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Background; Assessment of male lower urinary tract symptoms (LUTS) needs to identify predictors of symptom outcomes, where interventional treatment is planned. Objective; Develop a novel prediction model for prostate surgery outcomes and validate it using a separate patient cohort, deriving thresholds for key clinical parameters. Design, Setting, and Participants; The UPSTREAM trial of 820 men seeking treatment for LUTS, analysing bladder diary (BD), IPSS, IPSS-QoL, and uroflowmetry data of 176 participants who underwent prostate surgery and provided complete data. External validation used a retrospective surgery outcomes database from a Japanese urology department (n = 227). Outcome Measurements and Statistical Analysis; Symptom improvement was defined as ≥3 points reduction in total IPSS. Multiple logistic regression, classification tree analysis and random forest models were generated, including versions with and without BD data. Results and Limitation; Multiple logistic regression without BD identified age (P=0.029), total IPSS (P=0.0016), and maximum flow rate (Qmax) (P=0.066) as predictors of outcome, with area under curve (AUC) of 77.1%. Classification tree analysis without BD gave thresholds of IPSS

Christopher Chapple,1 Roger Dmochowski2 1Department of Urology, Royal Hallamshire Hospital, Sheffield, UK; 2Department of Urology, Vanderbilt University Medical Center, Nashville, TN, USACorrespondence: Christopher ChappleDepartment of Urology, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, UKTel +44 114 271 3048Fax +44 114 279 7841Email c.r.chapple@shef.ac.ukAbstract: Stress urinary incontinence (SUI) has been treated surgically with the midurethral sling but in recent years, this option has come under scrutiny and the risk–benefit balance continues to be reviewed. The low-risk alternative for women with uncomplicated SUI is the bulking agent, which aims to achieve continence through coaptation of the urethra. Two classes of bulking agents can be identified: those made from solid microparticles in an absorbable liquid or gel carrier (particulate agents) and those comprising a homogenous gel (non-particulates) that resists absorption. Polydimethylsiloxane®, carbon-coated zirconium oxide®, calcium hydroxyapatite® and polyacrylate polyalcohol copolymer® are currently marketed particulate agents. With the exception of calcium hydroxyapatite, the particles are non-degradable. Each agent achieves its long-term bulking effect through reactive changes around the persisting particles while the carrier volume is lost. Bulkamid® is a non-particulate agent with the bulking effect resulting from the volume of gel injected. The lasting network of fine fibers formed by the host tissue anchors the gel in situ. Foreign-body granulomas, erosion and migration/material extrusion and loss of bulk have been observed in connection with the particle-based products. Bulkamid may be mechanistically less liable to these events; however, there are minimal data directly comparing the two types of bulking agent. The question of durability is inevitable based on their differing modes of action.Keywords: stress urinary incontinence, bulking agents, safety, particulate, non-particulate

Background\ud \ud Polypropylene meshes cause severe complications in some patients. Materials that are biomechanically compatible and can better integrate into host tissues are urgently needed.\ud \ud Objective\ud \ud To design an oestradiol-releasing electrospun poly-l-lactic acid (PLA) mesh and evaluate its ability to stimulate new extracellular matrix and new blood vessel formation.\ud \ud Design, setting, and participants\ud \ud Human adipose derived mesenchymal cells (ADMSC) were isolated from fat. PLA meshes with micro- to nano-sized fibres containing 1%, 5%, and 10% oestradiol were constructed and used for in vitro and in vivo experiments.\ud \ud Intervention\ud \ud The angiogenic potential of the fibrous meshes was evaluated using an in vivo chorioallantoic membrane and an in vitro chick aortic arch assays.\ud \ud Outcome measurements and statistical analysis\ud \ud Oestradiol release was measured fluorometrically. The effect of fibrous meshes on proliferation and extracellular matrix (ECM) production of ADMSC was assessed using immunohistology. Mechanical properties were tested using a tensiometer.\ud \ud Results and limitations\ud \ud The ultrastructure of the mesh was not affected by the inclusion of oestradiol and mechanical properties were only slightly modified. Oestradiol was released from PLA meshes over a 5-mo period. ADMSCs cultured on oestradiol-releasing PLA meshes produced more ECM involving collagen I, collagen III, and elastin. Oestradiol-releasing meshes doubled new blood vessel formation in the chorioallantoic membrane assay (p = 0.001) and outgrowth of pro-angiogenic cells in the aortic arch assay (p = 0.001). Further studies in longer-term animal models are required to confirm these results.\ud \ud Conclusions\ud \ud Oestradiol-releasing PLA meshes increase ECM production and stimulate angiogenesis. As such, they are promising candidate materials to be used in pelvic floor repair and to improve the initial healing phase of a repair material following implantation.\ud \ud Patient summary\ud \ud In this study, we designed a tissue engineered material to be used to support weakened pelvic floor tissues in women to avoid the complications associated with current surgical mesh. Our results showed that this material can stimulate new blood vessel formation in simple chick assays and tissue production in vitro. Both properties should help with the integration of this material into patients’ tissues and merit further study in physiologically relevant animal models.

This study investigates viewers’ trust in and response towards disclosed paid-for endorsements by YouTube lifestyle vloggers. With the law now enforcing disclosure of sponsorship within vlogger endorsements, this research is topical. This study explored the credibility of lifestyle vloggers, viewers’ attitudes towards paid-for endorsements and disclosure, and viewers’ responses towards endorsements. The research employed a qualitative method and found that lifestyle vloggers are considered by their viewers as highly credible and influential individuals. Disclosure was seen to increase vlogger credibility, improving the acceptance of the endorsement message. This was however only seen where the viewer had a positive pre-existing relationship with the vlogger. Where the viewer did not have a positive pre-existing relationship with the vlogger, a perception of opportunistic behavior commonly arose in association with the paid-for endorsement. Thus, the research found the disclosed sponsorship can still be effective where the recipient is an avid viewer.

Lichen sclerosus affecting the male genitalia is a poorly understood but potentially devastating condition. The natural history of the condition is beginning to be understood better with longer follow-up of patients. Recent long-term data suggest that circumcision for lichen sclerosus limited to the prepuce may not be curative as was once thought. In addition, surgical treatments should be followed up for longer periods as recurrences may occur after urethroplasty and perineal urethrostomy.

Graphical abstract, Objective An underlying abnormality in collagen turnover is implied in the occurrence of complications and recurrences after mesh augmented pelvic floor repair surgeries. Ascorbic acid is a potent stimulant of collagen synthesis. The aim of this study is to produce ascorbic acid releasing poly-lactic acid (PLA) scaffolds and evaluate them for their effects on extracellular matrix production and the strength of the materials. Materials and methods Scaffolds which contained either l-ascorbic acid (AA) and Ascorbate-2-Phosphate (A2P) were produced with emulsion electrospinning. The release of both drugs was measured by UV spectrophotometry. Human dermal fibroblasts were seeded on scaffolds and cultured for 2 weeks. Cell attachment, viability and total collagen production were evaluated as well as mechanical properties. Results No significant differences were observed between AA, A2P, Vehicle and PLA scaffolds in terms of fibre diameter and pore size. The encapsulation efficiency and successful release of both AA and A2P were demonstrated. Both AA and A2P containing scaffolds were significantly more hydrophilic and stronger in both dry and wet states compared to PLA scaffolds. Fibroblasts produced more collagen on scaffolds containing either AA or A2P compared to cells grown on control scaffolds. Conclusion This study is the first to directly compare the two ascorbic acid derivatives in a tissue engineered scaffold and shows that both AA and A2P releasing electrospun PLA scaffolds increased collagen production of fibroblasts to similar extents but AA scaffolds seemed to be more hydrophilic and stronger compared to A2P scaffolds. Statement of significance Mesh augmented surgical repair of the pelvic floor currently relies on non-degradable materials which results in severe complications in some patients. There is an unmet and urgent need for better pelvic floor repair materials. Our current understanding suggests that the ideal material should be able to better integrate into sites of implantation both biologically and mechanically. The impact of vitamin C on extracellular matrix production is well established but we in this study have undertaken a critical comparison of two derivatives of vitamin C as they are released from a biodegradable scaffold. This strategy proved to be equally useful with both derivatives in terms of new tissue production yet we observed significant differences in mechanical properties of these biomaterials.

Overactive bladder syndrome (OAB) is a chronic condition characterised by urgency, with or without associated urge incontinence. Solifenacin succinate is a once daily, bladder selective antimuscarinic available in two doses (5 and 10 mg). The recommended dose is 5 mg once daily and can be increased to 10 mg once daily if 5 mg is well tolerated. This article presents pooled efficacy and safety data from four large, placebo-controlled, multinational phase III trials of solifenacin succinate with a total enrolment of over 2800 patients. Data from these trials show that solifenacin 5 and 10 mg once daily is significantly more effective than placebo at reducing urgency, incontinence, micturition frequency and nocturia and at increasing volume voided per micturition. Adverse events were mainly mild-to-moderate in all treatment groups. The results of these phase III trials support the use of solifenacin in the treatment of OAB.

We have assessed ultraviolet-B (UV-B)-induced injury in wild-type Arabidopsis thaliana and two mutants with altered aromatic secondary product biosynthesis. Arabidopsis mutants defective in the ability to synthesize UV-B-absorbing compounds (flavonoids in transparent testa 5 [tt5] and sinapate esters in ferulic acid hydroxylase 1 [fah1]) are more sensitive to UV-B than is the wild-type Landsberg erecta. Despite its ability to accumulate UV-absorptive flavonoid compounds, the ferulic acid hydroxylase mutant fah1 exhibits more physiological injury (growth inhibition and foliar lesions) than either wild type or tt5. The extreme UV-B sensitivity of fah1 demonstrates the importance of hydroxycinnamate esters as UV-B protectants. Consistent with the whole-plant response, the highest levels of lipid and protein oxidation products were seen in fah1. Ascorbate peroxidase enzyme activity was also increased in the leaves of UV-B-treated plants in a dose- and genotype-dependent manner. These results demonstrate that, in A. thaliana, hydroxycinnamates are more effective UV-B protectants than flavonoids. The data also indicate that A. thaliana responds to UV-B as an oxidative stress, and sunscreen compounds reduce the oxidative damage caused by UV-B.

Aims Disturbed bladder sensations, or in broader terms, sensory dysfunctions are increasingly recognized as key elements in the origin and manifestation of symptom syndromes of urinary dysfunction. Adequate assessment of bladder sensation is crucial to improve our understanding of the pathophysiology and treatment of urinary dysfunction. This manuscript summarizes the discussions of a think tank on How to measure bladder sensation held at the ICI-RS meeting in 2011. Methods: Based upon literature reviews on bladder sensation presented at the think tank in the ICI-RS meeting, discussions evolved which were summarized in the ICI-RS report. Different physicians/researchers further elaborated on this report, which is presented in this manuscript. Results: Bladder sensations are not merely the result of bladder distension. Other factors inside the bladder or bladder wall: central processing and/or cognitive manipulation may play an important role. Current methods to measure sensations such as urodynamics, voiding diaries, forced diuresis, electrical stimulation and brain imaging are likely sub-optimal as they only consider part of these factors in isolation. Conclusions: Different methods to measure bladder sensations have been described and are used in clinical practice. Current methods only address part of the parameters responsible for the generation and perception of urinary sensations. Further focused research is required, and several recommendations are provided. Neurourol. Urodynam. 31:370-374, 2012. (C) 2012 Wiley Periodicals, Inc.

OBJECTIVE To assess the (i) the overlap between voiding, storage, and postmicturition symptoms; and (ii) the relative effect of bother and implications for treatment seeking within these symptom groups, using data from the EpiLUTS study. SUBJECTS AND METHODS This cross-sectional population-representative survey was conducted via the Internet in the USA, the UK and Sweden. Participants were asked to rate the frequency and symptom-specific bother of individual LUTS. Descriptive statistics were used to examine differences in International Continence Society LUTS subgroups. Logistc regressions were used with treatment seeking as the dependent variable and the bother of individual symptoms as predictors. RESULTS The survey response rate was 59%. The sample included 30 000 participants (14 139 men and 15 861 women); 71% of men and 75% of women reported at least one LUTS, and about half reported LUTS from more than one symptom group. Rates of bother were greatest for those who reported multiple storage, voiding and postmicturition LUTS (men 83%, women 89%). Less than a third of participants with LUTS from all three groups reported seeking treatment. Consistent correlates of treatment seeking across genders included bother due to weak stream, incomplete emptying, perceived daytime frequency, nocturia and urgency. There were also significant associations for several types of incontinence, most commonly stress incontinence in women and leaking during sexual activity in men. Despite high rates of symptom overlap and symptom-specific bother, few participants sought treatment for LUTS. CONCLUSION Common conditions such as BPH and OAB are treatable, and clinicians should proactively ask patients about urinary symptoms. Given the many types of LUTS that patients experience, it is imperative that clinicians assess all LUTS to ensure that appropriate treatments are prescribed.

Contains fulltext : 69019.pdf (Publisher’s version ) (Closed access) Guidelines for the management of continence and overactive bladder are generally available across Europe. For a majority of countries, these have been adopted by professional societies in either urology or gynaecology for local use. There has, however, been little monitoring of formal implementation of these guidelines and seldom any attempt to audit their operation. The state of continence care therefore remains largely unknown. This article reviews current guidelines and their status across Europe and examines what might be relevant from other disease areas to promote successful implementation.

Understanding bladder afferent pathways may reveal novel targets for therapy of lower urinary tract disorders such as overactive bladder syndrome and cystitis. Several potential candidate molecules have been postulated as playing a significant role in bladder function. One such candidate is the transient receptor potential vanilloid 1 (TRPV1) ion channel. Mice lacking the TRPV1 channel have altered micturition thresholds suggesting that TRPV1 channels may play a role in the detection of bladder filling. The aim of this study was therefore to investigate the role of TRPV1 receptors in controlling bladder afferent sensitivity in the mouse using pharmacological receptor blockade and genetic deletion of the channel. Multiunit afferent activity was recorded in vitro from bladder afferents taken from wild-type (TRPV+/+) mice and knockout (TRPV1-/-) mice. In wild-type preparations, ramp distension of the bladder to a maximal pressure of 40 mmHg produced a graded increase in afferent activity. Bath application of the TRPV1 antagonist capsazepine (10 mum) caused a significant attenuation of afferent discharge in TRPV1+/+ mice. Afferent responses to distension were significantly attenuated in TRPV1-/- mice in which sensitivity to intravesical hydrochloric acid (50 mm) and capsaicin (10 microm) were also blunted. Altered mechanosensitivity occurred in the absence of any changes in the pressure-volume relationship during filling indicating that this was not secondary to a change in bladder compliance. Single-unit analysis was used to classify individual afferents into low-threshold and high-threshold fibres. Low threshold afferent responses were attenuated in TRPV1-/- mice compared to the TRPV1+/+ littermates while surprisingly high threshold afferent sensitivity was unchanged. While TRPV1 channels are not considered to be mechanically gated, the present study demonstrates a clear role for TRPV1 in the excitability of particularly low threshold bladder afferents. This suggests that TRPV1 may play an important role in normal bladder function.

Ectopic production and secretion of hormones by a wide variety of tumours has been known for many years. Recently human chorionic gonadotropin (HCG) production and/or secretion have been noted in 15 cases with prostatic adenocarcinoma (Fukutani et al. 1983; Papapetrou et al. 1980: Broder et al. 1977; Menon & Stefani 1980; McManus et al. 1976) and in two with upper urinary tract transitional cell carcinoma (Fukutani et al. 1983; McManus et al. 1976). In this study we utilised the indirect immunoperoxidate technique to demonstrate beta-HCG production in prostatic adenocarcinoma and upper urinary tract urothelial tumours. Of 100 cases of prostatic adenocarcinoma beta-HCG production was demonstrated in nine cases, eight of which were poorly differentiated, and of 14 urothelial tumours of the upper urinary tract beta-HCG production was present in two high grade transitional cell carcinomas.

We present the first model to simulate the adaptive growth and remodeling (G&R) response of the bladder wall to bladder outlet obstruction (BOO). The model is calibrated and validated with an experimental rodent model of BOO. The bladder is modeled as a multi-layered, nonlinear elastic spherical membrane using a constrained mixture model that includes both passive and active components. The mechanical model is integrated with a shorter time scale micturition model that accounts for the active mechanics of voiding and dependence of flowrate on urethral resistance. Over a second time scale, constituents are configured and subsequently remodel to achieve a homeostatic state at the onset of voiding. Simulations of remodeling in response to the tenfold increase in outlet resistance arising from BOO, predict an initial loss of voiding capacity. Subsequent smooth muscle cell (SMC) hypertrophy enables the bladder wall to generate sufficient active tension to restore voiding functionality. Consistent with the experimental observations, the model predicts: hypertrophy of SMC and enlargement of the bladder over realistic timescales; collagen remodeling to maintain its role as a protective sheath; and increased voiding duration with lower average flow rate. This integrative G&R modeling approach provides fundamental insight into the adaptation of the bladder’s structural-functional relationship in response to outlet obstruction.

The function of the bladder urothelium in modulating contractile responses of the underlying detrusor smooth muscle to muscarinic stimulation has been examined in the pig bladder. Saturation curves for [3H]-QNB binding demonstrated a greater muscarinic receptor density in the urothelium than in the detrusor smooth muscle. The presence of an intact urothelium on isolated bladder strips inhibited contractions induced by carbachol but not KCl. Contractions of a urothelium-denuded muscle strip were inhibited in the presence of a second bladder strip with an intact urothelium, but not if the second strip was denuded. The urothelium-induced inhibition of contractions was not prevented in the presence of L-NOARG, methylene blue, indomethacin, propranolol, suramin, TEA or apamin. The data suggest the presence of a diffusable, urothelium-derived inhibitory factor, which could not be identified but appears to be neither nitric oxide, a cyclo-oxygenase product, a catecholamine, adenosine, GABA nor an EDHF sensitive to apamin.

Prostate cancer (PCa) is one of the first three causes of cancer mortality in Europe. Screening in asymptomatic men (aged 55–69 yr) using prostate-specific antigen (PSA) is associated with a migration toward lower staged disease and a reduction in cancer-specific mortality. By 20 yr after testing, around 100 men need to be screened to prevent one PCa death. While this ratio is smaller than for breast and colon cancer, the long natural history of PCa means many men die from other causes. As such, the nonselective use of PSA testing and radical treatments can lead to overdiagnosis and overtreatment. The European Association of Urology (EAU) supports measures to encourage appropriate PCa detection through PSA testing, while reducing overdiagnosis and overtreatment. These goals may be achieved using personalized risk-stratified approaches. For diagnosis, the greatest benefit from early detection is likely to come in men assessed using baseline PSA levels at the age of 45 yr to individualize screening intervals. Multiparametric magnetic resonance imaging as well as risk calculators based on family history, ethnicity, digital rectal examination, and prostate volume should be considered to triage the need for biopsy, thus reducing the risk of overdiagnosis. For treatment, the EAU advocates balancing patient's life expectancy and cancer's mortality risk when deciding an approach. Active surveillance is encouraged in well-informed patients with low-risk and some intermediate-risk cancers, as it decreases the risks of overtreatment without compromising oncological outcomes. Conversely, the EAU advocates radical treatment in suitable men with more aggressive PCa. Multimodal treatment should be considered in locally advanced or high-grade cancers. Patient summary: Implementation of prostate-specific antigen (PSA)-based screening should be considered at a population level. Men at risk of prostate cancer should have a baseline PSA blood test (eg, at 45 yr). The level of this test, combined with family history, ethnicity, and other factors, can be used to determine subsequent follow-up. Magnetic resonance imaging scans and novel biomarkers should be used to determine which men need biopsy and how any cancers should be treated. The European Association of Urology supports the implementation of prostate-specific antigen (PSA)-based screening at a population level in Europe. Men at risk of prostate cancer should have a baseline PSA blood test (eg, at 45 yr). This, together with family history, ethnicity, and other factors, should be used to determine subsequent follow-up. Magnetic resonance imaging scans and novel biomarkers should be used to determine which men need biopsy and how any cancers should be treated.

Contains fulltext : 220648.pdf (Publisher’s version ) (Closed access) The coronavirus disease 2019 (COVID-19) pandemic is unlike anything seen before by modern science-based medicine. Health systems across the world are struggling to manage it. Added to this struggle are the effects of social confinement and isolation. This brings into question whether the latest guidelines are relevant in this crisis. We aim to support urologists in this difficult situation by providing tools that can facilitate decision making, and to minimise the impact and risks for both patients and health professionals delivering urological care, whenever possible. We hope that the revised recommendations will assist urologist surgeons across the globe to guide the management of urological conditions during the current COVID-19 pandemic.

Background: Several drugs are approved for the treatment of lower urinary tract symptoms (LUTS) in men, but these are mostly used by clinicians as monotherapies. The combination of different compounds, each of which targets a different aspect of LUTS, seems appealing. However, only few clinical trials have evaluated the effects of combination therapies. Objective: This systematic review analyzes the efficacy and adverse events of combination therapies for male LUTS. Evidence acquisition: PubMed and Cochrane databases were used to identify clinical trials and meta-analyses on male LUTS combination therapy. The search was restricted to studies of level of evidence >= 1b. A total of 49 papers published between January 1988 and March 2012 were identified. Evidence synthesis: The alpha(1)-adrenoceptor antagonist (alpha(1)-blocker)/5 alpha-reductase inhibitor (5-ARI) combination provides the most data. This combination seems to be more efficacious in terms of several outcome variables in patients whose prostate volume is between 30 ml and 40 ml when treatment is maintained for >1 yr; when given for 6 yr. The alpha(1)-blocker/muscarinic receptor antagonist (antimuscarinic) combination was most frequently assessed as an add-on therapy to already existing alpha(1)-blocker therapy. Inconsistent data derive from heterogeneous study populations and different study designs. Currently, the alpha(1)-blocker/antimuscarinic combination appears to be a second-line add-on for patients with insufficient symptom relief after monotherapy. The combination seems to be safe in men with postvoid residual 4 mo concerning safety and efficacy of this combination. The alpha(1)-blocker/phosphodiesterase type 5 inhibitor combination is a new treatment option with only preliminary reports. More studies are needed before definitive conclusions can be drawn. Conclusions: An alpha(1)-blocker/5-ARI combination is beneficial for patients whose prostate volume is between 30 ml and 40 ml when medical treatment is intended for >1 yr. Based on short-term follow-up studies, add-on of antimuscarinics to alpha(1)-blockers is an option when postvoid residual is

Contains fulltext : 89828.pdf (Publisher’s version ) (Closed access) AIMS: In this review we try to shed light on the following questions: *How frequently are symptoms of overactive bladder (OAB) and is detrusor overactivity (DO) present in patients with pelvic organ prolapse (POP) and is there a difference from women without POP? *Does the presence of OAB symptoms depend on the prolapsed compartment and/or stage of the prolapse? *What is the possible pathophysiology of OAB in POP? *Do OAB symptoms and DO change after conservative or surgical treatment of POP? METHODS: We searched on Medline and Embase for relevant studies. We only included studies in which actual data about OAB symptoms were available. All data for prolapse surgery were without the results of concomitant stress urinary incontinence (SUI) surgery. RESULTS: Community- and hospital-based studies showed that the prevalence of OAB symptoms was greater in patients with POP than without POP. No evidence was found for a relationship between the compartment or stage of the prolapse and the presence of OAB symptoms. All treatments for POP (surgery, pessaries) resulted in an improvement in OAB symptoms. It is unclear what predicts whether OAB symptoms disappear or not. When there is concomitant DO and POP, following POP surgery DO disappear in a proportion of the patients. Bladder outlet obstruction is likely to be the most important mechanism by which POP induces OAB symptoms and DO signs. However, several other mechanisms might also play a role. CONCLUSIONS: There are strong indications that there is a causal relationship between OAB and POP.

Das Haus in der romantischen Erzählkunst stellt sich bei näherer Betrachtung als ein Paradox heraus, denn es kann keine Geborgenheit schenken. Es ist dafür ungastlich, unbetretbar, exzentrisch, utopisch, nicht dauerhaft, unfest, aus Glas oder bewegt. Insofern ist es eine Hanifestation der romantischen Unruhe oder Sehnsucht, die das Subjekt forttreibt, mit anderen Worten eine Manifestation des Selbstverlusts des Ich. Master of Arts (MA)