The efficacy and safety of intravesical chondroitin sulphate solution in recurrent urinary tract infections.

BACKGROUND: Urinary tract infections are among the most common indications for antibiotic therapy. The emergence of resistant uropathogens indicates the need for treatment alternatives. Replenishment of the glycosaminoglycan layer of the bladder, achieved by intravesical instillation of e.g. chondroitin sulphate (CS), is described to be a cornerstone in the therapy of cystitis. To retrospectively evaluate the efficacy of a therapy with 0.2% CS in patients suffering recurrent urinary tract infections (rUTI) in comparison to a treatment with low-dose long-term antibiotics (LDLTAB) and a combination of both. METHODS: A total of 151 patients with recurrent UTI who underwent intravesical therapy at Diaconesse hospital in Leiden, The Netherlands were included. 50 patients had been treated with CS, 51 patients had received LDLTAB, and 50 patients had received a combination therapy (LDLTABCS). Data recorded for baseline, after 6, and 12 months of treatment were evaluated. Descriptive statistics were calculated. Exploratory comparisons between groups and within groups were performed by using one-tailed and paired t-tests. Patients filled in a standardized quality of life questionnaire (EQ-5D). RESULTS: We found a statistically significant reduction of number of infections from 7.10 ± 0.50 SEM to 0.45 ± 0.07 SEM after 12 months therapy with CS compared to 12 months therapy with LDLTAB (from 7.04 ± 0.47 SEM to 1.8 ± 0.15 SEM). The number of visits to the urologist significantly decreased in the CS group from 7.46 ± 0.80 SEM to 1.28 ± 0.11 SEM and from 4.10 ± 0.29 SEM to 1.35 ± 0.11 SEM in the LDLTABCS group. In addition, a significant increase in Quality of life (QoL) was seen in the CS-group (from 58.2 ± 0.82 SEM to 80.43 ± 0.82 SEM) and in the LDLTABCS group (from 62.4 ± 0.97 SEM to 76.73 ± 1.06 SEM). There was no improvement in QoL with LDLTAB (from 58.24 ± 1.08 SEM to 58.96 ± 1.19 SEM). Evaluation's evidence is limited due to its retrospective character. CONCLUSIONS: Retrospective analysis of data from patients that underwent therapy for rUTIs confirms the safety and efficacy of CS and indicate a superiority to antibiotic treatment of rUTIs.

Prostate Cancer Drug Therapy: What Have Clinicians Missed During the COVID-19 Pandemic.

Due to the COVID-19 pandemic, major congresses and many teaching opportunities as well as the usual visits from medical advisors of pharmaceutical firms have been postponed and canceled. The major trials of prostate cancer in the last 5 years in each state are shortly discussed providing a panoramic overview of the available evidence and data on prostate cancer treatment. Apalutamide, enzalutamide, and darolutamide have proven to have clinical benefits when added to androgen deprivation therapy for patients with nonmetastatic castration-resistant prostate cancer. In patients in the metastatic hormone-sensitive setting, next to docetaxel, abiraterone, enzalutamide, and apalutamide have been shown to significantly improve overall survival and progression-free survival in comparison to standard hormone therapy. In addition, docetaxel abiraterone and enzalutamide are widely used in the metastatic setting. For second-line therapy of metastasized prostate cancer patients who have received either docetaxel or abiraterone or enzalutamide, olaparib, cabazitaxel, radium, and lutetium therapy have been shown to be beneficial in selected patient groups.

The discrepancy between European Association of Urology (EAU) guidelines and daily practice in the evaluation and management of nocturia: results of a Dutch survey.

BACKGROUND AND OBJECTIVE: In addition to the evaluation of voiding symptoms, in the evaluation of patients with nocturia, one should also consider other related causes such as sleep disorders, obstructive sleep apnoea (OSAS), diabetes and heart failure. In this study, we have aimed to assess the current knowledge and implementation of the EAU guidelines regarding nocturia in common urological practice in the Netherlands. SETTING AND PARTICIPANTS: In a national cross-sectional survey distributed among 450 urologists and urology residents in the Netherlands, the implementation of the recommendations of the European Association of Urology (EAU) guidelines on nocturia evaluation and management was studied. RESULTS AND LIMITATIONS: This survey revealed that only some aspects of the EAU guidelines are applied in the daily clinical practice and that some important parts are not. For example, only a minority asks about alcohol consumption and symptoms suggestive for diabetes or OSAS. In addition, a majority reported to use a bladder diary for 1-3 days instead of for a minimum of 3 days as recommended by the EAU guidelines. In the management of nocturia, a trial of timed diuretic therapy is only reported by a minority, whereas the use of beta-3 antagonists, which is not mentioned in the guidelines, is applied by a large majority. Desmopressin recommended for nocturnal polyuria is prescribed by two-third of Dutch urologists. CONCLUSIONS: These observations mandate better education and campaigns to raise the awareness on the EAU-guideline recommendations for nocturia.

Long-term follow-up of intravesical botulinum toxin-A injections in women with idiopathic overactive bladder symptoms.

INTRODUCTION: Intravesical botulinum toxin (BoNT-A) is a safe and effective treatment for overactive bladder syndrome. There are many reports on the clinical experience with BoNT-A, especially in patients with neurogenic detrusor overactivity. The US Food and Drug Administration has recently approved its use for idiopathic overactive bladder (iOAB). Various studies have reported positive results for iOAB in the short-term. Yet little is known about the results after repeated BoNT-A injections. In this study, we evaluated the long-term results of botulinum toxin (BoNT-A) in women with iOAB. METHODS: Patients treated with BoNT-A from 2004 until 2009 were evaluated in a non-academic teaching hospital (Zuyderland MC, Heerlen, the Netherlands). All female patients with a follow-up of >5 years with idiopathic bladder dysfunction were included. All patients received 200 U of onabotulinum toxin-A in 20 intradetrusor injections. In some patients, we applied a dose adjustment for repeated injections. Patients were instructed how to use clean intermittent self-catheterization (CISC) before the treatment. We advised patients to commence CISC if post-void residual exceeded 150 ml. RESULTS: A total of 128 women were included. All patients had at least 5-year follow-up after their first injection. The mean follow-up was 97 (60-125) months. The mean age was 67 (46-88) years. Of all patients, 30 % were still on BoNT-A treatment at the last follow-up visit. Of the 70 % that discontinued treatment, 27 % had insufficient effect and 43 % had tolerability issues. Most patients discontinued treatment after the first (79 %) and second (19 %) injections. Only 2 % of patients discontinued treatment after more than two injections during follow-up. CONCLUSION: Intravesical BoNT-A is an effective treatment for women with idiopathic OAB. However, in time, almost two-thirds of patients in our study discontinued therapy. Most patients discontinue treatment after one or two injections and mainly due to tolerability issues.

Distribution and sub-types of afferent fibre in the mouse urinary bladder.

AIM: Increased afferent fibre activity contributes to pathological conditions such as the overactive bladder syndrome. Nerve fibres running near the urothelium are considered to be afferent as no efferent system has yet been described. The aim of this study was to identify sub-types of afferent nerve fibres in the mouse bladder wall based on morphological criteria and analyse regional differences. MATERIALS AND METHODS: 27 bladders of six month old C57BL/6 mice were removed and tissues were processed for immunohistochemistry. Cryostat sections were cut and stained for Protein Gene Product 9.5 (PGP), calcitonin gene related polypeptide (CGRP), neurofilament (NF), vesicular acetylcholine transporter (VAChT) and neuronal nitric oxide synthase (nNOS). RESULTS: In the sub-urothelium, different types of afferent nerve fibre were found, i.e. immunoreactive (IR) to; CGRP, NF, VAChT, and/or nNOS. At the bladder base, the sub-urothelium was more densely innervated by CGRP-IR and VAChT-IR nerve fibres, then at the lateral wall. NF- and nNOS nerves were sparsely distributed in the sub-urothelium throughout the bladder. At the lateral wall the inner muscle is densely innervated by CGRP-IR nerve fibres. NF, VAChT and nNOS nerves were evenly distributed in the different muscle layers throughout the bladder. Nerve fibre terminals expressing CGRP and NF were found within the extra-mural ganglia at the bladder base. CONCLUSIONS: Different types of afferent nerve fibres were identified in the sub-urothelium of the mouse bladder. At the bladder base the sub-urothelium is more densely innervated than the lateral wall by CGRP-IR and VAChT-IR afferent nerve fibres. CGRP and NF afferent nerve fibres in the muscle layer probably relay afferent input to external ganglia located near the bladder base. The identification of different afferent nerves in the sub-urothelium suggests a functional heterogeneity of the afferent nerve fibres in the urinary bladder.

Changes in voiding behavior in a mouse model of Alzheimer's disease.

Besides cognitive decline and behavioral alteration, urinary incontinence often occurs in patients suffering from Alzheimer's disease (AD). To determine whether the transgenic mouse model of AD, APP/PS1 (APP(SL)/PS1(M146L)) mouse, shows alteration of the urinary bladder function and anxiety, as for patients with AD, we examined the urinary marking behavior in relation to affective behavior. At 18 months of age voiding behavior of APP/PS1 and wild type (WT) mice was assessed by using a modified filter paper assay in combination with video tracing, with the cage divided into a center and corner zones. Anxiety-related behavior and locomotion were respectively tested in an elevated zero maze (EZM) and an open field (OF). The APP/PS1 mice urinated more in the center zone than the WT mice. The total volume of markings was significantly lower in the APP/PS1 mice. In both groups, the average volume of a marking in the corner zone was larger than in the center zone. In the EZM, the APP/PS1 mice spent less time in the open arms of the arena, considered as anxiogenic zones, than the WT mice. During the OF task, the APP/PS1 mice covered a longer distance than the WT mice. These findings show that the APP/PS1 mice have a different voiding behavior compared to the WT mice, i.e., urinating with small volumes and voiding in the center of the cage, and suggest that increased locomotor activity and anxiety-related behaviors are factors in the change in voiding pattern in the APP/PS1 mouse.

Phosphodiesterase type 2 distribution in the guinea pig urinary bladder.

INTRODUCTION: Nitric oxide-stimulated cGMP synthesis represents an important signalling pathway in the urinary bladder. Inhibitors of the PDE1 and PDE5 enzyme have been studied to treat storage and voiding disorders in clinical settings. The distribution of PDE2 in the bladder is unknown. This study focuses on the distribution and site of action of PDE2 within the guinea pig urinary bladder wall. METHODS: Six male guinea pig bladders were dissected and treated in 2 ml Krebs' solution and 10 µM of the specific PDE2 inhibitor, Bay 60-7550 at 36 °C for 30 min. After stimulating tissues with 100 µM of diethylamine-NONOate for 10 min, the tissues were snap frozen and cut in 10 µm sections which were examined for cGMP immune-reactivity, co-stained with either vimentin, synaptic vesicle protein 2, calcitonin gene-related protein and protein gene product 9.5. RESULTS: PDE2 inhibitor Bay 60-7550 inhibits cGMP breakdown the most in the urothelial and suburothelial layers, as well as on the nerve fibres. After inhibition by Bay 60-7550, cGMP was mainly expressed in the intermuscle interstitial cells and the nerve fibres of the outer muscle layers of lateral wall, indicating the presence of PDE2 activity. DISCUSSION AND CONCLUSION: Our study is the first to show the distribution of PDE2 in the bladder which was shown to be present in the urothelium, mainly umbrella cells, the interstitial cells of the suburothelium and the outer muscle, as well as in nerve fibres.

Robotic extravesical anti-reflux operations in complex cases: technical considerations and preliminary results.

OBJECTIVES: To evaluate technical aspects and outcome of robotic laparoscopic extravesical anti-reflux surgery in the treatment of high-grade vesicoureteral reflux (VUR) with associated complicating conditions. MATERIALS AND METHODS: Retrospective database and chart reviews were performed to identify a subgroup of patients with high-grade VUR who underwent robot-assisted anti-reflux surgery using the extravesical Lich-Gregoir repair and who additionally had preoperatively known complicating factors. Five such patients were operated on from 2005 to 2009. All had bilateral VUR, bladder dysfunction, breakthrough infections, renal scarring or at least one of the following complicating factors: posterior urethral valve bladders, duplex systems or para-ostial diverticula. Outcome and surgical aspects were assessed. RESULTS: At follow-up 9 of 10 ureters were free of reflux and diverticulae had disappeared completely. No lasting urinary retentions occurred but two boys needed reinsertion of a catheter for 24 h after surgery. No further complications were noted. There were no signs of obstruction, infections did not persist and there was no negative effect on bladder function. Dissection of para-ostial diverticula seemed the only additional technical challenge. CONCLUSIONS: Robot-assisted extravesical anti-reflux surgery seems a promising technique in the operative management of this unfavorable subset of patients. Reflux cure rate is higher than expected using injection therapy and at the same time morbidity seems lower than with open surgery. Further experience is needed to confirm these first impressions.

Amoxicillin/clavulanate (Augmentin) resistant Escherichia coli in bacterial peritonitis after abdominal surgery--clinical outcome in ICU patients.

Bacterial resistance to antimicrobial agents is of great concern to clinicians. Patient outcome after infection is mainly dependent on the sensitivity of the bacterium to the agent used. We retrospectively studied 89 postoperative intensive care unit (ICU) patients with proven Escherichia coli peritonitis and investigated the clinical consequences of the E. coli resistance to amoxicillin/clavulanate. Significantly increased mortality, days of ventilation and ICU stay were noted in the co-amoxicillin/clavulanate resistant group. Furthermore, our results demonstrate that the sensitivity of E. coli to amoxicillin/clavulanate in the postoperative ICU setting has decreased in recent years. We can conclude that the current antibiotic regimen for the empirical treatment of ICU patients with peritonitis, as used in our hospital, needs to be changed. A switch, for instance, to ceftriaxone (Rocephin) in combination with metronidazole and gentamicin, instead of the present regimen of amoxicillin/clavulanate in combination with gentamicin, seems preferable.

Which clinical signs and symptoms predict hypoxemia in acute childhood asthma?

OBJECTIVE: To find the clinical signs that are the best predictors of hypoxemia (SpO2 =92%) in acute asthma in children. METHODS: Color of skin, dyspnea (by single breath counting), alertness, respiratory rate, presence of audible wheeze, wheezing on auscultation, accessory muscle use, nasal flaring, pulse rate, systolic and diastolic blood pressure, pulsus paradoxus and oxygen saturation at room air (by pulse oximetry) were recorded at the time of presentation and one hour after presentation after completion of 3 doses of nebulized salbutamol and budesonide. RESULTS: Hypoxemia (SpO2 92% pounds sterling) was seen in 45% children at presentation and 14(28.6%) after one hour. The clinical signs that correlated significantly with hypoxemia at both time points were dyspnea assessed by single breath count (OR 3.3, 95% CI 0.9-12.9), accessory muscle use score > or = 3 (OR 3.0, 95% CI 0.9-15.4) and pulsus paradoxus> 10 (OR 3.0, 95% CI 0.7-13.6). In a multiple logistic regression model accessory muscle score > or = 3 and pulsus paradoxus> 10 were identified as independent predictors of hypoxemia (sensitivity 64.3%, specificity 91%). CONCLUSION: Physical assessment in a child with acute exacerbation of asthma should at least include accessory muscle use and pulsus paradoxus, since these predict hypoxemia the best.