Fifty years of basic and clinical renal stone research: have we achieved major breakthroughs? A debate.

PURPOSE OF REVIEW: After 50 years of basic and clinical renal stone research, it is appropriate to evaluate whether breakthroughs have been achieved and if so, how they may be harnessed to combat stone disease therapeutically and prophylactically. RECENT FINDINGS: Regarding stone therapeutics and prophylaxis, recent innovative studies are sparse. Researchers have resorted to publishing articles derived from data mining. Stone incidence and prevalence have increased during the past 50 years, suggesting the absence of any major breakthroughs. However, new sciences and technologies have created fresh opportunities. Information technology stores huge epidemiological databases leading to identification of new risk factors. Genetic coding has prompted identification of monogenic diseases associated with urolithiasis. Genome-wide association studies in combination with epigenomics, transcriptomics, proteomics, and metabolomics are providing new insights. High-throughput and culture-independent techniques promise to define the impact of microbiome on stone formation while artificial intelligent techniques contribute to diagnosis and prediction of treatment outcomes. These technologies, as well as those which are advancing surgical treatment of stones represent major breakthroughs in stone research. SUMMARY: Although efforts to cure stones have not yielded major breakthroughs, technological advances have improved surgical management of this disease and represent significant headway in applied stone research.

Erectile and Ejaculatory Dysfunction Associated with Use of Psychotropic Drugs: A Systematic Review.

BACKGROUND: Sexual dysfunction may be a side effect of treatment with antipsychotics, antidepressants, and other psychotropic drugs. AIM: To review the evidence concerning male sexual dysfunctions in patients taking psychotropic drugs to provide specific information to nonpsychiatric physicians for the management of these dysfunctions. METHODS: A systematic search of Medline and Embase databases was performed up to October 15th, 2020. We included randomized controlled trials comparing the effects of psychotropic drugs versus placebo or versus another drug of the same class, for at least 5 weeks. OUTCOMES: We considered studies whose male population could be evaluated separately from the female population and with a separate analysis of the different phases of the male sex cycle. RESULTS: We included 41 studies in the final review. There was a significant association between sexual dysfunction and antidepressant drug therapy, compared to placebo (decreased libido OR 1.89, 95% CI:1.40 to 2.56, 22 series, 11 trials, 7706 participants; erectile dysfunction OR = 2.28, 95% CI: 1.31 to 3.97; 11 trials, 3008 participants; ejaculatory dysfunction OR = 7.31, 95% CI: 4.38 to 12.20,19 trials, 3973 participants). When the effects of selective serotonin reuptake inhibitors (SSRIs) were evaluated separately from those of serotonin/norepinephrine reuptake inhibitors (SNRIs), the use of SNRIs but not that of SSRIs was characterized by significantly higher odds of erectile dysfunction compared to placebo. Only limited data were found regarding the effects of antipsychotics on the phases of the male sexual cycle, as it was shown that aripiprazole and risperidone showed lower and higher odds for erectile or ejaculatory dysfunction, respectively, compared to other atypical antipsychotics. CLINICAL IMPLICATIONS: Treatment of male sexual dysfunction in patients taking psychotropics requires a basic knowledge of the different drugs that affect sexual function with different mechanisms. STRENGTHS & LIMITATIONS: The effects of psychotropic drugs on erectile function and ejaculation were evaluated separately. The great variability of the mechanisms of action makes it difficult to make comparisons between the effects of the different classes of psychotropic drugs. CONCLUSIONS: Administration of antipsychotics affects male sexual function with different mechanisms, although the increase in prolactin values associated with the administration of first-generation antipsychotics and some atypical, such as risperidone, seems to play a primary role in determining male sexual dysfunction. Most antidepressants cause decreased libido, ejaculatory and erectile dysfunction, however the administration of SNRIs appears to be possibly associated with a specific risk of erectile dysfunction. Trinchieri M, Trinchieri M, Perletti G, et al. Erectile and Ejaculatory Dysfunction Associated with Use of Psychotropic Drugs: A Systematic Review. J Sex Med 2021;18:1354-1363.

Urinary side effects of psychotropic drugs: A systematic review and metanalysis.

OBJECTIVE: To evaluate the effects of psychotropic drugs on bladder function. MATERIALS AND METHODS: A systematic review was carried out by searching PubMed and Embase databases for randomized controlled trials enrolling patients treated with psychotropic drugs with available information on treatment-related urinary disorders. RESULTS: A total of 52 studies was selected. In antidepressant therapy, bladder voiding symptoms, rather than storage symptoms, were more frequently observed. Pooled analysis demonstrated a higher odds ratio (OR) of voiding  disorders in comparison with placebo (OR: 3.30; confidence interval [CI]: 1.90-5.72; 7856 participants; p < 0.001). Odds for voiding dysfunction was higher for tricyclic antidepressants and for Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) when compared to Selective Serotonin Reuptake Inhibitors (SSRIs). Treatment with antipsychotics was associated with heterogeneous urinary disorders  including emptying and storage disorders. OR for incontinence in patients with dementia taking  antipsychotics was higher than placebo (OR: 4.09; CI: 1.71-9.79, p = 0.002) with no difference between different atypical antipsychotics. Rate of voiding disorders was not different between conventional and atypical antipsychotics (OR: 1.64; CI: 0.79-3.39, p = 0.19), although quetiapine showed higher odds to cause voiding dysfunction than other atypical antipsychotics (OR: 2.14; CI: 1.41-3.26; p > 0.001). CONCLUSIONS: In patients taking tricyclic antidepressants or SNRIs, bladder voiding disorders, could be the side effects of therapy rather than symptoms of a urological disease. Patients treated with these drugs should be actively monitored for the appearance of urinary symptoms. Antipsychotic treatment is associated with various urinary side effects requiring a tailored approach.

Lithogenic Potential of Ureaplasma in Chronic Prostatitis.

INTRODUCTION: The role of Ureaplasma spp. (UPs) in the pathogenesis of chronic prostatitis is debated. The lithogenic potential of UPs could be a risk factor for the development of chronic prostatitis. METHODS: A total of 143 patients with identification of UPs were retrospectively selected from a database including patients with prostatitis-like symptoms who were studied according to the same protocol including clinical, microbiological and microscopic evaluation, and transrectal prostate ultrasound. A control group of patients with negative UPs was considered including 393 with chronic bacterial prostatitis (CBP), 42 patients with Chlamydia trachomatis (CT), and 781 patients with chronic pelvic pain syndrome. UPs and Mycoplasma hominis (MH) were identified using a semiquantitative assay. RESULTS: Calcifications were observed more frequently in patients with UPs (64%) than in patients with CBP without UPs (39%), CT infection (37%), and chronic pelvic pain syndrome (29%) (p < 0.0001). UPs were isolated in VB1 alone in 35 patients (urethral UPs), in expressed prostatic secretion (EPS) or post-massage urine (VB3) or sperm in 77 patients (prostatic UPs) and associated with other pathogens in 31 patients (associated UPs). Calcifications were more frequent in prostatic UPs (71%) and associated UPs (73%) than in urethral UPs (34%). Mean NIH-CPSI scores were not significantly different between groups, although mean WBC counts of sperm of patients with urethral UPs were significantly lower than in patients with prostatic UPs (p = 0.000) and associated UPs (p = 0.002). CONCLUSIONS: UPs identification in the urogenital fluids is related to higher rates of prostate calcifications. The ability of UPs to promote the formation of calcifications could be related to the chronicization of prostate infection. In particular, the presence of UPs in VB3/EPS/sperm is associated with higher rates of calcifications and high WBC sperm counts, suggesting a partial or full causative role of UPs in the pathogenesis of this disease.

Impact of Kidney Transplantation on Male Sexual Function: Results from a Ten-Year Retrospective Study.

BACKGROUND: The effects of kidney transplantation on male sexual function are controversial. AIM: To evaluate the impact of kidney transplantation on erectile and ejaculatory function and to assess a possible correlation between some selected characteristics of patients and their erectile and ejaculatory function after renal transplantation. METHODS: An observational retrospective analysis was conducted on male patients who had undergone kidney transplantation from January 2009 to April 2019. A prospectively maintained database was used to collect all data. Patients were evaluated before kidney transplant and 6 and 12 months after kidney transplant. Male patients undergoing renal transplantation for any cause who were sexually active with a stable partner were included in the study. OUTCOMES: The main outcome measures included the International Index of Erectile Function (IIEF-15) and the 4-item version of Male Sexual Health Quality-Ejaculation Disorders (MSHQ-EjD Short Form) questionnaires. The first 3 questions of the MSHQ-EjD Short Form were used to assess the ejaculatory function, whereas the fourth question was used to evaluate the ejaculation bother. RESULTS: A total of 95 patients were eligible in the study. The evaluation of sexual function was available in 56 patients (58.9%). Mean IIEF-15 significantly decreased at 6 months (P < .001) remaining unchanged at 12 months (P = .228). Mean MSHQ-EjD Short Form (1-3) significantly decreased at 6-month follow-up (P < .001) and at 12-month follow-up (P = .024). Mean MSHQ-EjD Short Form (4) was significantly increased compared with the baseline at both 6 and 12 months (P < .05). IIEF-15 was significantly related to the MSHQ-EjD Short Form at 6-month and 12-month follow-up (P < .001). Age, diabetes, hypertension, smoking, pretransplantation testosterone, time for transplantation, baseline IIEF-15, and baseline MSHQ-EjD Short Form (1-3) were significantly associated (P < .05) with both IIEF-15 and the MSHQ-EjD Short Form (1-3) at 6-month and 12-month follow-up after kidney transplantation. CLINICAL IMPLICATIONS: Improvement of knowledge regarding the effects of kidney transplantation on sexual function and about the patient characteristics related to sexual health after transplantation. STRENGTH & LIMITATIONS: This is the first article that analyzes in depth the ejaculatory function in patients who had undergone kidney transplantation assessing ejaculation with a validated questionnaire. The main limitation is the retrospective design of the study. CONCLUSION: Kidney transplantation appears to have a negative impact on sexual health, significantly worsening both erectile and ejaculatory functions. Age, diabetes, hypertension, smoking, pretransplantation testosterone levels, time for transplantation, as well as erectile and ejaculatory function before transplant were significantly related to erectile and ejaculatory functions after renal transplantation. Spirito L, Manfredi C, Carrano R, et al. Impact of Kidney Transplantation on Male Sexual Function: Results from a Ten-Year Retrospective Study. J Sex Med 2020;17:2191-2197.

Bacterial spectrum and antibiotic resistance of urinary tract infections in patients treated for upper urinary tract calculi: a multicenter analysis.

The purpose of this study is to collect information on the bacterial resistance to antibiotics of bacteria isolated from urine cultures of patients treated for upper urinary tract calculi. Data of patients with urinary tract infection and urolithiasis were retrospectively reviewed to collect information on age, gender, stone size, location, hydronephrosis, procedure of stone removal and antibiotic treatment, identification and susceptibility of pathogens, symptoms, and infectious complications. A total of 912 patients from 11 centers in 7 countries (Bulgaria, Greece, Italy, North Macedonia, Spain, and Turkey) were studied. Mean age was 54 ± 16 years and M/F ratio 322/590. Out of 946 microbial isolates, the most common were E. coli, Gram-positive, KES group (Klebsiella, Enterobacter, Serratia), Proteus spp., and P. aeruginosa. Carbapenems, piperacillin/tazobactam and amikacin showed low resistance rates to E. coli (2.5%, 7%, and 3.6%) and Proteus spp. (7.7%, 16%, and 7.4%), but higher rates were observed with Klebsiella spp., P. aeruginosa, and Gram-positive. Fosfomycin had resistance rates less than 10% to E. coli, 23% to KES group, and 19% to Gram-positive. Amoxicillin/clavulanate, cephalosporins, quinolones, and TMP/SMX showed high resistance rates to most bacterial strains. High rates of antibiotic resistance were observed in patients candidate to stone treatment from South-Eastern Europe. The empirical use of antibiotics with low resistance rates should be reserved to the most serious cases to avoid the increase of multidrug resistant bacteria. Basing on our results, carbapenems, piperacillin/tazobactam, and amikacin may be a possible option for empiric treatment of urinary stone patients showing systemic symptoms.

Time changes in the spectrum of urinary stone composition: a role for climate variations?

BACKGROUND: An increase of the frequency of uric acid urinary stones compared to calcium-containing ones has been recently described. This study was aimed at assessing the frequency of different types of urinary stones in the population of northern Italy in the period 2016-18 compared to 2001-2003. METHODS: Analyses by infrared spectroscopy of 1007 stones endoscopically removed at two institutions in the area of Milan (Northern Italy) were retrospectively considered. Stones were classified as calcium oxalate monohydrate (COM) and dihydrate (COD), mixed uric acid/calcium oxalate (UC); uric acid (UA), struvite (ST); apatite (CAP); mixed calcium oxalate / apatite (CAPOX); others. The patients were divided into two groups: 2001-2003 and 2016-2018. The average temperature values of the region over the two time periods were obtained by the national statistical institute. RESULTS: The average age of the 2001-2003 group (45.8+/- 15.4 years) was significantly lower than the average age of the 2016-18 group (57.9+/- 14.8) (0.000). M / F ratio was similar in the two groups: 119 / 69 (1,0.58) in 2001-2003 and 527 / 292 (1,0.55) in 2016-18 (p = 0.862). COM stones tended to more frequent in 2016-18 group than in 2001-03. COD stones were significantly more frequent in 2001-03 than in 2016-18. ST stone frequency was increased from 2001 to 03 to 2016-18. No increase of uric acid containing stones was observed in 2016-18. Results were confirmed after adjustment by age. Averages annual regional temperatures increased from 14 °C to 15.4 °C during the two observation periods. CONCLUSIONS: No increase of UA stones was observed, probably due to the limited impact of the global warming in our temperate climate.

Radiation exposure of patients during endourological procedures: IAEA-SEGUR study.

Fluoroscopy is increasingly used to guide minimally invasive endourological procedures and optimised protocols are needed to minimise radiation exposure while achieving best treatment results. This multi-center study of radiation exposure of patients was conducted by the South-Eastern European Group for Urolithiasis Research (SEGUR), in cooperation with the International Atomic Energy Agency. Seven clinical centers from the SEGUR group collected data for 325 procedures performed within a three-months period, including standard percutaneous nephrolithotomy (PCNL), mini PCNL, retrograde intrarenal surgery (RIRS), semirigid ureterorenoscopy (URS) and flexible URS. Data included: air kerma area product (PKA), air kerma at the patient entrance reference point (Ka,r), fluoroscopy time (FT), number of radiographic images (N) and fluoroscopy pulse rate, as well as total procedure duration, size and location of stones. Data were centrally analysed and statistically compared. MedianPKAvalues per center varied 2-fold for RIRS (0.80-1.79 Gy cm2), 7.1 fold for mini-PCNL (1.39-9.90 Gy cm2), 7.3 fold for PCNL (2.40-17.50 Gy cm2), 19 fold (0.13-2.51 Gy cm2) for semi-rigid URS and 29-fold for flexible URS (0.10-2.90 Gy cm2). LowerPKAandKa,rwere associated with use of lower FT,Nand lower fluoroscopy pulse rate. FT varied from 0.1 to 14 min, a small fraction of the total procedure time, ranging from 10 to 225 min. HigherNwas associated with higherPKAandKa,r. Higher medianPKAin PCNL was associated with the use of supine compared to prone position. No correlation was found between the concrement size and procedure duration, FT,PKAorKa,r. Dose values for RIRS were significantly lower compared to PCNL. The maximumKa,rvalue of 377 mGy was under the threshold for radiation induced skin erythema. The study demonstrated a potential for patient dose reduction by lowering FT andN, using pulsed fluoroscopy and beam collimation.

Levofloxacin for NIH Category II Chronic Bacterial Prostatitis: A Real-Life Study.

BACKGROUND: Mounting worldwide resistance trends make the use of fluoroquinolone (FQ) antibacterial agents increasingly difficult. This is felt more acutely in the case of urogenital infections, which are mainly caused by Gram-negative pathogens. For years, levofloxacin and other FQs have been the first-line drugs for treating National Institutes of Health (NIH) category II chronic bacteria prostatitis (CBP). Eradication rates achieved by levofloxacin in the frame of randomized trials vary greatly, ranging between 71 and 86%. OBJECTIVES: This was a retrospective observational study to investigate the efficacy of levofloxacin against CBP in a real-life setting (urological outpatient wards). METHODS: A database including the clinical records of >2,500 CBP patients was reviewed. Patients were selected based on strict inclusion criteria. They were treated for 4 weeks with 500 mg levofloxacin per day, alone or combined with other antibacterials. Besides standard urological procedures including the 4-glass test for pathogen isolation, international symptom questionnaires (the NIH Chronic Prostatitis Symptom Index [NIH-CPSI] and International Prostate Symptom Score [IPSS]) were administered. RESULTS: Pathogen eradication was achieved in 79% of the cases treated with levofloxacin as a single agent and 87.8% of patients who received a combination of levofloxacin and azithromycin. The 11% increase in the eradication rate in the latter group is statistically significant. In addition, the levofloxacin-azithromycin combination caused a significant decrease in prostate volume and significantly increased the bladder-voided volume. IPSS and NIH-CPSI values and the urinary peak flow rate decreased to a similar extent in both treatment groups. No adverse effects were reported by patients belonging to either treatment group. CONCLUSION: Levofloxacin retained its therapeutic efficacy in patients assessed in a real-life setting, and high eradication rates were attained when it was administered as a single agent. A combination of an FQ with azithromycin induced a significant improvement of eradication rates. This strategy may be an interesting option in both first-referral and relapsing cases, although caution should be exercised when patients are at risk of developing arrhythmias, tendinitis, or other adverse effects.

Multidisciplinary approach to prostatitis.

The modern clinical research on prostatitis started with the work of Stamey and coworkers who developed the basic principles we are still using. They established the segmented culture technique for localizing the infections in the males to the urethra, the bladder, or the prostate and to differentiate the main categories of prostatitis. Such categories with slight modifications are still used according to the NIH classification: acute bacterial prostatitis, chronic bacterial prostatitis, Chronic Pelvic Pain Syndrome (CPPS) and asymptomatic prostatitis. Prostatic inflammation is considered an important factor in influencing both prostatic growth and progression of symptoms of benign prostatic hyperplasia and prostatitis. Chronic inflammation/neuroinflammation is a result of a deregulated acute phase response of the innate immune system affecting surrounding neural tissue at molecular, structural and functional levels. Clinical observations suggest that chronic inflammation correlates with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and benign prostatic hyperplasia (BPH) and an history of clinical chronic prostatitis significantly increases the odds for prostate cancer. The NIHNIDDK classification based on the use of the microbiological 4- glasses localization test or simplified 2-glasses test, is currently accepted worldwide. The UPOINT system identifies groups of clinicians with homogeneous clinical presentation and is used to recognize phenotypes to be submitted to specific treatments. The UPOINTS algorithm implemented the original UPOINT adding to the urinary domains (U), psycho-social (P), organspecific (O), infection (I), neurological (N), muscle tension and tenderness (T) a further domain related to sexuality (S). In fact sexual dysfunction (erectile, ejaculatory, libido loss) has been described in 46-92% of cases with a high impact on the quality of life of patients with CP/CPPS. Prostatic ultrasound represents the most popular imaging test in the work-up of either acute and chronic prostatitis although no specific hypo-hyperechoic pattern has been clearly associated with chronic bacterial prostatitis and CPPS. Use of a digital-processing software to calculate the extension of prostatic calcification area at ultrasound demonstrated a higher percentage of prostatic calcification in patients with chronic bacterial prostatitis. Multiparametric Magnetic Resonance Imaging (mpMRI) is the current state-of-the art imaging modality in the assessment of patients with prostate cancer although a variety of benign conditions, including inflammation, may mimic prostate cancer and act as confounding factors in the discrimination between neoplastic and non-neoplastic lesions. Bacteria can infect prostate gland by: ascending the urethra, reflux of urine into the prostatic ducts, direct inoculation of bacteria through inserted biopsy needles or hematogenous seeding. Enterobacteriaceae are the predominant pathogens in acute and chronic bacterial prostatitis, but an increasing role of Enterococci has been reported. Many strains of these uropathogens exhibit the ability to form biofilm and multidrug- resistance. Sexually Transmitted Infections (STI) agents, in particular Chlamydia trachomatis and Mycoplasma genitalium, have been also considered as causative pathogens of chronic bacterial prostatitis. On the contrary the effective role in genital diseases of other "genital mycoplasmas" is still a much debated issue. Sexually Transmitted Infections agents should be investigated by molecular methods in both patient and sexual partner. "Next generation" investigations, such as cytokine analysis, cytological typing of immune cells could help stratifying the immune response. Epigenetic dysregulation of inflammatory factors should be investigated according to systemic and compartment-specific signals. The search for biomarkers should also include evaluation of hormonal pathways, as measurement of estrogen levels in semen. Antimicrobials are the first line agents for the treatment of bacterial prostatitis. The success of antimicrobial treatment depends on the antibacterial activity and the pharmacokinetic characteristics of the drug which must reach high concentrations in prostate secretion and prostate tissue. Acute bacterial prostatitis can be a serious infection with a potential risk for urosepsis For iInitial treatment of severely ill patients, intravenous administration of high doses of bactericidal antimicrobials, such as broad-spectrum penicillins, third-generation cephalosporins or fluoroquinolones, is recommended in combination with an aminoglycoside. Use of piperacillin-tazobactam and meropenem is justified in presence of multiresistant gramnegative pathogens. The antibiotic treatment of chronic prostatitis is currently based on the use of fluoroquinolones that, given for 2 to 4 weeks, cured about 70% of men with chronic bacterial prostatitis. For the treatment of Chlamydial prostatitis macrolides were shown to be more effective than fluoroquinolones, whereas no differences were observed in microbiological and clinical efficacy between macrolides and tetracyclines for the treatment of infections caused by intracellular pathogens. Aminoglycosides and fosfomycin could be considered as a therapeutic alternative for the treatment of quinolone resistant prostatitis. Use of alpha-blockers in CP/CPPS patients with urinary symptoms and analgesics +/- non steroidal anti-inflammatory drugs (NSAID), in presence of pain demonstrated a reduction of symptoms reduction and an improvement of quality of life, although long term use of NSAID is limited by side effect profile. However, the multimodal therapeutic regimen by contemporary use of alphablockers, antibiotics and anti-inflammatory showed a better control of prostatitis symptoms than single drug treatment. Novel therapeutic substances for the treatment of pain, such as the cannabinoid anandamide would be highly interesting to test. An alternative for the treatment of chronic prostatitis/chronic pelvic pain syndrome is phytotherapy, as primary therapy or in association with other drugs. Quercetin, pollen extract, extract of Serenoa repens and other mixtures of herbal extracts showed a positive effect on symptoms and quality of life without side effects. The association of CP/CPPS with alterations of intestinal function has been described. Diet has its effects on inflammation by regulation of the composition of intestinal flora and direct action on the intestinal cells (sterile inflammation). Intestinal bacteria (microbiota) interacts with food influencing the metabolic, immune and inflammatory response of the organism. The intestinal microbiota has protective function against pathogenic bacteria, metabolic function by synthesis of vitamins, decomposition of bile acids and production of trophic factors (butyrate), and modulation of the intestinal immune system. The alteration of the microbiota is called "dysbiosis" causing invasive intestinal diseases pathologies (leaky gut syndrome and food intolerances, irritable bowel syndrome or chronic inflammatory bowel diseases) and correlating with numerous systemic diseases including acute and chronic prostatitis. Administration of live probiotics bacteria can be used to regulate the balance if intestinal flora. Sessions of hydrocolontherapy can represent an integration to this therapeutic approach. Finally, microbiological examination of sexual partners can offer supplementary information for treatment.

Computer-Assisted Quantitative Assessment of Prostatic Calcifications in Patients with Chronic Prostatitis.

BACKGROUND: The aim of this study was the development of quantitative assessment of prostatic calcifications at prostatic ultrasound examination by the use of an image analyzer. MATERIALS AND METHODS: A group of 82 patients was evaluated by medical history, physical, and transrectal ultrasound examination. Patients had a urethral swab, a 4-specimen study and culture of the seminal fluid. Patients were classified according to National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health. Subjective symptoms were scored by Chronic Prostatitis Symptom Index (CPSI) questionnaire. Ultrasound images were analyzed by the digital processing software Image J to quantitatively assess the presence of calcifications. RESULTS: Computer-assessed calcified areas were significantly higher in chronic bacterial prostatitis (n = 18; group II; 6.76 ± 8.09%) than in the chronic pelvic pain syndrome group IIIa (n = 26; 2.07 ± 1.01%) and IIIb (n = 38; 2.31 ± 2.18%). The area of calcification of the prostate was significantly related to the CPSI score for domains of micturition (r = 0.278, p = 0.023), Prostatic Specific Antigen values (r = 0341, p = 0.005), postvoiding residual urine (r = 0.262, p = 0.032), total prostate volume (r = 0.592, p = 0.000), and adenoma volume (r = 0.593; p = 0.000). CONCLUSIONS: The presence of calcifications is more frequently observed in patients with chronic bacterial prostatitis and is related to urinary symptoms.

Resistance of uropathogens to antibacterial agents: Emerging threats, trends and treatments.

Urinary tract infections are among the most common infectious diseases in humans. Today, resistance to nearly all antimicrobial classes is dramatically growing, and extremely drug-resistant or even pan-drug resistant pathogens are increasingly isolated around the world. It is foreseen that in the next decades the world will be facing a major medical emergency generated by the rapid spread of pathogens carrying resistance determinants of unprecedented power. Carbapenemase-producing Enterobacteriaceae, multidrug- resistant Enterococci and fluoroquinolone resistance determinants in both Gram-negative and Gram-positive uropathogens are among the greatest emergencies. In this article, the major emerging threats of particular interest to urologists are reviewed, worldwide resistance trends are illustrated, and novel and older - but still active - recommended drugs are summarized.

Clinical utility of computed tomography Hounsfield characterization for percutaneous nephrolithotomy: a cross-sectional study.

BACKGROUND: Computed Tomography (CT) is considered the gold-standard for the pre-operative evaluation of urolithiasis. However, no Hounsfield (HU) variable capable of differentiating stone types has been clearly identified. The aim of this study is to assess the predictive value of HU parameters on CT for determining stone composition and outcomes in percutaneous nephrolithotomy (PCNL). METHODS: Seventy seven consecutive cases of PCNL between 2011 and 2016 were divided into 4 groups: 40 (52%) calcium, 26 (34%) uric acid, 5 (6%) struvite and 6 (8%) cystine stones. All images were reviewed by a single urologist using abdomen/bone windows to evaluate: stone volume, core (HUC), periphery HU and their absolute difference. HU density (HUD) was defined as the ratio between mean HU and the stone's largest diameter. ROC curves assessed the predictive power of HU for determining stone composition/stone-free rate (SFR). RESULTS: No differences were found based on the viewing window (abdomen vs bone). Struvite stones had values halfway between hyperdense (calcium) and low-density (cystine/uric acid) calculi for all parameters except HUD, which was the lowest. All HU variables for medium-high density stones were greater than low-density stones (p < 0.001). HUC differentiated the two groups (cut-off 825 HU; specificity 90.6%, sensitivity 88.9%). HUD distinguished calcium from struvite (mean ± SD 51 ± 16 and 28 ± 12 respectively; p = 0.02) with high sensitivity (82.5%) and specificity (80%) at a cut-off of 35 HU/mm. Multivariate analysis revealed HUD ≥ 38.5 HU/mm to be an independent predictor of SFR (OR = 3.1, p = 0.03). No relationship was found between HU values and complication rate. CONCLUSIONS: HU parameters help predict stone composition to select patients for oral chemolysis. HUD is an independent predictor of residual fragments after PCNL and may be fundamental to categorize it, driving the imaging choice at follow-up.

The association between prostatitis and prostate cancer. Systematic review and meta-analysis.

OBJECTIVE: The main outcome of this review was the association between a history of clinical chronic prostatitis (NIH category II or III) and a histologically confirmed diagnosis of prostate cancer. MATERIALS AND METHODS: Crude odds ratios and 95% confidence intervals (CI) were calculated to analyze dichotomous data. For analysis of pooled data we adopted a random-effects model and the inverse variance weighing method. Heterogeneity was assessed by calculating the I2 value. RESULTS: Out of 2794 screened records, we retrieved 16 full-text articles written in English, reporting the data of 15 case-control studies, involving 422.943 patients. Pooled analysis resulted in a significant crude odds ratio of 1.83 (95% CI: 1.43 to 2.35; P < 0.00001). The total set of data showed considerable heterogeneity (I2 = 91%). Both the Egger's test and the Begg's test for funnel plot asymmetry did not reach statistical significance. The 'trim and fill' method applied to the funnel plot imputed 3 missing studies and the resulting adjusted estimate of the odds ratio was 2.12 (95% CI: 1.38 to 3.22). According to GRADE criteria, the overall quality of the meta-analysis data is low, mainly due to the presence of bias, confounders and extreme effect size outliers. Five among the included studies reported data assessed in 8015 African-American subjects. Pooled analysis resulted in a non-significant crude odds ratio of 1.59 (95% CI: 0.71 to 3.57; P = 0.26), and considerable heterogeneity (I2 = 90%). CONCLUSIONS: Meta-analysis of 15 case-control studies shows that a history of clinical chronic prostatitis can significantly increase the odds for prostate cancer in the general population, whereas such association in African-American individuals remains uncertain.

Epidemiologic study of urolithiasis in seven countries of South-Eastern Europe: S.E.G.U.R. 1 study.

OBJECTIVE: To investigate some epidemiological aspects of kidney stones in the South- Eastern European area. MATERIALS AND METHODS: From September 2015 to December 2015, 538 consecutive patients were treated and evaluated for reno-ureteral stones in eight departments in Bulgaria, Greece, Italy, FYR Macedonia, Romania, Serbia and Turkey. RESULTS: The age of onset was lower in Turkey and higher in Italy. The rate of recurrent patients was higher in Romania and Serbia, while first renal stone formers were more frequent in Italy. The previous history of kidney stones, the characteristics of the stones and the dietary habits of the patients were different in different countries. In Bulgaria, Greece and Romania larger calculi from recurrent patients were more frequent. In Italy and Turkey smaller calculi from first renal stone formers were more frequent. CONCLUSIONS: The previous history of kidney stones, the characteristics of the stones and the dietary habits of the patients were different in different countries. A common dietary pattern associated with the formation of kidney stones was not observed, but each country showed different risk factors.

Herbal medicines for urinary stone treatment. A systematic review.

OBJECTIVE: To analyze the clinical evidence on the efficacy of phytotherapy in the treatment of calculi in the urinary tract. METHODS: To be eligible, full-length articles should include the results of randomized controlled trials enrolling patients affected by urolithiasis, reporting any comparison between an experimental herbal agent versus placebo or any active comparator, aimed at preventing the formation or facilitating the dissolution of calculi in any portion of the urinary tract. Fifteen databases were searched for relevant references. The primary outcomes investigated were (i) the reduction of stone size and/or number and (ii) the urinary excretion rates of calcium, urate, or oxalate. The secondary outcome of the review was the adverse effects (AE) of treatment. Risk of bias (ROB) and quality of the evidence were assessed according to Cochrane and GRADE guidelines. We performed a random-effect meta-analysis. RESULTS: 541 articles were retrieved and 16 studies were finally confirmed as eligible. Multiple Cochrane ROB tool items were rated as having high risk of bias in each analyzed trial report. Pooled analysis of continuous data could be performed for three different comparisons: (i) phytotherapy versus citrate as single agent (ii) phytotherapy versus placebo, (iii) preparation of Didymocarpus pedicellata (DP)--combined with other herbal agents--versus placebo. Results showed that citrate is superior to phytotherapy in significantly decreasing both the size of urinary stones (mean difference: phytotherapy, 0.42 mm higher; 95% CI: 0.23 to 0.6; Z = 4.42, P < 0.0001; I2 = 30%) and the urinary excretion rate of urate (mean difference: 42.32 mg/24h higher, 95% CI: 19.44 to 65.19; Z = 3.63, P = 0.0003; I2 = 96%), assessed after 3 months on-therapy. No significant differences in the excretion rates of urinary calcium or oxalate were found. The DP preparation was superior to placebo in inducing total clearance (risk ratio: 6.19, 95% CI: 2.60 to 14.74; Z = 4.12, P < 0.0001; I2 = 0%) and size reduction (mean difference: DP preparation, 4.93 mm lower; 95% CI: -9.18 to -0.67; Z = 2.27, P = 0.02; I2 = 99%) of renal and ureteral stones after 3 months of therapy. No significant differences in the inter-arm variation of excretion rates of urinary calcium or urate were found as result of the pooled phytotherapy-placebo comparison. Herbal remedies were in general devoid of side effects and in few cases citrate appeared to induce GI disturbances in a higher fraction of patients. Most reports did not provide inferential data concerning AE, and meta-analysis was not feasible. CONCLUSIONS: Citrate is more effective than phytotherapy in decreasing the size of existing calculi in the urinary tract and in decreasing the urinary excretion rate of uric acid. A preparation containing Didymocarpus pedicellata combined with other herbal agents induces stone size reduction and clearance significantly better than placebo. Mayor limitations in the applicability of these results are the low quality of the evidence and the multiple sources of bias assessed in the studies included in the present review.

Retrograde intrarenal surgery (RIRS), regular and small sized percutaneous nephrolithotomy (PCNL) in daily practice: European Association of Urology Section of Urolithiasis (EULIS) Survey.

OBJECTIVE: A wide selection of both anterograde and retrograde mini-invasive procedures exist for stones' treatment. The 2016 European Association of Urology (EAU) guidelines still don't univocally define a best option. Our purpose is to give an overview on some European Stone Centers' customs and to compare real life clinical practice with statements of opinion leaders and Guidelines. MATERIALS AND METHODS: In 2015 we performed a survey in 3 step about the spread of retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PCNL) techniques among EAU Section of Urolithiasis (EULIS) members. The 1st and 2nd steps dealt with the definition of EULIS urologist and department by collecting personal opinions about the endoscopic techniques. The third step was about clinical results. This paper presents data from the first two steps. RESULTS: Ninety-one people answered. Out of them, 80% are European and 42% work in Centres fully dedicated to stone treatment. In particular, 50% of responders perform more than 80 RIRS/year, 25% more than 80 PCNL/year, 48% more than 100 extracorporeal shock wave lithotripsy (SWL)/year. RIRS is mainly used to treat stones < 2 cm both as primary treatment and after SWL failure. 73% don't perform routine pre-stenting and 66% ordinarily use a ureteral sheath. Hospital stay for RIRS is 24h for 70% of responders. Regular PCNL is performed by 87% of the responders, MiniPCNL by 58%, Ultra-MiniPCNL by 23% and MicroPCNL by 28%. Pneumatic balloon dilation is the favourite dilation technique (49%). 37% of responders perform PCNL always in the supine position, 21% always in the prone one. Almost all the responders agree about using Mini, Ultra-Mini and MicroPCNL for 1-2 cm stones. Approximately 50% also use MiniPCNL for stones > 2 cm. CONCLUSION: our survey confirms the great heterogeneity existing in stones' treatment techniques in daily practice.

Efficacy and safety of second-line agents for treatment of metastatic castration-resistant prostate cancer progressing after docetaxel. A systematic review and meta-analysis.

OBJECTIVE: We performed a systematic review of the literature to assess the efficacy and the safety of second-line agents targeting metastatic castration-resistant prostate cancer (mCRPC) that has progressed after docetaxel. Pooled-analysis was also performed, to assess the effectiveness of agents targeting the androgen axis via identical mechanisms of action (abiraterone acetate, orteronel). MATERIALS AND METHODS: We included phase III randomized controlled trials that enrolled patients with mCRPC progressing during or after first-line docetaxel treatment. Trials were identified by electronic database searching. The primary outcome of the review was overall survival. Secondary outcomes were radiographic progression-free survival (rPFS) and severe adverse effects (grade 3 or higher). RESULTS: Ten articles met the inclusion criteria for the review. These articles reported the results of five clinical trials, enrolling in total 5047 patients. The experimental interventions tested in these studies were enzalutamide, ipilimumab, abiraterone acetate, orteronel and cabazitaxel. Compared to control cohorts (active drug-treated or placebo-treated), the significant overall survival advantages achieved were 4.8 months for enzalutamide (hazard ratio for death vs. placebo: 0.63; 95% CI 0.53 to 0.75, P < 0.0001), 4.6 months for abiraterone (hazard ratio for death vs. placebo: 0.66, 95% CI 0.58 to 0.75, P < 0.0001) and 2.4 months for cabazitaxel (hazard ratio for death vs. mitoxantrone-prednisone: 0.70, 95% CI 0.59 to 0.83, p < 0.0001). Pooled analysis of androgen synthesis inhibitors orteronel and abiraterone resulted in significantly increased overall and progression-free survival for anti-androgen agents, compared to placebo (hazard ratio for death: 0.76, 95% CI 0.67 to 0.87, P < 0.0001; hazard ratio for radiographic progression: 0.7, 95% CI 0.63 to 0.77, P < 0.00001). Androgen synthesis inhibitors induced significant increases in risk ratios for adverse effects linked to elevated mineralocorticoid secretion, compared to placebo (risk ratio for hypokalemia: 5.75, 95% CI 2.08 to 15.90; P = 0.0008; risk-ratio for hypertension: 2.29, 95% CI 1.02 to 5.17; P = 0.05). CONCLUSIONS: In docetaxel-pretreated patients enzalutamide, abiraterone-prednisone and cabazitaxel-prednisone can improve overall survival of patients, compared to placebo or to best of care at the time of study (mitoxantrone-prednisone). Agents targeting the androgen axis (enzalutamide, abiraterone, orteronel) significantly prolonged rPFS, compared to placebo. Further investigation is warranted to evaluate the benefit of combination or sequential administration of these agents. Large-scale studies are also necessary to evaluate the impact of relevant toxic effects observed in a limited number of patients (e.g., enzalutamide-induced seizures, orteronel-induced pancreatitis, and others).

Dietary treatment of urinary risk factors for renal stone formation. A review of CLU Working Group.

OBJECTIVE: Diet interventions may reduce the risk of urinary stone formation and its recurrence, but there is no conclusive consensus in the literature regarding the effectiveness of dietary interventions and recommendations about specific diets for patients with urinary calculi. The aim of this study was to review the studies reporting the effects of different dietary interventions for the modification of urinary risk factors in patients with urinary stone disease. MATERIALS AND METHODS: A systematic search of the Pubmed database literature up to July 1, 2014 for studies on dietary treatment of urinary risk factors for urinary stone formation was conducted according to a methodology developed a priori. Studies were screened by titles and abstracts for eligibility. Data were extracted using a standardized form and the quality of evidence was assessed. RESULTS: Evidence from the selected studies were used to form evidence-based guideline statements. In the absence of sufficient evidence, additional statements were developed as expert opinions. CONCLUSIONS: General measures: Each patient with nephrolithiasis should undertake appropriate evaluation according to the knowledge of the calculus composition. Regardless of the underlying cause of the stone disease, a mainstay of conservative management is the forced increase in fluid intake to achieve a daily urine output of 2 liters. HYPERCALCIURIA: Dietary calcium restriction is not recommended for stone formers with nephrolithiasis. Diets with a calcium content ≥ 1 g/day (and low protein-low sodium) could be protective against the risk of stone formation in hypercalciuric stone forming adults. Moderate dietary salt restriction is useful in limiting urinary calcium excretion and thus may be helpful for primary and secondary prevention of nephrolithiasis. A low-normal protein intake decrease calciuria and could be useful in stone prevention and preservation of bone mass. Omega-3 fatty acids and bran of different origin decreases calciuria, but their impact on the urinary stone risk profile is uncertain. Sports beverage do not affect the urinary stone risk profile. HYPEROXALURIA: A diet low in oxalate and/or a calcium intake normal to high (800-1200 mg/day for adults) reduce the urinary excretion of oxalate, conversely a diet rich in oxalates and/or a diet low in calcium increase urinary oxalate. A restriction in protein intake may reduce the urinary excretion of oxalate although a vegetarian diet may lead to an increase in urinary oxalate. Adding bran to a diet low in oxalate cancels its effect of reducing urinary oxalate. Conversely, the addition of supplements of fruit and vegetables to a mixed diet does not involve an increased excretion of oxalate in the urine. The intake of pyridoxine reduces the excretion of oxalate. HYPERURICOSURIA: In patients with renal calcium stones the decrease of the urinary excretion of uric acid after restriction of dietary protein and purine is suggested although not clearly demonstrated. HYPOCITRATURIA: The administration of alkaline-citrates salts is recommended for the medical treatment of renal stone-formers with hypocitraturia, although compliance to this treatment is limited by gastrointestinal side effects and costs. Increased intake of fruit and vegetables (excluding those with high oxalate content) increases citrate excretion and involves a significant protection against the risk of stone formation. Citrus (lemons, oranges, grapefruit, and lime) and non citrus fruits (melon) are natural sources of dietary citrate, and several studies have shown the potential of these fruits and/or their juices in raising urine citrate levels. CHILDREN: There are enought basis to advice an adequate fluid intake also in children. Moderate dietary salt restriction and implementation of potassium intake are useful in limiting urinary calcium excretion whereas dietary calcium restriction is not recommended for children with nephrolithiasis. It seems reasonable to advice a balanced consumption of fruit and vegetables and a low consumption of chocolate and cola according to general nutritional guidelines, although no studies have assessed in pediatric stone formers the effect of fruit and vegetables supplementation on urinary citrate and the effects of chocolate and cola restriction on urinary oxalate in pediatric stone formers. Despite the low level of scientific evidence, a low-protein (< 20 g/day) low-salt (< 2 g/day) diet with high hydration (> 3 liters/day) is strongly advised in children with cystinuria. ELDERLY: In older patients dietary counseling for renal stone prevention has to consider some particular aspects of aging. A restriction of sodium intake in association with a higher intake of potassium, magnesium and citrate is advisable in order to reduce urinary risk factors for stone formation but also to prevent the loss of bone mass and the incidence of hypertension, although more hemodynamic sensitivity to sodium intake and decreased renal function of the elderly have to be considered. A diet rich in calcium (1200 mg/day) is useful to maintain skeletal wellness and to prevent kidney stones although an higher supplementation could involve an increase of risk for both the formation of kidney stones and cardiovascular diseases. A lower content of animal protein in association to an higher intake of plant products decrease the acid load and the excretion of uric acid has no particular contraindications in the elderly patients, although overall nutritional status has to be preserved.

The Post-Ureteroscopic Lesion Scale (PULS): a multicenter video-based evaluation of inter-rater reliability.

PURPOSE: The Post-Ureteroscopic Lesion Scale (PULS) offers a simple grading system for the description of ureteral lesions after ureteroscopy. In this article, we present the results of a video-based multicenter evaluation of the inter-rater reliability of clinically important PULS grades 0-3. METHODS: Video sequences at the end of ureteroscopy (final passage) were recorded for 100 consecutive patients at a single institution and assessed by experienced urologists (n = 20) and senior residents (n = 17) at 19 international centers. The cohort included only patients with lesions grades 0-3 (with grades 2 and 3 subsumed as 2 + since distinction is defined by an extravasation of contrast medium in fluoroscopy). The gradings were evaluated for inter-rater reliability and in terms of simplicity, validity, comprehensibility, reproducibility, and usefulness. RESULTS: Overall, inter-rater reliability was high (Kendall's W = 0.69, p < 0.001) and was comparable between specialists (Kendall's W = 0.69, p < 0.001) and residents (Kendall's W = 0.71, p < 0.001). The matched ratings showed grade 0 in 43.0 % of patients and grades 1 or 2 + in 44.0 and 13.0 % of patients, respectively. Results of the questionnaires indicated a high degree of acceptance, with an overall rating of 1.76 (1.64-1.93 for different items, scale 1-6). CONCLUSIONS: Inter-rater reliability of the endoscopically assessable PULS was high among urologists with different levels of experience in different countries worldwide. The validated PULS system may be used for standardized reporting of ureteral lesions/injuries after ureteroscopy. In addition, PULS will enable more selective standardization of indications for postoperative DJ stenting based on the randomized controlled trials.