Human epicardial fat has a beige profile and contains higher type 2 innate lymphoid cells than subcutaneous fat.

OBJECTIVE: Epicardial adipose tissue (EAT) is a visceral fat that has been associated with coronary artery disease and atrial fibrillation. Previous work has revealed that EAT exhibits beige features. METHODS: First, a new pan-genomic microarray analysis was performed on previously collected paired human EAT and thoracic subcutaneous AT (thSAT) from the EPICAR study (n = 31) to decipher a specific immune signature and its link with browning genes. Then, adaptive (T and B cells) and innate lymphoid cell (ILC1, ILC2, and ILC3) immunophenotyping assay panels, including CD127, CD117, and prostaglandin D2 receptor 2, were performed on prospectively collected paired human multiorgan donors (n = 18; INTERFACE study). RESULTS: In the EPICAR study, a positive correlation between the T helper cell subtype Th2 immune pathway and browning genes was found in EAT versus thSAT (r = 0.82; p < 0.0001). In the INTERFACE study, this correlation was also observed (r = 0.31; p = 0.017), and a preponderance of CD4+T cells, CD8+T cells, and a few B cells was observed in all ATs (p < 0.0001). An increase in ILCs was observed in visceral AT (VAT) (i.e., EAT + VAT; 30 ± 5 ILCs per gram of AT) compared with subcutaneous counterparts (i.e., thSAT + abdominal SAT; 8 ± 2 ILCs per gram of AT; p = 0.001), with ILC1 being the most frequent (ILC1 > ILC3 > ILC2). Numbers of ILCs per gram of AT correlated with several Th2 or browning genes (IL-13, TNF receptor superfamily member 9 [TNFRSF9], and alkaline phosphatase, biomineralization associated [ALPL]). Interestingly, a specific increase in EAT-ILC2 compared with other ATs was observed, including a significant proportion expressing CD69 and/or CD25 activation markers (97.9% ± 1.2%; p < 0.0001). Finally, more natural killer cells were observed in EAT + VAT than in thSAT + abdominal SAT (p = 0.01). Exclusion of patients with coronary artery disease in the EPICAR and INTERFACE studies did not modify the main findings. Gene expression phenotyping confirmed specific upregulation of Th2 pathway and browning genes (IL-33 and uncoupling protein 1 [UCP-1]) in EAT. CONCLUSIONS: This is the first study, to our knowledge, to provide a comparison between innate and adaptive lymphoid cells in human EAT. Further studies are ongoing to decipher whether these cells could be involved in EAT beiging.

Asymptomatic Bacteriuria and Urological Surgery: Risk Factor or Not? Results from the National and Multicenter TOCUS Database.

PURPOSE: Current guidelines recommend screening and treatment of asymptomatic bacteriuria prior to all urological surgeries breaching the mucosa. But few evidence is supporting this recommendation. At least, risk stratification for postoperative urinary tract infection to support this strategy is lacking. The aim of this study was to define the associated factors for postoperative febrile infectious complications (urinary tract infection 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 urinary tract infection or surgical site infection occurring within 30 days after surgery. RESULTS: rom 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 a positive mono/bi-microbial urine cultures (40%) and 20 had a polymicrobial urine cultures (19%). In multivariable analysis, urinary tract infections during the previous 12 months of surgery (OR 3.43; CI 95 2.07-5.66; P < .001), monomicrobial/bimicrobial preoperative urine culture (OR 3.68; CI 95 1.57-8.42; P 0.02), polymicrobial preoperative urine culture (OR 2.85; CI 95 1.52-5.14; P < .001), operative time (OR 1.09; CI 95 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.

Asymptomatic bacteriuria prior to partial and radical nephrectomy: To screen or not to screen? Results from the national and multicenter TOCUS database.

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.

Practices and knowledge of general practitioners on erectile dysfunction: A practice survey.

INTRODUCTION: Erectile dysfunction (ED) is a common and underestimated sexual disorder. This sexual concern, which should raise the suspicion of an underlying coronary artery disease, is rarely broached by general practitioners (GPs). The aim of this work was to establish an inventory of the practices and knowledge of general practitioners when faced with a case of ED. METHODS: This survey is a descriptive cross-sectional epidemiological study targeting GPs' practice. Answers were collected through a self-questionnaire, "KIKI SAIT?", online that explored: demographic data, level of practice and theoretical knowledge regarding ED. RESULTS: One hundred and seventy-seven GPs took part in this study. Regarding their practice, 80.2% of doctors expected the patient to bring up the subject. Few clinicians managed ED according to recommendations of the French Association of Urology. More than 30% referred the patient to a urologist, cardiologist or endocrinologist. In total, 57.6% of practitioners prescribed a phosphodiesterase 5 inhibitor (PDE5I) as first-line treatment. Regarding their knowledge, 67.8% of doctors considered their level of knowledge about PDE5I to be poor, 96.6% about intracavernosal injections, 88.7% about vacuum devices and 91% about penis rings. The main obstacle retained was the lack of medical knowledge (71.2%). Clinicians who rarely consulted for ED were less confident in explaining possible treatments (25/63 versus 18/113, P<0.001). CONCLUSION: Strengthening initial training and providing a practical algorithm for the management of ED could be useful to help general practitioners detect ED, which could be a sentinel of coronary heart disease.

Efficient pathway for men fertility preservation in testicular cancer or lymphoma: a cross-sectional study of national 2018 data.

BACKGROUND: In 15-49 years-old men, the main cancers are testicular cancer (TC) and lymphomas (L): freezing of ejaculated sperm is primarily used for male fertility preservation (FP) before cancer treatment. Our objective was to analyze the French FP rate in 15-49 years-old men diagnosed with TC or L in 2018. We designed a national descriptive cross-sectional study of sperm banking rate in men with a diagnosis of TC, Hodgkin L (HL) or non-Hodgkin L (NHL). From the French National Cancer Institute (INCa) 2018 data, we extracted the estimated incidence of TC and L in metropolitan France. From the 2018 activity report of CECOS network (Centers for Study and Banking of Eggs and Sperm), we extracted the number of men with TC or L who banked ejaculated sperm. We estimated the proportion of 15-49 years-old men diagnosed with TC or L who banked sperm. RESULTS: Among 15-49 years-old men, INCa estimated 38,048 new cancer diagnoses in metropolitan France in 2018: 2,630 TC and 3,913 L (943 HL and 2,970 NHL). The CECOS network provided data from 26/27 metropolitan centers (96% response rate): 1,079 sperm banking for men with TC, 375 for HL and 211 for NHL. We estimated that the 2018 sperm banking rate in France was 41% for TC, 40% for HL, and 7% for NHL. CONCLUSIONS: To our knowledge, our paper is the first cross-sectional study with multicenter and national data analyzing FP rate in cancer men: it suggests an efficient pathway for men to FP before cancer treatment, compared to previously published studies. Although sperm banking rate in 15-49 years-old men could definitely be improved, further studies should evaluate the information given to patients before gonadotoxic treatments, the factors associated with the absence of sperm banking and whether this lack of referral induces a loss of chance for these men.

RéSUMé: CONTEXTE: Chez les hommes de 15 à 49 ans, les principaux cancers sont le cancer du testicule (CT) et les lymhomes (L): la congélation de spermatozoïdes éjaculés est utilisée en première intention pour leur préservation de fertilité (PF) avant traitement du cancer. Notre objectif était d'analyser le taux de PF chez les hommes de 15 à 49 ans diagnostiqués avec un CT ou un L en 2018 en France. Nous avons réalisé une étude nationale transversale descriptive du taux de congelation de spermatozoïdes chez les hommes âgés de 15 à 49 ans diagnostiqués avec un CT, un L de Hodgkin (LH) ou un L non-Hodgkinien (LNH). A partir des données de l'Institut National du Cancer (INCa) de 2018, nous avons extrait l'incidence estimée de CT et de L en France métropolitaine. A partir des données du bilan d'activité 2018 de la Federation Française des CECOS (Centre d'Etude et de Conservation des Oeufs et du Sperme), nous avons extrait le nombre d'hommes avec un CT ou un L qui ont congelé leurs spermatozoïdes. Nous avons enfin estimé la proportion d'hommes de 15 à 49 ans diagnostiqués avec un CT ou un L qui ont congelé leurs spermatozoïdes. RéSULTATS: Chez les hommes de 15 à 49 ans, l'INCa a estimé en 2018 38 048 nouveaux cas de cancers diagnostiqués en France métropolitaine en 2018: 2 630 CT et 3 913 L (943 LH et 2 970 LNH). Le réseau des CECOS a produit les résultats issus de 26/27 centres métropolitains (taux de réponse de 96%): 1 079 congélations de sperme pour des hommes atteints de CT, 375 pour LH et 211 pour LNH. Nous avons estimé que le taux de congelation de spermatozoïdes de 2018 en France était de 41% pour le CT, 40% pour le LH et 7% pour le LNH. CONCLUSIONS: A notre connaissance, notre travail est la première étude transversale multicentrique de données nationales analysant le taux de PF chez les hommes atteints de cancer: il suggère un parcours patient efficace pour la PF des hommes avant traitement d'un cancer, par rapport aux études précédemment publiées. Bien que le taux de PF chez les hommes puisse certainemen être amélioré, des études futures devraient évaluer l'information donnée aux patients avant traitement gonadotoxique, les facteurs associés à l'absence de PF et si le défaut d'adressage au CECOS induit un perte de chance pour ces hommes. MOTS-CLéS: Chimiothérapie, Radiothérapie, Oncofertiité, Azoospermia, Paternité.

Reuse and Reprocessing of Endoscopic Instruments: Con.

Reprocessing of endoscopic equipment generates greenhouse gas emissions, releases toxic substances into the environment, and consumes large quantities of water. The use of alternative materials, such as single-use devices with a low carbon footprint and recycled materials, and reprocessing without the use of water and toxic products represent sustainable solutions.

Early Evaluation of a New French Surgery Course in the Best Practice of Dealing With Major Incidents and Mass Casualty Events.

OBJECTIVE: The main objective of this study is to evaluate the impact of a nationwide 5-month course aimed to prepare surgeons for Major Incidents through the acquisition of key knowledge and competencies. Learners' satisfaction was also measured as a secondary objective. DESIGN: This course was evaluated thanks to various teaching efficacy metrics, mainly based on Kirkpatrick's hierarchy in medical education. Gain in knowledge of participants was evaluated by multiple-choice tests. Self-reported confidence was measured with 2 detailed pre and post training questionnaires. SETTING: Creation in 2020 of a nationwide, optional and comprehensive Surgical Training in War and Disaster Situation as part of the French surgery residency program. In 2021, data was gathered regarding the impact of the course on participants' knowledge and competencies. PARTICIPANTS: The study included 26 students in the 2021 cohort (13 residents and 13 practitioners). RESULTS: Mean scores were significantly higher in the post-test compared to the pre-test, showing significant increase in participants' knowledge during the course: 73,3% vs. 47,3% respectively (p ≤ 0.001). Average learners' confidence scores to perform technical procedures showed at least a +1-point increase on the Likert scale for 65% of items tested (p ≤ 0.001). 89% of items showed at least a +1-point increase on the Likert scale when it came to average learners' confidence score on dealing with complicated situations (p ≤ 0.001). Our post-training satisfaction survey showed that 92% of all participants have noticed the impact of the course on their daily practice. CONCLUSION: Our study shows that the third level of Kirkpatrick's hierarchy in medical education was reached. This course therefore appears to be meeting the objectives set by the Ministry of Health. Being only 2 years old, it is on the road to gathering momentum and further development.

MRI lesion size is more important than the number of positive biopsy cores in predicting adverse features and recurrence after radical prostatectomy: implications for active surveillance criteria in intermediate-risk patients.

INTRODUCTION: To determine associations between prostate cancer (PCa) tumor burden measured on biopsy or multiparametric magnetic resonance imaging (mpMRI) and outcomes in intermediate-risk (IR) International Society of Urological Pathology (ISUP) grade 2 men managed with primary radical prostatectomy (RP). METHODS: This retrospective, multicenter study was conducted in eight referral centers. The cohort included IR PCa patients who had ISUP 2 at biopsy. We defined biopsy tumor burden as low/high based on the absence/presence of more than 25% positive cores. Tumor burden on imaging was defined as low/high based on maximum lesion diameter, <15 mm and ≥15 mm at mpMRI, respectively. The histological endpoint of the study was adverse features at RP, defined as ≥pT3a stage and/or lymph node invasion and/or ISUP ≥3 at final pathology. The clinical endpoint was biochemical recurrence (BCR) after RP. RESULTS: A total of 698 IR patients was included, of whom 335 (48%) had adverse features. In multivariate logistic regression analysis, there was no statistical association between tumor burden at biopsy and adverse features (p = 0.7). Tumor size ≥15 mm at mpMRI was significantly associated with adverse pathology (OR 1.65, 95%CI 1.14-2.39; p = 0.01). No significant association was observed between tumor burden at biopsy and BCR (p = 0.4). Tumor size ≥15 mm at mpMRI was significantly associated with BCR (HR 1.96, 95% CI 1.01-3.80; p = 0.04). CONCLUSIONS: Our data support extending the inclusion criteria to ISUP 2 men with >25% positive cores, provided they have a low tumor size at mpMRI (<15 mm). Prospective studies should be performed to validate these findings.

Is CIS a Contraindication to Hyperthermic Intravesical Chemotherapy (HIVEC) after BCG-Failure?

CIS of the bladder is associated with a high risk of progression. In the case of BCG failure, radical cystectomy should be performed. For patients who refuse or are ineligible, bladder-sparing alternatives are evaluated. This study aims to investigate the efficacy of Hyperthermic IntraVesical Chemotherapy (HIVEC) depending on the presence or absence of CIS. This retrospective, multicenter study was conducted between 2016 and 2021. Patients with non-muscle-invasive bladder cancer (NMIBC) with BCG failure received 6-8 adjuvant instillations of HIVEC. The co-primary endpoints were recurrence-free survival (RFS) and progression-free survival (PFS). A total of 116 consecutive patients met our inclusion criteria of whom 36 had concomitant CIS. The 2-year RFS rate was 19.9% and 43.7% in patients with and without CIS, respectively (p = 0.52). Fifteen patients (12.9%) experienced progression to muscle-invasive bladder cancer with no significant difference between patients with and without CIS (2-year PFS rate = 71.8% vs. 88.8%, p = 0.32). In multivariate analysis, CIS was not a significant prognostic factor in terms of recurrence or progression. In conclusion, CIS may not be considered a contraindication to HIVEC, as there is no significant association between CIS and the risk of progression or recurrence after treatment.

Expanding inclusion criteria for active surveillance in intermediate-risk prostate cancer: a machine learning approach.

PURPOSE: To develop new selection criteria for active surveillance (AS) in intermediate-risk (IR) prostate cancer (PCa) patients. METHODS: Retrospective study including patients from 14 referral centers who underwent pre-biopsy mpMRI, image-guided biopsies and radical prostatectomy. The cohort included biopsy-naive IR PCa patients who met the following inclusion criteria: Gleason Grade Group (GGG) 1-2, PSA < 20 ng/mL, and cT1-cT2 tumors. We relied on a recursive machine learning partitioning algorithm developed to predict adverse pathological features (i.e., ≥ pT3a and/or pN + and/or GGG ≥ 3). RESULTS: A total of 594 patients with IR PCa were included, of whom 220 (37%) had adverse features. PI-RADS score (weight:0.726), PSA density (weight:0.158), and clinical T stage (weight:0.116) were selected as the most informative risk factors to classify patients according to their risk of adverse features, leading to the creation of five risk clusters. The adverse feature rates for cluster #1 (PI-RADS ≤ 3 and PSA density < 0.15), cluster #2 (PI-RADS 4 and PSA density < 0.15), cluster #3 (PI-RADS 1-4 and PSA density ≥ 0.15), cluster #4 (normal DRE and PI-RADS 5), and cluster #5 (abnormal DRE and PI-RADS 5) were 11.8, 27.9, 37.3, 42.7, and 65.1%, respectively. Compared with the current inclusion criteria, extending the AS criteria to clusters #1 + #2 or #1 + #2 + #3 would increase the number of eligible patients (+ 60 and + 253%, respectively) without increasing the risk of adverse pathological features. CONCLUSIONS: The newly developed model has the potential to expand the number of patients eligible for AS without compromising oncologic outcomes. Prospective validation is warranted.

Efficacy of hyperthermic intravesical chemotherapy (HIVEC) in patients with non-muscle invasive bladder cancer after BCG failure.

PURPOSE: To evaluate hyperthermic intravesical chemotherapy (HIVEC) efficacy regarding 1-year disease-free survival (RFS) rate and bladder preservation rate in patients with non-muscle invasive bladder cancer (NMIBC) who fail bacillus Calmette-Guérin (BCG) therapy. METHODS: This is a multicenter retrospective series from a national database (7 expert centers). Between January 2016 and October 2021, patients treated with HIVEC for NMIBC who failed BCG have been included in our study. These patients had a theoretical indication for cystectomy but were ineligible for surgery or refused it. RESULTS: A total of 116 patients treated with HIVEC and with a follow-up > 6 months were included in this study and retrospectively analyzed. The median follow-up was 20.6 months. The 12 month-RFS (recurrence-free survival) rate was 62.9%. The bladder preservation rate was 87.1%. Fifteen patients (12.9%) progressed to muscle infiltration, three of them having a metastatic disease at the time of progression. Predictive factors of progression were T1 stage, high grade and very high-risk tumors according to the EORTC classification. CONCLUSION: Chemohyperthermia using HIVEC achieved an RFS rate of 62.9% at 1 year and enabled a bladder preservation rate of 87.1%. However, the risk of progression to muscle-invasive disease is not negligible, particularly for patients with very high-risk tumors. In these patients who fail BCG, cystectomy should remain the standard of care and HIVEC may be discussed cautiously for patients who are not eligible for surgery and well informed of the risk of progression.

Life Cycle Assessment of Reusable and Disposable Cystoscopes: A Path to Greener Urological Procedures.

BACKGROUND: The environmental impact of reusable and disposable devices is unclear; reuse is expected to reduce the carbon footprint, but the environmental impact of reprocessing of reusable devices is increasingly being questioned. OBJECTIVE: The aim was to provide the first rigorous life cycle assessment of reusable and disposable flexible cystoscopes. DESIGN, SETTING, AND PARTICIPANTS: We performed a life cycle assessment of reusable flexible cystoscopes and the aS4C single-use cystoscope (aScope; Ambu, Ballerup, Denmark). For the aScope, the complete lifespan of the scope was evaluated, including raw material extraction, material formulation, component production, product assembly, distribution, transportation after use, and final disposal. For reusable cystoscopes, we limited our analysis to their reprocessing, using a model consisting of standard high-level disinfection with peracetic acid. The environmental impact was evaluated by an independent third-party consulting company APESA (Technopole Hélioparc, Pau, France) dedicated to such risk assessments. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The environmental footprint of both cystoscopes was assessed using five environmental impact categories, namely, climate change, mineral resource depletion, ecotoxicity, acidification, and eutrophication. To perform the life cycle assessment, Simapro v9.3.3 software was used and the Ecoinvent v3.5 database was employed as the primary life cycle inventory database. A Monte Carlo analysis was used to account for the inherent uncertainty in life cycle inventory data and the variability in material and energy consumption for each type of flexible cystoscope. RESULTS AND LIMITATIONS: By only comparing the disinfection reprocessing of reusable cystoscopes with the complete lifespan of the single-use cystoscope, the use of the aScope would allow a reduction of at least 33% in the climate change category, 50% in the mineral resources' depletion category, 51% in the ecotoxicity category, 71% in the acidification category, and 49% in the eutrophication category. Our results cannot be generalized to all health care facilities as we studied only one type of reprocessing method and one disposable flexible cystoscope. CONCLUSIONS: Disinfection reprocessing of reusable cystoscopes was found to have a significantly larger environmental footprint and impact than the whole lifespan of the single-use cystoscope aScope. PATIENT SUMMARY: Using a cradle-to-grave life cycle analysis, we showed that the environmental footprint of a flexible cystoscopy procedure can be reduced by using a disposable cystoscope instead of a reusable cystoscope.

Climate-smart Actions in the Operating Theatre for Improving Sustainability Practices: A Systematic Review.

CONTEXT: Surgical activity contributes to global warming though the production of greenhouse gases and consumption of resources. To date, no clinical practice guidelines have been made to promote and implement climate-smart actions. OBJECTIVE: To perform a systematic review of the available actions that could limit CO2 emission in the operating room (OR) and their potential benefits upon the environment, whilst preserving quality of care. EVIDENCE ACQUISITION: MEDLINE and Cochrane databases were searched from January 1, 1990 to April 2021. We included studies assessing carbon footprint (CF) in the OR and articles detailing actions that limit or reduce CF. EVIDENCE SYNTHESIS: Thirty-eight studies met the inclusion criteria. We identified six core climate-smart actions: (1) waste reduction by segregation; (2) waste reduction by recycling, reuse, and reprocessing; (3) sterilisation; (4) anaesthesia gas management; and (5) improvement of energy use. Quantitative analysis regarding the CF was not possible due to the lack of homogeneous data. For climate-smart actions, the analysis was limited by discrepancies in study scope and in the methodology of CO2 emission calculation. Improvement of education and awareness was found to have an important impact on waste segregation and reduction. Waste management is the area where health care workers could have the strongest impact, whereas the main field to reduce CF in the OR was found to be energy consumption. CONCLUSIONS: This review provides arguments for many climate-smart actions that could be implemented in our daily practice. Improving awareness and education are important to act collectively in a sustainable way. Further studies are mandatory to assess the impact of these climate-smart actions in the OR. PATIENT SUMMARY: We performed a systematic review of the available scientific literature to reference all the climate-smart actions proposed to improve the sustainability of surgical activities. Waste segregation, waste reduction and recycling, reuse and reprocessing, sterilisation, anaesthesia gas changes, and improvement of energy use in the operating room were found to be the main areas of research. There is still a long way to go to homogenise and improve the quality of our climate-smart actions.

Antitumor immunity induced by antibody-based natural killer cell engager therapeutics armed with not-alpha IL-2 variant.

Harnessing innate immunity is emerging as a promising therapeutic approach in cancer. We report here the design of tetraspecific molecules engaging natural killer (NK) cell-activating receptors NKp46 and CD16a, the ß-chain of the interleukin-2 receptor (IL-2R), and a tumor-associated antigen (TAA). In vitro, these tetraspecific antibody-based natural killer cell engager therapeutics (ANKETs) induce a preferential activation and proliferation of NK cells, and the binding to the targeted TAA triggers NK cell cytotoxicity and cytokine and chemokine production. In vivo, tetraspecific ANKETs induce NK cell proliferation and their accumulation at the tumor bed, as well as the control of local and disseminated tumors. Treatment of non-human primates with CD20-directed tetraspecific ANKET leads to CD20+ circulating B cell depletion, with minimal systemic cytokine release and no sign of toxicity. Tetraspecific ANKETs, thus, constitute a technological platform for harnessing NK cells as next-generation cancer immunotherapies.

Radical nephroureterectomy for UTUC conferred survival benefits irrespective of age and comorbidities.

PURPOSE: We investigated the effects of age, American Society of Anesthesiologists Physical Status Classification (ASA) grading and Charlson Comorbidity Index (CCI) on the survival outcomes of upper tract urothelial carcinoma (UTUC). METHODS: The CROES-UTUC registry was an international, multicenter study on patients with UTUC. Primary outcomes were overall survival (OS) and disease-free survival (DFS). Kaplan-Meier and multivariate Cox regression analyses were performed by stratifying patients according to their age (≤ 70 and > 70 years old) and ASA grade (I-II and III-V)/CCI (0-1 and ≥ 2). RESULTS: A total of 2352 patients were included in this study. Patients aged ≤ 70 years with ASA grading of I-II (p = 0.002), and patients aged ≤ 70 years with a CCI of 0-1 (p = 0.002) had the best OS. Upon multivariate analysis, both in patients aged ≤ 70 and > 70 years, ASA grading and CCI were not significantly associated with OS. Patients aged ≤ 70 years with ASA grading of III-IV (p = 0.024) had the best DFS. When stratified according to age and CCI, no significant difference in DFS was noted. Upon multivariate analysis, radical nephroureterectomy (RNU) was significantly associated with better DFS in patients aged ≤ 70 and > 70 years; CCI of ≥ 3 was significantly associated with worse DFS in patients ≤ 70 years; ASA grading was not associated with DFS in patients aged ≤ 70 and > 70 years. CONCLUSIONS: A high ASA grading and CCI should not be considered contraindications for RNU. RNU should be considered even in elderly patients when it is deemed feasible and achievable after a geriatric assessment.

An enhanced level of VCAM in transplant preservation fluid is an independent predictor of early kidney allograft dysfunction.

Background: We aimed to evaluate whether donor-related inflammatory markers found in kidney transplant preservation fluid can associate with early development of kidney allograft dysfunction. Methods: Our prospective study enrolled 74 consecutive donated organs who underwent kidney transplantation in our center between September 2020 and June 2021. Kidneys from 27 standard criteria donors were allocated to static cold storage and kidneys from 47 extended criteria donors to hypothermic machine perfusion. ELISA assessment of inflammatory biomarkers (IL-6, IL6-R, ICAM, VCAM, TNFα, IFN-g, CXCL1 and Fractalkine) was analyzed in view of a primary endpoint defined as the occurrence of delayed graft function or slow graft function during the first week following transplantation. Results: Soluble VCAM levels measured in transplant conservation fluid were significantly associated with recipient serum creatinine on day 7. Multivariate stepwise logistic regression analysis identified VCAM as an independent non-invasive predictor of early graft dysfunction, both at 1 week (OR: 3.57, p = .04, 95% CI: 1.06-12.03) and 3 Months (OR: 4.039, p = .034, 95% CI: 1.11-14.73) after transplant surgery. Conclusions: This prospective pilot study suggests that pre-transplant evaluation of VCAM levels could constitute a valuable indicator of transplant health and identify the VCAM-CD49d pathway as a target to limit donor-related vascular injury of marginal transplants.