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Abstract Background Sepsis is characterized by a dysregulated immune response and metabolic alterations, including decreased high-density lipoprotein cholesterol (HDL-C) levels. HDL exhibits beneficial properties, such as lipopolysaccharides (LPS) scavenging, exerting anti-inflammatory effects and providing endothelial protection. We investigated the effects of CER-001, an engineered HDL-mimetic, in a swine model of LPS-induced acute kidney injury (AKI) and a Phase 2a clinical trial, aiming to better understand its molecular basis in systemic inflammation and renal function. Methods We carried out a translational approach to study the effects of HDL administration on sepsis. Sterile systemic inflammation was induced in pigs by LPS infusion. Animals were randomized into LPS (n = 6), CER20 (single dose of CER-001 20 mg/kg; n = 6), and CER20 × 2 (two doses of CER-001 20 mg/kg; n = 6) groups. Survival rate, endothelial dysfunction biomarkers, pro-inflammatory mediators, LPS, and apolipoprotein A-I (ApoA-I) levels were assessed. Renal and liver histology and biochemistry were analyzed. Subsequently, we performed an open-label, randomized, dose-ranging (Phase 2a) study included 20 patients with sepsis due to intra-abdominal infection or urosepsis, randomized into Group A (conventional treatment, n = 5), Group B (CER-001 5 mg/kg BID, n = 5), Group C (CER-001 10 mg/kg BID, n = 5), and Group D (CER-001 20 mg/kg BID, n = 5). Primary outcomes were safety and efficacy in preventing AKI onset and severity; secondary outcomes include changes in inflammatory and endothelial dysfunction markers. Results CER-001 increased median survival, reduced inflammatory mediators, complement activation, and endothelial dysfunction in endotoxemic pigs. It enhanced LPS elimination through the bile and preserved liver and renal parenchyma. In the clinical study, CER-001 was well-tolerated with no serious adverse events related to study treatment. Rapid ApoA-I normalization was associated with enhanced LPS removal and immunomodulation with improvement of clinical outcomes, independently of the type and gravity of the sepsis. CER-001-treated patients had reduced risk for the onset and progression to severe AKI (stage 2 or 3) and, in a subset of critically ill patients, a reduced need for organ support and shorter ICU length of stay. Conclusions CER-001 shows promise as a therapeutic strategy for sepsis management, improving outcomes and mitigating inflammation and organ damage. Trial registration The study was approved by the Agenzia Italiana del Farmaco (AIFA) and by the Local Ethic Committee (N° EUDRACT 2020–004202-60, Protocol CER-001- SEP_AKI_01) and was added to the EU Clinical Trials Register on January 13, 2021.

Nighttime organ transplantation aims to decrease cold ischemia duration, yet conflicting data exists on its impact on graft function and perioperative complications. This multicenter TRANSPLANT’AFUF study including 2,854 patients, transplanted between 1 January 2011, and 31 December 2022, investigated nighttime kidney transplantation’s impact (8:00 p.m.–8:00 a.m.) versus daytime (8:00 a.m.–8:00 p.m.) on surgical complications and graft survival. Overall, 2043 patients (71.6%) underwent daytime graft, while 811 (28.4%) underwent nighttime graft. No impact was observed of timing of graft surgery on graft survival with a median survival of 98 months and 132 months for daytime and nightime grafting, respectively (p = 0.1749). Moreover, no impact was observed on early surgical complications (Clavien I-II = 20.95% for DG and 20.10% for NG; Clavien III-IV-V = 15.42% for DG and 12.94% for NG; p = 0.0889) and late complications (>30 days) (Clavien I-II = 6.80% for DG and 5.67% for NG; Clavien III-IV-V = 12.78% for DG and 12.82% for NG; p = 0.2444). Noteworthy, we found a significant increase in Maastricht 3 donors’ rates in nighttime transplantation (5.53% DG vs. 21.45% NG; p < 0.0001). In conclusion, nighttime kidney transplantation did not impact early/late surgical complications nor graft survival.

Introduction: Water vapor thermal therapy (WVTT; REZUM™; Boston, USA) offers symptom relief with reduced risks of complications in patients with lower urinary tract symptoms (LUTS) related to benign prostatic obstruction (BPO). WVTT therapy has been validated in the pivotal study in men with smaller prostates (< 80 cc). Yet, its feasibility for larger prostates (≥ 80 cc) remains underexplored. Methods: This retrospective study assessed WVTT efficacy and safety in 131 patients with symptomatic BPH treated between January 2022 and March 2024. Patients were categorized based on prostate size: smaller prostates (SP) (< 80 cc) and larger prostates (LP) (≥ 80 cc). Baseline characteristics, treatment specifics, and post-procedure outcomes—including retreatment rates, symptom scores, and adverse events (AEs)—were recorded. All patients who required surgical retreatment underwent Holmium laser enucleation of the prostate (HoLEP). Statistical analyses compared results between groups over 6- and 12-month follow-up periods. Results: Among the 131 patients, 48 (37%) had LP, with a median volume of 93 cc (Interquartile range (IQR) 88–110). Patients with LP experienced more non-serious AEs, primarily hematuria (p = 0.001), although serious AEs were similar across groups and limited to urinary retention (p = 0.35). At 6 months postoperatively, LP patients had a higher PVR (42 mL(IQR 21–75) vs. 21 mL (IQR2-40); p = 0.032), though this resolved by 12 months. No significant differences were observed between the groups in IPSS, maximum flow rate (Qmax), or erectile function (IIEF-5) scores at either follow-up point. Medical retreatment rates at 12 months were similar (LP: 4% vs. SP: 7%; p = 0.39), as were surgical retreatment rates (LP: 2% vs. SP: 2%; p = 0.51). Ejaculatory function was largely preserved in both groups (LP: 96%, SP: 95%). Conclusion: WVTT therapy in LP is associated with a higher risk of minor post-operative AEs, with similar functional outcomes at one year compared to SP. Longer follow-up studies are needed to compare the durability of treatment in LP. [ABSTRACT FROM AUTHOR]

Upper tract urothelial carcinoma (UTUC) is a rare and challenging-to-treat malignancy. In most patients it is a sporadic tumor entity, less commonly it falls on the spectrum of Lynch syndrome, an autosomal dominant familial tumor syndrome. Localized UTUC with high-risk features as well as the metastatic disease scenario might require systemic therapy. Platinum-based combination chemotherapy is currently the recommended management option. However, the introduction of immune checkpoint inhibitors into the therapeutic armamentarium has led to a paradigm shift in treatment standards. Immunotherapy has been shown to be safe and effective in treating at least metastatic UTUC, although UTUC-specific high-level evidence is still lacking. Recent technological advances and noteworthy research efforts have greatly improved the general understanding of the biological landscape of UTUC. According to the main findings, UTUC represent a particular subtype of urothelial carcinoma frequently associated with activated FGFR3 signaling, a luminal–papillary phenotype and a T-cell-depleted microenvironment. This improved knowledge promises precision oncology approaches that match treatment decision strategies and genomic profile to ultimately result in better clinical outcomes. The aim of this review was to summarize the main currently available evidence on immune checkpoint inhibition and clinical genomics in UTUC.

Purpose: To systematically evaluate and synthesize the existing literature on environmental aspects related to urological endoscopy procedures. Methods: A literature search was conducted through January 2024 using PubMed/Medline, and Web of Science databases. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed to identify eligible studies. Results: The review reveals varying environmental footprints across procedures. In cystoscopy, studies suggest that disposable scopes result in decreased waste and water usage compared to reusable ones. However, life-cycle assessments did not conclusively highlight environmental superiority in favor of disposable devices. This discrepancy might dwell in the reprocessing methods used for the reusable cystoscopes that vary greatly among centers. For ureteroscopy, studies tend to show comparable carbon footprints for disposable and reusable scopes. Regarding transurethral resection of bladder tumors, a shift towards day-case surgery is associated with a substantial reduction in carbon emissions. Transurethral prostatic surgery assessments reveal significant discrepancies in the carbon footprints of disposable minimally invasive surgical devices, highlighting the need for recycling programs and manufacturing modifications. Conclusions: This review shed light on the necessity to develop strategies to reduce environmental impact such as individual assessments of single-use devices, optimizing reusable scope reprocessing, reconsidering the use of draping during cystoscopies, and minimizing hospital stays. This study serves as a call to industries to conduct similar audits and standardized studies for healthcare products and services, fostering evidence-based decisions to mitigate the environmental impact of urological endoscopy procedures. [ABSTRACT FROM AUTHOR]

Le Comité de cancérologie de l'Association française d'urologie propose une mise à jour des recommandations dans la prise en charge du cancer de la prostate (CaP) récidivé et/ou métastatique. Une revue systématique de la littérature de 2022 à 2024 a été conduite par le CCAFU concernant les éléments de prise en charge thérapeutique du CaP en récidive après traitement local ou métastatique, en évaluant les références avec leur niveau de preuve. L'imagerie moléculaire est le bilan standard de la récidive après traitement local. Sa réalisation ne doit pas retarder le traitement de rattrapage précoce. La suppression androgénique (SAd) est le pilier du traitement du CaP métastatique. L'intensification de la SAd est désormais un standard dans la prise en charge du CaP métastatique, associant au moins une hormonothérapie de nouvelle génération (HTNG). Pour les patients d'emblée métastatiques au diagnostic de haut volume, un traitement par docétaxel en plus de l'association SAd + HTNG peut être discuté pour les patients éligibles. Chez les patients avec un CaP résistant à la castration (CPRC), les inhibiteurs de PARP et radiothérapie interne vectorisée par ligands du PSMA sont de nouvelles options thérapeutiques. La combinaison et le séquençage des traitements dépendent de nombreux facteurs (caractéristiques du patient et de la maladie, lignes précédentes, statut génomique, imagerie moléculaire). Cette actualisation des recommandations françaises doit contribuer à améliorer la prise en charge des patients porteurs d'un CaP en récidive ou métastatique. The Oncology Committee of the French Urology Association is proposing updated recommendations for the management of recurrent and/or metastatic prostate cancer (PCa). A systematic review of the literature from 2022 to 2024 was conducted by the CCAFU on the elements of therapeutic management of PCa in recurrence after local or metastatic treatment, evaluating the references with their level of evidence. Molecular imaging is the standard assessment of recurrence after local treatment. It should not delay early remedial treatment. Androgen deprivation therapy (ADT) is the main stay of treatment for metastatic PCa. Intensification of ADT is now the standard treatment for metastatic PCa, involving at least one new-generation hormone therapy (ARPI). For patients with high-volume metastatic disease at the time of diagnosis, treatment with docetaxel in addition to ADT + ARPI may be discussed for eligible patients. In patients with castration-resistant PCa (CRPC), PARP inhibitors and PSMA radioligand therapy are new treatment options. The combination and sequencing of treatments depend on many factors (patient and disease characteristics, previous lines, genomic status, molecular imaging). This update of French recommendations should help to improve the management of patients with recurrent or metastatic PCa. [ABSTRACT FROM AUTHOR]

Le but du comité de cancérologie de l'Association française d'urologie est de proposer une mise à jour des recommandations dans le diagnostic et la prise en charge du cancer de la prostate (CaP) localisé. Une revue systématique de la littérature de 2022 à 2024 a été conduite par le CCAFU concernant les éléments de diagnostic et de prise en charge thérapeutique du CaP localisé, en évaluant les références avec leur niveau de preuve. Les recommandations précisent la génétique, l'épidémiologie et les moyens diagnostiques du CaP, les notions de dépistage et de détection précoce. L'IRM, examen d'imagerie de référence du cancer localisé, est recommandée avant la réalisation de biopsies prostatiques. L'imagerie moléculaire est une option pour la réalisation du bilan d'extension. La voie transpérinéale permet de réduire les risques infectieux. La surveillance active est le traitement de référence pour les tumeurs de faible risque évolutif. Les moyens thérapeutiques sont détaillés, et recommandés en fonction des situations cliniques. Cette actualisation des recommandations françaises doit contribuer à améliorer la prise en charge du CaP localisé. The aim of the Oncology Committee of the French Urology Association is to propose updated recommendations for the diagnosis and management of localised prostate cancer (PCa). A systematic review of the literature from 2022 to 2024 was conducted by the CCAFU on the elements of diagnosis and therapeutic management of localised PCa, evaluating references with their level of evidence. The recommendations set out the genetics, epidemiology and diagnostic methods of PCa, as well as the concepts of screening and early detection. MRI, the reference imaging test for localised cancer, is recommended before prostate biopsies are performed. Molecular imaging is an option for extension assessment. The transperineal route reduces the risk of infection. Active surveillance is the standard treatment for tumours with a low risk of progression. Therapeutic methods are described in detail, and recommended according to the clinical situation. This update of French recommendations should help to improve the management of localised PCa. [ABSTRACT FROM AUTHOR]

Although it is the gold standard for assessing the malignancy of thyroid nodules (TNs) preoperatively, the cytological analysis of fine-needle aspiration cytology (FNAC) samples results in 20–30% of cases in indeterminate lesions (ITNs). As two-thirds of these lesions will appear benign after diagnostic surgery, improved preoperative diagnostic methods need to be developed. In this pilot study, we evaluate if the metabolomic profiles of liquid-based (CytoRich®) FNAC samples of benign and malignant nodules can allow the molecular diagnosis of TNs. We performed untargeted metabolomic analyses with CytoRich® FNAC in a monocentric retrospective study. The cohort was composed of cytologically benign TNs, histologically benign or papillary thyroid carcinomas (PTCs) cytologically ITNs, and suspicious/malignant TNs histologically confirmed as PTCs. The diagnostic performance of the identified metabolomic signature was assessed using several supervised classification methods. Seventy-eight patients were enrolled in the study. We identified 7690 peaks, of which 2697 ions were included for further analysis. We selected a metabolomic signature composed of the top 15 metabolites. Among all the supervised classification methods, the supervised autoencoder deep neural network exhibited the best performance, with an accuracy of 0.957 (0.842–1), an AUC of 0.945 (0.833–1), and an F1 score of 0.947 (0.842–1). Here, we report a promising new ancillary molecular technique to differentiate PTCs from benign TNs (including among ITNs) based on the metabolomic signature of FNAC sample fluids. Further studies with larger cohorts are now needed to identify a larger number of biomarkers and obtain more robust signatures.

Although lymphonodal dissection is well-accepted for muscle-invasive bladder cancer management, its role is still debated during radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). The aim of this study was to summarize the current knowledge concerning the indication, anatomical template, prognostic, and therapeutic roles of lymph node dissection (LND) performed at the time of RNU. Quality control markers, such as the number of lymph nodes (LN) removed, lymph node density, and safety of the different surgical approaches, were assessed. We performed a narrative review using the PubMed and ClinicalTrials.gov databases. We identified and analyzed articles based on the practice and the role of lymph node dissection for non-metastatic UTUC. There are no clear guidelines regarding the indication of LND for UTUC, but aggressive tumors may beneficiate from lymphadenectomy since lymph node invasion is a clear independent poor prognostic factor, allowing for adjuvant treatments. It seems that an extended lymphadenectomy may provide therapeutic advantages as a higher number of nodes removed may be related to the removal of undetected LNs micrometastases and a subsequent improvement in recurrence rate and cancer-specific survival. Clear anatomical templates are thus needed based on the location and the laterality of the primary tumor.

BackgroundSince 2010, nationwide networks of reference centers for sarcomas (RREPS/NETSARC/RESOS) collected and prospectively reviewed all cases of sarcomas and connective tumors of intermediate malignancy (TIM) in France.MethodsThe nationwide incidence of sarcoma or TIM (2013-2016) was measured using the 2013 WHO classification and confirmed by a second independent review by expert pathologists. Simple clinical characteristics, yearly variations and correlation of incidence with published clinical trials are presented and analyzed.ResultsOver 150 different histological subtypes are reported from the 25172 patients with sarcomas (n = 18712, 74,3%) or TIM (n = 6460, 25.7%), with n = 5838, n = 6153, n = 6654, and n = 6527 yearly cases from 2013 to 2016. Over these 4 years, the yearly incidence of sarcomas and TIM was therefore 70.7 and 24.4 respectively, with a combined incidence of 95.1/106/year, higher than previously reported. GIST, liposarcoma, leiomyosarcomas, undifferentiated sarcomas represented 13%, 13%, 11% and 11% of tumors. Only GIST, as a single entity had a yearly incidence above 10/106/year. There were respectively 30, 64 and 66 different histological subtypes of sarcomas or TIM with an incidence ranging from 10 to 1/106, 1-0.1/106, or < 0.1/106/year respectively. The 2 latter incidence groups represented 21% of the patients with 130 histotypes. Published phase III and phase II clinical trials (pConclusionsThis nationwide registry of sarcoma patients, with exhaustive histology review by sarcoma experts, shows that the incidence of sarcoma and TIM is higher than reported, and that tumors with a very low incidence (1