Explore the vast range of titles available.

The diagnosis and management of renal cell carcinoma have changed remarkably rapidly. Although the incidence of renal cell carcinoma has been increasing, survival has improved substantially. As incidental diagnosis of small indolent cancers has become more frequent, active surveillance, robot-assisted nephron-sparing surgical techniques, and minimally invasive procedures, such as thermal ablation, have gained popularity. Despite progression in cancer control and survival, locally advanced disease and distant metastases are still diagnosed in a notable proportion of patients. An integrated management strategy that includes surgical debulking and systemic treatment with well established targeted biological drugs has improved the care of patients. Nevertheless, uncertainties, controversies, and research questions remain. Further advances are expected from translational and clinical studies.

PurposeTo provide an overview of the currently available evidence relating to the prevention and management strategies of urinary incontinence (UI) after radical prostatectomy (RP).Materials and MethodsA comprehensive research was carried out on MEDLINE/PubMed database to identify pertinent studies concerning post-RP UI. The search strategy included these words: urinary continence; urinary continence recovery; urinary incontinence; radical prostatectomy; and prostate cancer.ResultsPost-RP UI still represents a challenging issue for both urologic patients and clinicians. A complete preoperative assessment of the risk factors associated with post-RP UI aids both in counseling those patients with a higher estimated likelihood of postoperative UI and in identifying those who would probably benefit from preventive strategies in the preoperative and in the intraoperative settings. Over the last decades different surgical strategies based on either the “preservation” or the “reconstruction” of the anatomical elements responsible for urinary continence (UC) led to an overall improvement of postoperative functional outcomes. Finally, several therapeutic strategies should be evaluated for the postoperative UI management. Artificial urinary sphincter implantation represents the gold standard for treatment, notwithstanding its wide adoption is limited due to high costs and significant risk of surgical revision. In this context, male sling positioning seems the most promising strategy, in particular in mild and moderate post-RP UI.ConclusionsTo enhance the likelihood of obtaining an optimal UC recovery after RP, it is here strongly suggested to intervene throughout the overall clinical management process thus including the pre-, intra- and postoperative settings.

Advanced glycation end-products (AGEs) are an assorted group of molecules formed through covalent bonds between a reduced sugar and a free amino group of proteins, lipids, and nucleic acids. Glycation alters their structure and function, leading to impaired cell function. They can be originated by physiological processes, when not counterbalanced by detoxification mechanisms, or derive from exogenous sources such as food, cigarette smoke, and air pollution. Their accumulation increases inflammation and oxidative stress through the activation of various mechanisms mainly triggered by binding to their receptors (RAGE). So far, the pathogenic role of AGEs has been evidenced in inflammatory and chronic diseases such as chronic kidney disease, cardiovascular disease, and diabetic nephropathy. This review focuses on the AGE-induced kidney damage, by describing the molecular players involved and investigating its link to the excess of body weight and visceral fat, hallmarks of obesity. Research regarding interventions to reduce AGE accumulation has been of great interest and a nutraceutical approach that would help fighting chronic diseases could be a very useful tool for patients’ everyday lives.

In an era of personalized medicine where genetic, environmental, and biometric factors are considered as a whole throughout the diagnostic and therapeutic approach to a disease, the association between several clinical factors and prostate cancer risk （PCa） has been thoroughly investigated. In the study ofZapata et al.,

ObjectivesTo evaluate the agreement among readers with different expertise in detecting suspicious lesions at prostate multiparametric MRI using Prostate Imaging Reporting and Data System (PI-RADS) version 2.1.MethodsWe evaluated 200 consecutive biopsy-naïve or previously negative biopsy men who underwent MRI for clinically suspected prostate cancer (PCa) between May and September 2017. Of them, 132 patients underwent prostate biopsy. Seven radiologists (four dedicated uro-radiologists and three non-dedicated abdominal radiologists) reviewed and scored all MRI examinations according to PI-RADS v2.1. Agreement on index lesion detection was evaluated with Conger’s k coefficient, agreement coefficient 1 (AC1), percentage of agreement (PA), and indexes of specific positive and negative agreement. Clinical and radiological features that may influence variability were evaluated.ResultsAgreement in index lesion detection among all readers was substantial (AC1 0.738; 95% CI 0.695–0.782); dedicated radiologists showed higher agreement compared with non-dedicated readers. Clinical and radiological parameters that positively influenced agreement were PSA density ≥ 0.15 ng/mL/cc, pre-MRI high risk for PCa, positivity threshold of PI-RADS score 4 + 5, PZ lesions, homogeneous signal intensity of the PZ, and subjectively easy interpretation of MRI. Positive specific agreement was significantly higher among dedicated readers, up to 93.4% (95% CI 90.7–95.4) in patients harboring csPCa. Agreement on absence of lesions was excellent for both dedicated and non-dedicated readers (respectively 85.1% [95% CI 78.4–92.3] and 82.0% [95% CI 77.2–90.1]).ConclusionsAgreement on index lesion detection among radiologists of various experiences is substantial to excellent using PI-RADS v2.1. Concordance on absence of lesions is excellent across readers’ experience.Key Points• Agreement on index lesion detection among radiologists of various experiences is substantial to excellent using PI-RADS v2.1.• Concordance between experienced readers is higher than between less-experienced readers.• Concordance on absence of lesions is excellent across readers’ experience.

Molecular mechanisms associated with human germ cell aplasia in infertile men remain undefined. Here we perform single-cell transcriptome profiling to highlight differentially expressed genes and pathways in each somatic cell type in testes of men with idiopathic germ cell aplasia. We identify immaturity of Leydig cells, chronic tissue inflammation, fibrosis, and senescence phenotype of the somatic cells, as well markers of chronic inflammation in the blood. We find that deregulated expression of parentally imprinted genes in myoid and immature Leydig cells, with relevant changes in the ratio of Lamin A/C transcripts and an active DNA damage response in Leydig and peritubular myoid cells are also indicative of senescence of the testicular niche. This study offers molecular insights into the pathogenesis of idiopathic germ cell aplasia. Molecular mechanisms associated with human germ cell aplasia in infertile men remain undefined. Here the authors perform single-cell transcriptome profiling to highlight differentially expressed genes and pathways in each somatic cell type in testes of men with idiopathic germ cell aplasia.

Since the beginning of the coronavirus disease 19 (COVID-19) pandemic, efforts in defining risk factors and associations between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinical, and molecular features have initiated. After three years of pandemic, it became evident that men have higher risk of adverse outcomes. Such evidence provided the impetus for defining the biological fundaments of such a gender disparity. Our objective was to analyze the most recent literature with the aim of defining the relationship between COVID-19 and fertility, in particular, we assessed the interplay between SARS-CoV-2 and testosterone in a systematic review of literature from December 2019 (first evidence of a novel coronavirus in the Hubei province) until March 2022. As a fundamental basis for understanding, articles pertaining preclinical aspects explaining the gender disparity (n=9) were included. The main review categories analyzed the risk of being infected with SARS-CoV-2 according to testosterone levels (n=5), the impact of serum testosterone on outcomes of COVID-19 (n=23), and the impact SARS-CoV-2 on testosterone levels after infection (n=19). Preclinical studies mainly evaluated the relation between angiotensin-converting enzyme 2 (ACE2) and its androgen-mediated regulation, articles exploring the risk of COVID-19 according to testosterone levels were few. Although most publications evaluating the effect of COVID-19 on fertility found low testosterone levels after the infection, follow-up was short, with some also suggesting no alterations during recovery. More conclusive findings were observed in men with low testosterone levels, that were generally at higher risk of experiencing worse outcomes ( , admission to intensive care units, longer hospitalization, and death). Interestingly, an inverse relationship was observed in women, where higher levels of testosterone were associated to worse outcomes. Our finding may provide meaningful insights to better patient counselling and individualization of care pathways in men with testosterone levels suggesting hypogonadism.

Dutasteride, an inhibitor of 5α-reductase in the prostate, was tested in a large, randomized trial to determine its ability to prevent prostate cancer. Over the 4 years of the trial, dutasteride, as compared with placebo, reduced the relative risk of biopsy-detected prostate cancer by 23%. The reduction was limited mainly to tumors with Gleason scores of 5 or 6; by year 4, there were 12 tumors with Gleason scores of 8 to 10 in the dutasteride group but only 1 in the placebo group. Dutasteride, an inhibitor of 5α-reductase in the prostate, reduced the relative risk of biopsy-detected prostate cancer by 23%; however, the reduction was limited mainly to tumors with Gleason scores of 5 or 6. The 5α-reductase inhibitors that are used to treat benign prostatic hyperplasia block the conversion of testosterone to dihydrotestosterone and may reduce the risk of prostate cancer. 1 The results of the Prostate Cancer Prevention Trial showed that finasteride, as compared with placebo, reduced the risk of prostate cancer by 25%, but among the tumors that were detected, there was a 27% increase in the number of those that had Gleason scores of 7 to 10. 2 (The Gleason score is the sum of the two most common histologic patterns or grades in a prostate tumor, each of which is graded on a . . .

Checkpoint immunotherapy (CPI) has increased survival for some patients with advanced-stage bladder cancer (BCa). However, most patients do not respond. Here, we characterized the tumor and immune microenvironment in pre- and post-treatment tumors from the PURE01 neoadjuvant pembrolizumab immunotherapy trial, using a consolidative approach that combined transcriptional and genetic profiling with digital spatial profiling. We identify five distinctive genetic and transcriptomic programs and validate these in an independent neoadjuvant CPI trial to identify the features of response or resistance to CPI. By modeling the regulatory network, we identify the histone demethylase KDM5B as a repressor of tumor immune signaling pathways in one resistant subtype (S1, Luminal-excluded) and demonstrate that inhibition of KDM5B enhances immunogenicity in FGFR3-mutated BCa cells. Our study identifies signatures associated with response to CPI that can be used to molecularly stratify patients and suggests therapeutic alternatives for subtypes with poor response to neoadjuvant immunotherapy. The response to checkpoint immunotherapy within bladder cancer patients is highly variable. Here, the authors use RNA-seq, ATAC-seq and digital spatial profiling of pre- and post-treatment samples from the PURE01 trial to identify subtypes associated with treatment response.

PurposeTo review the currently available literature reporting the patterns of recurrence and their predictive factors after open radical cystectomy (RC) for bladder cancer.MethodsA review of the literature was performed using the MEDLINE, Scopus and Web of Sciences databases from January 1997 to May 2017. The PRISMA guidelines were followed for the conduct of the study.ResultsLocal recurrence rate ranges between 30 and 54%. Distant recurrence is not often standardized and is reported in up to 50% of cases. The overall 5-year recurrence-free survival rates from 58 to 81%. The mean follow-up of studies included in the analysis ranged from 18 to 350 months. Details on the most important demographic and epidemiological, clinical, histologic and pathologic predictors of recurrence after radical cystectomy are provided through an evidence-based approach. The impact of the extension of lymph node dissection on recurrence after RC is investigated.ConclusionsA correct prognostic assessment is essential for patients undergoing radical cystectomy for bladder cancer, thereby potentially improving their oncologic outcomes.