Microbial Trends in Infection-related Readmissions Following Radical Cystectomy for Bladder Cancer.

OBJECTIVE: To report microbial pathogens detected at infection-related readmissions, including their susceptibility to antimicrobials. MATERIALS AND METHODS: A retrospective review of 785 patients who underwent radical cystectomy for bladder cancer at a tertiary center in Denmark between 2009 and 2019. All patients received prophylactic cefuroxime preoperatively and pivmecillinam at stent- or catheter removal. Data were collected through the national medical records and microbiology database. The primary outcome was readmission rate and pathogens detected at infection-related readmissions. Univariable and multivariable regression analyses were carried out to identify risk factors of readmission. RESULTS: Within 90days of surgery, 225 (29%) patients experienced at least one infection-related readmission. The most common pathogen identified was Enterococcus spp (24% of all positive samples). In blood cultures, the most dominant species were Escherichia coli (29%) and Staphylococcus spp (26%). Due to the heterogeneity in microbial species identified, more than one-third of the bacteria where mecillinam was tested showed resistance. Most isolates were susceptible to piperacillin+tazobactam. Orthotopic neobladder and continent cutaneous reservoir were associated with the highest risk of infection-related readmission compared to ileal conduit (odds ratios 2.78 [95%CI 1.66;4.65] and 3.08 [95%CI 1.58;5.98], respectively). Patients with diabetes had an increased risk of infection-related readmission compared to patients without diabetes (odds ratio 1.67 [95%CI 1.02;2.73]). CONCLUSION: Nearly one-third of all patients experienced at least one postoperative infection-related readmission with a wide range of microbial etiologies. Generalizability of our results is uncertain, but the data can be used to plan interventional trials of antibiotic prophylaxis.

Acute Kidney Injury Within 90Days of Radical Cystectomy for Bladder Cancer: Incidence and Risk Factors.

OBJECTIVE: To report incidence of acute kidney injury (AKI) following radical cystectomy (RC) for bladder cancer and evaluate risk factors for AKI as well as the impact of AKI on development of long-term renal insufficiency. METHODS: A retrospective analysis of patients undergoing RC between 2010 and 2020 at a high-volume tertiary referral center. AKI was graded according to the Kidney Disease Improving Global Outcome (KDIGO) criteria within 90days of surgery. Long-term renal insufficiency was defined as estimated glomerular function <45 mL/min. Cumulative incidence and Cox Proportional Hazards models were used to evaluate both short- and long-term loss of renal function and investigate their association with pre- and perioperative variables. RESULTS: AKI occurred in 332 out of 755 patients (44%) within 90days. Preoperative chronic hypertension and obesity were independent preoperative risk factors. Robot-assisted RC was associated with a higher risk of AKI compared to open RC in multivariable analyses. The absolute risk of developing long-term renal insufficiency was 8.7% (95%CI: 5.6-12) after 5years in patients without AKI and 26% (95%CI: 16-36) in patients with KDIGO-stage ≥2. In multivariable analysis, both KDIGO-stage 1 and ≥2 were independently associated with long-term estimated glomerular filtration rate <45 mL/min. CONCLUSION: A significant number of patients experienced AKI after RC, and even patients with KDIGO-stage 1 were at increased risk of long-term renal insufficiency. Recognizing pre- and perioperative risk factors can identify patients where close surveillance and early intervention may help minimize renal function decline following RC.

Haemodynamic and respiratory perioperative outcomes for open versus robot-assisted radical cystectomy: A double-blinded, randomised trial.

BACKGROUND: The clinical impact of prolonged steep Trendelenburg position and CO2 pneumoperitoneum during robot-assisted radical cystectomy (RC) on intraoperative conditions and immediate postoperative recovery remains to be assessed. The current study investigates intraoperative and immediate postoperative outcomes for open RC (ORC) versus robot-assisted RC with intracorporal urinary diversion (iRARC) in a blinded randomised trial. We hypothesised that ORC would result in a faster haemodynamic and respiratory post-anaesthesia care unit (PACU) recovery compared to iRARC. METHODS: This study is a predefined sub-analysis of a single-centre, double-blinded, randomised feasibility study. Fifty bladder cancer patients were randomly assigned to ORC (n = 25) or iRARC (n = 25). Patients, PACU staff, and ward personnel were blinded to the surgical technique. Both randomisation arms followed the same anaesthesiologic procedure, fluid treatment plan, and PACU care. The primary outcome was immediate postoperative recovery using a standardised PACU Discharge Criteria (PACU-DC) score. Secondary outcomes included respiration- and arterial O2 saturation scores as well as perioperative interventions and recordings. RESULTS: All patients underwent the allocated treatment. The total PACU-DC score was highest 6 h postoperatively with no difference in the total score between randomisation arms (p = 0.80). Both the ORC and iRARC groups maintained a mean respiration- and arterial O2 saturation score below 1 (out of 3) throughout PACU stay. The iRARC patients had significantly, but clinically acceptable, higher maximum airway pressure and arterial blood pressure, as well as lower minimum pH levels. The ORC group received significantly more opioids after extubation but marginally less analgesics in the PACU, compared to the iRARC group. CONCLUSIONS: A prolonged Trendelenburg position and CO2 pneumoperitoneum was well-tolerated during iRARC, and immediate postoperative recovery was similar for ORC and iRARC patients.

Reasons for lack of treatment in patients with locally advanced, unresectable or metastatic urothelial carcinoma.

BACKGROUND: The proportion of patients with locally advanced, unresectable or metastatic urothelial carcinoma that do not receive systemic anticancer treatment and the reasons for lack of treatment are largely unknown. The aim of this study was to investigate the prevalence and overall survival of this patient group and reasons for omission of treatment. MATERIAL AND METHODS: This retrospective, single-center cohort study from Rigshospitalet, Denmark included patients diagnosed with locally advanced, unresectable or metastatic urothelial carcinoma during the study period from 1 January 2010 to 31 March 2016 who did not receive systemic anticancer treatment. Patients were identified through the Danish Pathology Register and the electronic medical records. RESULTS: 100 patients were included, representing 34% of all patients diagnosed with locally advanced, unresectable or metastatic urothelial carcinoma at Rigshospitalet during the study period. Lack of treatment was most often due to poor physical condition (59%), decreased renal function (15%), or patient preferences (14%). Median overall survival was 1.9 months (95% CI: 1.6-2.8 months). CONCLUSION: One in three patients diagnosed with locally advanced, unresectable or metastatic urothelial carcinoma in the pre-immunotherapy era did not receive systemic anticancer treatment. Prompt identification of advanced disease and interventions to optimize these patients for treatment are essential. Our findings underscore the compelling need for novel, better tolerated treatment regimens in this frail patient group.

Long-Term Renal Function Following Radical Cystectomy for Bladder Cancer.

OBJECTIVE: To evaluate long-term renal function following radical cystectomy (RC) for bladder cancer and identify risk factors associated with postoperative decline in renal function. METHODS: The study included patients who underwent RC at a single centre in Denmark between 2009 and 2019. Data was collected through national electronic medical records. Renal function was evaluated by estimated glomerular filtration rate (eGFR) using pre- and postoperative creatinine measurements. Cumulative incidence and Cox Proportional Hazards models were used to describe the loss of renal function and its association with clinicopathological variables, as well as its effect on mortality. RESULTS: After exclusions, 670 patients were eligible for analyses. Median follow-up time was 6.2 years (interquartile range 4.0 -8.4). The proportion of patients with renal insufficiency (eGFR<45 mL/min) increased from 8.9% before RC to 19% 5 years after surgery. A total of 610 patients with preoperative eGFR≥45 were included in survival analyses. The absolute risk of renal function decline to CKD stage G3b or worse (eGFR<45 mL/min) was 17% (95% CI 14 -20) at 5 years postoperatively. Loss of renal function was not significantly associated with higher all-cause mortality. In multivariate analysis lower preoperative eGFR, diabetes mellitus, prior pelvic radiation therapy, continent urinary diversion types, and postoperative ureteral stricture were all independently associated with renal function decline. CONCLUSION: The long-term renal function decreases considerably for a large number of RC patients. Recognizing preoperative risk factors could identify patients who benefit from enhanced renal surveillance or early intervention for modifiable factors to minimize renal insufficiency following RC.

Open vs robot-assisted radical cystectomy (BORARC): a double-blinded, randomised feasibility study.

OBJECTIVE: To examine surgical outcomes and feasibility of blinding patients and care providers to the surgical technique of radical cystectomy (RC). PATIENTS AND METHODS: Single-centre, parallel-group, double-blinded, randomised feasibility study of open RC (ORC) vs robot-assisted RC with intracorporeal urinary diversion (iRARC) in an 'Enhanced Recovery After Surgery' setup. A total of 50 patients aged ≥18 years with bladder cancer planned for RC with an ileal conduit were included. Patients with previous major abdominal/pelvic surgery, pelvic radiation or anaesthesiological contraindications were excluded. Primary outcomes were proportion of unblinded patients and success of blinding using Bang's Blinding Index. Secondary outcomes included length of stay (LOS), complication rates, blood loss, pain, and opioid consumption. RESULTS: A total of 26% of the patients were unblinded before discharge. We demonstrated that patients and doctors remained blinded for the allocated treatment, but nurses did not. Blood loss was greater in the ORC group as was operative time in the iRARC group. We found no difference in complication rate, LOS, or use of analgesics. CONCLUSIONS: The present study demonstrates that blinding of surgical technique in RC is possible. The results of secondary outcomes are consistent with the findings of previous unblinded randomised controlled trials. Our study highlights that it is possible to perform a blinded phase III study to explore the optimal surgical technique in RC.

[Treatment of andrological conditions in men with spinal cord injury].

Men with spinal cord injuries often suffer from erectile dysfunction, ejaculatory dysfunction, infertility and hypogonadism. However, efficient and safe treatments exist as summarised in this review. Erectile dysfunction can be treated step by step with phosphodiesterase 5 inhibitors, intracavernous injections and penile implant surgery. Ejaculatory dysfunction can in almost all cases be treated by using penile vibratory stimulation and electroejaculation. Surgical sperm retrieval can be used as a last resort. These patients have a high prevalence of hypogonadism, and testosterone replacement therapy can be used to alleviate symptoms of low testosterone levels.

Morbidity and Days Alive and Out of Hospital Within 90 Days Following Radical Cystectomy for Bladder Cancer.

BACKGROUND: Morbidity after radical cystectomy (RC) is usually quantified in terms of rates of complications, mortality, reoperations, and readmissions, and length of stay (LOS). The overall burden following RC within the first 90 d following RC may be better described using days alive and out of hospital (DAOH), which is a validated, patient-centred proxy for both morbidity and mortality. OBJECTIVE: To report short-term morbidity, LOS, and DAOH within 90 d after RC and risk factors associated with these parameters. DESIGN SETTING AND PARTICIPANTS: The study included 729 patients undergoing RC for bladder cancer at a single academic centre from 2009 to 2019. Data were retrieved from national electronic medical charts. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariate analysis was used to investigate variables associated with a major complication, LOS >7 d, and DAOH <80 d. RESULTS AND LIMITATIONS: The 90-d complication rate was 80%, including major complications in 37% of cases. Median LOS was 7 d (interquartile range (IQR) 6-9) and median DAOH was 80 d (IQR 71-83) days. Body mass index and the Charlson comorbidity index (CCI) predicted major complications. CCI predicted LOS >7 d and DAOH <80 d. CONCLUSIONS: RC was associated with significant short-term morbidity and DAOH was a good marker for cumulative morbidity after RC. We propose that DAOH should be a standard supplement for reporting surgical outcomes following RC for bladder cancer, which may facilitate better comparison of outcomes across treating institutions. PATIENT SUMMARY: We studied complications after surgical removal of the bladder for bladder cancer. We assessed a novel patient-centred tool that more accurately describes the total burden of complications after surgery than traditional models. We found that patients with a high body mass index and coexisting chronic diseases had a higher risk of a complicated surgical course.

[Ejaculatory dysfunction].

This review summarises the current knowledge of ejaculatory dysfunction, which is a group of prevalent sexual disorders with a substantial impact on sexual health of men and their partners. A thorough medical history is the most important evaluation tool. Several treatments for premature ejaculation are available; however, a successful treatment outcome depends on pre-treatment alignment of expectations. Infertility due to delayed ejaculation, retrograde ejaculation or anejaculation can be treated effectively.

Male Sexual and Reproductive Health-Does the Urologist Have a Role in Addressing Gender Inequality in Life Expectancy?

Despite considerable public health initiatives in the past century, there remains a significant gender inequality in life expectancy. The Global Burden of Diseases study has highlighted that the life expectancy for men is 70.5years, compared with 75.6years for women. This discrepancy in mortality appears to be related to a disproportionately higher number of preventable and premature male deaths. Whilst there has been an increased focus on men's health, as evidenced by the establishment of men's health charities and governmental legislation promoting equality, a recent World Health Organization report has highlighted that there is still a prevailing misconception that the higher rate of premature mortality amongst men is a natural phenomenon. We explore the association of male sexual and reproductive health-related diseases and the potential role of a urologist in addressing gender inequality in life expectancy. PATIENT SUMMARY: In this report, we discuss the causes for the gender gap in life expectancy and highlight that men continue to have a higher rate of premature death than women, which is associated with diseases of the male reproductive system. Furthermore, this not only appears to be related to a number of metabolic and lifestyle factors, but may also be the result of the increased risk of cancer in men with sexual and reproductive health-related diseases.

Exposure to phenols, parabens and UV filters: Associations with loss-of-function mutations in the filaggrin gene in men from the general population.

BACKGROUND: Filaggrin is an epidermal protein that is important for normal skin barrier functions. Up to 10% of Europeans and Asians carry filaggrin gene (FLG) loss-of function mutations that appear to facilitate trans-epidermal penetration of certain chemicals. We previously showed that mutation carriers have higher internal exposure to certain phthalates, compared to controls, and hypothesized that they could have increased trans-epidermal penetration of other chemicals. OBJECTIVES: We investigated exposure to non-persistent chemicals in young Danish men with and without FLG mutations. METHODS: Concentrations of eight simple phenols, six parabens and nine UV filters were analysed in urine from 65 FLG loss-of-function mutation carriers and 130 non-carriers (controls). Regression analyses, controlling for urinary dilution and confounders, were performed to estimate associations between FLG mutation status and chemical concentrations in urine. RESULTS: FLG mutation carriers had 80% (13-180%) higher urinary concentrations of methyl paraben (MeP) and 91% (13-219%) higher concentrations of n-propyl paraben (n-PrP) than controls. For 13 compounds, levels were higher in FLG mutation carriers, although differences were only statistically significant for MeP and n-PrP. Combined statistical analysis of concentrations of all the 18 compounds that were detectable in >10% of subjects, suggested that concentrations were generally higher in mutation carriers (p=0.03). CONCLUSION: FLG loss-of-function mutation carriers have a higher internal exposure to some non-persistent chemicals, independently of atopic dermatitis. This may be due to increased trans-epidermal absorption and/or higher exposure, and mutation carriers may constitute a group susceptible to increased absorption of chemicals and topical medication.

Gynaecomastia in 786 adult men: clinical and biochemical findings.

OBJECTIVE: Gynaecomastia is a benign proliferation of glandular tissue of the breast; however, it is an important clinical observation because it can be the first symptom of an underlying disease. Some controversy exists concerning the clinical importance of an in-depth investigation of men who develop gynaecomastia. We hypothesise that a thorough work-up is required in adult men with gynaecomastia. DESIGN: All adult men (n = 818) referred to a secondary level andrological department at Rigshospitalet in Copenhagen, Denmark during a four-year period (2008-2011) under the diagnosis of gynaecomastia (ICD-10: N62) were included. METHODS: Thirty-two men who did not have gynaecomastia when examined were excluded; leaving 786 men for final analyses. They underwent an andrological examination, ultrasound of the testicles and analysis of endogenous serum hormones levels. RESULTS: In 43% of men with adult onset of gynaecomastia (≥18 years) an underlying, and often treatable, cause could be detected. In men younger at onset an underlying cause for gynaecomastia could be detected in merely 7.7%. The study is limited by the fact that we did not have access to investigate men who were referred directly by their GP to private clinics for plastic surgery or who sought cosmetic correction without consulting their GP first. CONCLUSIONS: Our study demonstrates the importance of a thorough examination and provides a comprehensible examination strategy to disclose the underlying pathology leading to the development of gynaecomastia in adulthood.

Varicocele Is Associated with Impaired Semen Quality and Reproductive Hormone Levels: A Study of 7035 Healthy Young Men from Six European Countries.

BACKGROUND: Present knowledge on the impact of varicoceles on testicular function is largely based on studies of subfertile and infertile men, making it difficult to extrapolate the impact of varicocele on the general population. OBJECTIVE: To describe associations between varicocele and testicular function assessed by semen analysis and reproductive hormones in men from the general population. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional multicentre study of 7035 young men, median age 19 yr, from the general population in six European countries (Denmark, Finland, Germany, Estonia, Latvia, and Lithuania) were investigated from 1996 to 2010. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We analysed results from physical examination, conventional semen variables, and serum reproductive hormones using multivariable regression analyses. RESULTS AND LIMITATIONS: A total of 1102 (15.7%) had grade 1-3 varicocele. Increasing varicocele grade was associated with poorer semen quality, even in grade 1 varicocele. In grade 3 varicocele, sperm concentration was less than half of that in men with no varicocele. Presence of varicocele was also associated with higher serum levels of follicle-stimulating hormone, lower inhibin B, and higher levels of luteinising hormone; testosterone and free testosterone were not significantly different between men with and without varicocele. This study cannot draw a conclusion on the progressiveness of varicocele or the effect of treatment. CONCLUSIONS: We demonstrated an adverse effect of increasing grade of varicocele on testicular function in men not selected due to fertility status. PATIENT SUMMARY: The presence and increasing grade of varicocele is adversely associated with semen quality and reproductive hormone levels in young men from the general population.

Urinary bisphenol A levels in young men: association with reproductive hormones and semen quality.

BACKGROUND: Few human studies have examined bisphenol A (BPA) exposure in relation to semen quality and reproductive hormones in men, and results are divergent. OBJECTIVES: We examined associations between urinary BPA concentration and reproductive hormones, as well as semen quality, in young men from the general population. METHODS: Our study population consisted of 308 young men from the general population. Urinary BPA concentration was measured by isotope dilution TurboFlow-liquid chromatography-tandem mass spectrometry. We used multiple linear regression analysis to estimate associations between BPA concentration and reproductive hormones and semen quality, adjusting for confounding factors. RESULTS: We found that 98% of the men had detectable urinary levels of BPA. Median (5th-95th percentiles) BPA concentration was 3.25 ng/mL (0.59-14.89 ng/mL). Men with BPA concentrations above the lowest quartile had higher concentrations of serum testosterone, luteinizing hormone (LH), estradiol, and free testosterone compared with the lowest quartile (p trend ≤ 0.02). Men in the highest quartile of BPA excretion had on average 18% higher total testosterone (95% CI: 8, 28%), 22% higher LH (95% CI: 6, 39%), and 13% higher estradiol (95% CI: 4, 24%) compared with lowest quartile. Men in the highest quartile of BPA also had significantly lower percentage progressive motile spermatozoa compared with men in the lowest quartile (-6.7 percentage points, 95% CI: -11.76, -1.63). BPA was not associated with other semen parameters. Adjusting for dietary patterns did not influence the results. CONCLUSIONS: The pattern of associations between BPA and reproductive hormones could indicate an antiandrogenic or antiestrogenic effect, or both, of BPA on the hypothalamic-pituitary-gonadal hormone feedback system, possibly through a competitive inhibition at the receptor level. However, additional research is needed to confirm our findings and to further test the suggested potential mechanisms.

High dietary intake of saturated fat is associated with reduced semen quality among 701 young Danish men from the general population.

BACKGROUND: Saturated fat intake has been associated with both cardiovascular disease and cancer risk, and a newly published study found an association between saturated fat intake and a lower sperm concentration in infertile men. OBJECTIVE: The objective was to examine the association between dietary fat intake and semen quality among 701 young Danish men from the general population. DESIGN: In this cross-sectional study, men were recruited when they were examined to determine their fitness for military service from 2008 to 2010. They delivered a semen sample, underwent a physical examination, and answered a questionnaire comprising a quantitative food-frequency questionnaire to assess food and nutrient intakes. Multiple linear regression analyses were performed with semen variables as outcomes and dietary fat intakes as exposure variables, adjusted for confounders. RESULTS: A lower sperm concentration and total sperm count in men with a high intake of saturated fat was found. A significant dose-response association was found, and men in the highest quartile of saturated fat intake had a 38% (95% CI: 0.1%, 61%) lower sperm concentration and a 41% (95% CI: 4%, 64%) lower total sperm count than did men in the lowest quartile. No association between semen quality and intake of other types of fat was found. CONCLUSIONS: Our findings are of potentially great public interest, because changes in diet over the past decades may be part of the explanation for the recently reported high frequency of subnormal human sperm counts. A reduction in saturated fat intake may be beneficial for both general and reproductive health.

Vitamin D is positively associated with sperm motility and increases intracellular calcium in human spermatozoa.

BACKGROUND: The vitamin D receptor (VDR) is expressed in human spermatozoa, and VDR-knockout mice and vitamin D (VD) deficiency in rodents results in impaired fertility, low sperm counts and a low number of motile spermatozoa. We investigated the role of activated VD (1,25(OH)(2)D(3)) in human spermatozoa and whether VD serum levels are associated with semen quality. METHODS: Cross-sectional association study of semen quality and VD serum level in 300 men from the general population, and in vitro studies on spermatozoa from 40 men to investigate the effects of VD on intracellular calcium, sperm motility and acrosome reaction. All men delivered samples for routine semen analysis and blood for measurements of follicle stimulating hormone, Inhibin B, 25-hydroxy-VD, albumin, alkaline phosphatase, calcium and parathyroid hormone (PTH). RESULTS: In the association study, 44% were VD insufficient (<50 nM), and VD was inversely correlated with PTH (P < 0.0005). VD serum levels correlated positively with sperm motility and progressive motility (P < 0.05), and men with VD deficiency (<25 nM) had a lower proportion of motile (P = 0.027), progressive motile (P = 0.035) and morphologically normal spermatozoa (P = 0.044) compared with men with high VD levels (>75 nM). 1,25(OH)(2)D(3) increased intracellular calcium concentration in human spermatozoa through VDR-mediated calcium release from an intracellular calcium storage, increased sperm motility and induced the acrosome reaction in vitro. CONCLUSIONS: 1,25(OH)(2)D(3) increased intracellular calcium concentration, sperm motility and induced the acrosome reaction in mature spermatozoa, and VD serum levels were positively associated with sperm motility, suggesting a role for VD in human sperm function.