 0.001; pentafecta: 83.5% vs 56%, P < 0.001). Both metrics showed high predictive accuracy for OS (area under the curve [AUC] 0.92 for tetrafecta; 0.93 for pentafecta, P = 0.41) and CSS (AUC 0.944 for tetrafecta; 0.945 for pentafecta, P = 0.6018). Pentafecta achievement was independently associated with better OS and CSS in multivariable analysis (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.16-0.55, P < 0.001 and (HR 0.24, 95% CI 0.10-0.54, P < 0.001, respectively). CONCLUSION:Tetrafecta and pentafecta are reliable tools for assessing oncological outcomes after RNU in localised UTUC. Pentafecta demonstrated stronger prognostic value for OS, particularly in high-risk populations. These metrics offer a standardised framework to guide clinical decisions, evaluate surgical quality, and counsel patients about prognosis.