Iron homeostasis alterations and erectile dysfunction: A new issue in erectile disfunction treatment?

To the Editor, Erectile dysfunction (ED) is one of the most prevalent conditions affecting men globally, with significant psychological and social consequences. The prevalence varies across different populations, and it is estimated around 50% in men aged between 40 to 70. The etiology of ED is multifactorial, involving a complex crosstalk between psychological, hormonal, neurogenic, vascular, and structural factors [...].

A mobile health application for prostate cancer antigen dosage: is it time to say goodbye to classic screening methods?

OBJECTIVE: To evaluate the quality of apps for prostate cancer antigen (PSA) dosage, available for downloading on the iOS and Android platforms, discussing the potential role of mobile health applications (MHAs) in update the screening protocol. METHODS: An observational cross-sectional descriptive study of all smartphone apps for PSA dosage was performed through the most used platforms (iOS and Android). On 10 February 2023, a total of 457 apps were found according to the search criteria. Mobile Application Rating Scale (MARS) was adopted to assess apps' quality. Then, MARS items were analyzed through descriptive statistics and bivariate correlations between study variables with Pearson's coefficient. RESULTS: Of all samples, 24 MHAs were included in the final analysis: 12% (n = 3) from the iTunes App Store and 88% (n = 21) from the Google Play Store. According to the MARS quality assessment, the mean values 2.61, 2.94, 3.11, 2.97, 2.94, and 2.63 were measured for the engagement, functionality, aesthetics, information, overall mean score, and subjective quality, respectively. CONCLUSION: The MHAs for PSA were under the acceptability threshold and future improvements are required. Moreover, MHAs appropriately developed could play an active role in PSA screening campaign and adherence of follow-up regimens. Finally, the virtual instrument could both reduce the social divide of access to care for patients in rural areas and improve PCA detection, speeding up the active treatment.

Recreation use of phosphodiesterase type 5 inhibitors, the other side of erectile dysfunction.

To the Editor, In 1998 Sildenafil was approved by the Food and Drug Administration as first line therapy for erectile dysfunction. Since then, phosphodiesterase type 5 inhibitors (PDE5i) represent the first-line treatment of erectile dysfunction (ED), improving physiological erectile function, sexual orgasmic function, psychological self-esteem, couples' relationship, and quality of life. [...].

Cytoreductive Nephrectomy and Metastatic Renal Cell Carcinoma: State of the Art and Future Perspectives.

In the past decades, several treatments have been proposed for the management of metastatic renal cell carcinoma (mRCC). Among these, cytoreductive nephrectomy (CN) represents a controversial and open issue in the era of targeted therapy and novel immunotherapy with immune checkpoint inhibitors. Two important studies, CARMENA and SURTIME, analyzed therapy with sunitinib with or without CN, and immediate CN followed by sunitinib versus a deferred CN after three cycles of sunitinib, respectively. CARMENA showed the non-inferiority of sunitinib alone versus sunitinib plus CN, whereas SURTIME showed no difference in progression-free survival (PFS), but a better median OS among patients with deferred CN. Therefore, more prospective clinical trials and appropriate patient identification are necessary to support CN in this new scenario. This review provides a snapshot of the current evidence for CN in mRCC, discusses the management strategies, and offers perspectives on the direction of future research.

Sexual dysfunction: Time for a multidisciplinary approach?

Sexual health impairment is one of the most important issues worldwide, with an increasing number of men and women affected. Specifically in male sexual dysfunction (SD), several risk factors were established such as atherosclerosis, hypertension, diabetes mellitus, smoking or obesity. The co-presence of more than one of risk factors identifies a condition, defined as the metabolic syndrome (MetS), related directly to the SD. However, not all the physicians involved in the MetS management routinely discussed the sexual impairment, increasing the bothering feelings of patients. Furthermore, the lack of knowledge, insufficient time, lack of attention, ambiguities about responsibility, insufficient training and experience, shared among physicians, regarding the communication and treatment of sexual dysfunction, are all reported factors involved in under-valuation of SD. The current paper represents a warning to the experts, with the aim of increasing the awareness of SD among clinicians and to promote the education, training and collaboration with sex therapists, through a multidisciplinary team, that can lead to a holistic approach in SD assessment and treatment.

Mobile health applications in kidney stone disease management: A reliable support for patients?

INTRODUCTION: Mobile health applications (MHAs) represent an interesting issue to assist and improve the quality of life of patients affected by Kidney Stone Disease (KSD). Despite this, their scientific quality and adherence to guidelines are not yet addressed. MATERIAL AND METHODS: On 2 November 2022, we conducted an observational cross-sectional descriptive study of all MHAs on KSD. A search in the Apple App Store and Google Play Store was performed. We reviewed all mobile apps from Apple App Store and Google Play Store for KSD and evaluated their usage in screening, prevention, management, and adherence to EAU guidelines. RESULTS: In total 13 MHA were included in the final analysis. All MHAs, 4 (30.8%) from the Apple App Store and 9 (69.2%) from the Google Play Store are geared towards the patient. Engagement ranged from 1.73 to 4.06; Functionality ranged from 3.17 to 4.75; Aesthetics ranged from 1.9 to 4.12; Information ranged from 2.25 to 4.27, and Subjective quality ranged from 1.58 to 3.23. MHAs reported low and medium adherence to EAU guidelines. CONCLUSIONS: MHAs provide a very useful assistance in several medical fields, including KSD. Despite MHAs development is constantly increasing, the scientific validation, content, and quality are not yet solved. Future research is necessary to improve the quality of the apps and promote new user designed, and high-quality apps.

Preoperative Fibrinogen-to-Albumin Ratio as Potential Predictor of Bladder Cancer: A Monocentric Retrospective Study.

Background and objective: Fibrinogen and albumin are two proteins widely used, singularly and in combination, in cancer patients as biomarkers of nutritional status, inflammation and disease prognosis. The aim of our study was to investigate the preoperative fibrinogen-to-albumin ratio (FAR) as a preoperative predictor of malignancy as well as advanced grade in patients with bladder cancer. Materials and Methods: A retrospective analysis of patients who underwent TURBT at our institution between 2017 and 2021 was conducted. FAR was obtained from preoperative venous blood samples performed within 30 days from scheduled surgery and was analyzed in relation to histopathological reports, as was the presence of malignancy. Statistical analysis was performed using a Kruskal−Wallis Test, and univariate and multivariate logistic regression analysis, assuming p < 0.05 to be statistically significant. Results: A total of 510 patients were included in the study (81% male, 19% female), with a mean age of 71.66 ± 11.64 years. The mean FAR was significantly higher in patients with low-grade and high-grade bladder cancer, with values of 80.71 ± 23.15 and 84.93 ± 29.96, respectively, compared to patients without cancer (75.50 ± 24.81) (p = 0.006). Univariate regression analysis reported FAR to be irrelevant when considered as a continuous variable (OR = 1.013, 95% CI = 1.004−1.022; p = 0.004), while when considered as a categorical variable, utilizing a cut-off set at 76, OR was 2.062 (95% CI = 1.378−3.084; p < 0.0001). Nevertheless, the data were not confirmed in the multivariate analysis. Conclusions: Elevated preoperative FAR is a potential predictor of malignancy as well as advanced grade in patients with bladder cancer. Further data are required to suggest a promising role of the fibrinogen-to-albumin ratio as a diagnostic biomarker for bladder tumors.

The Role of Testosterone in the Elderly: What Do We Know?

Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains.

Numerical and experimental characterization of a novel modular passive micromixer.

This paper reports a new low-cost passive microfluidic mixer design, based on a replication of identical mixing units composed of microchannels with variable curvature (clothoid) geometry. The micromixer presents a compact and modular architecture that can be easily fabricated using a simple and reliable fabrication process. The particular clothoid-based geometry enhances the mixing by inducing transversal secondary flows and recirculation effects. The role of the relevant fluid mechanics mechanisms promoting the mixing in this geometry were analysed using computational fluid dynamics (CFD) for Reynolds numbers ranging from 1 to 110. A measure of mixing potency was quantitatively evaluated by calculating mixing efficiency, while a measure of particle dispersion was assessed through the lacunarity index. The results show that the secondary flow arrangement and recirculation effects are able to provide a mixing efficiency equal to 80 % at Reynolds number above 70. In addition, the analysis of particles distribution promotes the lacunarity as powerful tool to quantify the dispersion of fluid particles and, in turn, the overall mixing. On fabricated micromixer prototypes the microscopic-Laser-Induced-Fluorescence (µLIF) technique was applied to characterize mixing. The experimental results confirmed the mixing potency of the microdevice.

Biomechanics of actin filaments: a computational multi-level study.

The actin microfilament (F-actin) is a structural and functional component of the cell cytoskeleton. Notwithstanding the primary role it plays for the mechanics of the cell, the mechanical behaviour of F-actin is still not totally explored. In particular, the relationship between the mechanics of F-actin and its molecular architecture is not completely understood. In this study, the mechanical properties of F-actin were related to the molecular topology of its building monomers (G-actin) by employing a computational multi-level approach. F-actins with lengths up to 500 nm were modelled and characterized, using a combination of equilibrium molecular dynamics (MD) simulations and normal mode analysis (NMA). MD simulations were performed to analyze the molecular rearrangements of G-actin in physiological conditions; NMA was applied to compute the macroscopic properties of F-actin from its vibrational modes of motion. Results from this multi-level approach showed that bending stiffness, bending modulus and persistence length are independent from the length of F-actin. On the contrary, the orientations and motions of selected groups of residues of G-actin play a primary role in determining the filament flexibility. In conclusion, this study (i) demonstrated that a combined computational approach of MD and NMA allows to investigate the biomechanics of F-actin taking into account the molecular topology of the filament (i.e., the molecular conformations of G-actin) and (ii) that this can be done using only crystallographic G-actin, without the need of introducing experimental parameters nor of reducing the number of residues.

Repeatability of innervation zone identification in the external anal sphincter muscle.

AIMS: Knowledge of the distribution of the innervation zones (IZs) of the external anal sphincter (EAS) may be useful for preventing anal sphincter incompetence during vaginal delivery. A method proposed for the automatic estimation of the distribution of IZs of EAS from high-density surface electromyography (EMG) was evaluated for repeatability in continent volunteers. METHODS: In 13 healthy female subjects (age: 35 +/- 11 years) surface EMG signals were acquired using an anal probe with three circumferential electrode arrays (of 16 contacts each) at different depths within the anal canal (15 mm distance between the centers of adjacent arrays), during four independent experimental sessions. Three maximal voluntary contractions (MVCs) of 10 sec were performed for each session for a total of 12 contractions per subject. Repeatability of the estimation of the distribution of IZ was tested by evaluating the coefficient of multiple correlations (CMC) between the IZ distributions estimated from the signals recorded from each subject. RESULTS: A high repeatability (CMC > 0.8) was found comparing IZ distributions estimated from signals recorded by each array within the same session. A slightly lower value was obtained considering signals recorded during different sessions (CMC > 0.7), but a higher value (CMC > 0.8) was obtained after aligning the estimated IZ distributions. The realignment compensates for the operator's error in repositioning the probe in the same position during different sessions. CONCLUSION: This result justifies clinical studies using high-density surface EMG in routine examinations, providing information about IZs of EAS and assessing the possibilities of preventing neuronal trauma during vaginal delivery.

Long-term results of a randomized study comparing three immunosuppressive schedules with cyclosporine in cadaveric kidney transplantation.

In this randomized controlled trial started in October 1990, 354 cadaveric kidney transplant recipients were assigned to receive either cyclosporine (CsA) monotherapy (115 patients), CsA + steroids (117 patients), or CsA + steroids + azathioprine (122 patients). The median follow-up was 85.1 mo. Thirty-one deaths occurred (infection, 12; cardiovascular disease, 11; neoplasia, 4; and others, 4), and 65 grafts were lost, mostly due to acute (15) or chronic rejection (50). The cumulative graft half-life was 18.1 yr. According to the "intention-to-treat," the 9-yr actuarial patient and graft survival were 94.0% and 73.3%, respectively, in monotherapy, 87.3% and 65.9% in dual therapy, and 87% and 72.2% in triple therapy (P = 0.647). At the last follow-up, the percentage of patients who remained with the original treatment was 51.2% in monotherapy, 81.7% in dual therapy, and 63.3% in triple therapy. At the seventh year, the mean creatinine clearances were 54.9 +/- 17.6 ml/min in monotherapy, 57.9 +/- 23.4 in dual therapy, and 60.6 +/- 20.7 in triple therapy (P = 0.375). Cataracts (P = 0.000), osteoporosis (P = 0.000), and cardiovascular complications (P = 0.000) were more frequent in dual or triple therapy than in monotherapy. Actuarial graft survival at 9 yr in patients on monotherapy who had to have steroids added was similar to that of the other two groups (62.2% versus 69.3%, P = 0.134). In conclusion, actuarial patient and graft survivals did not differ among the three schemes. The long-term renal function and survival were not affected in the patients on monotherapy who needed the addition of steroids. Monotherapy was associated with a lower incidence of extrarenal complications than the other two regimens.