Effect of body mass and physical activity at younger age on the risk of prostatic enlargement and erectile dysfunction : Results from the 2018 #Controllati survey

Objective: Overweight and low physical activity (PA) increase the risk of prostatic enlargement and erectile dysfunction (ED). Less clear is the role of these factors at young age on the lifelong risk. Materials and methods: During June 2018 the Italian Society of Urologists organized the month of Male Urologic Prevention "#Controllati". Men aged 18 years or more were invited to attend urologic centers for a visit and counselling about urologic/andrologic conditions. Each participating man underwent a physical examination and was asked about urologic symptoms, sexual activity and possible related problems. Results: We analyzed data from 2786 men, aged 55.1 years (SD 10.9, range 19-97). A total of 710 (25.5%) subjects had a diagnosis of prostatic enlargement and 632 (22.7%) of DE. Overweight/obese men were at increased risk of prostatic enlargement and ED with corresponding odds ratio (0R) in comparison with normal or underweight men, being respectively 1.18 (95% Confidence Interval (CI) 1.00-1.44) and 1.69 (95% CI 1.39-2.05). The OR of prostatic enlargement in comparison with men reporting at age 25 a BMI < 25.0 was 1.22 (95% CI 1.01-1.51) for men with a BMI at 25 years of age 65 25; the corresponding OR value for ED was 1.17 (0.92- 1.48). Considering total PA at diagnosis, the OR of prostatic enlargement in comparison with no or low PA, was 0.69 (95%CI 0.55-0.86) for men reporting moderate PA and 0.75 (95%CI 0.58-0.98) for those reporting intense PA. When we considered PA at 25 years of age, the OR of subsequent diagnosis of prostatic enlargement, in comparison with men reporting no/low PA at 25 years of age was 0.81 (95%CI 0.63-1.04) for men reporting moderate PA and 0.70 (95%CI 0.52-0.99) for those reporting intense PA. Conclusions: These findings underline the utility of encouraging healthy lifestyle habits among young men in order to reduce the subsequent risk of prostatic enlargement and ED

Shock induction by arterial hypoperfusion of the gut involves synergistic interactions between the peripheral enkephalin and nitric oxide systems.

To determine whether critical splanchnic artery hypoperfusion can provoke systemic shock and to identify the roles of the peripheral opioid and nitric oxide (NO) systems in this process, various degrees of superior mesenteric artery hypoperfusion (SMA-H) were produced in anesthetized adult rabbits (n=40), and hemodynamic and metabolic indices were measured. Metabolic acidosis and irreversible hypodynamic shock occurred with SMA-H at levels representing 25–20% of mean baseline SMA blood flow. In 112 other rabbits subjected to SMA-H at 20% (SMA-H20%), we studied plasma NO and enkephalin (ENK) levels, cardiovascular reactivity to selected physiological agonists, effects of ENKs on plasma NO levels, and effects of peripheral opioid receptor blockade and inducible NO synthase (iNOS) inhibition. SMA-H20% progressively increased systemic blood levels of NO and ENKs. Exogenous ENK administration accentuated SMA-H20%-induced increases in plasma NO levels, and their cardiovascular depressing effects were significantly greater when they were administered during SMA-H20% (vs. administration under baseline conditions). Selective blockade of cardiovascular δ-opioid receptors improved hemodynamics, prevented shock irreversibility and reduced plasma NO levels; similar effects were obtained by selective iNOS inhibition. These findings demonstrate that critical arterial hypoperfusion of the gut can induce hypodynamic systemic shock through ENK-induced hyperactivation of cardiovascular δ-opioid receptors, which leads to increased plasma levels of NO related in part to increased iNOS activity. Since pronounced splanchnic artery hypoperfusion occurs in all advanced systemic shock states, selective δ-opioid receptor antagonists and/or iNOS inhibitors may prove to be useful in improving shock hemodynamics and metabolic derangements and/or preventing progression toward irreversibility

Comparison between Two Different Two-Stage Transperineal Approaches to Treat Urethral Strictures or Bladder Neck Contracture Associated with Severe Urinary Incontinence that Occurred after Pelvic Surgery: Report of Our Experience

Introduction. The recurrence of urethral/bladder neck stricture after multiple endoscopic procedures is a rare complication that can follow prostatic surgery and its treatment is still controversial. Material and Methods. We retrospectively analyzed our data on 17 patients, operated between September 2001 and January 2010, who presented severe urinary incontinence and urethral/bladder neck stricture after prostatic surgery and failure of at least four conservative endoscopic treatments. Six patients underwent a transperineal urethrovesical anastomosis and 11 patients a combined transperineal suprapubical (endoscopic) urethrovesical anastomosis. After six months the patients that presented complete incontinence and no urethral stricture underwent the implantation of an artificial urethral sphincter (AUS). Results. After six months 16 patients were completely incontinent and presented a patent, stable lumen, so that they underwent an AUS implantation. With a mean followup of 50.5 months, 14 patients are perfectly continent with no postvoid residual urine. Conclusions. Two-stage procedures are safe techniques to treat these challenging cases. In our opinion, these cases could be managed with a transperineal approach in patients who present a perfect operative field; on the contrary, in more difficult cases, it would be preferable to use the other technique, with a combined transperineal suprapubical access, to perform a pull-through procedure

Mobile Daily Centre (Mdc) for Elder People with Cognitive Impairment: a Retrospective Observational Study

Introduction Trieste is a city characterized by a high mean age of the resident population, with 6,000 people with a cognitive impairment. Evidences show that is necessary to have a multidisciplinary approach, making alliances with the social network and families, while dealing with people with cognitive impairment. Because of this, the 3rd catchment district has developed a Mobile Daily Centre that aims to promote health, abilities and socialization giving the possibilities for these people to stay in a social context. Objectives Evaluating the impact of the Mobile Daily Centre on QoL of people with Cognitive Impairment. Aims Considering the rate of hospitalization and access to the first aid unit at the general hospital. Methods Retrospective Observational Study for the period between 01.01.2012 and 30.04.2014 on people in charge to the MDC. We have considered socio-demographic variables such as age, gender, care-givers; clinical variables such as psychopharmacotherapy and acetylcolinesterase-inhibitors drugs; rates of hospitalization, number of accesses to the first aid unit and of interventions of the MDC. Results in the period of the study 20 patients have been followed by the MDC; half of them had a psycho-pharmacological prescription. Very low rates of institutionalization have been detected. Conclusions MDC, in these small numbers, has shown to reduce the number of improper institutionalizations while guaranteeing to the elder people to maintain their abilities and socialization and to their care-givers periods of relief. Moreover, it promotes social inclusion and destigmatization. These results suggest that more territorial work and further studies should be done

Does Exist a Differential Impact of Degarelix Versus LHRH Agonists on Cardiovascular Safety? Evidences From Randomized and Real-World Studies

The main systemic therapy for the management of hormone-sensitive prostate cancer (PC) is androgen deprivation therapy (ADT), with the use of long-acting luteinizing hormone releasing-hormone (LHRH) agonists considered the main form of ADT used in clinical practice to obtain castration in PC. The concomitant administration of antiandrogens for the first weeks could reduce the incidence of clinical effects related to the testosterone flare-up in the first injection of LHRH. On the contrary, Gonadotropin Rh (GnRH) antagonists produce a rapid decrease of testosterone levels without the initial flare-up, with degarelix commonly used in clinical practice to induce castration in PC patients. Even if no long-term data are reported in terms of survival to define a superiority of GnRH or LHRH, for oncological efficacy and PC control, data from randomized clinical trials and from real-life experiences, suggest a difference in cardiovascular risk of patients starting ADT. The age-related decline in testosterone levels may represent a factor connected to the increase of cardiovascular disease risk, however, the role of ADT in increasing CV events remains controversial. For these reasons, the aim of the paper is to synthesize the difference in cardiovascular risk between LHRH and degarelix in patients undergoing ADT. A difference in cardiovascular risk could be indeed an important parameter in the evaluation of these two forms of castration therapy. The Randomized trials analyzed in this paper sustain a possible protective role for degarelix versus LHRH agonists in reducing the rate of new CV events and interventions in the short-term period. On the contrary, real-word data are contradictory in different national experiences and are strongly conditioned by huge differences between the LHRH agonists group and the degarelix group

Safety and feasibility of thullium laser transurethral resection of prostate for the treatment of benign prostatic enlargement in overweight patients

Objective: We aimed to determine safety and feasibility of thulium laser transurethral vapoenucleation of prostate (ThuVEP) for treatment of obese patients affected by benign prostatic hyperplasia (BPH). Methods: We retrospectively analysed data of 452 patients with BPH who underwent ThuVEP from February 2012 to March 2016 in a single center. Patients were divided into three groups according to body mass index (BMI, kg/m2): Normal weight (18.5 64 BMI < 25; Group A), overweight (25 64 BMI < 30; Group B) and obese (BMI 65 30; Group C), for a total of 412 patients evaluable for this study. Preoperative total serum prostate-specific antigen (PSA), digital rectal examination of the prostate, transrectal ultrasound (TRUS), renal ultrasound, urine culture, uroflowmetry, International Prostate Symptoms Score (IPSS), and Quality of Life (QoL) score were analyzed. Post-operative complications, hospital stay and days of catheterization, questionnaires and uroflowmetry at 1 and 3 months after surgery were evaluated. Preoperative data, surgical outcomes, complication rate and clinical outcomes were compared between groups. Results: The median age of patients was 69 years (Interquartile Range [IQR 10]). The preoperative median IPSS among groups was 19 (IQR 8.75), 20 (IQR 10), and 18 (IQR 10) respectively. At 1 and 3 months of follow-up, this value was 8 (IQR 7), 8 (IQR 4), 7 (IQR 5) and 5 (IQR 6.25), 5 (IQR 6), 6 (IQR 5), respectively (all p between groups > 0.05). There was no statistically significant difference among three groups as for hospital stay and days of catheterization (p > 0.05). Conclusion: Our results showed that ThuVEP was safe and feasible even in overweight patients with substantially enlarged prostate

An optimized derivative of an endogenous CXCR4 antagonist prevents atopic dermatitis and airway inflammation

Aberrant CXCR4/CXCL12 signaling is involved in many pathophysiological processes such as cancer and inflammatory diseases. A natural fragment of serum albumin, named EPI-X4, has previously been identified as endogenous peptide antagonist and inverse agonist of CXCR4 and is a promising compound for the development of improved analogues for the therapy of CXCR4-associated diseases. To generate optimized EPI-X4 derivatives we here performed molecular docking analysis to identify key interaction motifs of EPI-X4/CXCR4. Subsequent rational drug design allowed to increase the anti-CXCR4 activity of EPI-X4. The EPI-X4 derivative JM#21 bound CXCR4 and suppressed CXCR4-tropic HIV-1 infection more efficiently than the clinically approved small molecule CXCR4 antagonist AMD3100. EPI-X4 JM#21 did not exert toxic effects in zebrafish embryos and suppressed allergen-induced infiltration of eosinophils and other immune cells into the airways of animals in an asthma mouse model. Moreover, topical administration of the optimized EPI-X4 derivative efficiently prevented inflammation of the skin in a mouse model of atopic dermatitis. Thus, rationally designed EPI-X4 JM#21 is a novel potent antagonist of CXCR4 and the first CXCR4 inhibitor with therapeutic efficacy in atopic dermatitis. Further clinical development of this new class of CXCR4 antagonists for the therapy of atopic dermatitis, asthma and other CXCR4-associated diseases is highly warranted