Mental Fatigue Evaluation of Surgical Teams during a Regular Workday in a High-Volume Tertiary Healthcare Center.

INTRODUCTION: Considering the complex set of manual and psychological tasks a surgeon has to perform during the day, it is very important to assess the surgeon's fatigability, reaction time, attention, and memory. OBJECTIVE: Here, we wanted to determine the mental fatigue status of surgeons and how their abilities are affected through a regular workday. METHODS: We included 3 senior urologists and 6 urology residents. In a set period of time, we assessed their fatigue through self-assessed fatigue, Samn-Perelli score, and Karolinska sleepiness scale score. Further, reaction time, attention, and memory correlated with the number of the operations in the day, and total number of operations in that day were assessed. RESULTS: As the number of tasks increases, and as the surgeons advance to the end of the workday, they become more fatigued, reaction time ultimately increases, and attention and memory become slightly altered. CONCLUSIONS: Complications resulting from the fatigue of surgeons could be serious. Their performance status and skills decrease as they perform more tasks or advance through the day.

Muscarinic receptors 2 and 5 regulate bitter response of urethral brush cells via negative feedback.

We have recently identified a cholinergic chemosensory cell in the urethral epithelium, urethral brush cell (UBC), that, upon stimulation with bitter or bacterial substances, initiates a reflex detrusor activation. Here, we elucidated cholinergic mechanisms that modulate UBC responsiveness. We analyzed muscarinic acetylcholine receptor (M1-5 mAChR) expression by using RT-PCR in UBCs, recorded [Ca2+]i responses to a bitter stimulus in isolated UBCs of wild-type and mAChR-deficient mice, and performed cystometry in all involved strains. The bitter response of UBCs was enhanced by global cholinergic and selective M2 inhibition, diminished by positive allosteric modulation of M5, and unaffected by M1, M3, and M4 mAChR inhibitors. This effect was not observed in M2 and M5 mAChR-deficient mice. In cystometry, M5 mAChR-deficient mice demonstrated signs of detrusor overactivity. In conclusion, M2 and M5 mAChRs attenuate the bitter response of UBC via a cholinergic negative autocrine feedback mechanism. Cystometry suggests that dysfunction, particularly of the M5 receptor, may lead to such symptoms as bladder overactivity.-Deckmann, K., Rafiq, A., Erdmann, C., Illig, C., Durschnabel, M., Wess, J., Weidner, W., Bschleipfer, T., Kummer, W. Muscarinic receptors 2 and 5 regulate bitter response of urethral brush cells via negative feedback.

Bitter triggers acetylcholine release from polymodal urethral chemosensory cells and bladder reflexes.

Chemosensory cells in the mucosal surface of the respiratory tract ("brush cells") use the canonical taste transduction cascade to detect potentially hazardous content and trigger local protective and aversive respiratory reflexes on stimulation. So far, the urogenital tract has been considered to lack this cell type. Here we report the presence of a previously unidentified cholinergic, polymodal chemosensory cell in the mammalian urethra, the potential portal of entry for bacteria and harmful substances into the urogenital system, but not in further centrally located parts of the urinary tract, such as the bladder, ureter, and renal pelvis. Urethral brush cells express bitter and umami taste receptors and downstream components of the taste transduction cascade; respond to stimulation with bitter (denatonium), umami (monosodium glutamate), and uropathogenic Escherichia coli; and release acetylcholine to communicate with other cells. They are approached by sensory nerve fibers expressing nicotinic acetylcholine receptors, and intraurethral application of denatonium reflexively increases activity of the bladder detrusor muscle in anesthetized rats. We propose a concept of urinary bladder control involving a previously unidentified cholinergic chemosensory cell monitoring the chemical composition of the urethral luminal microenvironment for potential hazardous content.

Systemic atherosclerosis causes detrusor overactivity: functional and morphological changes in hyperlipoproteinemic apoE-/-LDLR-/- mice.

PURPOSE: The prevalence of systemic atherosclerosis and overactive bladder/detrusor overactivity increases almost simultaneously with age but an association between these diseases has not yet been proved. We evaluated changes in bladder function and morphology, including vascularization, in apoE(-/-)LDLR(-/-) double knockout mice with systemic atherosclerosis but without central nervous system involvement. MATERIALS AND METHODS: Cystometry was performed in awake, freely moving 60-week-old apoE(-/-)LDLR(-/-) mice and C57BL/6N controls. The mice were sacrificed and perfused with Microfil® contrast medium. The bladder was excised, dissected and scanned by nano-computerized tomography, including 3-dimensional reconstruction. Samples then underwent histomorphological analysis. RESULTS: In apoE(-/-)LDLR(-/-) mice cystometry revealed a significant decrease in the peak-peak interval, micturition interval, functional bladder capacity and micturition volume. However, maximum bladder pressure increased. Nano-computerized tomography revealed a significant reduction in bladder wall thickness, segment volume, vascular volume and the vascular volume fraction. Histomorphologically bladder specimens showed a thickened media of intramural vessels, activated endothelial cells and intramural inflammatory cells. CONCLUSIONS: To our knowledge this study presents a new in vivo mouse model of nonneurogenic detrusor overactivity caused by systemic atherosclerosis. Decreased bladder wall vascularization seems to be a major factor for detrusor overactivity onset. Capillaries are rarified with reduced lumina due to thickened media. Activated endothelial cells and the infiltration of inflammatory cells in apoE(-/-)LDLR(-/-) mice underlines once more that atherosclerosis is an inflammatory process that may also be relevant to the onset of detrusor overactivity.

Long-term results after acute therapy of obstructive pyelonephritis.

INTRODUCTION: To evaluate therapeutic results till 5 years after therapy of obstructive pyelonephritis (OPN) emphasizing regular follow-up. MATERIAL AND METHODS: During 5 years, 57 patients with OPN were treated. The patients' charts were reviewed retrospectively for clinical data. These were completed by a questionnaire. RESULTS: In the group of 57 patients (average age 56 years), about two third were women. Urolithiasis (65%) and tumors (21%) were the main causes of obstruction; fever (91%) and loin pain (86%) the main symptoms. Three fourth of the patients showed renal insufficiency and nearly 50% anemia. E. coli and Proteus spp. were the dominating organisms. Sonography detected obstruction in 93% cases. In one third of cases, CT scan was added; 81% percutaneous nephrostomy and 19% ureteral stenting were the initial methods of urinary drainage. During therapy, 23% nephrectomies (19% complete, 4% partial) were performed. Long-term follow-up showed 11% recurrent OPN and 33% recurrent UTI. CONCLUSIONS: After diagnosis of OPN, primary nephrostomy or ureteral stenting and antibiotic therapy are the first measures. If recurrent urinary tract infections or OPN occur, long-term follow-up and low-dose antibiotic prophylaxis may be discussed.

The Integral Theory System Questionnaire: an anatomically directed questionnaire to determine pelvic floor dysfunctions in women.

PURPOSE: Anatomical damage to pelvic floor structures may cause multiple symptoms. The Integral Theory System Questionnaire (ITSQ) is a holistic questionnaire that uses symptoms to help locate damage in specific connective tissue structures as a guide to reconstructive surgery. It is based on the integral theory, which states that pelvic floor symptoms and prolapse are both caused by lax suspensory ligaments. The aim of the present study was to psychometrically validate the ITSQ. MATERIALS AND METHODS: Established psychometric properties including validity, reliability, and responsiveness were considered for evaluation. Criterion validity was assessed in a cohort of 110 women with pelvic floor dysfunctions by analyzing the correlation of questionnaire responses with objective clinical data. Test-retest was performed with questionnaires from 47 patients. Cronbach's alpha and "split-half" reliability coefficients were calculated for inner consistency analysis. RESULTS: Psychometric properties of ITSQ were comparable to the ones of previously validated Pelvic Floor Questionnaires. Face validity and content validity were approved by an expert group of the International Collaboration of Pelvic Floor surgeons. Convergent validity assessed using Bayesian method was at least as accurate as the expert assessment of anatomical defects. Objective data measurement in patients demonstrated significant correlations with ITSQ domains fulfilling criterion validity. Internal consistency values ranked from 0.85 to 0.89 in different scenarios. CONCLUSIONS: The ITSQ proofed accurate and is able to serve as a holistic Pelvic Floor Questionnaire directing symptoms to site-specific pelvic floor reconstructive surgery.

[Case-based presentation of the S2e guideline on the diagnosis and treatment of benign prostatic hyperplasia]. / Fallbasierte Vorstellung der S2e-Leitlinie Diagnostik und Therapie des benignen Prostatasyndroms (BPS).

Benign prostatic hyperplasia (BPH) is the most common disease of the lower urinary tract in men. The prevalence increases continuously with increasing age and a chronic progressive course is to be expected. In order to reduce the morbidity of affected patients and to improve their quality of life, the expert panel Benign Prostatic Hyperplasia (BPH) of the German Society of Urology (DGU) has written a new version of the evidence-based "S2e guideline on the diagnosis and treatment of BPH". Using a current patient case, the contents of the new S2e guideline are illustrated, from diagnosis to the decision-making process for a suitable treatment choice. The case presented here shows the possible complexity and difficulty that can arise in the diagnosis of BPH, the need for further diagnostic steps and the finding of a suitable therapy in order to fulfill the patient's wishes, if possible.

[Minimally invasive treatment of benign prostatic hyperplasia : The German S2e guideline 2023-part 4]. / Minimalinvasive Therapien des benignen Prostatasyndroms : Die deutsche S2e-Leitlinie 2023 ­ Teil 4/4.

BACKGROUND: Lower urinary tract symptoms suggestive for benign prostatic obstruction (LUTS/BPO) are one of the most frequent diseases in men and can have a significant impact on quality of life. Instrumental therapies are common, and many patients seek minimally invasive treatment options. OBJECTIVE: Presentation and evidence-based evaluation of the minimally invasive therapy for benign prostatic syndrome. MATERIALS AND METHODS: Summary and overview of chapters 11-13 on minimally invasive therapies for LUTS/BPO of the current long version of the German S2e guideline. RESULTS: In case of absolute indication for surgery or after unsatisfactory or undesired medical therapy, minimally invasive treatments such as UroLift® (Neotract Inc., Pleasanton, CA, USA), Rezá¿¡m™ (Boston Scientific, Malborough, MA, USA), iTIND™ (Olympus America Inc., Westborough, MA, USA), and prostatic artery embolization (PAE) can be considered. These indirect/delayed ablative therapies offer lower morbidity and the possibility of performing them under local anesthesia, but they are inferior to direct ablative/resective techniques in terms of effectiveness and sustainability. CONCLUSIONS: The updated German S2e guideline summarizes evidence-based recommendations for new minimally invasive therapies for LUTS/BPO, which present alternative treatment options for selected patients.

Bacterial prostatitis.

OBJECTIVES: The prostatitis syndrome is classified into bacterial prostatitis (acute and chronic), chronic pelvic pain syndrome and asymptomatic prostatitis. The aim of this report is to review current management standards for bacterial prostatitis. METHODS: A research was performed on literature dealing with acute and chronic bacterial prostatitis. RESULTS: There is a consensus on diagnostic management of bacterial prostatitis comprising microbiological sampling of midstream urine in acute bacterial prostatitis and performance of a bacterial localisation test in chronic bacterial prostatitis. Approximately 10 % of acute bacterial prostatitis cases eventually develop into chronic bacterial prostatitis and further 10 % into chronic pelvic pain syndrome. Bacterial isolates causing acute bacterial prostatitis are highly virulent strains comprising an array of different virulence factors. Presumably, the additional ability of isolates to form biofilms might be one factor amongst others to facilitate development of chronic bacterial prostatitis. Therapy for infectious prostatitis is standardised with antibiotics as the primary agents, empirically administered in acute prostatitis and after susceptibility testing in chronic bacterial prostatitis. Fluoroquinolones exhibit more favourable pharmacological properties; therefore, fluoroquinolones have been recommended as first-line agents in the treatment for chronic bacterial prostatitis. Antibiotic resistance to fluoroquinolones, however, is increasing and is posing significant clinical problems. Further studies on alternative antibiotics active within the prostate are therefore needed both for prophylaxis in transrectal prostate biopsy, for example, and for therapy of chronic bacterial prostatitis. CONCLUSIONS: Bacterial prostatitis has developed into well-managed entities with increasing antimicrobial resistance being the most severe drawback of yielding therapeutic success.

[Diagnostic work-up of benign prostatic hyperplasia : The German S2e-guideline 2023 part 1]. / Diagnostik des benignen Prostatasyndroms : Die deutsche S2e-Leitlinie 2023 Teil 1.

BACKGROUND: Lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH; in German guidelines: benign prostatic syndrome [BPS]) is the most frequent urological disease in men and can result in a considerable deterioration of quality-of-life. BPS can be associated with LUTS, benign prostatic enlargement (BPE), and bladder outlet obstruction (BOO) or benign prostatic obstruction (BPO), respectively. The expert group on BPS of the German Society of Urology has re-evaluated the tests for the assessment of BPH and provides evidence-based recommendations. OBJECTIVES: Presentation and evidence-based rating of tests for the assessment of patients with BPS. MATERIALS AND METHODS: Summary and overview of chapters 5, 6, and 8 of the latest long version of the German S2e guideline on BPS. RESULTS: The diagnostic work-up should clarify (1) whether the complaints of the patient are caused by BPS, (2) how relevant the complaints are and whether treatment is necessary, (3) whether complications of the lower or upper urinary tract already exist, and (4) which treatment will be most suitable. Baseline assessment should be done in all BPS patients and include history, measurement of LUTS and quality-of-life, urinalysis, serum prostate-specific antigen, post-void residual, ultrasound of the lower urinary tract, including measurements of prostate volume, intravesical prostatic protrusion and detrusor wall thickness, and ultrasound of the upper urinary tract. Additional tests can follow when questions remain unanswered after baseline assessment. These optional tests include bladder diaries, uroflowmetry, serum creatinine, urethrocystoscopy, other noninvasive tests for the determination of BOO/BPO such as penile cuff test, condom catheter method and near-infrared spectroscopy, and other imagining tests such as X­ray and MRI investigations. CONCLUSIONS: The updated German S2e guideline summarizes evidence-based recommendations on the diagnostic work-up, including the assessment of the BPS components BPE, LUTS, and BOO/BPO.

[Conservative and pharmacological treatment of benign prostatic hyperplasia : The German S2e-guideline 2023-part2]. / Konservative und medikamentöse Therapie des benignen Prostatasyndroms : Die deutsche S2e-Leitlinie 2023 ­ Teil 2.

BACKGROUND: Lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH, in German guidelines: benign prostatic syndrome [BPS]) is considered the most common disease of the lower urinary tract in men and can have a tremendous impact on the quality-of-life of affected patients. Conservative and pharmacological therapy of this disease are of great importance, both in improving LUTS and reducing progression-related complications. OBJECTIVES: Presentation of the conservative and pharmacological treatment options according to the current German S2e guideline on BPS. MATERIALS AND METHODS: Summary and overview of chapters 9 and 10 of the current German S2e guideline on BPS. RESULTS: In addition to a controlled watchful waiting for BPS patients without an absolute indication for prostate surgery, a variety of phytopharmacological formulations and synthetic drugs according to the symptomatology and clinical progress are available. Phytotherapy should, due to inconsistent study data, only be considered for mild to moderate symptoms. Synthetic drugs include alpha-blockers, 5α-reductase inhibitors, phosphodiesterase inhibitors, antimuscarinics and, more recently, the ß3-agonist mirabegron in the current guideline. In addition, various combination therapies are listed and evaluated according to their indications, effects and side effects. CONCLUSIONS: The current German S2e guideline on the diagnosis and treatment of BPS provides an evidence-based foundation for finding the best possible and most effective medication.

[Surgical treatment options of lower urinary tract symptoms due to benign prostatic obstruction : The German S2e guideline 2023-part 3]. / Operative Therapie des benignen Prostatasyndroms ­ klassische Desobstruktion : Die deutsche S2e-Leitlinie 2023 ­ Teil 3.

BACKGROUND: Lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) are one of the most common diagnoses in clinical practice. Bothersome LUTS impact considerably quality of life of men and may cause severe complications without treatment. According to the diagnostic assessment every patient should be treated with an adequate therapy. Management comprises a conservative approach, medication, novel minimally invasive options, and surgical procedures with the aim to remove the obstructing adenoma. The German guideline panel has updated the German guidelines on diagnostic evaluation and management of LUTS due to BPO. OBJECTIVES: Evidence-based recommendations of surgical treatment options of LUTS due to BPO are evaluated. MATERIALS AND METHODS: Chapters 11.1.1 and 11.2 of the updated German S2e guideline on the management of LUTS due to BPO are summarized as a review article. RESULTS: A treatment algorithm based on current evidence has been proposed. It is considered to provide guidance for the selection of the best procedure according to the needs of the patient. Anatomic features of the prostate, the patients' morbidity, and the preservation of ejaculatory function are taken into account for the choice of the best procedures. These surgical options can be divided into techniques with direct, delayed or no removal of the adenoma, procedures with suprapubic access, and embolizing approaches. CONCLUSIONS: The updated German S2e guideline on the management of LUTS due to BPO provides evidence-based recommendations for the selection of the best procedure according to the needs of the individual patient.

Diagnosis and Therapy of Female Urinary Incontinence. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry No. 015/091, January 2022): Part 2 with Recommendations on Interventional/Surgical Therapy of Overactive Bladder, Surgical Treatment of Stress Urinary Incontinence and Diagnosis and Therapy of Iatrogenic Urogenital Fistula.

Aim This completely revised interdisciplinary S2k-guideline on the diagnosis, therapy, and follow-up care of female patients with urinary incontinence (AWMF registry number: 015-091) was published in December 2021. This guideline combines and summarizes earlier guidelines such as "Female stress urinary incontinence," "Female urge incontinence" and "Use of Ultrasonography in Urogynecological Diagnostics" for the first time. The guideline was coordinated by the German Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG) and the Working Group for Urogynecology and Plastic Pelvic Floor Reconstruction (Arbeitsgemeinschaft für Urogynäkologie und plastische Beckenbodenrekonstruktion e. V., AGUB). Methods This S2k-guideline was developed using a structured consensus process involving representative members from different medical specialties and was commissioned by the Guidelines Commission of the DGGG, OEGGG and SGGG. The guideline is based on the current version of the guideline "Urinary Incontinence in Adults" published by the European Association of Urology (EAU). Country-specific items associated with the respective healthcare systems in Germany, Austria and Switzerland were also incorporated. Recommendations The short version of this guideline consists of recommendations and statements on the surgical treatment of female patients with stress urinary incontinence and urge incontinence. Specific solutions for the diagnostic workup and treatment of uncomplicated and complicated urinary incontinence are discussed. The diagnostics and surgical treatment of iatrogenic urogenital fistula are presented.

Diagnosis and Therapy of Female Urinary Incontinence. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/091, January 2022): Part 1 with Recommendations on Diagnostics and Conservative and Medical Treatment.

Aim This completely revised interdisciplinary S2k-guideline on the diagnosis, therapy, and follow-up care of female patients with urinary incontinence (AWMF registry number: 015-091) was published in December 2021. This guideline combines and summarizes earlier guidelines such as "Female stress urinary incontinence," "Female urge incontinence" and "Use of Ultrasonography in Urogynecological Diagnostics" for the first time. The guideline was coordinated by the German Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG) and the Working Group for Urogynecology and Plastic Pelvic Floor Reconstruction (Arbeitsgemeinschaft für Urogynäkologie und plastische Beckenbodenrekonstruktion e. V., AGUB). Methods This S2k-guideline was developed using a structured consensus process involving representative members from different medical specialties and was commissioned by the Guidelines Commission of the DGGG, OEGGG and SGGG. The guideline is based on the current version of the guideline "Urinary Incontinence in Adults" published by the European Association of Urology (EAU). Country-specific items associated with the respective healthcare systems in Germany, Austria and Switzerland were also incorporated. Recommendations The short version of this guideline consists of recommendations and statements on the epidemiology, etiology, classification, symptoms, diagnostics, and treatment of female patients with urinary incontinence. Specific solutions for the diagnostic workup and appropriate conservative and medical therapies for uncomplicated and complication urinary incontinence are discussed.

Bladder Microbiome in the Context of Urological Disorders-Is There a Biomarker Potential for Interstitial Cystitis?

Since the development of modern cultivation and sequencing techniques, the human microbiome has increasingly become the focus of scientific attention. Even in the bladder, long considered to be a sterile niche, a highly variable and complex microbial colonization has now been demonstrated. Especially in the context of diseases such as interstitial cystitis, whose etiopathogenesis is largely unknown, and whose diagnosis is based on a process of exclusion of confusable diseases, science hopes to gain far-reaching insights for etiology and diagnosis, including the identification of potential biomarkers. While for functional disorders such as urge urinary incontinence and overactive bladder syndrome, initial associations have been demonstrated between reduced microbial diversity and increased symptomatology, as well as shifts in the abundance of specific microorganisms such as Lactobacillus or Proteus, studies in interstitial cystitis show conflicting results and have failed to identify a putative organism or urotype that clearly distinguishes the urinary microbiome of patients with IC/BPS from that of healthy controls. At the present time, therefore, the new insights into the bladder microbiome and its potential influence on urologic disease cannot yet be used in the context of elucidating possible etiopathogenetic causes, as well as in the use of a biomarker for diagnostic or prognostic purposes. Further studies should focus primarily on uniform procedures and detection methods to achieve better comparability of results and increase the likelihood of detecting hidden patterns.

[Physical and psychological comorbidities of interstitial cystitis/bladder pain syndrome]. / Physische und psychische Komorbiditäten der Interstitiellen Zystitis/Bladder Pain Syndrom.

Compared with the healthy population, patients diagnosed with IC/BPS have a higher risk of developing further pain syndromes. Common comorbidities include endometriosis, irritable bowel syndrome, fibromyalgia, chronic fatigue, migraine, anxiety, multiple chemical sensitivity and autoimmune diseases. Chronic pain may lead to depression, which often results in social isolation. Chronic pain can only be explained and treated successfully if a person is seen as a biopsychosocial entity. Interrelations between a person and their environment are of central importance for the maintenance of health and the development of disease. The fact that the pain is located in the urogenital area makes the situation even more delicate. In this location, we find the functions of excretion, reproduction und sexual desire - a constellation that predisposes to a high incidence of psychosomatic events. This means that urogenital pain not only involves an unpleasant sensory experience but also feelings of fear, guilt, shame and impotence.

[Interstitial cystitis: interventions and surgery - more than a last resort?] / Interstitielle Zystitis: Interventionelle und operative Therapie ­ mehr als eine Ultima Ratio.

Interstitial cystitis is an underdiagnosed chronic-relapsing to chronic-progressive urinary bladder disease, whose pathogenesis and aetiology has not been fully elucidated. The disease itself cannot be cured and treatment is symptomatic. Treatment options comprise conservative and medicinal approaches as well as a large number of interventional/surgical procedures. These include intravesical instillation, transurethral procedures such as injections of botulinum toxin A, corticosteroids and local anaesthetics, hydrodistension and neuromodulation as well as (laser) fulguration, resection and cystectomy. Although surgical procedures are considered a late option and are often referred to as last-resort therapy, these interventional options often show good to very good response rates, manageable complications and a favourable risk-benefit evaluation. An overall generalisation of surgery as a last-resort treatment option should therefore be avoided and its use should be discussed based on the individual needs of each patient.

Beyond Antimuscarinics: A Review of Pharmacological and Interventional Options for Overactive Bladder Management in Men.

CONTEXT: The role of overactive bladder (OAB) treatment in women beyond antimuscarinics has been evaluated extensively. Beta-3 agonists, botulinum toxin-A (BTX-A), and nerve stimulation are indicated in these patients. However, data on male patients in this clinical scenario are scarce. OBJECTIVE: The aim of this systematic review was to evaluate the evidence on treatment options beyond antimuscarinics in men with OAB. EVIDENCE ACQUISITION: A search of PubMed, EMBASE, Scopus, Web of science, Cochrane Central Register of Controlled Trials, and Cochrane Central Database of Systematic Reviews databases was performed for relevant articles published between January 2000 and October 2020, using the following Medical Subject Headings: "male/man," "LUTS," "overactive bladder," "storage symptoms," "urgency," "nocturia," "incontinence," "beta-3 agonist," "PDE-5 inhibitors," "botulinum toxin," "sacral nerve stimulation/neurostimulation," "percutaneous/transcutaneous tibial nerve stimulation," "PTENS," and "combination therapy." Evidence acquisition was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. PROSPERO registration number is CRD42020201223. EVIDENCE SYNTHESIS: Overall, 24 studies were retrieved. In male OAB, mirabegron (MIRA) is the most intensively investigated pharmacological option. A pooled analysis of five randomized clinical trials (RCTs), including 1187 patients, concluded that MIRA 50 mg was associated with a greater reduction in frequency versus placebo (-0.37, 95% confidence interval [CI]: -0.74, -0.01, p < 0.05). A pooled analysis of three RCTs, including 1317 male patients, has also shown that the addition of MIRA 50 mg in men receiving the α1-blocker tamsulosin improved the mean number of micturitions per day (-0.27, 95% CI: -0.46 to -0.09, p < 0.05), urgency episodes (-0.50, 95% CI: -0.77 to -0.22, p < 0.05), total OAB symptom score (-0.66, 95% CI: -1.00 to -0.38, p < 0.05), and mean volume voided (+10.76 ml, 95% CI: 4.87-16.64, p < 0.05). MIRA treatment is well tolerated in men. Other pharmacological treatment options, such as phosphodiesterase-5 (PDE-5) inhibitors, should be considered investigational. BTX-A seems to be effective as third-line treatment in male OAB patients. A higher rate of intermittent self-catheterization (5-42%) is observed in male than in female patients. Data on nerve stimulation are scarce. CONCLUSIONS: MIRA has the most robust data in terms of safety and efficacy in this patient population. Preliminary data in men suggest that BTX-A is indicated as an interventional treatment. Evidence for PDE-5 inhibitors and nerve stimulation is too limited to provide recommendations. Future studies in this population should aim to better define the best treatment sequence and to identify predictors for treatment response and failure, to determine a therapeutic approach tailored to patients' characteristics. PATIENT SUMMARY: Overactive bladder is highly prevalent in men. Mirabegron 50 mg is the treatment option supported by the highest level of evidence when antimuscarinics failed. Botulinum toxin A injections seems to be an effective treatment as interventional option. Roles of nerve stimulation and phosphodiesterase inhibitors in male OAB patients are still to be defined.

[Interstitial cystitis/bladder pain syndrome (IC/BPS)]. / Interstitielle Zystitis/Blasenschmerzsyndrom (IC/BPS).

As an orphan disease interstitial cystitis/bladder pain syndrome (IC/BPS) is a frequently underdiagnosed and inadequately treated disease of the urinary bladder, often after years of symptoms. Caused by an unknown etiology, a high variability of symptoms, a lack of biomarkers and a gradual onset, IC/BPS is a diagnosis by exclusion and poses a special challenge to doctors and patients. In addition to conventional and complementary medical treatment, oral medication, intravesical and transurethral procedures are available as treatment options. Due to the invasiveness or irreversibility, however, interventional surgical procedures should only be used after careful consideration or as a last resort. In order to find a suitable individualized treatment, a classification of the patients according to the severity and type of symptoms can be advantageous.

Expression and distribution of cholinergic receptors in the human urothelium.

The bladder urothelium not only provides a diffusion barrier but it also serves a sensor function and releases signalling molecules that are considered to act in a paracrine and autocrine fashion, e.g. by acetylcholine. Its actions are conferred by two classes of receptors, i.e. G-protein-coupled muscarinic receptors (MR) and ionotropic nicotinic receptors (nAChR). In this study we set out to determine the expression and distribution of all MR subtypes (M1R-M5R) and nAChR alpha-subunits 7, 9 and 10 in the human urothelium by means of RT-PCR and immunohistochemistry, respectively. Real-time RT-PCR revealed a rank order of MR subtype expression of M2R>>M3R=M5R>M4R=M1R. Immunohistochemistry demonstrated differential distribution patterns with M1R being restricted to basal cells, M2R nearly exclusively found in umbrella cells, whereas M3R and M4R were homogenously distributed and M5R was seen in a decreasing gradient from luminal to basal. As for nAChR alpha-subunits, rank order of expression is alpha7>>alpha10>alpha9, and they were observed throughout the urothelium with a gradient decreasing from luminal to basal in intensity. In conclusion, the human urothelium carries multiple cholinergic receptor subtypes, with predominant expression of M2R, M3R and alpha7-nAChR. Their distribution as well as that of the less expressed subtypes is layer-specific in the urothelium. In view of the multiplicity of pathways to which different cholinergic receptor subtypes are coupled, we propose that this layer-specific distribution serves to stratify cholinergic regulation of human urothelial function.