Publications by authors named "Thomas M Kessler"

207 Publications

Prediction of bowel management independence after ischemic spinal cord injury.

Eur J Phys Rehabil Med 2022 Jun 6. Epub 2022 Jun 6.

Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Zürich, Switzerland -

Background: Ischemic spinal cord injury (SCI) belongs to the heterogeneous group of non-traumatic SCI, while the course of sensorimotor and functional recovery is comparable to traumatic SCI. Recently, we derived from data of patients with traumatic SCI a valid model to predict an independent and reliable bowel management one year after SCI.

Aim: To evaluate the performance of this model to predict an independent and reliable bowel management one year following ischemic SCI.

Design: Prognostic study - observational study.

Setting: European Multicenter Study about Spinal Cord Injury (EMSCI) ClinicalTrials.gov: NCT01571531.

Population: One hundred and forty-two patients with ischemic SCI of various level and severity of injury.

Methods: The prediction model relied on a single predictor collected within 40 days from injury, the International Standards for Neurological Classification of Spinal Cord Injury total motor score. Bowel outcome one year after SCI derived from the dichotomization of the Spinal Cord Independence Measure (SCIM) item 7 scores. We defined a positive outcome as independent bowel management with regular movements and appropriate timing with no or rare accidents (score of 10 in SCIM version II and score of 8 or 10 in version III).

Results: The model showed a fair discrimination with an area under the receiver operating characteristic (ROC) curve of 0.780 (95% confidence interval=0.702-0.860). In addition, the model displayed an acceptable accuracy and calibration.

Conclusions: The study extends the validity of our rule to patients with ischemic SCI, thus providing the first model to predict an independent and reliable bowel management in this population.

Clinical Rehabilitation Impact: The model may be employed in clinical practice to counsel patients, to define the rehabilitation aims and to estimate the need of assistance after discharge, as well as in the research field for the optimization of patients' allocation in the design of future clinical trials.
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http://dx.doi.org/10.23736/S1973-9087.22.07366-XDOI Listing
June 2022

Effects of Deep Brain Stimulation on Lower Urinary Tract Function in Neurological Patients.

Eur Urol Focus 2022 May 31. Epub 2022 May 31.

Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Zürich, Switzerland. Electronic address:

Background: Deep brain stimulation (DBS) has clear beneficial effects on motor signs in movement disorders, but much less is known about its impact on lower urinary tract (LUT) function.

Objective: To evaluate the effects of DBS on LUT function in patients affected by movement disorders.

Design, Setting, And Participants: We prospectively enrolled 58 neurological patients affected by movement disorders, who were planned to receive DBS.

Intervention: DBS in the globus pallidus internus, ventral intermediate nucleus of the thalamus, or subthalamic nucleus.

Outcome Measurements And Statistical Analysis: Subjective symptom questionnaires (International Prostate Symptom Score) and objective urodynamic studies were carried out before implantation of the DBS leads and several months after surgery. After DBS surgery, urodynamic investigations were performed with DBS ON as well as DBS OFF.

Results And Limitations: We enrolled patients suffering from Parkinson's disease (n = 39), dystonia (n = 11), essential tremor (n = 5), Holmes tremor (n = 2), and multiple sclerosis with tremor (n = 1). DBS of the globus pallidus internus resulted in worsening of LUT symptoms in 25% (four of 16) of the cases. DBS of the subthalamic nucleus in patients with Parkinson's disease led to normalization of LUT function in almost 20% (six of 31 patients), while a deterioration was seen in only one (3%) patient. DBS of the ventral intermediate nucleus of the thalamus improved LUT function in two (18%) and deteriorated it in one (9%) patient with tremor.

Conclusions: DBS effects on LUT varied with stimulation location, highly warranting patient counseling prior to DBS surgery. However, more well-designed, large-volume studies are needed to confirm our findings.

Patient Summary: In this report, we looked at outcomes of deep brain stimulation on lower urinary tract function. We found that outcomes varied with stimulation location, concluding that counseling of patients about the effects on lower urinary tract function is highly recommended prior to surgery.
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http://dx.doi.org/10.1016/j.euf.2022.05.004DOI Listing
May 2022

Urological Management at Discharge from Acute Spinal Cord Injury Rehabilitation: A Descriptive Analysis from a Population-based Prospective Cohort.

Eur Urol Open Sci 2022 Apr 15;38:1-9. Epub 2022 Feb 15.

Swiss Paraplegic Research, Nottwil, Switzerland.

Background: There is limited epidemiological evidence describing contemporary neuro-urological management of persons with acute spinal cord injury (SCI).

Objective: To describe neurogenic lower urinary tract dysfunction (NLUTD) management at discharge from SCI rehabilitation.

Design Setting And Participants: The population-based Swiss Spinal Cord Injury (SwiSCI) cohort study prospectively collected data from 602 adults undergoing specialized postacute SCI rehabilitation from 2013 to 2020. The management strategy was based on the European Association of Urology (EAU) Guidelines on Neuro-Urology.

Outcome Measurements And Statistical Analysis: Data were collected at discharge using the International SCI Lower Urinary Tract Function Basic Data Set. Multivariable logistic regression adjusting for demographics, SCI characteristics, and center, with inverse probability weighting accounting for sampling bias, was used to produce prevalence estimates and identify predictors of lower urinary tract symptoms (LUTS) and NLUTD management outcomes.

Results And Limitations: At discharge (median time after SCI: 5.0 mo [Q1-Q3: 3.0-7.2]), the prevalence of LUTS or managed NLUTD was 82% (95% confidence interval [CI]: 79-85%). SCI completeness was the main predictor of LUTS and managed NLUTD. The risk of urinary incontinence was elevated in females (odds ratio 1.98 [95% CI: 1.18-3.32]) and with complete lesions (odds ratio 4.71 [95% CI: 2.52-8.81]). Voiding dysfunction was most commonly managed with intermittent catheterization (prevalence 39% [95% CI: 35-42%]), followed by indwelling catheterization (prevalence 22% [95% CI: 18-25%]). The prevalence of antimuscarinic or mirabegron use was 29% (95% CI: 26-33%). Urodynamic and renal function data were not collected.

Conclusions: Our population-based description of urological management in Swiss SCI centers utilizing the EAU Guidelines on Neuro-Urology may be used as a reference for evaluation in other settings. Data further indicate a need for sex-specific neuro-urological management research.

Patient Summary: At discharge from spinal cord injury (SCI) rehabilitation, a majority of patients have lower urinary tract problems, especially those with complete SCI. Women have a higher risk of urinary incontinence.
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http://dx.doi.org/10.1016/j.euros.2022.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9051958PMC
April 2022

Early Transcutaneous Tibial Nerve Stimulation Acutely Improves Lower Urinary Tract Function in Spinal Cord Injured Rats.

Neurotrauma Rep 2022 14;3(1):15-26. Epub 2022 Feb 14.

Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Zürich, Switzerland.

Despite the fact that a majority of patients with an injury to the spinal cord develop lower urinary tract dysfunction, only few treatment options are available currently once the dysfunction arises. Tibial nerve stimulation has been used in pilot clinical trials, with some promising results. Hence, we investigated whether the early application of transcutaneous tibial nerve stimulation in the animal model of spinal cord injured rats can prevent the development of detrusor overactivity and/or detrusor-sphincter-dyssynergia. Rats were implanted with a bladder catheter and external urethral sphincter electromyography electrodes. A dorsal over-hemisection, resulting in an incomplete spinal cord injury at the T8/9 spinal level, induced immediate bladder paralysis. One week later, the animals received daily tibial nerve or sham stimulation for 15 days. Effects of stimulation on the lower urinary tract function were assessed by urodynamic investigation. Measurements showed improvements of several key parameters of lower urinary tract function-in particular, non-voiding bladder contractions and intravesical pressure-immediately after the completion of the stimulation period in the stimulated animals. These differences extinguished one week later, however. In the dorsal horn of the lumbosacral spinal cord, a small significant increase of the density of C-fiber afferents layers I-II was found in the stimulated animals at four weeks after spinal cord injury. Tibial nerve stimulation applied acutely after spinal cord injury in rats had an immediate beneficial effect on lower urinary tract dysfunction; however, the effect was transitory and did not last over time. To achieve more sustainable, longer lasting effects, further studies are needed looking into different stimulation protocols using optimized stimulation parameters, timing, and treatment schedules.
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http://dx.doi.org/10.1089/neur.2021.0058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8863914PMC
February 2022

Bladder management in patients undergoing spine surgery: An assessment of care delivery.

N Am Spine Soc J 2021 Jun 6;6:100059. Epub 2021 Apr 6.

Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Zürich, Switzerland.

Background: Lower urinary tract dysfunction is common in the early postoperative phase after spine surgery. Although it is essential for an optimal patient management to balance benefits and harms, it is not known which patient benefit from a perioperative indwelling catheter. We therefore evaluated urological parameters prior and after spine surgery performing a quality assessment of our current clinical practice in bladder management.

Methods: Preoperatively, all patients completed the International Prostate Symptom Score and were interviewed for urological history. Decision for preoperative urethral catheter placement was individually made by the responsible anesthesiologist according to an in-house protocol. Within and between group analyses using univariate and probability matching statistics were performed for patients with intraoperative urethral catheter-free management ( = 54) and those with a preoperatively placed catheter ( = 46). Post void residual (PVR) was measured prior and after surgery or after removal of the urethral catheter, respectively. The outcome measures consisted of postoperative urinary retention (POUR) and postoperative urological complications (PUC), defined as POUR and any catheter-related adverse events.

Results: Hundred patients undergoing spine surgery were prospectively evaluated. Sixteen of the 54 (30%) patients with urethral catheter-free management developed POUR. Length of surgery and volume of intravenous infusion were associated with POUR ( < 0.05). In the 46 preoperatively catheterized patients, re-catheterization was required in 6 (13%). In a fairly homogenous subgroup of 72 patients with a probability of PUC between 15 and 40%, no significant association between intraoperative urethral catheter-free management and the occurrence of PUC was found (odds ratio 2.09, 95% confidence interval 0.69 to 6.33;  = 0.193).

Conclusions: In case of postoperative PVR monitoring allowing de novo catheterization as appropriate, urethral catheter-free management seems to be a valuable option in spine surgery since it does not to increase PUC but minimizes unnecessary catheterizations with their related complications.
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http://dx.doi.org/10.1016/j.xnsj.2021.100059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820009PMC
June 2021

Slow development of bladder malfunction parallels spinal cord fiber sprouting and interneurons' loss after spinal cord transection.

Exp Neurol 2022 02 24;348:113937. Epub 2021 Nov 24.

Institute for Regenerative Medicine, University of Zürich, Switzerland; Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland.

Neurogenic lower urinary tract dysfunction typically develops after spinal cord injury. We investigated the time course and the anatomical changes in the spinal cord that may be causing lower urinary tract symptoms following injury. Rats were implanted with a bladder catheter and external urethral sphincter electromyography electrodes. Animals underwent a large, incomplete spinal transection at the T8/9 spinal level. At 1, 2-3, and 4 weeks after injury, the animals underwent urodynamic investigations. Urodynamic investigations showed detrusor overactivity and detrusor-sphincter-dyssynergia appearing over time at 3-4 weeks after injury. Lower urinary tract dysfunction was accompanied by an increase in density of C-fiber afferents in the lumbosacral dorsal horn. CRF-positive Barrington's and 5-HT-positive bulbospinal projections drastically decreased after injury, with partial compensation for the CRF fibers at 3-4 weeks. Interestingly, a decrease over time was observed in the number of GABAergic neurons in the lumbosacral dorsal horn and lamina X, and a decrease of glutamatergic cells in the dorsal horn. Detrusor overactivity and detrusor-sphincter-dyssynergia might therefore arise from a discrepancy in inhibitory/excitatory interneuron activity in the lumbosacral cord as well as input changes which develop over time after injury. The processes point to spinal plastic changes leading to malfunction of the important physiological pathway of lower urinary tract control.
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http://dx.doi.org/10.1016/j.expneurol.2021.113937DOI Listing
February 2022

Deep brain stimulation for locomotion in incomplete human spinal cord injury (DBS-SCI): protocol of a prospective one-armed multi-centre study.

BMJ Open 2021 09 30;11(9):e047670. Epub 2021 Sep 30.

Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland.

Introduction: Spinal cord injury (SCI) is a devastating condition with immediate impact on the individual's health and quality of life. Major functional recovery reaches a plateau 3-4 months after injury despite intensive rehabilitative training. To enhance training efficacy and improve long-term outcomes, the combination of rehabilitation with electrical modulation of the spinal cord and brain has recently aroused scientific interest with encouraging results. The mesencephalic locomotor region (MLR), an evolutionarily conserved brainstem locomotor command and control centre, is considered a promising target for deep brain stimulation (DBS) in patients with SCI. Experiments showed that MLR-DBS can induce locomotion in rats with spinal white matter destructions of >85%.

Methods And Analysis: In this prospective one-armed multi-centre study, we investigate the safety, feasibility, and therapeutic efficacy of MLR-DBS to enable and enhance locomotor training in severely affected, subchronic and chronic American Spinal Injury Association Impairment Scale C patients in order to improve functional recovery. Patients undergo an intensive training programme with MLR-DBS while being regularly followed up until 6 months post-implantation. The acquired data of each timepoint are compared with baseline while the primary endpoint is performance in the 6-minute walking test. The clinical trial protocol was written in accordance with the Standard Protocol Items: Recommendations for Interventional Trials checklist.

Ethics And Dissemination: This first in-man study investigates the therapeutic potential of MLR-DBS in SCI patients. One patient has already been implanted with electrodes and underwent MLR stimulation during locomotion. Based on the preliminary results which promise safety and feasibility, recruitment of further patients is currently ongoing. Ethical approval has been obtained from the Ethical Committee of the Canton of Zurich (case number BASEC 2016-01104) and Swissmedic (10000316). Results will be published in peer-reviewed journals and presented at conferences.

Trial Registration Number: NCT03053791.
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http://dx.doi.org/10.1136/bmjopen-2020-047670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487195PMC
September 2021

Efficacy and Safety of Surgical Treatments for Neurogenic Stress Urinary Incontinence in Adults: A Systematic Review.

Eur Urol Focus 2021 Sep 8. Epub 2021 Sep 8.

Department of Urology, University College London and London Spinal Injuries Unit, London, UK.

Context: Controversy still exists regarding the balance of benefits and harms for the different surgical options for neurogenic stress urinary incontinence (N-SUI).

Objective: To identify which surgical option for N-SUI offers the highest cure rate and best safety without compromising urinary tract function and bladder management.

Evidence Acquisition: A systematic review was performed under the auspices of the European Association of Urology Guidelines Office and the European Association of Urology Neuro-Urology Guidelines Panel according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement.

Evidence Synthesis: A total of 32 studies were included. Overall, 852 neurourological patients were surgically treated for N-SUI. The treatment offered most often (13/32 studies) was an artificial urinary sphincter (AUS; 49%, 416/852) and was associated with a need for reintervention in one-third of patients. More than 200 surgical revisions were described. Overall, 146/852 patients (17%) received concomitant bladder augmentation, mainly during placement of an AUS (42%, 62/146) or autologous sling (34% of women and 14% of men). Following pubovaginal sling placement, dryness was achieved in 83% of cases. A significant improvement in N-SUI was observed in 87% (82/94) of women following placement of a synthetic midurethral sling. Efficacy after insertion of an adjustable continence therapy device (ACT 40%, proACT 60%) was reported for 38/128 cases (30%). The cure rate for bulking agents was 35% (9/25) according to 2/32 studies, mainly among men (90%). The risk of bias was highly relevant. Baseline and postoperative cystometry were missing in 13 and 28 studies, respectively.

Conclusions: The evidence is mainly reported in retrospective studies. More than one intervention is often required to achieve continence because of coexisting neurogenic detrusor overactivity, low compliance, or the onset of complications in the medium and long term. Urodynamic data are needed to better clarify the success of N-SUI treatment with the different techniques.

Patient Summary: Our review shows that insertion of an artificial urinary sphincter for urinary incontinence is effective but is highly associated with a need for repeat surgery. Other surgical options may have lower continence rates or a risk of requiring intermittent catheterization, which patients should be informed about before deciding on surgery for their incontinence.
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http://dx.doi.org/10.1016/j.euf.2021.08.007DOI Listing
September 2021

Definitions of Urinary Tract Infection Used in Interventional Studies Involving Neurourological Patients-A Systematic Review.

Eur Urol Focus 2021 Aug 14. Epub 2021 Aug 14.

Neuro-Urology, Swiss Paraplegic Center, Nottwil, Switzerland.

Context: Neurourological patients often encounter bacteriuria without any symptoms or may experience symptoms suspicious of urinary tract infections (UTIs). However, there is a lack of guidelines that unequivocally state the definition of UTIs in this specific patient group.

Objective: To present all used definitions of UTIs in neurourological patients.

Evidence Acquisition: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Studies were identified by electronic search of Medline, Embase, Cochrane controlled trials databases, and clinicaltrial.gov without a time limitation (last search September 2020) and by screening of reference lists and reviews. The occurrences of the various UTI definitions were counted and the frequencies calculated.

Evidence Synthesis: After screening 7164 abstracts, we included 32 studies enrolling a total of 8488 patients with a neurourological disorder who took part in an interventional clinical study. UTI definitions were heterogeneous. The concordance to predefined definitions was low.

Conclusions: Interventional clinical studies rarely report specific definitions for UTIs, and both clinical and laboratory criteria used are heterogeneous. A generally accepted UTI definition for neurourological patients is urgently needed.

Patient Summary: Patients suffering from neurological disorders often experience symptoms in their lower urinary tract that resemble urinary tract infections. Furthermore, they can have positive urine cultures without symptoms (the so-called asymptomatic bacteriuria). However, clinical studies rarely report specific definitions for urinary tract infections, and when it is done, they are heterogeneous. A generally accepted urinary tract infection definition for neurourological patients is urgently needed. TAKE  HOME MESSAGE: Interventional clinical studies on neurourological patients rarely report specific definitions for urinary tract infections (UTIs), and both clinical and laboratory criteria used are heterogeneous. A generally accepted UTI definition for neurourological patients is urgently needed.
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http://dx.doi.org/10.1016/j.euf.2021.07.012DOI Listing
August 2021

Lower urinary tract electrical sensory assessment: a systematic review and meta-analysis.

BJU Int 2022 08 28;130(2):166-180. Epub 2021 Oct 28.

Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Zürich, Switzerland.

Objectives: To summarize the current literature on lower urinary tract electrical sensory assessment (LUTESA), with regard to current perception thresholds (CPTs) and sensory evoked potentials (SEPs), and to discuss the applied methods in terms of technical aspects, confounding factors, and potential for lower urinary tract (LUT) diagnostics.

Methods: The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Medline (PubMed), Embase and Scopus were searched on 13 October 2020. Meta-analyses were performed and methodological qualities of the included studies were defined by assessing risk of bias (RoB) as well as confounding.

Results: After screening 9925 articles, 80 studies (five randomized controlled trials [RCTs] and 75 non-RCTs) were included, comprising a total of 3732 patients and 692 healthy subjects (HS). Of these studies, 61 investigated CPTs exclusively and 19 reported on SEPs, with or without corresponding CPTs. The recording of LUTCPTs and SEPs was shown to represent a safe and reliable assessment of LUT afferent nerve function in HS and patients. LUTESA demonstrated significant differences in LUT sensitivity between HS and neurological patients, as well as after interventions such as pelvic surgery or drug treatments. Pooled analyses showed that several stimulation variables (e.g. stimulation frequency, location) as well as patient characteristics might affect the main outcome measures of LUTESA (CPTs, SEP latencies, peak-to-peak amplitudes, responder rate). RoB and confounding was high in most studies.

Conclusions: Preliminary data show that CPT and SEP recordings are valuable tools to more objectively assess LUT afferent nerve function. LUTESA complements already established diagnostics such as urodynamics, allowing a more comprehensive patient evaluation. The high RoB and confounding rate was related to inconsistency and inaccuracy in reporting rather than the technique itself. LUTESA standardization and well-designed RCTs are crucial to implement LUTESA as a clinical assessment tool.
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http://dx.doi.org/10.1111/bju.15574DOI Listing
August 2022

Re: Antimicrobial use in a cohort of US nursing homes, 2017.

Authors:
Thomas M Kessler

Eur Urol 2021 11 3;80(5):670. Epub 2021 Aug 3.

Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Zürich, Switzerland. Electronic address:

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http://dx.doi.org/10.1016/j.eururo.2021.07.017DOI Listing
November 2021

External Validation Confirms Validity of a Simple Model to Predict Bowel Outcome After Traumatic Spinal Cord Injury.

Neurorehabil Neural Repair 2021 Aug 11;35(8):659-662. Epub 2021 Jun 11.

Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Switzerland.

. The prediction of functional outcomes after spinal cord injury (SCI) is essential to plan the rehabilitation phase and the social reintegration. Recently, 2 models to predict independent and reliable bowel management 1 year after traumatic SCI have been derived and validated in 2 cohorts of patients included in the European Multicenter Study about Spinal Cord Injury (EMSCI). . We aimed to validate 2 prediction models for bowel outcome after traumatic SCI in a patient sample external to EMSCI. . The simplified model (based on a single predictor, the International Standards for Neurological Classification of Spinal Cord Injury [ISNCSCI] total motor score) and the full model (based on 2 predictors, the ISNCSCI total motor score and item 3a of the Spinal Cord Independence Measure) were applied to the retrospectively collected data of 111 patients with traumatic SCI. . The simplified and the full models showed excellent discrimination with an area under the receiver operating characteristic curve of .939 (95% confidence interval (CI) .87-1.00) and .922 (95% CI 0.85-.99), respectively. Both models displayed similar results for sensitivity and negative predictive values; however, the simplified model showed higher values for specificity, positive predictive values, and accuracy. The calibration analysis showed a partial overlap between predicted probabilities and observed proportion, with better and acceptable calibration for the simplified model. . Using an independent sample, our study demonstrates the validity of a simple model to predict independent and reliable bowel management 1 year after traumatic SCI.
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http://dx.doi.org/10.1177/15459683211023191DOI Listing
August 2021

Detrusor sphincter dyssynergia: can a more specific definition distinguish between patients with and without an underlying neurological disorder?

Spinal Cord 2021 09 7;59(9):1026-1033. Epub 2021 May 7.

Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Zürich, Switzerland.

Study Design: Cross-sectional study.

Objectives: To evaluate if specific definitions of detrusor sphincter dyssynergia (DSD) might distinguish between individuals with spinal cord injury (SCI) and those with no underlying neurological disorder (NO ND).

Setting: Single tertiary university SCI center.

Methods: A series of 153 individuals, 81 with traumatic SCI and 72 with NO ND, were prospectively evaluated and included in this study. All individuals underwent a clinical neuro-urological examination, a neurophysiological work-up and a video-urodynamic investigation and were diagnosed with DSD as defined by the International Continence Society (ICS). We determined the DSD grades/types according to the classifications by Yalla (grade 1-3), Blaivas (type 1-3) and Weld (type 1-2). Distribution of the DSD grades/types were compared between SCI and NO ND individuals. Associations between the various DSD grades/types and clinical parameters, such as risk factors for upper urinary tract damage (all individuals) or lower extremity motor scores, SCI injury levels and severity scores (only SCI group), were assessed.

Results: The distribution of all DSD types were similar between groups (p > 0.05). None of the DSD classifications allowed risk assessment for upper urinary tract damage. A significant association between DSD type and other clinical parameters could not be found (p > 0.05).

Conclusions: None of the investigated DSD definitions can distinguish between patients with SCI and with NO ND. The more complex DSD classifications by Yalla, Blaivas or Weld cannot compete with the ICS binary yes-no definition which is pragmatic and straightforward for managing patients in daily clinical practice.

Sponsorship: None.
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http://dx.doi.org/10.1038/s41393-021-00635-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397615PMC
September 2021

Bacteriophages: what role may they play in life after spinal cord injury?

Spinal Cord 2021 09 7;59(9):967-970. Epub 2021 May 7.

Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Zürich, Switzerland.

Bacterial infections are the leading cause of death in people with a spinal cord injury (SCI). Bacteriophages (phages) are viruses that solely infect and kill bacteria. The idea of using phages to treat bacterial infections, i.e., phage therapy, is very promising and potentially allows a more specific and personalized treatment of bacterial infections than antibiotics. While multi-drug resistant infections affect individuals from the general population, alternative therapeutic options are especially warranted in high-risk populations, such as individuals with SCI. However, more clinical data must be collected before phage therapy can be implemented in clinical practice, with numerous possible, subsequent applications.
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http://dx.doi.org/10.1038/s41393-021-00636-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102843PMC
September 2021

Treatment of Stress Urinary Incontinence with Muscle Stem Cells and Stem Cell Components: Chances, Challenges and Future Prospects.

Int J Mol Sci 2021 Apr 12;22(8). Epub 2021 Apr 12.

Department of Urology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.

Urinary incontinence (UI) is a major problem in health care and more than 400 million people worldwide suffer from involuntary loss of urine. With an increase in the aging population, UI is likely to become even more prominent over the next decades and the economic burden is substantial. Among the different subtypes of UI, stress urinary incontinence (SUI) is the most prevalent and focus of this review. The main underlying causes for SUI are pregnancy and childbirth, accidents with direct trauma to the pelvis or medical treatments that affect the pelvic floor, such as surgery or irradiation. Conservative approaches for the treatment of SUI are pelvic physiotherapy, behavioral and lifestyle changes, and the use of pessaries. Current surgical treatment options include slings, colposuspensions, bulking agents and artificial urinary sphincters. These treatments have limitations with effectiveness and bear the risk of long-term side effects. Furthermore, surgical options do not treat the underlying pathophysiological causes of SUI. Thus, there is an urgent need for alternative treatments, which are effective, minimally invasive and have only a limited risk for adverse effects. Regenerative medicine is an emerging field, focusing on the repair, replacement or regeneration of human tissues and organs using precursor cells and their components. This article critically reviews recent advances in the therapeutic strategies for the management of SUI and outlines future possibilities and challenges.
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http://dx.doi.org/10.3390/ijms22083981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069473PMC
April 2021

Considering non-bladder aetiologies of overactive bladder: a functional neuroimaging study.

BJU Int 2021 11 8;128(5):586-597. Epub 2021 Mar 8.

Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Zürich, Switzerland.

Objectives: To better understand the neuropathophysiology of overactive bladder (OAB) in women by characterising supraspinal activity in response to bladder distention and cold stimulation.

Subjects/patients And Methods: 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.

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1111/bju.15354DOI Listing
November 2021

Evaluation of Urinary Sphincter Function by Rapid Magnetic Resonance Diffusion Tensor Imaging.

Int Neurourol J 2020 Dec 31;24(4):349-357. Epub 2020 Dec 31.

Department of Urology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Purpose: This study aimed to assess the feasibility of a rapid diffusion tensor imaging (DTI) for evaluation of the female urinary sphincter function based on differentiation between rest and muscle contraction.

Methods: Magnetic resonance imaging (MRI) of the lower pelvis was performed at 3 Tesla in 10 healthy female volunteers (21-36 years; body mass index, 20.8±3.6 kg/m2) between June and July 2019. High-resolution T1- and T2-weighted images were acquired for anatomical reference, and following DTI performed in 4 experiment phases: twice during rest (denoted rest-1, rest-2) and contraction (contraction-1, contraction-2). Manual segmentation of the urinary sphincter and the levator ani muscles were performed by 2 independent readers. Mean diffusivity (MD) and fractional anisotropy (FA) values derived from DTI volumes were compared in search for significant differences between the experiment phases. Interreader agreement was assessed by intraclass correlation coefficient (ICC).

Results: Kruskal-Wallis test showed significant differences between MD values among all the experiment phases, by both independent readers (1st: X2 [3,76]=17.16, P<0.001 and 2nd: X2 [3,76]=15.88, P<0.01). Post hoc analysis revealed differences in MD values by both readers between: rest-1 vs. contraction-1 (least P<0.05), rest-1 vs. contraction-2 (P<0.01), rest-2 vs. contraction-1 (P<0.03), rest-2 vs. contraction-2 (P=0.02) with overall mean 'rest' to 'contraction' ΔMD=20.6%. No MD or FA differences were found between rest-1 vs. rest-2 and contraction-1 vs. contraction-2 among all the experiment phases, and interreader agreement was ICC=0.85 (MD) and ICC=0.79 (FA).

Conclusion: Rapid DTI might prospectively act as a supporting tool for the evaluation of female pelvic floor muscle function, and incontinence assessment.
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http://dx.doi.org/10.5213/inj.2040208.104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788323PMC
December 2020

Optimizing clinical trial design using prospective cohort study data: a case study in neuro-urology.

Spinal Cord 2021 09 24;59(9):1003-1012. Epub 2020 Nov 24.

Swiss Paraplegic Research, Nottwil, Switzerland.

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 (SCI) rehabilitation centers in Switzerland.

Methods: TASCI is nested in the multicenter Swiss Spinal Cord Injury Cohort Study (SwiSCI), which prospectively includes patients with acute SCI. 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 3-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.
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http://dx.doi.org/10.1038/s41393-020-00588-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611589PMC
September 2021

Scalp Topography of Lower Urinary Tract Sensory Evoked Potentials.

Brain Topogr 2020 11 16;33(6):693-709. Epub 2020 Oct 16.

Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Forchstrasse 340, 8008, Zürich, Switzerland.

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.
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http://dx.doi.org/10.1007/s10548-020-00796-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593393PMC
November 2020

Intravesical bacteriophages for treating urinary tract infections in patients undergoing transurethral resection of the prostate: a randomised, placebo-controlled, double-blind clinical trial.

Lancet Infect Dis 2021 03 16;21(3):427-436. Epub 2020 Sep 16.

Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Zürich, Switzerland. Electronic address:

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.
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http://dx.doi.org/10.1016/S1473-3099(20)30330-3DOI Listing
March 2021

Deep brain stimulation effects on lower urinary tract function: Systematic review and meta-analysis.

Parkinsonism Relat Disord 2020 10 26;79:65-72. Epub 2020 Aug 26.

Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Zürich, Switzerland. Electronic address:

Introduction: While efficacy of deep brain stimulation for motor symptoms of neurological disorders is well accepted, its effects on the autonomic system remain controversial. We aimed to systematically assess all available evidence of deep brain stimulation effects on lower urinary tract function.

Methods: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were identified by electronic search of Cochrane Central Register of Controlled Trials, Embase, Medline, Scopus, and Web of Science (last search July 12, 2019) and by screening of reference lists and reviews.

Results: After screening 577 articles, we included 29 studies enrolling a total of 1293 patients. Deep brain stimulation of the globus pallidus internus (GPi), pedunculopontine nucleus (PPN), and subthalamic nucleus (STN) had an inhibitory effect on detrusor function, while deep brain stimulation of the ventral intermediate nucleus of the thalamus (VIM) showed an excitatory effect. In the meta-analysis, deep brain stimulation of the STN led to a significant increase in maximum bladder capacity (mean difference 124 mL, 95% confidence interval 60-187 mL, p = 0.0001) but had no clinically relevant effects on other urodynamic parameters. Adverse events (reported in thirteen studies) were most commonly respiratory issues, postural instability, and dysphagia. Risk of bias and confounding was relatively low.

Conclusions: Deep brain stimulation does not impair lower urinary tract function and might even have beneficial effects. This needs to be considered in the deep brain stimulation decision-making process helping to encourage and to reassure prospective patients.
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http://dx.doi.org/10.1016/j.parkreldis.2020.08.032DOI Listing
October 2020

TASCI-transcutaneous tibial nerve stimulation in patients with acute spinal cord injury to prevent neurogenic detrusor overactivity: protocol for a nationwide, randomised, sham-controlled, double-blind clinical trial.

BMJ Open 2020 08 13;10(8):e039164. Epub 2020 Aug 13.

Department of Trauma, University Hospital Zürich, Zürich, Switzerland.

Introduction: Neurogenic lower urinary tract dysfunction (NLUTD), including neurogenic detrusor overactivity (NDO) and detrusor sphincter dyssynergia, is one of the most frequent and devastating sequelae of spinal cord injury (SCI), as it can lead to urinary incontinence and secondary damage such as renal failure. Transcutaneous tibial nerve stimulation (TTNS) is a promising, non-invasive neuromodulatory intervention that may prevent the emergence of the C-fibre evoked bladder reflexes that are thought to cause NDO. This paper presents the protocol for TTNS in acute SCI (TASCI), which will evaluate the efficacy of TTNS in preventing NDO. Furthermore, TASCI will provide insight into the mechanisms underlying TTNS, and the course of NLUTD development after SCI.

Methods And Analysis: TASCI is a nationwide, randomised, sham-controlled, double-blind clinical trial, conducted at all four SCI centres in Switzerland. The longitudinal design includes a baseline assessment period 5-39 days after acute SCI and follow-up assessments occurring 3, 6 and 12 months after SCI. A planned 114 participants will be randomised into verum or sham TTNS groups (1:1 ratio), stratified on study centre and lower extremity motor score. TTNS is performed for 30 min/day, 5 days/week, for 6-9 weeks starting within 40 days after SCI. The primary outcome is the occurrence of NDO jeopardising the upper urinary tract at 1 year after SCI, assessed by urodynamic investigation. Secondary outcome measures assess bladder and bowel function and symptoms, sexual function, neurological structure and function, functional independence, quality of life, as well as changes in biomarkers in the urine, blood, stool and bladder tissue. Safety of TTNS is the tertiary outcome.

Ethics And Dissemination: TASCI is approved by the Swiss Ethics Committee for Northwest/Central Switzerland, the Swiss Ethics Committee Vaud and the Swiss Ethics Committee Zürich (#2019-00074). Findings will be disseminated through peer-reviewed publications.

Trial Registration Number: NCT03965299.
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http://dx.doi.org/10.1136/bmjopen-2020-039164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430472PMC
August 2020

Neuro-Urology, Quo Vadis?

Authors:
Thomas M Kessler

Eur Urol Focus 2020 09 29;6(5):801-803. Epub 2020 Apr 29.

Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Zürich, Switzerland. Electronic address:

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http://dx.doi.org/10.1016/j.euf.2020.04.006DOI Listing
September 2020

Guidelines on urinary incontinence: it is time to join forces!

Authors:
Thomas M Kessler

BJU Int 2020 05;125(5):625-626

Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Zürich, Switzerland.

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http://dx.doi.org/10.1111/bju.15075DOI Listing
May 2020

Half the message is just mess: judging the value of urodynamics based on partial or poor-quality results.

BJU Int 2020 07 29;126(1):4-5. Epub 2020 Apr 29.

Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Zürich, Switzerland.

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http://dx.doi.org/10.1111/bju.15063DOI Listing
July 2020

Sacral Neuromodulation: Mechanism of Action.

Eur Urol Focus 2020 09 1;6(5):823-825. Epub 2020 Feb 1.

Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Zürich, Switzerland.

Although the mechanism of action of sacral neuromodulation (SNM) is still not fully elucidated, it seems to involve modulation of spinal cord reflexes and brain networks by peripheral afferents according to findings from neurophysiology, electroencephalography, positron emission tomography, and magnetic resonance imaging studies. Moreover, motor effects mediated via efferents on direct stimulation cannot be fully excluded. In this mini-review, we summarize current knowledge on the mechanism of action of SNM. PATIENT SUMMARY: We reviewed the literature on the mechanism of action of sacral neuromodulation, in which electrical stimulation is applied to the nerves that regulate bladder activity. The mechanism seems to involve modulation of spinal cord reflexes and brain networks by peripheral sensory and possibly motor neurons.
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http://dx.doi.org/10.1016/j.euf.2019.11.018DOI Listing
September 2020

Methods for Assessing Lower Urinary Tract Function in Animal Models.

Eur Urol Focus 2021 01 11;7(1):186-189. Epub 2020 Jan 11.

Institute for Regenerative Medicine, University of Zürich, Zürich, Switzerland.

Lower urinary tract dysfunction affects a multitude of patients. Current therapeutic approaches are limited and very little is known about the mechanisms in failure of bladder control. Thus, more basic research is clearly needed to elucidate the underlying pathological mechanisms and to develop novel treatment strategies in urology. Noninvasive tests such as the void-spot assay and the metabolic cage and more invasive urodynamics investigations are currently used to assess lower urinary tract function in animals, in particular rodents. The noninvasive tests give some insights into the functionality of the system, whereas urodynamics testing yields an objective evaluation that allows distinction of different pathologies and investigations of the underlying neuronal malfunctions. PATIENT SUMMARY: We briefly summarize methods currently used to assess impairments of bladder function in animal models. Both noninvasive and invasive methods are available and can be used to understand and improve human health. An accurate and detailed diagnosis is, however, possible only with urodynamics assessments.
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http://dx.doi.org/10.1016/j.euf.2019.12.004DOI Listing
January 2021

Metaepidemiological Inventory of Diagnostic Studies on Urodynamics.

Eur Urol Focus 2020 09 20;6(5):880-908. Epub 2019 Dec 20.

Medignition Inc., Research Consultants, Zürich, Switzerland. Electronic address:

Background: Urodynamic investigations have a pivotal role in the diagnosis of lower urinary tract symptoms. Despite expert statements and guidelines supporting their usefulness for clinical decision making in various clinical domains, the academic debate remains controversial.

Objective: To provide a metaepidemiological inventory of studies assessing the diagnostic properties of urodynamic investigations.

Design, Setting, And Participants: Systematic searches without language restrictions were performed in (Pre-)Medline, EMBASE, and the Cochrane Library from inception until August 31, 2018. Checking of reference lists of included studies and reviews complemented searches. Records were compiled and screened for possible inclusion by reading title and abstracts by two teams of two research fellows. Inclusion criteria were as follows: prospective data collection and urodynamic investigations performed either as a diagnostic test or using a therapy monitoring instrument. No a priori selection on clinical domain was done. Double reading was performed on records marked "included." Extraction into a developed and piloted matrix was performed in duplicate and checked by a third research fellow.

Outcome Measurements And Statistical Analysis: Of each included article, study specifics, objective, study design, type of data collection, clinical domain, type and description of test used, and type of outcome were extracted and attributed to a framework.

Results And Limitations: Electronic searches retrieved 20 841 records. After screening, 299 abstracts were considered relevant. The main reasons for exclusion were as follows: animal studies, no primary data, editorial/opinion based on published data or reviews, primary objective of the study being not the assessment of urodynamic investigations, and post hoc (opportunistic) correlation studies.

Conclusions: To our knowledge, this is the first comprehensive collection of studies assessing the clinical usefulness of urodynamic investigations. The collection is the starting point for a series of systematic reviews assessing the diagnostic properties of urodynamic investigations.

Patient Summary: The usefulness of urodynamic investigations for clinical decision making is under debate. We established an inventory of diagnostic studies on urodynamics to assess the value of urodynamics in various clinical applications.
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http://dx.doi.org/10.1016/j.euf.2019.11.017DOI Listing
September 2020

Optimized Measurement Parameters of Sensory Evoked Cortical Potentials to Assess Human Bladder Afferents - A Randomized Study.

Sci Rep 2019 12 20;9(1):19478. Epub 2019 Dec 20.

Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Zürich, Switzerland.

Overactive bladder and voiding dysfunction are highly prevalent and often associated with malfunction of the bladder afferent pathways. Appropriate diagnostic tools for an objective assessment of afferent nerve function of the human bladder are currently missing. One promising possibility is the assessment of sensory evoked potentials (SEP) during repetitive electrical bladder stimulation, which proved feasible in healthy subjects. For an implementation into clinical practice, however, further refinements for efficient and reliable data acquisition are crucial. The aim of this randomized study was to find the optimal measurement settings regarding stimulation frequency, repetition number, and data acquisition. Forty healthy subjects underwent two visits of SEP (Cz-Fz) assessments using repetitive (500 stimuli) electrical stimulation of 0.5 Hz, 1.1 Hz, and 1.6 Hz and pulse width of 1 ms at the bladder dome or trigone. SEP analyses revealed higher amplitudes and better signal-to-noise ratio (SNR) with lower stimulation frequencies, while latencies remained unchanged. Decreasing amplitudes and SNR were observed with continuing stimulation accompanied by decreasing responder rate (RR). When applying stimuli at a frequency of 0.5 Hz, averaging across 200 stimuli revealed optimal reliability with best SNR, RR and sufficiently high amplitudes. This constitutes an optimal compromise between the duration of the assessment and SEP peak-to-peak amplitudes.
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http://dx.doi.org/10.1038/s41598-019-54614-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925113PMC
December 2019

Quantitative electrical pain threshold assessment in the lower urinary tract.

Neurourol Urodyn 2020 01 10;39(1):420-431. Epub 2019 Dec 10.

Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Zürich, Switzerland.

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.
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http://dx.doi.org/10.1002/nau.24225DOI Listing
January 2020
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