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Natural killer (NK) cells, effector lymphocytes of the innate immunity, have been shown to be altered in several cancers, both at tissue and peripheral levels. We have shown that in Non-Small Cell Lung Cancer (NSCLC) and colon cancer, tumour associated circulating NK (TA-NK) and tumour infiltrating NK (TI-NK) exhibit pro-angiogenic phenotype/functions. However, there is still a lack of knowledge concerning the phenotype of peripheral blood (PB) NK (pNK) cells in prostate cancer (PCa). Here, we phenotypically and functionally characterized pNK from PCa patients (PCa TA-NKs) and investigated their interactions with endothelial cells and monocytes/macrophages. NK cell subset distribution in PB of PCa patients was investigated, by multicolor flow cytometry, for surface antigens expression. Protein arrays were performed to characterize the secretome on FACS-sorted pNK cells. Conditioned media (CM) from FACS-sorted PCa pTA-NKs were used to determine their ability to induce pro-inflammatory/pro-angiogenic phenotype/functions in endothelial cells, monocytes, and macrophages. CM from three different PCa (PC-3, DU-145, LNCaP) cell lines, were used to assess their effects on human NK cell polarization in vitro , by multicolor flow cytometry. We found that PCa pTA-NKs acquire the CD56 bright CD9 + CD49a + CXCR4 + phenotype, increased the expression of markers of exhaustion (PD-1, TIM-3) and are impaired in their degranulation capabilities. Similar effects were observed on healthy donor-derived pNK cells, exposed to conditioned media of three different PCa cell lines, together with increased production of pro-inflammatory chemokines/chemokine receptors CXCR4, CXCL8, CXCL12, reduced production of TNFα, IFNγ and Granzyme-B. PCa TA-NKs released factors able to support inflammatory angiogenesis in an in vitro model and increased the expression of CXCL8, ICAM-1, and VCAM-1 mRNA in endothelial cells. Secretome analysis revealed the ability of PCa TA-NKs to release pro-inflammatory cytokines/chemokines involved in monocyte recruitment and M2-like polarization. Finally, CMs from PCa pTA-NKs recruit THP-1 and peripheral blood CD14 + monocyte and polarize THP-1 and peripheral blood CD14 + monocyte-derived macrophage towards M2-like/TAM macrophages. Our results show that PCa pTA-NKs acquire properties related to the pro-inflammatory angiogenesis in endothelial cells, recruit monocytes and polarize macrophage to an M2-like type phenotype. Our data provides a rationale for a potential use of pNK profiling in PCa patients.

Focal therapy modalities achieved interest in the management of prostate cancer (PCa) over the last a few years. This systematic review was aimed to investigate erectile function after focal therapy for localized PCa. Twenty-six out of 1287 reports were identified through a database systematic search in MEDLINE, EMBASE, and Web of Science, supplemented with hand search, on June 1st, 2020, according to PRISMA guidelines. Focal therapy modalities investigated were cryotherapy, high-intensity focused ultrasound (HIFU), photodynamic therapy (TOOKAD), irreversible electroporation (IRE), and focal radiotherapy (RT) (i.e. brachytherapy or stereotactic RT). Overall, reported sexual function outcomes after these treatment modalities were generally good, with many studies reporting a complete recovery of EF at 1-year follow-up. However, the quality of current evidence is affected both by the lack of well-conducted comparative studies and by a significant heterogeneity in terms of study design, study population, erectile and sexual function assessment modalities.

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.

Extracorporeal treatment with low intensity shock-wave therapy (LI-ESWT) is a recently introduced non-invasive method which purposes the restoration of the pathophysiological alterations at the base of vasculogenic ED in male patients. The evidence in favour of the neoangiogenic potential of this treatment derived from in vitro studies and on animal models. The purpose of this study, in which the Power Doppler method was applied, is to demonstrate ‘objectively’ the real efficacy of LI-ESWT at the level of the microcirculation of the corpora cavernosa (neoangiogenesis) in patients affected by vasculogenic ED. Data from this study show, for the first time, that LI-ESWT treatment promotes neovascularisation of the functional arteries in patients affected by vasculogenic ED.

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.

We aimed to assess the correlation between premature ejaculation (PE), lower urinary tract symptoms (LUTS), erectile dysfunction (ED), and depression in the cohort of the last 329 patients seeking medical help for distressing early ejaculation at a single tertiary-referral center. All patients completed the premature ejaculation diagnostic tool (PEDT), the International Index of Erectile Function (IIEF), the Beck’s Inventory for Depression (BDI), and the International Prostate Symptom Score (IPSS) at their first assessment. Overall, 133 (0.4) patients had PEDT ≥ 11, suggestive for PE. The characteristics of patients with and without PE according to PEDT findings were compared with the Mann–Whitney and Fisher’s exact tests. Linear regression analysis tested the association between LUTS and PEDT score. Patients with PE depicted lower median scores for IIEF-overall satisfaction, intercourse satisfaction and erectile function than non-PE individuals (all p < 0.004). Similarly, patients with PE showed higher median BDI scores (7 versus 4; p < 0.0002), median IPSS total score (7 versus 5), storage (4 versus 2), and voiding (3 versus 2) subscores (all p < 0.01) compared to those without PE. At linear regression analysis, IPSS storage subscore (Coeff: 0.28; 95%CI: 0.05–0.51, p = 0.01) and BDI score (Coeff: 0.10; 95%CI: 0.01–0.19, p = 0.02) were associated with higher PEDT values, after accounting for IIEF-EF score, patients’ age, body mass index and Charlson Comorbidity Index. Our findings suggest that storage symptoms and depression should be carefully investigated when assessing patients complaining of PE in the real-life setting.

Introduction: Neurological disease is a known entity for causing erectile dysfunction (ED). Pharmacological therapies are not always effective these patients – penile prosthesis implant (PPI) is an established surgical treatment option. For a variety of reasons, neurological patients may experience differing outcomes of PPI compared to those whose ED arises from other causes. We investigated outcomes of PPI in neurological patients using the Italian multi-institutional national registry of penile prostheses [Italian Nationwide Systematic Inventarization of Surgical Treatment for ED (INSIST-ED)]. Methods: Patients undergoing PPI were investigated via the INSIST-ED registry, from 2014 to 2021. Data were prospectively recorded by 45 surgeons on a dedicated website (www.registro.andrologiaitaliana.it) and reviewed by a data manager. We subselected patients with neurological disease undergoing PPI for ED, and these patients were reviewed at 3, 6, and 12 months, and annually thereafter. Postoperative complications and functional outcomes were evaluated through validated questionnaires [International Index of Erectile Function-5 (IIEF-5), Sexual Encounter Profile 2–3, and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS)]. A nonvalidated questionnaire was administered to assess patient satisfaction. Results: A total of 33 patients were included with a median age of 49 [interquartile range (IQR) 41–55]. Median follow-up was 83 months (IQR 67–99.5). A penoscrotal approach for PPI was performed in most cases (90.9%), while infrapubic was used in three cases (9.1%). Inflatable and malleable devices were implanted in 30 (90.9%) and 3 cases (9.1%), respectively. Intraoperative complications occurred in one case (3%). Early postoperative complications (<90 days) were observed in three cases (9.1%): two wound dehiscence (Clavien-Dindo G1 and G3a respectively) and one device infection requiring prosthesis explant (Clavien-Dindo G3a). Mechanical failures of inflatable devices were not observed during the follow-up period. Median IIEF-5 before surgery was 8 (IQR 7–9). At the latest follow-up, IIEF-5 was 22 (IQR 19–23.5), and median EDITS was 79 (IQR 64–88). A total of 28 patients (84.8%) self-reported to be fully satisfied with the PPI. Conclusion: Although PPI in the neurological population has been historically considered to be at increased risk, in our study, PPI complications and infections rates in this cohort did not differ from general population.

Hyaluronic acid (HA) is a glycosaminoglycan widely utilised in different fields of medicine. We aimed to provide a comprehensive overview of the scientific evidence on the use of HA in andrology. A review of the literature to identify pertinent studies concerning the use of HA in andrology was carried out on the Medline, EMBASE, and the Cochrane databases, with no time restriction up to December 2022. Penile girth enlargement (PGE) using HA proved to be safe and effective in enhancing the diameter of the penis, with durable and satisfactory outcomes in long-term follow-up. Injection of HA in the glans seems to represent an alternative treatment option for those patients with premature ejaculation (PE) who fail to respond to conventional medications. HA intra-plaque injections represent a valid option which may contribute to restore sexual activity in patients with Peyronie’s disease (PD). The adoption of HA filler injections should always be tailored to the patient’s peculiar anatomy and underlying condition. More robust evidence is required to achieve a uniformed consensus regarding the use of HA in andrology, and further efforts should continue to improve the current injection techniques and HA products.