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Background: According to the European guidelines, any urological surgery breaching the mucosa requires preoperative screening and antibiotic treatment of any asymptomatic bacteriuria (ABU)., Methods: The aim of this study was to determine whether the preoperative antibiotic treatment duration of ABU in urological surgery impact postoperative infectious complications. National multicenter, retrospective study including all consecutive patients screened for ABU before urologic surgery in 10 centers from 1 st April 2019 to April 2023. The primary endpoint was all postoperative infectious complications occurring within 30 days after surgery. Short antibiotic treatment (SAT) of ABU was defined by 5- day regimen or less. Long antibiotic treatment (LAT) was defined by duration longer than 5 days., Results: Among the 2389 patients included, 839 (35.1%) patients had positive urine culture (UC), of whom 546 (65%) had positive mono or bimicrobial UC and 292 (34.8%) polymicrobial UC. There were 106 (4.4%) postoperative infectious complications occurring within 30 days including 62 (58.5%) in the positive UC group. In the positive UC group, 336 (40%) had received SAT, 261 (31.1%) LAT and 231 (27.5%) had not received any treatment. The 30-day surgery-related infection rates were 8.3%, 6.1% and 7.36% respectively. There was no statistical difference between SAT versus LAT in the univariate analysis (P=0.6) or in the multivariate analysis OR 1.97 [0.37, 1.86] (P=0.06)., Conclusions: Our results found no association between antibiotic treatment duration and urinary infectious complication among patients with preoperative ABU who undergo urological surgery. These results need a RCT to be confirmed.

Purpose: Current guidelines recommend screening and treatment of asymptomatic bacteriuria prior to all urological surgeries breaching the mucosa. But little evidence supports this recommendation. At the least, risk stratification for postoperative UTI to support this strategy is lacking. The aim of this study was to define the associated factors for postoperative febrile infectious complications (UTI or surgical site infection) in urological surgery., Materials and Methods: We conducted a retrospective, multicentric study including all consecutive patients undergoing any urological surgery with preoperative urine culture. The primary outcome was the occurrence of a UTI or surgical site infection occurring within 30 days after surgery., Results: From 2016 to 2023, in 10 centers, 2389 patients were included with 838 (35%) positive urine cultures (mono-/bi-/polymicrobial). Postoperative infections occurred in 106 cases (4.4%), of which 44 had negative urine cultures (41%), 42 had positive mono-/bimicrobial urine cultures (40%), and 20 had polymicrobial urine cultures (19%). In multivariable analysis, UTI during the previous 12 months of surgery (odds ratio [OR] 3.43; 95% CI 2.07-5.66; P < .001), monomicrobial/bimicrobial preoperative urine culture (OR 3.68; 95% CI 1.57-8.42; P = .002), polymicrobial preoperative urine culture (OR 2.85; 95% CI 1.52-5.14; P < .001), and operative time (OR 1.09; 95% CI 1.04-1.15; P < .001) were independent associated factors for postoperative febrile infections., Conclusions: Positive urine culture, including preoperative polymicrobial urine culture, prior to urological surgery was associated with postoperative infection. Additionally, patients experiencing infectious complications also had a higher incidence of other complications. The effectiveness of systematic preventive antibiotic therapy for a positive urine culture has not been conclusively established.

Introduction: In the era of increased bacterial resistance, the main strategy is to reduce the prescription of antibiotics when possible. Nowadays, it is highly recommended to screen for asymptomatic bacteriuria (ABU), prior to urological surgery with potential mucosal breach or urine exposure. Screening and treating urinary colonization is a strategy widely adopted before radical and partial nephrectomy but without any evidence. Our main end point in this study is to analyze the relationship between preoperative urine culture and the risk of postoperative febrile urinary tract infection (UTI) or surgical-site infection (SSI) in partial or radical nephrectomy patients., Methods: We conducted a multicenter retrospective cohort study between January 2016 and January 2023 in 11 French tertiary referral hospitals (TOCUS database). We collected the data for 269 patients including several pre-, intra-, and post-operative variables that could potentially increase the risk of postoperative UTI and SSI including preoperative urinary culture results., Results: The incidence rate of postoperative UTI and SSI was 8.9% in our study. After conducting a logistic multivariate analysis, a propensity score matching analysis, and a subgroup analysis, we found no significant correlation between the urine culture and the postoperative UTI risk [OR = 1.2 (0.5-2.7) (p = 0.7)]. Only the postoperative non-infectious complications were related to a higher risk of postoperative UTI [OR = 12 (4-37), p < 0.001)]., Conclusion: Our research shows that screening and treating for ABU prior to radical or partial nephrectomy seems to be unnecessary to prevent postoperative UTI and SSI., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: A single immediate instillation of mitomycin C is recommended after a complete transurethral resection of the bladder (TURB) in low- and intermediate-risk patients with NMIBC. Actually, post-TURB instillation is seldom used due to logistical difficulties and surgical contraindications. Our aim was to compare patients with single pre-TURB intra-vesical instillation and patients with a single, immediate post-TURB intra-vesical instillation of mitomycin C., Methods: We performed a multicenter randomized trial between February 17, 2014 and November 24, 2016 (registration number 2012-004341-32). Sixty patients with two or less, primary or recurrent papillary bladder tumors and a negative urinary cytology were planned. Cystoscopy was performed at 3, 6 and 12 months after TURB. Our primary endpoint was disease-free interval. Secondary endpoints were recurrence rate at 3 and 12 months, rate of patients in whom instillation could not be performed and tolerance 1 month after TURB using BCI-Fr score., Results: Among 35 eligible participants, 20 were randomly assigned in the pre-TURB instillation group and 15 in the post-TURB instillation group. Follow-up was comparable: 12,3±1,6 months in the SI group and 10,2±4,5 months in the pre-TURB instillation group. In the post-TURB instillation group, 2 patients didn't have any instillation. We did not identify significant differences in disease-free interval. Tolerance at 1 month after TURB was similar in both groups., Conclusion: Tolerance and efficacy were not significantly different. As expected, logisitics were easier for the health providers in the pre-TURB group where all patients had their instillation conversely to the post-TURB group. These results suggest that the advantages of a single immediate pre-TURB instillation warrant further evaluation of this strategy in a phase III randomized trial., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

The medical device M101 is an extracellular hemoglobin featuring high oxygen-carrying capabilities. Preclinical studies demonstrated its safety as an additive to organ preservation solutions and its beneficial effect on ischemia/reperfusion injuries. OXYgen carrier for Organ Preservation (OXYOP) is a multicenter open-label study evaluating for the first time the safety of M101 added (1 g/L) to the preservation solution of one of two kidneys from the same donor. All adverse events (AEs) were analyzed by an independent data and safety monitoring board. Among the 58 donors, 38% were extended criteria donors. Grafts were preserved in cold storage (64%) or machine perfusion (36%) with a mean cold ischemia time (CIT) of 740 minutes. At 3 months, 490 AEs (41 serious) were reported, including two graft losses and two acute rejections (3.4%). No immunological, allergic, or prothrombotic effects were reported. Preimplantation and 3-month biopsies did not show thrombosis or altered microcirculation. Secondary efficacy end points showed less delayed graft function (DGF) and better renal function in the M101 group than in the contralateral kidneys. In the subgroup of grafts preserved in cold storage, Kaplan-Meier survival and Cox regression analysis showed beneficial effects on DGF independent of CIT (P = .048). This study confirms that M101 is safe and shows promising efficacy data., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Static cold storage (SCS) and hypothermic machine perfusion (HMP) are currently standard methods for renal grafts clinical preservation. Both methods are predominantly implemented without the active delivery of oxygen, even for donation after circulatory death-like kidneys. However, even under severe hypothermia (4°C-6°C), kidneys can consume oxygen and produce ATP. What is not established, though, is to what extent and how SCS and HMP compare in terms of oxygen. Using a porcine preclinical model of renal warm ischemia (WI) to compare SCS and HMP methods, we continuously monitored and quantified oxygen level and consumption along preservation; we also determined prepreservation and postpreservation cortical ATP level; values were given as median and [min; max] range. One-hour WI reduced ATP by ∼90% (from 3.3 [1.7; 4.5] mmol/L tissue in Controls). Oxygen consumption (QO 2 , μmol/min per 100 g) was determined from initial solution PO 2 decrease (SCS and HMP) and from arterio-venous difference (HMP). In SCS and HMP, PO 2 decreased rapidly (t 1/2 ∼1 h) from atmospheric levels to 52.9 [38.0; 65.9] and 8.2 [3.0, 16.0] mmHg, respectively. In HMP, QO 2 was 2.7 [0.4; 3.9] versus 0.5 [0.0; 1.3] in SCS (P < 0.05); postpreservation ATP amounted to 5.8 [3.2; 6.5] in HMP versus 0.1 [0.0; 0.2] in SCS. Despite hypothermic conditions in SCS or HMP, donation after circulatory death-like renal grafts require oxygen. Increased oxygen consumption, restored ATP level, and improved histological profile in HMP might explain the established HMP superiority over SCS. These results establish a rational basis for the use of oxygen in hypothermic preservation. Optimal levels required for preservation and graft-type variants remain to be determined., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A minimum delay of 4 to 6 weeks between biopsy and multiparametric prostatic MRI (mpMRI) is admitted due to post-biopsy hemorrhage that can impact MRI reading without strong scientific evidence. The objective of the study was to evaluate the best period between prostate biopsy and 3Tesla mpMRI and searching for predictive factors of intraprostatic blood., Method: A prostate biopsy followed by a 4-week prostate MRI (MRIp M1) was performed. In case of hemorrhage, MRI was rescheduled at 8 and 12 weeks (M2/M3). We analyzed the persistant bleeding to identify risk factors: anticoagulant/antiaggregant, post-biopsy side effects, histological criteria., Results: In this prospective, single-center study, we included 40 patients followed for suspected prostate cancer between December 2014 and March 2016. At the MRIpM1, blood was found for 97.5 % of the patients. The rates were 90.9 % and 88.9 % respectively at the M2 and M3 mpMRI. Compared to initial blood volume on MRIpM1, a significant decrease in blood volume was observed between M1 and M2 (55 %; P=0.0091). We showed a 75 % decrease between M1 and M3 (P=0.0003). Low urinary tract symptoms (LUTS) suggesting urinary infection at 4 weeks were significantly correlated with blood volume on MRIpM1 (P=0.0063). The blood volume was higher in case of unconformity between biopsy and mpMRI results for detection of significant tumors (11.3 vs. 2.3; P=0.0051)., Conclusions: A minimum of 8-week biopsy and mpMRI period would limit post-biopsy hemorrhage, predicted by LUTS suggesting urinary infection. A delay of 12 weeks would be optimal without delaying the management of the patient., Level of Evidence: 4., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

The relationship between cold ischaemia time (CIT) and adverse outcome is now acknowledged. However, the underlying mechanisms remain to be defined, which slows the development of adapted therapeutics and diagnostics. We explored the impact of CIT in both preclinical and in vitro models of preservation. We determined that the endoplasmic reticulum (ER) and its stress response (unfolded protein response, UPR) were regulated in close association with CIT; the eIF2α-ATF4 pathway was inhibited early (1-8 h) at the detriment of cell survival, while the ATF6 pathway was activated late (12-24 h) and associated with cell death. The IRE1α-XBP1 branch was activated at reperfusion only if CIT extended beyond 8 h, and had a dual role on cell fate - deleterious through IRE1's RNase activity and beneficial through IRE1α other roles. Finally, the pro-apoptotic factor CHOP was a common target of both ATF6 and IRE1α pathways and was associated with elongated CIT and increased cell death. Microarray analysis of human transplanted kidney confirmed that UPR markers were regulated by CIT and that CHOP was associated with adverse outcome. We show that UPR could be a critical pathway explaining the relationship between CIT and graft outcome, highlighting the potential for UPR-based therapeutics and diagnostics to improve transplantation.

Introduction: Alike becoming a pilot requires competences, acquisition of technical skills is essential to become a surgeon. Halsted's theory on surgical education "See one, do one, and teach one" is not currently compatible with the reality of socio-economic constraints of the operating room, the patient's safety demand and the reduction of residents' work hours., Materiel and Methods: In all countries, this brings mandatory to simulation education for surgery resident's training. Many models are available: video trainers or pelvi-trainers, computed simulator, animal models or human cadaver… Human cadaveric dissection has long been used to teach surgical anatomy., Results: Surgery on human cadaveric model brings greatest accuracy to the haptic characteristics of surgical procedures. Learning in an appropriate and realistic simulation context increases the level of acquisition of the residents' skills and reduces stress and anxiety when performing real procedures., Conclusion: We present a technique of perfusion and ventilation of a fresh human cadaver that restores pulsatile circulation and respiratory movements of the model., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Purpose: In primary and continuing medical education, simulation is becoming a mandatory technique. In surgery, simulation spreading is slowed down by the distance which exists between the devices currently available on the market and the reality, in particular anatomical, of an operating room. We propose a new model for surgical simulation with the use of cadavers in a circulation model mimicking pulse and artificial respiration available for both open and laparoscopic surgery., Methods: The model was a task trainer designed by four experts in our simulation laboratory combining plastic, electronic, and biologic material. The cost of supplies needed for the construction was evaluated. The model was used and tested over 24 months on 35 participants, of whom 20 were surveyed regarding the realism of the model., Results: The model involved a cadaver, connected to a specific device that permits beating circulation and artificial respiration. The demonstration contributed to teaching small groups of up to four participants and was reproducible over 24 months of courses. Anatomic correlation, realism, and learning experience were highly rated by users CONCLUSION: This model for surgical simulation in both open and laparoscopic surgery was found to be realistic, available to assessed objectively performance in a pedagogic program.

Background: Ischemia reperfusion injury (IRI) induced immune response is a critical issue in transplantation. Complement and contact system activation are among its key mechanisms., Study Design: We investigated the benefits of pre-reperfusion treatment with recombinant human C1INH (rhC1INH), inhibitor of both complement and contact activation, in a pig model of kidney autotransplantation, subjecting the organ to 60 min warm ischemia prior to 24 h static preservation to maximize damage., Results: Serum creatinine measurement showed that treated animals recovered glomerular function quicker than the Vehicle group. However, no difference was observed in tubular function recovery, and elevated level of urinary NGal (Neutrophil gelatinase-associated lipocalin) and plasma AST (Aspartate Aminotransferase) were detected, indicating that treatment did not influence IRI-mediated tubular cell necrosis. Regarding chronic graft outcome, rhC1INH significantly prevented fibrosis development and improved function. Immunohistochemistry and western blot showed decreased invasion by macrophages and T lymphocytes, and reduction of epithelial to mesenchymal transition. We determined the effect of treatment on complement activation with immunofluorescence analyses at 30 min post reperfusion, showing an inhibition of C4d deposition and MBL staining in treated animals., Conclusions: In this model, the inhibition of complement activation by rhC1INH at reperfusion, while not completely counteracting IRI, limited immune system activation, significantly improving graft outcome on the short and long term.

Background: Deceased after cardiac death donors represent an important source of organs to reduce organ shortage in transplantation. However, these organs are subjected to more ischaemia-reperfusion injury (IRI). Reducing IRI by targeting coagulation is studied here in an experimental model., Methods: The effect of an anti-Xa compound (fondaparinux) was evaluated using an autotransplanted kidney model in pigs. Kidneys were clamped for 60 min (warm ischaemia) and then preserved for 24 h at 4 °C in University of Wisconsin solution (UW). The anti-Xa compound was injected intravenously before warm ischaemia and used during cold storage, and its effects were compared with those of intravenous injection of unfractionated heparin (UFH) before warm ischaemia and use during cold storage, or use of UW alone during cold storage., Results: At 3 months after transplantation, anti-Xa treatment improved recovery of renal function and chronic serum creatinine levels compared with UW and UFH (mean(s.e.m.) 89(4), 250(4) and 217(8) µmol/l respectively). The anti-Xa treatment also reduced fibrosis, and decreased tissue expression of markers of the epithelial-mesenchymal transition compared with UW and UFH. Cleaved protease-activated receptor 2 was overexpressed in the UW group compared with the anti-Xa and UFH groups. Leucocyte infiltrates were decreased in the anti-Xa group compared with the UW and UFH groups. Macrophage invasion was also decreased by anticoagulation treatment., Conclusion: Peritransplant anticoagulation therapy was beneficial to graft outcome, in both the acute and chronic phases. Moreover, specific inhibition of coagulation Xa protease further protected kidney grafts, with better recovery and decreased expression of chronic lesion markers. Surgical relevance The increasing use of marginal donors highlights the importance of organ quality in transplantation. Renal ischaemia-reperfusion injury (IRI), which includes a deleterious activation of coagulation, plays a central role in determining graft quality and outcome. Using an established porcine renal autotransplantation preclinical model with high clinical relevance, the benefits of anticoagulation therapy using an antifactor Xa molecule were evaluated. Peritransplantion anticoagulation treatment, specifically with an anti-Xa compound, protected marginal kidney grafts, improving functional recovery and reducing chronic lesions. This study demonstrates the benefits of anticoagulation therapy at the time of organ collection, particularly for marginal organs, encountered in cases of extended criteria and deceased after circulatory death donors. This anticoagulation strategy could be an important addition to current donor and organ management protocols in order to limit IRI and improve outcome., (© 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.)

Background: The increased use of marginal donors highlights the importance of organ quality in transplantation and the identification of prognostic biomarkers. This experimental study investigated modulation of the hypoxia-inducible factor (HIF) 1α pathway in kidney grafts in relation to different degrees of ischaemia., Methods: In a porcine autotransplantation model, two different kidney graft protocols were compared: standard 24-h cold storage (CS) and 24-h CS preceded by 1 h warm ischaemia (WI + CS). The renal HIF-1α pathway and tubular dedifferentiation were analysed in the early phase of reperfusion and at 3 months., Results: There was a relationship between the degree of ischaemic injury and the outcome of the kidney graft. During the first week of reperfusion, WI + CS grafts showed a higher degree of injury. The observed tubular dedifferentiation was associated with delayed HIF-1α expression, and with loss of its role in transcription. In highly injured kidneys, deregulation of the HIF-1α pathway was also observed in the chronic phase, with reduced production of vascular endothelial growth factor (VEGF) A, and upregulation of VEGF receptor 1 (Flt-1) and thrombospondin 1. In addition, these kidneys displayed altered kidney histology and decreased function., Conclusion: The HIF-1α pathway appears to be abolished early in response to severe ischaemia. A high degree of ischaemic injury also results in chronic activation of the HIF-1α pathway, diverting it away from the beneficial activation of angiogenesis. Further studies on the finely tuned balance of signals in this pathway may provide diagnostic biomarkers that can determine organ quality during kidney transplantation. Surgical relevance The increased use of marginal donors has highlighted the importance of organ quality in transplantation. Renal ischaemia-reperfusion injury following transplantation induces graft dysfunction. In a porcine model of renal autotransplantation, the induction of regenerative processes, in response to graded degrees of ischaemia, was studied in the post-transplantation phase. There was early abrogation of the hypoxia-inducible factor (HIF) 1α pathway in response to severe ischaemia. High degrees of ischaemic injury induced chronic activation of the HIF-1α pathway, diverting it from the beneficial activation of angiogenesis. Identification of the mechanisms involved in renal regeneration, such as those related to the HIF-1α pathway, are important as these mechanisms can be used to identify novel therapeutic targets or develop diagnostic biomarkers to determine organ quality early in the transplantation process., (© 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.)

Protection of endothelial cell function may explain the benefits of nonoxygenated hypothermic machine perfusion (MP) for marginal kidney preservation. However, this hypothesis remains to be tested with a preclinical model. We postulated that MP protects the nitric oxide (NO) signaling pathway, altered by static cold storage (CS), and improves renal circulation recovery compared to CS. The endothelium releases the vasodilator NO in response to flow via either increased endothelial NO synthase (eNOS) expression (KLF2-dependent) or activation of eNOS by phosphorylation (via Akt, PKA or AMPK). Using a porcine model of kidney transplantation, including 1 h of warm ischemia and preserved 24 h by CS or MP (n=5), we reported that MP did not alter the cortical levels of KLF2 and eNOS at the end of preservation, but significantly increased eNOS activating phosphorylation compared to CS. eNOS phosphorylation appeared AMPK-dependent and was concomitant to an increased NO-dependent vasodilation of renal arteries measured, ex situ, at the end of preservation. In vivo, laser Doppler showed that cortical microcirculation was improved at reperfusion in MP kidneys. In conclusion, we demonstrate for the first time, in a large-animal model, that MP protects the NO signaling pathway, confirming the value of MP for marginal kidney preservation., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Extracorporeal membranous oxygenation is proposed for abdominal organ procurement from donation after circulatory determination of death (DCD). In France, the national Agency of Biomedicine supervises the procurement of kidneys from DCD, specifying the durations of tolerated warm and cold ischemia. However, no study has determined the optimal conditions of this technique. The aim of this work was to develop a preclinical model of DCD using abdominal normothermic oxygenated recirculation (ANOR). In short, our objectives are to characterize the mechanisms involved during ANOR and its impact on abdominal organs., Methods: We used Large White pigs weighing between 45 and 55 kg. After 30 minutes of potassium-induced cardiac arrest, the descending thoracic aorta was clamped and ANOR set up between the inferior vena cava and the abdominal aorta for 4 hours. Hemodynamic, respiratory and biochemical parameters were collected. Blood gasometry and biochemistry analysis were performed during the ANOR procedure., Results: Six ANOR procedures were performed. The surgical procedure is described and intraoperative parameters and biological data are presented. Pump flow rates were between 2.5 and 3 l/min. Hemodynamic, respiratory, and biochemical objectives were achieved under reproducible conditions. Interestingly, animals remained hemodynamically stable following the targeted protocol. Arterial pH was controlled, and natremia and renal function remained stable 4 hours after the procedure was started. Decreased hemoglobin and serum proteins levels, concomitant with increased lactate dehydrogenase activity, were observed as a consequence of the surgery. The serum potassium level was increased, owing to the extracorporeal circulation circuit., Conclusions: Our ANOR model is the closest to clinical conditions reported in the literature and will allow the study of the systemic and abdominal organ impact of this technique. The translational relevance of the pig will permit the determination of new biomarkers and protocols to improve DCD donor management.

As the impact of ischemia reperfusion injury on graft outcome is now well defined, efforts are made towards decreasing these lesions, typically through the improvement of preservation techniques. The use of pharmacological supplements which could be compatible with any preservation solution used by the transplant center and target specific pathways of IR is an interesting strategy to improve graft quality. However, the extensive number of studies showing the benefits a molecule in an animal model of IR without thorough mechanistic determination of the effects of this agent make it difficult to opt for specific pharmaceutical intervention. Herein we expose studies which demonstrate the benefits of several molecules relying on a thorough mechanical analysis of the events occurring during preservation, both at the cellular and the systemic levels. We believe this approach is the most appropriate to truly understand the potential benefits of a molecule and particularly to design a comprehensive pharmaceutical regiment, with several agents acting synergistically against IR, to improve organ preservation and graft outcome., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

In 1990's, use of machine perfusion for organ preservation has been abandoned because of improvement of preservation solutions, efficient without perfusion, easy to use and cheaper. Since the last 15 years, a renewed interest for machine perfusion emerged based on studies performed on preclinical model and seems to make consensus in case of expanded criteria donors or deceased after cardiac death donations. We present relevant studies highlighted the efficiency of preservation with hypothermic machine perfusion compared to static cold storage. Machines for organ preservation being in constant evolution, we also summarized recent developments included direct oxygenation of the perfusat. Machine perfusion technology also enables organ reconditioning during the last hours of preservation through a short period of perfusion on hypothermia, subnormothermia or normothermia. We present significant or low advantages for machine perfusion against ischemia reperfusion injuries regarding at least one primary parameter: risk of DFG, organ function or graft survival., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Decreasing organ quality is prompting research toward new methods to alleviate ischemia reperfusion injury (IRI). Oxidative stress and nuclear factor kappa beta (NF-κB) activation are well-described elements of IRI. We added cyclodextrin-complexed curcumin (CDC), a potent antioxidant and NF-κB inhibitor, to University of Wisconsin (UW) solution (Belzer's Solution, Viaspan), one of the most effective clinically approved preservative solutions. The effects of CDC were evaluated on pig endothelial cells and in an autologous donation after circulatory death (DCD) kidney transplantation model in large white pigs. CDC allowed rapid and lasting uptake of curcumin into cells. In vitro, CDC decreased mitochondrial loss of function, improved viability and lowered endothelial activation. In vivo, CDC improved function recovery, lowered histological injury and doubled animal survival (83.3% vs. 41.7%). At 3 months, immunohistochemical staining for epithelial-to-mesenchymal transition (EMT) and fibrosis markers was intense in UW grafts while it remained limited in the UW + CDC group. Transcriptional analysis showed that CDC treatment protected against up-regulation of several pathophysiological pathways leading to inflammation, EMT and fibrosis. Thus, use of CDC in a preclinical transplantation model with stringent IRI rescued kidney grafts from an unfavorable prognosis. As curcumin has proved well tolerated and nontoxic, this strategy shows promise for translation to the clinic., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Introduction: An elevated PSA and a negative prostate biopsy (PB) can be a false negative PB that ignores a prostate cancer (PCa) or a false positive PSA not related to PCa. The objective of this study was to analyze a group of patients who had a negative first BP for a PSA superior to 4 ng/mL and at least one additional PB and to compare these cases with controls who had the diagnosis PCa from the first PB., Methods: Retrospective single-center study comparing patients with an elevated PSA and repeat biopsy following a first negative PB and patients with PCa diagnosed from the first PB., Results: The 63 cases were younger than the 75 controls and had more often a normal digital rectal examination. Their prostate volume was larger and their number of PSA before the first PB lower: this corresponded to a lower PSA in the second (7/64), third (6/31), fourth (3/9) and sixth (1/1) PB. Among these cases with PCa, the length of core invaded by cancer and the total length of cancer of the entire PB were smaller than controls. In 76% of cases, the Gleason score among cases was 6 or less., Conclusion: PCa discovered on repeat biopsy had features of better prognosis than those of controls. We propose an algorithm for management of patients with elevated PSA and negative first PB., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)