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Transcutaneous tibial nerve stimulation (TTNS) is a promising treatment for neurogenic lower urinary tract symptoms. However, the evidence is limited due to a general lack of randomised controlled trials (RCTs) and, also, inconsistency in the sham and blinding conditions. In the context of much-needed RCTs, we aimed to develop a suitable sham-control protocol for a clinical setting to maintain blinding but avoid meaningful stimulation of the tibial nerve. Three potential electrode positions (lateral malleolus/5th metatarsal/plantar calcaneus) and two electrode sizes (diameter: 2.5 cm/3.2 cm) were tested to determine which combination provided the optimal sham configuration for a TTNS approach, based on a visible motor response. Sixteen healthy volunteers underwent sensory and motor assessments for each sham configuration. Eight out of them came back for an extra TTNS visit. Sensory thresholds were present for all sham configurations, with linear regression models revealing a significant effect regarding electrode position (highest at plantar calcaneus) but not size. In addition, motor thresholds varied with the position—lowest for the 5th metatarsal. Only using this position and 3.2 cm electrodes attained a 100% response rate. Compared to TTNS, sensory and motor thresholds were generally higher for the sham configurations; meanwhile, perceived pain was only higher at the lateral malleolus. In conclusion, using the 5th metatarsal position and 3.2 cm electrodes proved to be the most suitable sham configuration. Implemented as a four-electrode setup with standardized procedures, this appears to be a suitable RCT protocol for maintaining blinding and controlling for nonspecific TTNS effects in a clinical setting.

We used clinical parameters to develop a prediction model for the occurrence of urodynamic risk factors for upper urinary tract (UUT) damage during the first year after acute spinal cord injury (SCI). A total of 97 patients underwent urodynamic investigation at 1, 3, 6, and 12 months after acute SCI, within the framework of a population-based longitudinal study at a single university SCI center. Candidate predictors included demographic characteristics and neurological and functional statuses 1 month after SCI. Outcomes included urodynamic risk factors for UUT damage: detrusor overactivity combined with detrusor sphincter dyssynergia, maximum storage detrusor pressure (pDetmax) ≥ 40 cmH2O, bladder compliance < 20 mL/cmH2O, and vesicoureteral reflux. Multivariable logistic regression was used for the prediction model development and internal validation, using the area under the receiver operating curve (aROC) to assess model discrimination. Two models showed fair discrimination for pDetmax ≥ 40 cmH2O: (i) upper extremity motor score and sex, aROC 0.79 (95% CI: 0.69–0.89), C-statistic 0.78 (95% CI: 0.69–0.87), and (ii) neurological level, American Spinal Injury Association Impairment Scale grade, and sex, aROC 0.78 (95% CI: 0.68–0.89), C-statistic 0.76 (95% CI: 0.68–0.85). We identified two models that provided fair predictive values for urodynamic risk factors of UUT damage during the first year after SCI. Pending external validation, these models may be useful for clinical trial planning, although less so for individual-level patient management. Therefore, urodynamics remains essential for reliably identifying patients at risk of UUT damage.

Overactive bladder (OAB) is a global problem reducing the quality of life of patients and increasing the costs of any healthcare system. The etiology of OAB is understudied but likely involves supraspinal network alterations. Here, we characterized supraspinal resting-state functional connectivity in 12 OAB patients and 12 healthy controls (HC) who were younger than 60 years. Independent component analysis showed that OAB patients had a weaker presence of the salience (Cohen’s d = 0.9) and default mode network (Cohen’s d = 1.1) and weaker directed connectivity between the fronto-parietal network and salience network with a longer lag time compared to HC. A region of interest analysis demonstrated weaker connectivity in OAB compared to HC (Cohen’s d > 1.6 or < −1.6), particularly within the frontal and prefrontal cortices. In addition, weaker seed (insula, ventrolateral prefrontal cortex) to voxel (anterior cingulate cortex, frontal gyrus, superior parietal lobe, cerebellum) connectivity was found in OAB compared to HC (Cohen’s d > 1.9). The degree of deviation in supraspinal connectivity in OAB patients (relative to HC) appears to be an indicator of the severity of the lower urinary tract symptoms and an indication that such symptoms are directly related to functional supraspinal alterations. Thus, future OAB therapy options should also consider supraspinal targets, while neuroimaging techniques should be given more consideration in the quest for better phenotyping of OAB.

To describe the temporal development of and risk factors for the occurrence of unfavourable urodynamic parameters during the first year after spinal cord injury (SCI).This population-based longitudinal study used data from 97 adult patients with a single-event traumatic or ischaemic SCI who underwent video-urodynamic investigation (UDI) at a university SCI centre. The first occurrences of unfavourable urodynamic parameters (detrusor overactivity combined with detrusor sphincter dyssynergia [DO-DSD], maximum storage detrusor pressure ≥40 cmHThe majority of the population (87/97 [90%]) had at least one unfavourable urodynamic parameter. Most unfavourable urodynamic parameters were initially identified during the 1- or 3-month UDI, including 92% of the DO-DSD (78/85), 82% of the maximum storage pressure ≥40 cmHThe first UDI should take place within 3 months after SCI as to facilitate early diagnosis of unfavourable urodynamic parameters and timely treatment. Neuro-urological guidelines and individualised management strategies for patients with SCI may be strengthened by considering sex and SCI characteristics in the scheduling of UDIs.

We aimed to provide a real-world description of neurogenic lower urinary tract dysfunction within the first year after spinal cord injury with a focus on unfavorable urodynamic parameters that are associated with urological morbidity.Urodynamic investigations from 97 patients with traumatic or ischemic acute spinal cord injury and managed according to the European Association of Urology Guidelines on Neuro-Urology were analyzed at a single university spinal cord injury center at 1 month, 3 months, 6 months, and 12 months after injury. Unfavorable urodynamic parameters were defined as detrusor overactivity in combination with detrusor sphincter dyssynergia, maximum storage detrusor pressure of 40 cm HOne or more unfavorable urodynamic parameter was observed in 87 out of 97 patients (90%) within the first year after spinal cord injury. Eighty-eight percent of the patients showed detrusor overactivity with detrusor sphincter dyssynergia, 39% a maximum storage detrusor pressure of 40 cm HUsing a standardized urodynamic follow-up schedule, we found unfavorable urodynamic parameters in a majority of the population within the first year after spinal cord injury. As early treatment based on urodynamic findings might reduce the risk of deterioration of upper and lower urinary tract function, thereby improving long-term outcomes, there is need for further research regarding recommendations for a urodynamic follow-up schedule during the first year after spinal cord injury.

Summary Background Urinary tract infections (UTIs) are among the most prevalent microbial diseases and their financial burden on society is substantial. In the context of increasing antibiotic resistance, finding alternative treatments for UTIs is a top priority. We aimed to determine whether intravesical bacteriophage therapy with a commercial bacteriophage cocktail is effective in treating UTI. Methods We did a randomised, placebo-controlled, clinical trial, at the Alexander Tsulukidze National Centre of Urology, Tbilisi, Georgia. Men older than 18 years of age, who were scheduled for transurethral resection of the prostate (TURP), with complicated UTI or recurrent uncomplicated UTI but no signs of systemic infection, were allocated by block randomisation in a 1:1:1 ratio to receive intravesical Pyo bacteriophage (Pyophage; 20 mL) or intravesical placebo solution (20 mL) in a double-blind manner twice daily for 7 days, or systemically applied antibiotics (according to sensitivities) as an open-label standard-of-care comparator. Urine culture was taken via urinary catheter at the end of treatment (ie, day 7) or at withdrawal from the trial. The primary outcome was microbiological treatment response after 7 days of treatment, measured by urine culture; secondary outcomes included clinical and safety parameters during the treatment period. Analyses were done in a modified intention-to-treat population of patients having received at least one dose of the allocated treatment regimen. This trial is registered with ClinicalTrials.gov , NCT03140085 . Findings Between June 2, 2017, and Dec 14, 2018, 474 patients were screened for eligibility and 113 (24%) patients were randomly assigned to treatment (37 to Pyophage, 38 to placebo, and 38 to antibiotic treatment). 97 patients (28 Pyophage, 32 placebo, 37 antibiotics) received at least one dose of their allocated treatment and were included in the primary analysis. Treatment success rates did not differ between groups. Normalisation of urine culture was achieved in five (18%) of 28 patients in the Pyophage group compared with nine (28%) of 32 patients in the placebo group (odds ratio [OR] 1·60 [95% CI 0·45–5·71]; p=0·47) and 13 (35%) of 37 patients in the antibiotic group (2·66 [0·79–8·82]; p=0·11). Adverse events occurred in six (21%) of 28 patients in the Pyophage group compared with 13 (41%) of 32 patients in the placebo group (OR 0·36 [95% CI 0·11–1·17]; p=0·089) and 11 (30%) of 37 patients in the antibiotic group (0·66 [0·21–2·07]; p=0·47). Interpretation Intravesical bacteriophage therapy was non-inferior to standard-of-care antibiotic treatment, but was not superior to placebo bladder irrigation, in terms of efficacy or safety in treating UTIs in patients undergoing TURP. Moreover, the bacteriophage safety profile seems to be favourable. Although bacteriophages are not yet a recognised or approved treatment option for UTIs, this trial provides new insight to optimise the design of further large-scale clinical studies to define the role of bacteriophages in UTI treatment. Funding Swiss Continence Foundation, the Swiss National Science Foundation, and the Swiss Agency for Development and Cooperation. Translations For the Georgian and German translations of the abstract see Supplementary Materials section.

Study Design Simulations using data from a prospective cohort study. Objectives To illustrate how prospective cohort data can be employed in randomized controlled trial (RCT) planning to assess feasibility and operational challenges, using TASCI (Transcutaneous tibial nerve stimulation in patients with Acute Spinal Cord Injury to prevent neurogenic detrusor overactivity: a nationwide randomized, sham-controlled, double-blind clinical trial) as a case study. Setting Spinal cord injury rehabilitation centers in Switzerland. Methods TASCI is nested in the multicenter Swiss Spinal Cord Injury Cohort Study (SwiSCI), which prospectively includes patients with acute spinal cord injury. In simulations, data from 640 patients, collected by SwiSCI, were used to investigate different scenarios of patient eligibility and study consent, as well as the performance of the randomization list. Descriptive analysis was used to describe the population of interest and the simulation results; multivariable logistic regression analysis was performed to identify predictors of discharge within the TASCI intervention time period. Results The recruitment target of 114 patients is obtainable within the originally envisioned three-year time period under the most favorable recruitment scenario examined. The distribution of the primary prognostic factor produced imbalance in the randomization lists and informed further discussion of the cut-off values used in stratification. Influxes of patients resulted in overlapping intervention periods for multiple participants, which guided resource allocation. Early discharge was related to the primary prognostic factor and study center, but is only anticipated in about 8% of participants. Conclusions Prospective cohort data are a very valuable resource for planning RCTs.

OBJECTIVES To investigated whether detrusor overactivity is missed in a relevant percentage if the urodynamic investigation (UDI) is stopped at a filling volume of 500 mL due to the fear of bladder overdistention in patients with lower urinary tract symptoms and high bladder capacity. PATIENTS & METHODS A consecutive series of 1598 patients with a bladder capacity of >500 mL in the bladder diary undergoing UDI due to lower urinary tract dysfunction was prospectively investigated. UDI was performed according to Good Urodynamic Practices recommended by the International Continence Society. UDI was stopped at strong desire to void or in case of autonomic dysreflexia, vesico-uretero-renal reflux, bladder pain or discomfort. RESULTS Of the 1598 patients (594 women, 1004 men), 1282 (80%) and 316 (20%) suffered from neurogenic and non-neurogenic lower urinary tract dysfunction (LUTD), respectively. Overall, detrusor overactivity was detected in 66% (1048/1598), in 71% (910/1282) with neurogenic and in 44% (138/316) with non-neurogenic LUTD. Detrusor overactivity occurred in 16% (263/1598, 95% CI 14.7-18.4%) only at a bladder volume above 500 mL. This phenomenon was significantly (p

OBJECTIVES To evaluate the possible influence of non-pharmacological interventions, such as compressive bandages and intermittent pneumatic compression (IPC), on leg oedema and nocturnal polyuria (NP), and the possible interrelation between both pathologies in patients with spinal cord injury (SCI), as patients with SCI often have leg oedema and during the night the oedema decreases as a result of natural drainage mechanisms that can cause NP. PATIENTS AND METHODS Patients with SCI who followed their first rehabilitation after their SCI with bilateral leg oedema and/or with as much or a larger urine volume at night as during the day. The patients were all wheelchair users and followed the rehabilitation programme daily for 3 weeks. In all, 24 patients, aged between 21 and 63 years, were selected for participation in the 3-week rehabilitation programme. During the first week, baseline data were collected. During the second week, IPC was executed from the moment the patient went to lie down. During the third week, the patients wore multilayer compressive bandages. Leg circumference was measured in the morning before sitting up and at the moment they went to lie down in bed. During each study week, a daily frequency-volume chart (24 h) was completed. RESULTS The leg volume of both legs was significantly different between the morning and evening (right leg F = 103.90, P

To highlight the current aspects and developments in the management of neurogenic urine storage dysfunction and to sensitize urologists for this interdisciplinary and important topic. Neurogenic lower urinary tract dysfunction affects a large proportion of patients with chronic neurological diseases or lesions such as multiple sclerosis, Parkinson’s disease, stroke, spina bifida, and spinal cord injury. Such a dysfunction is not only highly bothersome and devastating for the quality of life but also poses a significant risk for health. Particularly, detrusor overactivity and detrusor-sphincter-dyssynergia are frequent pathological patterns in neurogenic lower urinary tract dysfunction that are associated with sequelae such as recurrent urinary tract infections and renal impairment. The current cornerstones of treatment for urine storage dysfunction in neurological patients such as intermittent self-catheterization, antimuscarinic drugs, botulinum neurotoxin A intradetrusor injections, augmentation cystoplasty, urinary diversion, and artificial urinary sphincter have significantly contributed to improvements in QoL, health, and survival of neurological patients affected by neurogenic lower urinary tract dysfunction. However, these treatments have not advanced much recently. Moreover, the level of evidence of many therapy options specifically regarding their application in neurological patients is quite low and the main and auxiliary mechanisms of action are often only poorly understood. Despite former accomplishments in Neuro-Urology, more specific evidence for treatments of lower urinary tract dysfunction in neurological patients as well as better knowledge on their mechanisms of action is needed to advance the field and exploit the full treatment potential of available therapies.

To better understand the neuropathophysiology of overactive bladder (OAB) in women by characterising supraspinal activity in response to bladder distention and cold stimulation.We recruited 24 female participants, 12 with OAB (median [interquartile range, IQR] age 40 [32-42] years) and 12 healthy controls (HCs) without lower urinary tract (LUT) symptoms (median [IQR] age 34 [28-44] years), and assessed LUT and cognitive function through neuro-urological examination, 3-day bladder diary, urodynamic investigation, and questionnaires. Functional magnetic resonance (MR) imaging using a 3-T scanner was performed in all participants during automated, repetitive bladder filling and draining (block design) with 100 mL body temperature (37 °C) saline using a MR-compatible and MR-synchronised infusion-drainage device until strong desire to void (HIGH-FILLING/DRAINING) and bladder filling with cold saline (4 °C, i.e. COLD). Whole-brain and region-of-interest analyses were conducted using Statistical Parametric Mapping, version 12.Significant between-group differences were found for 3-day bladder diary variables (i.e. voiding frequency/24 h, P 0.001; voided volume/void, P = 0.04; and urinary incontinence [UI] episodes/24 h, P = 0.007), questionnaire scores (International Consultation on Incontinence Questionnaire-Female LUT symptoms [overall, filling, and UI scores, all P 0.001]; the Overactive Bladder Questionnaire short form [symptoms and quality-of-life scores, both P 0.001]; the Hospital Anxiety and Depression Scale [anxiety P = 0.004 and depression P = 0.003 scores]), as well as urodynamic variables (strong desire to void, P = 0.02; maximum cystometric capacity, P = 0.007; and presence of detrusor overactivity, P = 0.002). Age, weight and cognitive function (i.e. Mini-Mental State Examination, P = 1.0) were similar between groups (P 0.05). In patients with OAB, the HIGH task elicited activity in the superior temporal gyrus, ventrolateral prefrontal cortex (VLPFC), and mid-cingulate cortex; and the COLD task elicited activity in the VLPFC, cerebellum, and basal ganglia. Compared to HCs, patients with OAB showed significantly stronger cerebellar activity during HIGH-FILLING and significantly less activity in the insula and VLPFC during HIGH-DRAINING.The present findings suggest a sensory processing and modulation deficiency in our OAB group, probably as part of their underlying pathophysiology, as they lacked activity in essential sensory processing areas, such as the insula. Instead, accessory areas, such as the cerebellum, showed significantly stronger activation compared to HCs, presumably supporting pelvic-floor motor activity to prevent UI. The novel findings of the present study provide physiological evidence of the necessity to consider non-bladder aetiologies of bladder symptoms.

Purpose Functional neuroimaging is a powerful and versatile tool to investigate central lower urinary tract (LUT) control. Despite the increasing body of literature there is a lack of comprehensive overviews on LUT control. Thus, we aimed to execute a coordinate based meta-analysis of all PET and fMRI evidence on descending central LUT control, i.e. pelvic floor muscle contraction (PFMC) and micturition. Materials and methods A systematic literature search of all relevant libraries was performed in August 2020. Coordinates of activity were extracted from eligible studies to perform an activation likelihood estimation (ALE) using a threshold of uncorrected p Results 20 of 6858 identified studies, published between 1997 and 2020, were included. Twelve studies investigated PFMC (1xPET, 11xfMRI) and eight micturition (3xPET, 5xfMRI). The PFMC ALE analysis (n = 181, 133 foci) showed clusters in the primary motor cortex, supplementary motor cortex, cingulate gyrus, frontal gyrus, thalamus, supramarginal gyrus, and cerebellum. The micturition ALE analysis (n = 107, 98 foci) showed active clusters in the dorsal pons, including the pontine micturition center, the periaqueductal gray, cingulate gyrus, frontal gyrus, insula and ventral pons. Overlap of PFMC and micturition was found in the cingulate gyrus and thalamus. Conclusions For the first time the involved core brain areas of LUT motor control were determined using ALE. Furthermore, the involved brain areas for PFMC and micturition are partially distinct. Further neuroimaging studies are required to extend this ALE analysis and determine the differences between a healthy and a dysfunctional LUT. This requires standardization of protocols and task-execution.

Transcutaneous tibial nerve stimulation has the potential to revolutionize the management of lower urinary tract dysfunction in patients with acute spinal cord injury. TASCI is a nationwide randomized, sham-controlled, double-blind clinical trial for which the preparatory phase has been successfully completed.

Neuroimaging allows in vivo visualization of neuronal structures/processes to assess their involvement in bodily functions. This is particularly valuable for the assessment of complex, multilevel neuronal controlled functions, such as urine storage and micturition. Using positron emission tomography or functional magnetic resonance imaging, significant alterations of supraspinal lower urinary tract (LUT) control have been described in patients with neurogenic LUT dysfunction due to spinal cord injury, Parkinson's disease, and multiple sclerosis. Severity of such alterations often correlates with symptom/dysfunction severity, both of which could be partly mitigated by therapeutic interventions. However, the overall evidence and study quality are presently very limited, and a multidisciplinary approach will be required to achieve clinical relevance in the long term. PATIENT SUMMARY: We reviewed the findings of neuroimaging studies in patients with bladder dysfunction due to neurological trauma/disease. Changes in the nervous systems of these patients alter bladder control, and neuroimaging may become a valuable tool for assessing these alterations.

Background Tibial nerve stimulation (TNS) is an effective and safe treatment for idiopathic lower urinary tract dysfunction (LUTD), but its value in neurological patients is unclear. Objective To test the feasibility, acceptability, and safety of a randomized, sham-controlled, double-blind transcutaneous TNS (TTNS) setup for treating neurogenic LUTD. Design, setting, and participants A pilot study including nine patients with refractory neurogenic LUTD investigated prospectively at a university neuro-urology department. Intervention Randomized, sham-controlled, double-blind verum and sham TTNS was performed for 30 min twice a week, for 6 wks. Outcome measurements and statistical analysis Outcomes were feasibility, acceptability, and safety of the TTNS protocol. Secondarily, potential efficacy was investigated. Descriptive statistics were used. Results and limitations All procedures were feasible and well tolerated by all nine patients. Using verum TTNS, a motor response could be triggered in all patients and a sensory response in all but one. At the beginning and end of treatment, seven and six (78% and 67%) patients believed to receive verum TTNS, and five and six (56% and 67%) correctly guessed their group allocation, respectively. No treatment-related adverse events occurred. A comparison of baseline versus 6 wks of verum and sham TTNS led to relevant symptom and functional changes in only a limited number of piloted patients. Conclusions Verum and sham TTNS combined with the blinding procedures proved feasible and safe. Both interventions and procedures, as well as the randomization process, were well accepted by the patients. While the subsensory threshold TTNS approach in combination with the sham condition is advantageous for patients’ blinding, the clinical findings raised some doubt regarding sufficient TNS. Hence, relevant methodological adjustments concerning the adequate stimulation current and corresponding sham condition are needed before starting randomized controlled trials to clarify the value and role of TTNS in neuro-urology. Patient summary Transcutaneous tibial nerve stimulation is a promising treatment option for neurogenic lower urinary tract dysfunction, but methodological adjustments in treatment application are required before further prospective studies can be initiated.

Lower urinary tract, bowel, and sexual dysfunctions are frequent sequelae of neurotrauma and neurodegenerative diseases that require adequate management. All three pelvic organ dysfunction severely compromise quality of life and can jeopardize health. Thus, treatment is mandatory and therapy options range from simple conservative measures to major surgery. The main therapeutic principles that should be considered in regard to treatment of pelvic organ dysfunction include protection of kidney function, reduction of urinary and/or faecal incontinence, independent management of lower urinary tract and bowel function, ability to sustain a satisfactory sexual relationship, fertility support, and improvement of quality of life. To comply with such principles and to select, initiate, maintain, and eventually adapt the ‘optimal’ treatment regimen for each patient requires a specialized multidisciplinary team not only during inpatient rehabilitation but also during outpatient follow-up. This chapter provides an overview on the management of lower urinary tract, bowel, and sexual dysfunction and aims to sensitize healthcare professionals for this essential part/aspect of neurorehabilitation.

This chapter provides a brief description of the structure and function of the autonomic nervous system (ANS), which is responsible for the involuntary control of visceral organs throughout the human body. The ANS has three main divisions: sympathetic, parasympathetic, and enteric. These continuously monitor and control cardiovascular, bronchopulmonary, sexual, thermoregulatory, lower urinary, and gastrointestinal tract functions. Normally the response of these systems to exercise, environmental challenges, and emotional stress are intricately regulated. ANS dysfunction is commonly prevalent in patients with various neurodegenerative disorders. These can present due to either central or peripheral nervous system aetiologies. In order to determine a correct prognosis for these patients, accurate assessment techniques, described herein, are necessary. The underlying causes of specific autonomic system disorders are also discussed, along with descriptions of various treatment strategies. Medical advances in the field of neurorehabilitation now also provide promising alternative options to address autonomic dysfunctions.

Background: Urinary tract infections (UTIs) are among the most prevalent microbial diseases and their financial burden on the society is substantial. Moreover, the continuing increase of antibiotic resistance worldwide is alarming. We aimed to determine whether intravesical bacteriophage therapy is effective to treat UTI. Methods: In this randomised, placebo-controlled, double-blind clinical trial 97 patients presenting with UTI were enrolled to receive intravesical Pyo bacteriophage (n=28), intravesical placebo solution (n=32), or oral antibiotic therapy (n=37). The primary outcome included clinical and microbiological treatment response. Secondary outcomes included safety parameters and quantitative microbiological urine assessments. Findings: At day seven, the treatment success rates were statistically similar between the three groups: Compared to the Pyo bacteriophage (5/28 (18%)) group, the placebo group had 9/32 (28%) (Odds Ratio (OR) 1.8, 95% confidence interval (CI) 0.52-6.2; p=0.352) and the antibiotic group had 13/37 (35%) (OR 2.49, 95% CI 0.77-8.1; p=0.129) successes. Also, adverse events were statistically similar between the three groups. They were seen in 6/28 patients (21%) in the Pyo bacteriophage group, in 13/32 (41%) in the placebo group (OR 0.4, 95% CI 0.13-1.25; p=0.116) and in 11/37 (30%) in the antibiotic group (OR 0.65, 95% CI 0.21-2.03; p=0.452). Interpretation: Beside antibiotics, bacteriophages and bladder irrigation appear to have specific but limited beneficial effects on UTI control. Moreover, the bacteriophage safety profile seems to be favourable. Although bacteriophages are not yet a valuable treatment option for UTIs, this randomized controlled trial provides new insights to optimize the setting for further large-scale clinical studies to define the role of bacteriophages for treating UTIs. Trial Registration: Trial registration number: ClinicalTrials.gov, number NCT03140085. Funding Statement: Swiss Continence Foundation (www.swisscontinencefoundation.ch) The Swiss National Science Foundation (www.snsf.ch) and the Swiss Agency for Development and Cooperation in the framework of the program SCOPES (Scientific cooperation between Eastern Europe and Switzerland, grant number 152304). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: The study protocol was approved by the institutional review board and ethical committee at TNCU (TNCU-02/283; Tbilisi, Georgia), complied with International Conference on Harmonization Guideline for Good Clinical Practice and the Declaration of Helsinki.

AIMS Assessing the reliability of electrical pain threshold (PT) and evaluating the impact of stimulation frequency at different locations in the healthy lower urinary tract (LUT). METHODS Ninety subjects (age: 18.3-35.8 years, 40 females, 50 males) were randomly allocated to one stimulation site (bladder dome [BD], trigone, proximal, membranous (only males), or distal urethra). Using 0.5 Hz/1.1 Hz/1.6 Hz electrical stimulation (square wave, pulse width:1 ms), current perception thresholds (CPTs), PTs and tolerance thresholds were assessed at two visits. Analyses were performed using linear mixed models, intraclass correlation coefficients (ICC) and Bland-Altman method. RESULTS PTs vary in relation to stimulation frequency, location and between genders. PT decreased with higher stimulation frequency. The highest PTs were measured at the BD and membranous urethra with males reporting higher PTs than females. Reliability of PT assessments according to ICC was good to excellent across all frequencies, locations, and genders (ICC = 0.61-0.97), except for BD and distal urethra in females showing poor to fair reliability (BD: all frequencies, distal urethra: 0.5 Hz). CONCLUSIONS PTs can be safely and reliably assessed from bladder and urethral locations. Semi-objective PT assessment may provide additional information on functionality and sensitivity of the LUT slow fiber afferents and complement findings from urodynamic investigations and CPT assessments. In conclusion, the developed methodology may open new opportunities for using electrical stimulation paradigms for LUT PT assessments and diagnostics. All this allows a more precise, location-specific characterization of pain origin and pain reaction towards therapy.

INTRODUCTION The quality of urodynamic measurements in clinical practice has been debated as a matter of concern. It is considered plausible that this has a direct bearing on patient care and the perceived value of urodynamic testing. METHODS This is a report of the proceedings of the Think Tank: "Is the value of urodynamics undermined by poor technique?" from the Annual International Consultation on Incontinence-Research Society, which took place in June 2018 in Bristol, UK. The Think Tank discussed the evidence for deficiencies in urodynamic test quality and considered the implications of improvements for clinical diagnosis and practice. RESULTS There is evidence that technique affects urodynamic quality, and that urodynamic practice is variable. Factors such as team skill set, technologies used, and training received will also affect the quality of urodynamic service. Questions exist regarding the influence of technique on the utility and perceived value of urodynamics. CONCLUSIONS We suggest research questions that will provide the necessary evidence on the link between technique, reporting, and outcome, and clarify the role of good practice in the utility of urodynamic testing.

We assessed urodynamic parameters within the first 40 days after spinal cord injury to investigate whether the detrusor is acontractile during the acute phase of spinal cord injury.We performed a prospective cohort study in 54 patients with neurogenic lower urinary tract dysfunction due to acute spinal cord injury who underwent urodynamic investigation within the first 40 days after injury at a single university spinal cord injury center.Urodynamic investigation revealed an acontractile detrusor in only 20 of the 54 patients (37%) but unfavorable urodynamic parameters in 34 (63%). We found detrusor overactivity in 32 patients, detrusor-sphincter dyssynergia in 25, maximum storage detrusor pressure greater than 40 cm HIn contrast to the common notion of an acontractile detrusor during acute spinal cord injury, almost two-thirds of our patients showed unfavorable urodynamic parameters within the first 40 days after spinal cord injury. Considering that early treatment of neurogenic lower urinary tract dysfunction in patients with acute spinal cord injury might improve the long-term urological outcome, urodynamic investigation should be performed timely to optimize patient tailored therapy.

Objective To evaluate if urinary continence after intradetrusor onabotulinumtoxinA injections is sufficient for appropriate outcome assessment or if urodynamic investigation (UDI) is needed. Patients and Methods A consecutive series of 148 patients undergoing intradetrusor onabotulinumtoxinA injections for refractory neurogenic detrusor overactivity (NDO) incontinence were prospectively evaluated. Patients underwent UDI prior and 6 weeks after onabotulinumtoxinA injections. Primary outcome was the prevalence of maximum storage detrusor pressure >40 cmH2O in continent patients 6 weeks after treatment. Secondary outcomes were treatment effects on other clinical and video-urodynamic parameters. Results 6 weeks after intradetrusor onabotulinumtoxinA injections, 98 (66%) of the 148 patients with NDO incontinence became continent. Of these patients, 18 (18%, confidence interval 12-27%) had a maximum storage detrusor pressure >40cmH2O. Gender, underlying neurological disorder and high storage detrusor pressures prior to treatment seem to increase the risk for poor urodynamic outcomes. Conclusions Urinary continence is not sufficient for outcome assessment after intradetrusor onabotulinumtoxinA injections, since high intravesical pressures threatening the upper urinary tract might be missed in a relevant percentage of continent patients. Therefore, we strongly recommend UDI as a routine part of the follow-up. This article is protected by copyright. All rights reserved.

Impaired lower urinary tract (LUT) afferents often cause LUT symptoms. Assessment of LUT afferent pathways is possible using bipolar cortical sensory evoked potential (SEP) recordings with the active electrode at the vertex during electrical stimulation in the LUT. This study aimed to investigate the topographical distribution and microstates of lower urinary tract sensory evoked potentials (LUTSEPs) using different stimulation frequencies. Ninety healthy subjects (18–36 years old, 40 women) were randomly assigned to one of five stimulation locations [bladder dome; trigone; proximal, membranous (men only) or distal urethra]. Cycles of 0.5 Hz/1.1 Hz/1.6 Hz electrical stimulation were applied using a custom-made catheter. Cortical activity was recorded from 64 surface electrodes. Marker setting was performed manually on an individual subject-level for the P1, N1, and P2 components of vertex recordings. N1 and P2 topographies presented with central negativities and positivities around the vertex. Regarding topographical distribution, Randomization Graphical User interface (RAGU) analyses revealed consistent frequency effects and microstates for N1/P2. Higher stimulation frequencies resulted in decreasing map strength for P1, N1, and P2. LUTSEP topographies suggest central generators in the somatosensory cortex, which are not detectable in a bipolar set-up. The observed frequency effect indicates fiber refractoriness at higher frequencies. The multichannel approach allows more comprehensive assessment of LUTSEPs and might therefore be sensitive to pathological changes. Examinations in patients with LUT symptoms are needed to further investigate this biomarker. Electronic supplementary material The online version of this article (10.1007/s10548-020-00796-z) contains supplementary material, which is available to authorized users.

We investigated the prevalence of asymptomatic bacteriuria and the incidence of symptomatic urinary tract infections in patients with neurogenic lower urinary tract dysfunction undergoing urodynamics. We also assessed predictors of symptomatic urinary tract infections.We evaluated a prospective consecutive series of 317 patients, including 106 women and 211 men, with neurogenic lower urinary tract dysfunction. Of the patients 111 (35%) voided spontaneously, 141 (44%) relied on intermittent self-catheterization and 65 (21%) relied on an indwelling catheter. Before urodynamics the urine samples were collected by sterile catheterization for dipstick testing and urine culture. We assessed the association of patient characteristics with symptomatic urinary tract infections after urodynamics in patients with asymptomatic bacteriuria and developed a prediction model based on the most important risk factors.Before urodynamics urine cultures were negative in 123 patients (39%) and positive in 194 (61%).A symptomatic urinary tract infection will develop in the followup year in about 1 of 5 patients with asymptomatic bacteriuria. This rather low overall probability precludes routine antibiotic prophylaxis or treatment in patients with neurogenic lower urinary tract dysfunction who have asymptomatic bacteriuria since 4 of 5 would be overtreated. However, in patients with a history of previous symptomatic urinary tract infections antibiotic prescription might be justified.

Background. Predicting functional outcomes after traumatic spinal cord injury (SCI) is essential for counseling, rehabilitation planning, and discharge. Moreover, the outcome prognosis is crucial for patient stratification when designing clinical trials. However, no valid prediction rule is currently available for bowel outcomes after a SCI. Objective. To generate a model for predicting the achievement of independent, reliable bowel management at 1 year after traumatic SCI. Methods. We performed multivariable logistic regression analyses of data for 1250 patients with traumatic SCIs that were included in the European Multicenter Study about Spinal Cord Injury. The resulting model was prospectively validated on data for 186 patients. As potential predictors, we evaluated age, sex, and variables from the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) and the Spinal Cord Independence Measure (SCIM), measured within 40 days of the injury. A positive outcome at 1 year post-SCI was assessed with item 7 of the SCIM. Results. The model relied on a single predictor, the ISNCSCI total motor score—that is, the sum of muscle strengths in 5 key muscle groups in each limb. The area under the receiver operating characteristics curve (aROC) was 0.837 (95% CI: 0.815-0.859). The prospective validation confirmed high predictive power: aROC = 0.817 (95% CI: 0.754-0.881). Conclusions. We generated a valid model for predicting independent, reliable bowel management at 1 year after traumatic SCI. Its application could improve counseling, optimize patient-tailored rehabilitation planning, and become crucial for appropriate patient stratification in future clinical trials.

To investigate whether detrusor overactivity (DO) is missed in a relevant percentage of patients if the urodynamic investigation (UDI) is stopped at a filling volume of 500 mL due to the fear of bladder overdistention, in patients with lower urinary tract symptoms and high bladder capacity.A consecutive series of 1598 patients with a bladder capacity of500 mL in the bladder diary undergoing UDI due to lower urinary tract dysfunction (LUTD) was prospectively investigated. UDI was performed according to Good Urodynamic Practices recommended by the International Continence Society. UDI was stopped at strong desire to void or in case of autonomic dysreflexia, vesico-uretero-renal reflux, bladder pain or discomfort.Of the 1598 patients (594 women, 1004 men), 1282 (80%) and 316 (20%) had neurogenic and non-neurogenic LUTD, respectively. Overall, DO was detected in 66% (1048/1598), in 71% (910/1282) with neurogenic and in 44% (138/316) with non-neurogenic LUTD. DO occurred in 16% (263/1598, 95% confidence interval [CI] 14.7-18.4%) only at a bladder volume500 mL. This phenomenon was significantly (P 0.001) more frequent in patients with neurogenic (18% [236/1282], 95% CI 16.4-20.6%) compared with non-neurogenic (9% [27/316], 95% CI 5.9-12.1%) LUTD.In both neurological and non-neurological patients with high bladder capacity, we strongly recommend not to stop UDI at a bladder volume of 500 mL, as DO might be missed in a relevant percentage leading to inappropriate patient treatment.

Previous functional neuroimaging studies provided evidence for a specific supraspinal network involved in lower urinary tract (LUT) control. However, data on the reliability of blood oxygenation level-dependent (BOLD) signal changes during LUT task-related functional magnetic resonance imaging (fMRI) across separate measurements are lacking. Proof of the latter is crucial to evaluate whether fMRI can be used to assess supraspinal responses to LUT treatments. Therefore, we prospectively assessed task-specific supraspinal responses from 20 healthy participants undergoing two fMRI measurements (test-retest) within 5-8 weeks. The fMRI measurements, conducted in a 3T magnetic resonance (MR) scanner, comprised a block design of repetitive bladder filling and drainage using an automated MR-compatible and MR-synchronized infusion-drainage device. Following transurethral catheterization and bladder pre-filling with body warm saline until participants perceived a persistent desire to void (START condition), fMRI was recorded during repetitive blocks (each 15 s) of INFUSION and WITHDRAWAL of 100 mL body warm saline into respectively from the bladder. BOLD signal changes were calculated for INFUSION minus START. In addition to whole brain analysis, we assessed BOLD signal changes within multiple 'a priori' region of interest (ROI), i.e. brain areas known to be involved in the LUT control from previous literature. To evaluate reliability of the fMRI results between visits, we applied different types of analyses: coefficient of variation (CV), intraclass correlation coefficient (ICC), Sorensen-Dice index, Bland-Altman method, and block-wise BOLD signal comparison. All participants completed the study without adverse events. The desire to void was rated significantly higher for INFUSION compared to START or WITHDRAWAL at both measurements without any effect of visit. At whole brain level, significant (p

INTRODUCTION AND OBJECTIVES:Urinary tract infections (UTIs) are among the most widespread microbial diseases and their economic impact on the society is substantial. The continuing increase of anti...

Neuro-urological symptoms/dysfunction result from a wide range of neurological disorders [1, 2]. The site of the lesion in the neurological axis determines the general pattern of lower urinary tract dysfunction, which is reflected in the patient’s symptoms (Fig. 10.1) [1]. Data on the prevalence/incidence of the underlying neurological disorder and the consecutive neuro-urological symptoms/dysfunction vary widely reflecting the high variability in the neurological cohort (i.e. early, medium and late stage of disease, limited number of included patients, often low level of evidence studies). The epidemiology of the neuro-urological data is summarized in Table 10.1.