Open versus Minimally Invasive Nephroureterectomy: Contemporary Analysis from a Wide National Population-Based Database.

BACKGROUND: It is generally perceived that minimally invasive nephroureterectomy (MINU), especially in the form of robotic-assisted laparoscopy, is gaining an increasing role in many institutions. OBJECTIVE: The aim of our study was to investigate contemporary trends in the adoption of MINU in the United States compared with open nephroureterectomy (ONU). METHODS: Patients who underwent ONU or MINU between 2011 and 2021 were retrospectively analyzed using PearlDiver Mariner, an all-payer insurance claims database. International Classification of Diseases diagnosis and procedure codes were used to identify the type of surgical procedure, patients' characteristics, social determinants of health (SDOH), and perioperative complications. The primary objective assessed different trends and costs in NU adoption, while secondary objectives analyzed factors influencing the postoperative complications, including SDOH. Outcomes were compared using multivariable regression models. RESULTS: Overall, 15,240 patients underwent ONU (n = 7675) and MINU (n = 7565). Utilization of ONU declined over the study period, whereas that of MINU increased from 29 to 72% (p = 0.01). The 60-day postoperative complication rate was 23% for ONU and 19% for MINU (p < 0.001). At multivariable analysis, ONU showed a significantly higher risk of postoperative complications (odds ratio 1.33, 95% CI 1.20-1.48). Approximately 5% and 9% of patients reported at least one SDOH at baseline for both ONU and MINU (p < 0.001). CONCLUSIONS: Contemporary trend analysis of a large national dataset confirms that there has been a significant shift towards MINU, which is gradually replacing ONU. A minimally invasive approach is associated with lower risk of complications. SDOH are non-clinical factors that currently do not have an impact on the outcomes of nephroureterectomy.

Trimodal therapy vs radical cystectomy in patients with muscle-invasive bladder cancer: a systematic review and meta-analysis of comparative studies.

OBJECTIVE: To perform a systematic review and meta-analysis of trials comparing trimodal therapy (TMT) and radical cystectomy (RC), evaluating differences in terms of oncological outcomes, quality of life, and costs. MATERIALS AND METHODS: In July 2023, a literature search of multiple databases was conducted to identify studies analysing patients with cT2-4 N any M0 muscle-invasive bladder cancer (MIBC; Patients) receiving TMT (Intervention) compared to RC (Comparison), to evaluate survival outcomes, recurrence rates, costs, and quality of life (Outcomes). The primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS) and metastasis-free survival (MFS). Hazard ratios (HRs) were used to analyse survival outcomes according to different treatment modalities and odds ratios were used to evaluate the likelihood of receiving each type of treatment according to T stage. RESULTS: No significant difference in terms of OS was observed between RC and TMT (HR 1.07, 95% confidence interval [CI] 0.81-1.4; P = 0.6), even when analysing radiation therapy regimens ≥60 Gy (HR 1.02, 95% CI 0.69-1.52; P = 0.9). No significant difference was observed in CSS (HR 1.12, 95% CI 0.79-1.57, P = 0.5) or MFS (HR 0.88, 95% CI 0.66-1.16; P = 0.3). The mean cost of TMT was significantly higher than that of RC ($289 142 vs $148 757; P < 0.001), with greater effectiveness in terms of cost per quality-adjusted life-year. TMT ensured significantly higher general quality-of-life scores. CONCLUSION: Trimodal therapy appeared to yield comparable oncological outcomes to RC concerning OS, CSS and MFS, while providing superior patient quality of life and cost effectiveness.

Robot-assisted nephroureterectomy: surgical and mid-term oncological outcomes in over 1100 patients (ROBUUST 2.0 collaborative group).

OBJECTIVE: To analyse surgical, functional, and mid-term oncological outcomes of robot-assisted nephroureterectomy (RANU) in a contemporary large multi-institutional setting. PATIENTS AND METHODS: Data were retrieved from the ROBotic surgery for Upper tract Urothelial cancer STtudy (ROBUUST) 2.0 database, an international, multicentre registry encompassing data of patients with upper urinary tract urothelial carcinoma undergoing curative surgery between 2015 and 2022. The analysis included all consecutive patients undergoing RANU except those with missing data in predictors. Detailed surgical, pathological, and postoperative functional data were recorded and analysed. Oncological time-to-event outcomes were: recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). Survival analysis was performed using the Kaplan-Meier method, with a 3-year cut-off. A multivariable Cox proportional hazard model was built to evaluate predictors of each oncological outcome. RESULTS: A total of 1118 patients underwent RANU during the study period. The postoperative complications rate was 14.1%; the positive surgical margin rate was 4.7%. A postoperative median (interquartile range) estimated glomerular filtration rate decrease of -13.1 (-27.5 to 0) mL/min/1.73 m2 from baseline was observed. The 3-year RFS was 59% and the 3-year MFS was 76%, with a 3-year OS and CSS of 76% and 88%, respectively. Significant predictors of worse oncological outcomes were bladder-cuff excision, high-grade tumour, pathological T stage ≥3, and nodal involvement. CONCLUSIONS: The present study contributes to the growing body of evidence supporting the increasing adoption of RANU. The procedure consistently offers low surgical morbidity and can provide favourable mid-term oncological outcomes, mirroring those of open NU, even in non-organ-confined disease.

Single-port robot-assisted simple prostatectomy: techniques and outcomes.

PURPOSE: To describe the surgical techniques and to analyse the outcomes of single-port robot-assisted simple prostatectomy (SP RASP) procedure for the surgical treatment of benign prostatic hyperplasia (BPH). METHODS: Three databases (PubMed®, Web of Science™, and Scopus®) were queried to identify studies reporting on the technical aspects and outcomes of SP RASP. Different combinations of keywords were used, according to a free-text protocol, to identify retrospective and prospective studies, both comparative and non-comparative, systematic reviews (SR) and meta-analysis (MA) describing surgical techniques for SP RASP and the associated surgical and functional outcomes. RESULTS: The transvesical approach represents the most common approach for SP RASP. A decrease in terms of estimated blood loss was observed when SP RASP was compared to open simple prostatectomy (OSP) and multi-port (MP) RASP. Furthermore, this technique allowed for a shorter length of hospital stay (LoS) and a lower post-operative complication rate, compared to OSP. Post-operative subjective and objective functional outcomes are satisfying and comparable to OSP and MP RASP. CONCLUSION: SP RASP represents a safe and feasible approach for the surgical management of BPH. It provides comparable surgical and functional outcomes to MP RASP, enabling for minimal invasiveness, enhanced recovery, and potential for improving patient care.

Upfront versus deferred cytoreductive nephrectomy following targeted or immunotherapy: a population-based propensity score-matched analysis of perioperative complications.

PURPOSE: To evaluate the incidence of postoperative complications after cytoreductive nephrectomy (CN) following first-line treatment for metastatic renal cell carcinoma (mRCC), and to compare it with postoperative complications of upfront CN. METHODS: For this population-based retrospective study, the PearlDiver Mariner database (PearlDiver Technologies, Colorado Springs, CO), a database of insurance billing records was analyzed. Using relevant ICD-9/10 and CPT codes, patients diagnosed with mRCC between 2011 and 2021, who received first-line systemic molecular therapy (SMT), either tyrosine kinase inhibitors (TKI) or immune-checkpoint inhibitors (ICI), were identified. The selected population was stratified into two cohorts according to the timing of CN (deferred: after SMT vs. upfront: before SMT). Propensity-score matching (PSM) was performed as per baseline patients' characteristics to control for potential confounders between the two cohorts. The primary outcome was to compare 30-day postoperative complications rate between patients undergoing upfront vs. deferred CN. RESULTS: After PSM, 162 patients who received upfront CN were compared with 162 patients who underwent deferred CN. The overall rate of 30-day postoperative complications was statistically significantly higher in patients undergoing deferred CN (33.9%), compared to patients treated with upfront CN (21%, p < 0.01). In addition, the rate of both medical (26.5% vs. 14.2%, p < 0.01) and surgical (14.8 vs. 7.4%, p = 0.03) complication rate was statistically significantly higher in deferred vs. upfront CN. Multivariable logistic regression analysis revealed that none of the treatment regimens significantly predicted the occurrence of postoperative complications. CONCLUSION: Patients undergoing deferred CN experience a higher rates of overall, medical, and surgical 30-day postoperative complications compared to those receiving upfront surgery. Findings from this study should be interpreted within the limitations of this type of analysis.

Trends and incidence of reported events associated with ureteral stents: an analysis of the food and drug administration's manufacturer and user facility device experience (MAUDE) database.

PURPOSE: Aim of this study is to summarize medical device reports (MDRs) between 2012 and 2022 relating to ureteral stents within the Manufacturer and User Facility Device Experience (MAUDE) database maintained by The Food and Drug Administration (FDA). METHODS: MAUDE was analyzed for all MDRs relating to each FDA-approved ureteral stent. Event descriptions were reviewed and characterized into specific event types. Outcome measures include specific ureteral stent and reported events as detailed by the MDRs. Data is presented as number of specific event/total events. Pooled Relative risk was used to compare data. RESULTS: 2652 reports were retrieved in 10 years and a progressive rise in reported events was recorded. 831/2652 (31%) were reported as injury while 1810/2652 (68%) as malfunction of the ureteral stent and 4 events of death. The most frequently reported adverse events (AEs) were stent break (627/2652: 23%); material problems (384/2652: 14%); calcification (222/2652: 8%); difficulty to insert, advance or remove the device (155/2652: 6%). Bard stents were associated with most material problems (19%), Resonance stents were associated with most difficulty to insert, advance or remove the device (9%) and calcification (15%) while filiform double pigtail stent set were associated with most breakage reports (56%) when compared to the other stents (PRR > 1, p < 0,05). CONCLUSIONS: According to MAUDE database the most frequent complications related to ureteral stents are breakage, material problems, calcification and difficulty to insert/advance/remove the device. As well Resonance ureteral stents seem to be associated with a higher risk of device problems.

Role of neoadjuvant chemotherapy in patients with locally advanced and clinically positive nodes Upper Tract Urothelial Carcinoma treated with Nephroureterectomy: real-world data from the ROBUUST 2.0 Registry.

PURPOSE: To assess the impact of neoadjuvant and adjuvant chemotherapy on survival outcomes, within a large multicenter cohort of Upper tract urothelial carcinoma patients treated with Nephroureterectomy. METHODS: A multicenter retrospective analysis utilizing the Robotic surgery for Upper Tract Urothelial Cancer Study registry was performed. Baseline, preoperative, perioperative, and pathologic variables of three groups of patients receiving surgery only, neoadjuvant or adjuvant chemotherapy were compared. Categorical and continuous variables among the three subgroups were compared with Chi square and ANOVA tests. The impact of perioperative chemotherapy on survival outcomes was assessed with the Kaplan Meier method. Univariable and multivariable Cox regression analyses were performed to identify predictors of survival. RESULTS: Overall, 1,994 patients were included. Overall and Clavien grade ≥3 complications rates were comparable among the three subgroups (p = 0.65 and p = 0.92). At Kaplan Meier analysis, neoadjuvant chemotherapy significantly improved cancer-specific survival (p = 0.03) and overall survival (p = 0.03) probabilities of patients with cT ≥ 3 tumors and of those with positive cN (p = 0.03 and p = 0.02). On multivariable analysis, neoadjuvant chemotherapy was independently associated with an improvement of cancer-specific survival in cT ≥ 3 patients (HR 0.44; p = 0.04), and of both cancer-specific survival (HR 0.50; p = 0.03) and overall survival (HR 0.53; p = 0.02) probabilities in positive cN patients. CONCLUSIONS: This large multicenter retrospective analysis suggests significant survival benefit in Upper tract urothelial carcinoma patients with either locally advanced or clinically positive nodes disease receiving neoadjuvant chemotherapy. These findings can be regarded as "hypothesis generating", stimulating future trials focusing on such advanced stages.

Magnetic seed versus skin tattoo localization of non-palpable breast lesions: a single institution cohort study.

OBJECTIVE: The objective of this retrospective study was to investigate the accuracy and feasibility of magnetic seed compared to skin tattoo in preoperative localization of impalpable breast lesions in terms of accuracy of placement, re-excision and positive margins rates, and breast/surgical specimen volume ratio. METHODS: We retrospectively analyzed 77 patients who underwent breast conservative surgery in our center from November 2020 to November 2021, with previous localization with skin tattoo or magnetic seed. RESULTS: Thirty-seven magnetic seeds were placed in 36 patients (48.6%) and 40 skin tattoos were performed in the remaining cases (51.4%). The seeds were placed correctly at the two-view mammogram acquired after the insertion in 97.6% (36/37) of cases. With both methods, 100% of the index lesions were completely removed and found in the surgical specimen. The reported re-excision rate was 0% for both groups. A significant difference was observed in the volume of breast parenchyma removed between the two groups, inferior in the seed group (p = 0.046), especially in case of voluminous breasts (p = 0.003) and small lesions (dimension < 8 mm, p = 0.019). CONCLUSIONS: Magnetic seed is a non-radioactive localization technique, feasible to place, recommended in case of non-palpable breast lesions, saving the breast parenchyma removed compared with skin tattoo, without reducing the accuracy. CLINICAL RELEVANCE STATEMENT: Our findings contribute to the current evidence on preoperative localization techniques for non-palpable breast lesions, highlighting the efficacy of magnetic seed localization for deep and small lesions. KEY POINTS: • Magnetic seed is a non-radioactive technique for the preoperative localization of non-palpable breast lesions studied in comparison with skin tattoo. • Magnetic seed is feasible to place in terms of post-placement migration and distance from the target lesion. • Magnetic seed is recommended in case of non-palpable breast lesions, saving the breast parenchyma removed without reducing the accuracy.

Antimicrobial activity of lipids extracted from Hermetia illucens reared on different substrates.

As the problem of antimicrobial resistance is constantly increasing, there is a renewed interest in antimicrobial products derived from natural sources, particularly obtained from innovative and eco-friendly materials. Insect lipids, due to their fatty acid composition, can be classified as natural antimicrobial compounds. In order to assess the antibacterial efficacy of Hermetia illucens lipids, we extracted this component from the larval stage, fed on different substrates and we characterized it. Moreover, we analyzed the fatty acid composition of the feeding substrate, to determine if and how it could affect the antimicrobial activity of the lipid component. The antimicrobial activity was evaluated against Gram-positive Micrococcus flavus and Gram-negative bacteria Escherichia coli. Analyzing the fatty acid profiles of larval lipids that showed activity against the two bacterial strains, we detected significant differences for C4:0, C10:0, C16:1, C18:3 n3 (ALA), and C20:1. The strongest antimicrobial activity was verified against Micrococcus flavus by lipids extracted from larvae reared on strawberry, tangerine, and fresh manure substrates, with growth inhibition zones ranged from 1.38 to 1.51 mm, while only the rearing on manure showed the effect against Escherichia coli. Notably, the fatty acid profile of H. illucens seems to not be really influenced by the substrate fatty acid profile, except for C18:0 and C18:2 CIS n6 (LA). This implies that other factors, such as the rearing conditions, larval development stages, and other nutrients such as carbohydrates, affect the amount of fatty acids in insects. KEY POINTS: • Feeding substrates influence larval lipids and fatty acids (FA) • Generally, there is no direct correlation between substrate FAs and the same larvae FAs • Specific FAs influence more the antimicrobial effect of BSF lipids.

Deficiencies in monitoring practices of marine protected areas in southern European seas.

Worldwide, states are gazetting new Marine Protected Areas (MPAs) to meet the international commitment of protecting 30% of the seas by 2030. Yet, protection benefits only come into effect when an MPA is implemented with activated regulations and actively managed through continuous monitoring and adaptive management. To assess if actively managed MPAs are the rule or the exception, we used the Mediterranean and Black Seas as a case study, and retrieved information on monitoring activities for 878 designated MPAs in ten European Union (EU) countries. We searched for scientific and grey literature that provides information on the following aspects of MPA assessment and monitoring: ecological (e.g., biomass of commercially exploited fish), social (e.g., perceptions of fishers in an MPA), economic (e.g., revenue of fishers) and governance (e.g., type of governance scheme). We also queried MPA authorities on their past and current monitoring activities using a web-based survey through which we collected 123 responses. Combining the literature review and survey results, we found that approximately 16% of the MPA designations (N = 878) have baseline and/or monitoring studies. Most monitoring programs evaluated MPAs based solely on biological/ecological variables and fewer included social, economic and/or governance variables, failing to capture and assess the social-ecological dimension of marine conservation. To increase the capacity of MPAs to design and implement effective social-ecological monitoring programs, we recommend strategies revolving around three pillars: funding, collaboration, and technology. Following the actionable recommendations presented herein, MPA authorities and EU Member States could improve the low level of MPA monitoring to more effectively reach the 30% protection target delivering benefits for biodiversity conservation.

Robotic salvage partial nephrectomy following surgical and ablative therapies.

PURPOSE: Partial nephrectomies in the salvage setting after ablative or surgical therapy remain challenging cases that are underreported in the literature (1-5). The aim of this video is to demonstrate techniques for robotic salvage partial nephrectomy to manage recurrent renal cell carcinoma (RCC) after failed prior partial nephrectomy and primary cryotherapy. MATERIALS AND METHODS: A 55-year-old man after previous robotic-assisted right partial nephrectomy presented with a 2.5 cm locally recurrent renal mass abutting the collecting system. A 59-year-old man with right renal cell carcinoma initially treated with cryoablation presented local recurrence. CT imaging demonstrated 2.6 cm right renal mass consistent with tumor recurrence at previous treatment site. RESULTS: Both procedures were completed in under 180 minutes. Clamp time was 22 minutes after the previous partial nephrectomy and 25 minutes after previous cryotherapy. There were no perioperative complications. Pathology in both cases demonstrated pT1a clear cell RCC with negative margins. Both patients have since no evidence of recurrent disease on follow-up imaging at 1 and 2 years, respectively. CONCLUSIONS: Salvage robotic partial nephrectomy should be considered as a feasible treatment option after failure of initial therapy-surgical or ablative. A salvage procedure is often more challenging than its standard therapy-naïve counterpart due to development of dense inflammation after previous interventions. Despite this, robotic partial nephrectomies in the salvage setting can be safely carried out with good surgical outcomes, particularly when utilizing intraoperative ultrasound to identify tumor margins and key anatomy.

Carbapenem-Resistant Enterobacteriaceae in Urinary Tract Infections: From Biological Insights to Emerging Therapeutic Alternatives.

Urinary tract infections (UTIs) are the second most frequent type of infection observed in clinical practice. Gram-negative Enterobacteriaceae are common pathogens in UTIs. Excessive antibiotic use in humans and animals, poor infection control, and increased global travel have accelerated the spread of multidrug-resistant strains (MDR). Carbapenem antibiotics are commonly considered the last line of defense against MDR Gram-negative bacteria; however, their efficacy is now threatened by the increasing prevalence of carbapenem-resistant Enterobacteriaceae (CRE). This comprehensive review aims to explore the biological mechanisms underlying carbapenem resistance and to present a focus on therapeutic alternatives currently available for complicated UTIs (cUTIs). A comprehensive bibliographic search was conducted on the PubMed/MEDLINE, Scopus, and Web of Science databases in December 2023. The best evidence on the topic was selected, described, and discussed. Analyzed with particular interest were the clinical trials pivotal to the introduction of new pharmacological treatments in the management of complicated cUTIs. Additional suitable articles were collected by manually cross-referencing the bibliography of previously selected papers. This overview provides a current and comprehensive examination of the treatment options available for CRE infections, offering a valuable resource for understanding this constantly evolving public health challenge.

Humoral response after the fourth dose of the SARS-CoV-2 vaccine in the CKD spectrum: a prespecified analysis of the SENCOVAC study.

BACKGROUND: There is scarce evidence on the fourth dose of severe acute respiratory syndrome coronavirus 2 vaccines in chronic kidney disease (CKD) patients. We evaluated the humoral response and effectivity of the fourth dose in the CKD spectrum: non-dialysis CKD (ND-CKD), haemodialysis (HD), peritoneal dialysis (PD) and kidney transplant (KT) recipients. METHODS: This is a prespecified analysis of the prospective, observational, multicentric SENCOVAC study. In patients with CKD who had received a complete initial vaccination and one or two boosters and had anti-Spike antibody determinations 6 and 12 months after the initial vaccination, we analysed factors associated with persistent negative humoral response and higher anti-Spike antibody titres as well as the efficacy of vaccination on coronavirus disease 2019 (COVID-19) severity. RESULTS: Of 2186 patients (18% KT, 8% PD, 69% HD and 5% ND-CKD), 30% had received a fourth dose. The fourth dose increased anti-Spike antibody titres in HD (P = .001) and ND-CKD (P = .014) patients and seroconverted 72% of previously negative patients. Higher anti-Spike antibody titres at 12 months were independently associated with repeated exposure to antigen (fourth dose, previous breakthrough infections), previous anti-Spike antibody titres and not being a KT recipient. Breakthrough COVID-19 was registered in 137 (6%) patients, 5% of whom required admission. Admitted patients had prior titres <620 UI/ml and median values were lower (P = .020) than in non-admitted patients. CONCLUSIONS: A fourth vaccine dose increased anti-Spike antibody titres or seroconverted many CKD patients, but those with the highest need for a vaccine booster (i.e. those with lower pre-booster antibody titres or KT recipients) derived the least benefit in terms of antibody titres. Admission for breakthrough COVID-19 was associated with low anti-Spike antibody titres.

Post-voided residual urine ratio as a predictor of bladder outlet obstruction in men with lower urinary tract symptoms: development of a clinical nomogram.

PURPOSE: To confirm the correlation between post-void residual urine ratio (PVR-R) and BOO diagnosed by pressure-flow studies (PFS) in males with lower urinary tract symptoms (LUTS) and to develop a clinical nomogram. METHODS: A consecutive series of patients aged 45 years or older with non-neurogenic LUTS were prospectively enrolled. Patients underwent standard diagnostic assessment for BOO including International Prostatic Symptoms Score, uroflowmetry, urodynamic studies, suprapubic ultrasound of the prostate, and ultrasound measurements of the bladder wall thickness (BTW). PVR-R was defined as follows: PVR-R = (PVR/total Bladder Volume [BV]) × 100). Logistic regression analysis was used to investigate predictors of pathological bladder emptying (BOO) defined as Schafer > II. A nomogram to predict BOO based on the multivariable logistic regression model was then developed. RESULTS: Overall 335 patients were enrolled. Overall, 131/335 (40%) presented BOO on PFS. In a multivariable logistic age-adjusted regression model BWT (odds ratio [OR]: 2.21 per mm; 95% confidence interval [CI], 1.57-3.09; p = 0.001), PVR-R (OR: 1.02 per %; 95% CI, 1.01-1.03; p = 0.034) and prostate volume (OR: 0.97 per mL; 95% CI, 0.95-0.98; p = 0.001) were significant predictors for BOO. The model presented an accuracy of 0.82 and a clinical net benefit in the range of 10-90%. CONCLUSIONS: The present study confirms the important role of PVR-ratio in the prediction of BOO. For the first time, we present a clinical nomogram including PVR-ratio for the prediction of BOO.

Metastasis-directed treatment in kidney cancer.

PURPOSE OF REVIEW: To provide a critical overview of the latest evidence on the role of metastasis-direct treatment (MDT) in the management of metastatic renal cell carcinoma (mRCC). RECENT FINDINGS: This is a nonsystematic review of the English language literature published since January 2021. A PubMed/MEDLINE search using various search terms was conducted, including only original studies. After title and abstract screening, selected articles were grouped into two main areas which mirror the main treatment options in this setting: surgical metastasectomy (MS) and stereotactic radiotherapy (SRT). While a limited number of retrospective studies have been reported on surgical MS, the consensus of these reports is that extirpation of metastasis should be part of a multimodal management strategy for carefully selected cases. In contrast, there have been both retrospective studies and a small number of prospective studies on the use of SRT of metastatic sites. SUMMARY: As the management of mRCC rapidly evolves, and evidence on MDT - both in the form of MS and SRT - has continued to build over the past 2 years. Overall, there is growing interest in this therapeutic option, which is increasingly being implemented and seems to be safe and potentially beneficial in well selected disease scenarios.

Assessing Tissue Transmission of Hepatitis C Virus From Viremic Donor to Seronegative Kidney Transplant Recipients: A Case Series.

The transmission of hepatitis C virus from viremic donors to seronegative recipients of kidney transplantation is well documented. Pre-transplant administration of direct-acting antivirals prevents viremia, but the seroconversion rate is high. We studied the transmission of the virus through the transplanted tissue by determining viral RNA in 15 kidneys from 8 deceased viremic donors, 5 males and 3 females aged 52.3 ± 15 years. HIV positive donors and active intravenous drugs abusers were discarded to avoid possible window periods in the virus transmission. Recipients, 9 males and 6 females aged 52.7 ± 18 years, were treated with glecaprevir/pibrentasvir for 8 weeks and received immunosuppression with thymoglobulin, tacrolimus, sirolimus and prednisone. Hepatitis C Virus was detected in 9 of the 15 histological samples analyzed but viremia was detected in no recipient at day 1 and 7 post-transplantation and 12 weeks after the treatment. However, 13 of the 15 recipients had seroconverted within 1 month. In conclusion, Hepatitis C virus was detected in a significant proportion of tissue of kidney grafts from viremic donors, but treatment with direct-acting antivirals avoids the transmission of the virus from donor to recipient. Then Donor pools should be expanded.

Prostate Cancer in Transgender Women: Epidemiology, Clinical Characteristics, and Management Challenges.

PURPOSE OF REVIEW: To systematically review the evidence on prostate cancer (PCa) in transgender women (TGW). RECENT FINDINGS: A total of 25 studies were included. Fourteen articles were case reports or case series describing 21 TGW with PCa; 11 papers focused primarily on assessing the incidence or screening of PCa in TGW. The median (range) age of patients with PCa was 63 (45-78) years. Median (range) PSA at diagnosis was 7.5 (0.4-1710) ng/mL. Prostate biopsy detected ISUP 3-5 in 10 (67%) cases. T3-4 stages were described in 7 (64%) patients. Three (14.3%) cases of nodal involvement and 2 (9.5%) of metastases were reported at diagnosis. First-line therapy included radical prostatectomy or radiotherapy ± androgen deprivation therapy in 14 (74 %) subjects. Median (range) follow-up was 24 (2-120) months. A good response to first-line therapy was recorded in 8 (47.1%) cases. Median (range) incidence of PCa in TGW was 44.1 (4.34-140) cases per 100,000 person-years. PCa was significantly less frequent in TGW than in cisgender males (HR 0.4, 95% CI 0.2-0.9). Risk of death after PCa diagnosis was significantly higher in TGW compared to cisgender males (HR 1.91, 95% CI 1.06-3.45). TGW had lower lifetime PSA rates (48% vs. 64.6%, p = 0.048) than cisgender males. Few cases of PCa in TGW are currently reported. PCa seems significantly less frequent in TGW than in cisgender males; however, some data suggest a possible higher mortality in this cohort. TGW appear to have less access to PSA testing than cisgender men.

Exposure considerations in human safety assessment: Report from an EPAA Partners' Forum.

Understanding and estimating the exposure to a substance is one of the fundamental requirements for safe manufacture and use. Many approaches are taken to determine exposure to substances, mainly driven by potential use and regulatory need. There are many opportunities to improve and optimise the use of exposure information for chemical safety. The European Partnership for Alternative Approaches to Animal Testing (EPAA) therefore convened a Partners' Forum (PF) to explore exposure considerations in human safety assessment of industrial products to agree key conclusions for the regulatory acceptance of exposure assessment approaches and priority areas for further research investment. The PF recognised the widescale use of exposure information across industrial sectors with the possibilities of creating synergies between different sectors. Further, the PF acknowledged that the EPAA could make a significant contribution to promote the use of exposure data in human safety assessment, with an aim to address specific regulatory needs. To achieve this, research needs, as well as synergies and areas for potential collaboration across sectors, were identified.

Selecting the optimal radiation modality in prostate cancer.

There are numerous radiation modalities for the definitive treatment of localized prostate cancer. Classic clinical trials have established the basic tenets of treatment approaches, and emerging data have generated new potential avenues of treatment that optimize the therapeutic ratio by increasing prostate cancer tumor control while minimizing treatment-related toxicity. In the definitive setting, the selection of the optimal radiation therapy approach depends largely on the appropriate up-front risk stratification of men with prostate cancer, with greater intensification of treatment and greater integration of multimodality therapies for men with higher-risk disease. Hormonal therapy should be selectively deployed based on prognostic information derived from the National Comprehensive Cancer Network risk group and biologic tumor aggressiveness informed by genomic classifiers. Moreover, treatment intensification and target volume delineation are increasingly informed by molecular imaging and multiparametric magnetic resonance imaging. Herein, we perform a critical appraisal of the literature focusing on the optimal selection of radiation therapy modality for localized prostate cancer. Collaboration among medical oncologists, surgeons, and radiation oncologists will be critical for coordinating evidence-based radiation therapies when clearly indicated and for supporting shared decision-making when the evidence is incomplete.

Gender differences in susceptibility to smoking among high school students.

AIMS: To analyse the degree of susceptibility to smoking according to gender in students between 12 and 16 years of age and study the role of factors associated with gender and the extended index of susceptibility to smoking. DESIGN: Cross-sectional study. METHODS: Between November 2019 and March 2020, 12- to 16-year-old students were recruited from three educational centres in western Spain. Sociodemographic, environmental, social and personal variables were analysed. The value of the extended index of susceptibility to smoking was calculated, and the associations between the students' genders and smoking susceptibility were studied. Multinomial logistic regression was used to study associations between the independent variables and Expanded Susceptibility Index (ESSI) results. The roles of factors in this association were explored through mediation analysis. RESULTS: A total of 364 students participated in the study (53% females). A total of 79.3% of females and 61.4% of males presented a medium-high level of the extended index of susceptibility. Females reported greater cigarette use (28% vs. 12.3%), hookah (19.9% vs 9.9%) and alcohol consumption (20.7% risk alcohol consumption). They obtained higher scores on the impulsivity scale in the urgency domain and the negative affect scale. Regardless of other factors, females showed more than double the smoking susceptibility (aOR: 2.05, 95% CI: 1.03-4.07, p = .041). Mediation analysis showed that gender had a total effect on the extended susceptibility index ß = .023 (95% CI: 0.07-0.38, p = .01). The effect appeared to be mediated only by having smoking friends (0.08; 95% CI: 0.03-0.15, p = .001). CONCLUSIONS: The greater susceptibility to smoking found in females may be related to a greater influence of smoking among friends. IMPACT: These results show that smoking friends have a strong influence among adolescent females; therefore, developing preventive programmes with gender approaches aimed at reducing the influence of these environmental factors would be of interest.