Neurogenic Lower Urinary Tract Dysfunction in the First Year After Spinal Cord Injury: A Descriptive Study of Urodynamic Findings.

PURPOSE: 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. MATERIALS AND METHODS: 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 H2O or higher, bladder compliance less than 20 mL/cm H2O, and vesicoureteral reflux of any grade. RESULTS: One 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 H2O or higher, and 7% vesicoureteral reflux. No patient developed a low-compliance bladder. CONCLUSIONS: Using 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.

Temporal development of unfavourable urodynamic parameters during the first year after spinal cord injury.

OBJECTIVES: 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). PATIENTS AND METHODS: 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 cmH2 O, bladder compliance <20 mL/cmH2 O, vesico-ureteric reflux [VUR] and any unfavourable parameter [composite outcome]) were evaluated using time-to-event analysis. RESULTS: The 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 cmH2 O (31/38), and 100% of the VUR (seven of seven) observations. No low bladder compliance was observed. The risk of DO-DSD was elevated in patients with thoracic SCI compared to those with lumbar SCI (adjusted hazard ratio [aHR] 2.38, 95% confidence interval [CI] 1.16-4.89). Risk of maximum storage detrusor pressure ≥40 cmH2 O was higher in males than females (aHR 8.33, 95% CI 2.51-27.66), in patients with a cervical SCI compared to those with lumbar SCI (aHR 14.89, 95% CI 3.28-67.55), and in patients with AIS Grade B or C compared to AIS Grade D SCI (aHR 6.17, 95% CI 1.78-21.39). No risk factors were identified for the composite outcome of any unfavourable urodynamic parameter. CONCLUSIONS: The 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.

bTUNED: transcutaneous tibial nerve stimulation for neurogenic lower urinary tract dysfunction.

OBJECTIVE: To present the protocol for a randomized controlled trial (RCT) evaluating the efficacy and safety of transcutaneous tibial nerve stimulation (TTNS) for refractory neurogenic lower urinary tract dysfunction (NLUTD). STUDY DESIGN AND RESULTS: bTUNED (bladder and TranscUtaneous tibial Nerve stimulation for nEurogenic lower urinary tract Dysfunction) is an international multicentre, sham-controlled, double-blind RCT investigating the efficacy and safety of TTNS. The primary outcome is success of TTNS, defined as improvements in key bladder diary variables at study end compared to baseline values. The focus of the treatment is defined by the Self-Assessment Goal Achievement (SAGA) questionnaire. Secondary outcomes are the effect of TTNS on urodynamic, neurophysiological, and bowel function outcome measures, as well as the safety of TTNS. CONCLUSIONS: A total of 240 patients with refractory NLUTD will be included and randomized 1:1 into the verum or sham TTNS group from March 2020 until August 2026. TTNS will be performed twice a week for 30 min during 6 weeks. The patients will attend baseline assessments, 12 treatment visits and follow-up assessments at the study end.

Indwelling catheter vs intermittent catheterization: is there a difference in UTI susceptibility?

BACKGROUND: Patients with neurogenic lower urinary tract dysfunction (NLUTD) often rely on some type of catheterization for bladder emptying. Intermittent catheterization (IC) is considered the gold standard and is preferred over continuous catheterization, since it is considered to cause fewer urinary tract infections (UTIs) than indwelling catheterization. The main objective of our study was to describe UTI prevalence (at visit) and incidence (within the last 12 months) and urine culture characteristics between patients using an indwelling catheter versus (vs) those performing IC. METHODS: In this cross-sectional study, we prospectively evaluated from 02/2020 to 01/2021 patients with NLUTD undergoing urine cultures for prophylactic reasons or due to UTI symptoms. At visit, all patients underwent a standardized interview on current UTI symptoms as well as UTI history and antibiotic consumption within the past year. Patients using an indwelling catheter (n = 206) or IC (n = 299) were included in the analysis. The main outcome was between-group differences regarding UTI characteristics. RESULTS: Patients using an indwelling catheter were older (indwelling catheter vs IC: median 66 (Q1-Q3: 55-77) vs 55 (42-67) years of age) and showed a higher Charlson comorbidity index (indwelling catheter vs IC: median 4 (Q1-Q3: 2-6) vs 2 (1-4) (both p < 0·001). A total of 40 patients from both groups were diagnosed with a UTI at visit (indwelling catheters vs IC: 8% (16/206) vs 8% (24/299); p = 0·782), and the number of UTIs within the past 12 months was not significantly different between groups. Overall, Escherichia coli (21%), Enterococcus faecalis (17%), and Klebsiella spp. (12%) were the most frequently detected bacteria. CONCLUSIONS: In this cohort of patients with NLUTD, we did not find relevant differences in UTI frequency between groups. These results suggest that UTI-related concerns should not be given undue emphasis when counseling patients for catheter-related bladder emptying methods.

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

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.

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

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.

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

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.

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

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.

The Challenge of Asymptomatic Bacteriuria and Symptomatic Urinary Tract Infections in Patients with Neurogenic Lower Urinary Tract Dysfunction.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: Before urodynamics urine cultures were negative in 123 patients (39%) and positive in 194 (61%). Escherichia coli and Klebsiella pneumoniae were the most frequent bacteria, found in 32% and 18% of patients, respectively. Of 194 patients with a positive culture 35 (18%) had at least 1 symptomatic urinary tract infection. In patients with a history of previous urinary tract infections the overall estimated probability of a symptomatic urinary tract infection was 45% regardless of the underlying neurological disorder. CONCLUSIONS: 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.

Reliability of supraspinal correlates to lower urinary tract stimulation in healthy participants - A fMRI study.

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), Sørensen-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 < 0.05, cluster corrected, k ≥ 41 voxels) BOLD signal changes were found for the contrast INFUSION compared to START in several brain areas. Overlap of activation maps from both measurements were observed in the orbitofrontal cortex, insula, ventrolateral prefrontal cortex (VLPFC), and inferior parietal lobe. The two highest ICCs, based on a ROI's mean beta weight, were 0.55 (right insular cortex) and 0.47 (VLPFC). Spatial congruency (Sørensen-Dice index) of all voxels within each ROI between measurements was highest in the insular cortex (left 0.55, right 0.44). In addition, the mean beta weight of the right insula and right VLPFC demonstrated the lowest CV and narrowest Bland and Altman 95% limits of agreement. In conclusion, the right insula and right VLPFC were revealed as the two most reliable task-specific ROIs using our automated, MR-synchronized protocol. Achieving high reliability using a viscero-sensory/interoceptive task such as repetitive bladder filling remains challenging and further endeavour is highly warranted to better understand which factors influence fMRI outcomes and finally to assess LUT treatment effects on the supraspinal level.

Prediction of autonomic dysreflexia during urodynamics: a prospective cohort study.

BACKGROUND: Autonomic dysreflexia is a severe and potentially life-threatening condition in patients with spinal cord injury, as it can lead to myocardial ischemia, brain hemorrhage, or even death. Urodynamic investigation is the gold standard to assess neurogenic lower urinary tract dysfunction due to spinal cord injury and reveal crucial pathological findings, such as neurogenic detrusor overactivity. However, neurogenic detrusor overactivity and urodynamic investigation are known to be leading triggers of autonomic dysreflexia. Therefore, we aimed to determine predictors of autonomic dysreflexia in individuals with spinal cord injury during urodynamic investigation. METHODS: This prospective cohort study included 300 patients with spinal cord injuries and complete datasets of continuous non-invasive cardiovascular monitoring, recorded during same session repeat urodynamic investigation. We used logistic regression to reveal predictors of autonomic dysreflexia during urodynamic investigation. RESULTS: We found that level of injury and presence of neurogenic detrusor overactivity were the only two independent significant predictors for autonomic dysreflexia during urodynamic investigation. A lesion at spinal segment T6 or above (odds ratio (OR) 5.5, 95% CI 3.2-9.4) compared to one at T7 or below, and presence of neurogenic detrusor overactivity (OR 2.7, 95% confidence interval (CI) 1.4-4.9) were associated with a significant increased odds of autonomic dysreflexia during urodynamic investigation. Both odds persisted after adjustment for age, sex, and completeness and stage of injury (adjusted OR (AOR) 6.6, 95% CI 3.8-11.7, and AOR 2.2, 95% CI 1.1-4.5, respectively). Further stratification by lesion level showed level-dependent significantly increased adjusted odds of autonomic dysreflexia, i.e., from C1-C4 (AOR 16.2, 95% CI 5.9-57.9) to T4-T6 (AOR 2.6, 95% CI 1.3-5.2), compared to lesions at T7 or below. CONCLUSIONS: In patients with neurogenic lower urinary tract dysfunction due to spinal cord injury, autonomic dysreflexia is independently predicted by lesion level and presence of neurogenic detrusor overactivity. Considering the health risks associated with autonomic dysreflexia, such as seizures, stroke, retinal bleeding, or even death, we recommend both continuous cardiovascular monitoring during urodynamic investigation in all spinal cord-injured patients with emphasis on those with cervical lesions, and appropriate neurogenic detrusor overactivity treatment to reduce the probability of potentially life-threatening complications. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01293110 .

Intradetrusor onabotulinumtoxinA injections for refractory neurogenic detrusor overactivity incontinence: do we need urodynamic investigation for outcome assessment?

OBJECTIVE: To evaluate if urinary continence in patients with refractory neurogenic detrusor overactivity (NDO) incontinence 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 NDO incontinence were prospectively evaluated. Patients underwent UDI before and at 6 weeks after onabotulinumtoxinA injections. The primary outcome was the prevalence of maximum storage detrusor pressure (Pdetmax storage) of >40 cmH2 O in continent patients at 6 weeks after treatment. The secondary outcomes were treatment effects on other clinical and video-urodynamic variables. RESULTS: At 6 weeks after intradetrusor onabotulinumtoxinA injections, 98 of the 148 patients (66%) with NDO incontinence were continent. Of these patients, 18 (18%, confidence interval 12-27%) had a Pdetmax storage of >40 cmH2 O. Gender, underlying neurological disorder, and high Pdetmax storage before treatment appear to increase the risk of poor urodynamic outcomes. CONCLUSIONS: Urinary continence is not sufficient for outcome assessment after intradetrusor onabotulinumtoxinA injections, as high intravesical pressures threatening the upper urinary tract may be missed in a relevant proportion of continent patients. Therefore, we strongly recommend UDI as a routine part of the follow-up.

A novel infusion-drainage device to assess lower urinary tract function in neuro-imaging.

OBJECTIVE: To evaluate the applicability and precision of a novel infusion-drainage device (IDD) for standardized filling paradigms in neuro-urology and functional magnetic resonance imaging (fMRI) studies of lower urinary tract (LUT) function/dysfunction. SUBJECTS/PATIENTS AND METHODS: The IDD is based on electrohydrostatic actuation which was previously proven feasible in a prototype setup. The current design includes hydraulic cylinders and a motorized slider to provide force and motion. Methodological aspects have been assessed in a technical application laboratory as well as in healthy subjects (n=33) and patients with LUT dysfunction (n=3) undergoing fMRI during bladder stimulation. After catheterization, the bladder was pre-filled until a persistent desire to void was reported by each subject. The scan paradigm comprised automated, repetitive bladder filling and withdrawal of 100 mL body warm (37 °C) saline, interleaved with rest and sensation rating. Neuroimaging data were analysed using Statistical Parametric Mapping version 12 (SMP12). RESULTS: Volume delivery accuracy was between 99.1±1.2% and 99.9±0.2%, for different flow rates and volumes. Magnetic resonance (MR) compatibility was demonstrated by a small decrease in signal-to-noise ratio (SNR), i.e. 1.13% for anatomical and 0.54% for functional scans, and a decrease of 1.76% for time-variant SNR. Automated, repetitive bladder-filling elicited robust (P = 0.05, family-wise error corrected) brain activity in areas previously reported to be involved in supraspinal LUT control. There was a high synchronism between the LUT stimulation and the blood oxygenation level-dependent (BOLD) signal changes in such areas. CONCLUSION: We were able to develop an MR-compatible and MR-synchronized IDD to routinely stimulate the LUT during fMRI in a standardized manner. The device provides LUT stimulation at high system accuracy resulting in significant supraspinal BOLD signal changes in interoceptive and LUT control areas in synchronicity to the applied stimuli. The IDD is commercially available, portable and multi-configurable. Such a device may help to improve precision and standardization of LUT tasks in neuro-imaging studies on supraspinal LUT control, and may therefore facilitate multi-site studies and comparability between different LUT investigations in the future.

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

BACKGROUND: Urinary tract infections (UTI) are among the most prevalent microbial diseases and their financial burden on society is substantial. The continuing increase of antibiotic resistance worldwide is alarming. Thus, well-tolerated, highly effective therapeutic alternatives are urgently needed. Although there is evidence indicating that bacteriophage therapy may be effective and safe for treating UTIs, the number of investigated patients is low and there is a lack of randomized controlled trials. METHODS AND DESIGN: This study is the first randomized, placebo-controlled, double-blind trial investigating bacteriophages in UTI treatment. Patients planned for transurethral resection of the prostate are screened for UTIs and enrolled if in urine culture eligible microorganisms ≥104 colony forming units/mL are found. Patients are randomized in a double-blind fashion to the 3 study treatment arms in a 1:1:1 ratio to receive either: a) bacteriophage (i.e. commercially available Pyo bacteriophage) solution, b) placebo solution, or c) antibiotic treatment according to the antibiotic sensitivity pattern. All treatments are intended for 7 days. No antibiotic prophylaxes will be given to the double-blinded treatment arms a) and b). As common practice, the Pyo bacteriophage cocktail is subjected to periodic adaptation cycles during the study. Urinalysis, urine culture, bladder and pain diary, and IPSS questionnaire will be completed prior to and at the end of treatment (i.e. after 7 days) or at withdrawal/drop out from the study. Patients with persistent UTIs will undergo antibiotic treatment according to antibiotic sensitivity pattern. DISCUSSION: Based on the high lytic activity and the potential of resistance optimization by direct adaptation of bacteriophages, and considering the continuing increase of antibiotic resistance worldwide, bacteriophage therapy is a very promising treatment option for UTIs. Thus, our randomized controlled trial investigating bacteriophages for treating UTIs will provide essential insights into this potentially revolutionizing treatment option. TRIAL REGISTRATION: This study has been registered at clinicaltrials.gov ( www.clinicaltrials.gov/ct2/show/NCT03140085 ). April 27, 2017.

Autonomic dysreflexia and repeatability of cardiovascular changes during same session repeat urodynamic investigation in women with spinal cord injury.

PURPOSE: To investigate autonomic dysreflexia (AD) and repeatability of cardiovascular changes during same session repeat urodynamic investigation (UDI) in women with spinal cord injury (SCI). METHODS: Prospective investigation of 33 consecutive women with suprasacral SCI suffering from neurogenic lower urinary tract dysfunction (NLUTD) undergoing same session repeat UDI and synchronous continuous cardiovascular monitoring [systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR)]. UDIs were performed according to the International Continence Society guidelines. AD was defined according to the International Standards to document remaining Autonomic Function after SCI. Neurological level of SCI was determined using the American Spinal Injury Association impairment scale. RESULTS: Mean age and duration since SCI of the 33 women were 58 ± 19 and 6 ± 11 years, respectively. Overall AD incidence was 73 % (24/33), and 19 of the 33 women (58 %) showed AD in both UDIs. The repeatability of detecting AD between the two same session UDIs was good (κ = 0.67, 95 % CI 0.4-0.94). When applying the Bland and Altman method, wide 95 % limits of agreement for differences in same session SBP, DBP and HR indicated poor repeatability. There was a significant increase in SBP (p < 0.001) and DBP (p < 0.001) and a significant decrease in HR (p = 0.007) in patients with compared to those without AD. CONCLUSIONS: In all women with NLUTD due to suprasacral SCI, we strongly recommend continuous cardiovascular monitoring during UDI and repeat measurements considering the high incidence of AD, the relevant risks involved with sudden hypertension and the poor repeatability of cardiovascular monitoring.

Protocol for a prospective magnetic resonance imaging study on supraspinal lower urinary tract control in healthy subjects and spinal cord injury patients undergoing intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity.

BACKGROUND: The control of the lower urinary tract is a complex, multilevel process involving both the peripheral and central nervous system. Due to lesions of the neuraxis, most spinal cord injury patients suffer from neurogenic lower urinary tract dysfunction, which may jeopardise upper urinary tract function and has a negative impact on health-related quality of life. However, the alterations to the nervous system following spinal cord injury causing neurogenic lower urinary tract dysfunction and potential effects of treatments such as intradetrusor onabotulinumtoxinA injections on lower urinary tract control are poorly understood. METHODS/DESIGN: This is a prospective structural and functional magnetic resonance imaging study investigating the supraspinal lower urinary tract control in healthy subjects and spinal cord injury patients undergoing intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity.Neuroimaging data will include structural magnetic resonance imaging (T1-weighted imaging and diffusion tensor imaging) as well as functional, i.e. blood oxygen level-dependent sensitive magnetic resonance imaging using a 3 T magnetic resonance scanner. The functional magnetic resonance imaging will be performed simultaneously to three different bladder stimulation paradigms using an automated magnetic resonance compatible and synchronised pump system.All subjects will undergo two consecutive and identical magnetic resonance imaging measurements. Healthy subjects will not undergo any intervention between measurements but spinal cord injury patients will receive intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity.Parameters of the clinical assessment including bladder diary, urinalysis, medical history, neuro-urological examination, urodynamic investigation as well as standardised questionnaires regarding lower urinary tract function and quality of life will serve as co-variates in the magnetic resonance imaging analysis. DISCUSSION: This study will identify structural and functional alterations in supraspinal networks of lower urinary tract control in spinal cord injury patients with neurogenic detrusor overactivity compared to healthy controls. Post-treatment magnetic resonance imaging measurements in spinal cord injury patients will provide further insights into the mechanism of action of treatments such as intradetrusor onabotulinumtoxinA injections and the effect on supraspinal lower urinary tract control. TRIAL REGISTRATION: ClinicalTrials.gov NCT01768910.

[Neurogenic, non-obstructive urinary retention: diagnosis and treatment]. / Neurogene, nicht-obstruktive Harnretention: Diagnose und Therapie.

Neurogenic, non-obstructive urinary retention has a varied aetiology. The condition can be caused by central-nervous diseases as well as by disorders of the peripheral nervous system. The formation of residual urine may lead to considerable problems that can have a significant impact on a patient's everyday life. A treatment appropriate for the lower urinary tract dysfunction and suited to the patient's situation in life is only possible if a differentiated diagnostic evaluation has been performed. Both conservative and surgical therapeutic strategies are available, while drug treatment approaches are less relevant. Neuromodulative procedures are particularly suitable for causal treatment of the dysfunction. For patients requiring artificial bladder voiding, intermittent self-catheterization is generally preferable to using an indwelling catheter.

European Association of Urology Guidelines on Urological Infections: Summary of the 2024 Guidelines.

BACKGROUND AND OBJECTIVE: Urological infections significantly impact the wellbeing and quality of life of individuals owing to their widespread occurrence and diverse clinical manifestations. The objective of the guidelines panel was to provide evidence-based guidance on the diagnosis, treatment, and prevention of urinary tract infections (UTIs) and male accessory-gland infections, while addressing crucial public health aspects related to infection control and antimicrobial stewardship. METHODS: For the 2024 guidelines on urological infections, new and relevant evidence was identified, collated, and appraised via a structured assessment of the literature. Databases searched included Medline, EMBASE, and the Cochrane Libraries. Recommendations within the guidelines were developed by the panel to prioritise clinically important care decisions. The strength of each recommendation was determined according to a balance between desirable and undesirable consequences of alternative management strategies, the quality of the evidence (including the certainty of estimates), and the nature and variability of patient values and preferences. KEY FINDINGS AND LIMITATIONS: Key recommendations emphasise the importance of a thorough medical history and physical examination for patients with urological infections. The guidelines stress the role of antimicrobial stewardship to combat the rising threat of antimicrobial resistance, providing recommendations for antibiotic selection, dosing, and duration on the basis of the latest evidence. CONCLUSIONS AND CLINICAL IMPLICATIONS: This overview of the 2024 EAU guidelines offers valuable insights into managing urological infections and are designed for effective integration into clinical practice. PATIENT SUMMARY: The European Association of Urology has issued an updated guideline on urological infections. The guidelines provide recommendations for diagnosis, treatment, and prevention, with a particular focus on minimising antibiotic use because of the increasing global threat of antimicrobial resistance.

Intracranial artery velocity measurement using 4D PC MRI at 3 T: comparison with transcranial ultrasound techniques and 2D PC MRI.

INTRODUCTION: 4D phase contrast MR imaging (4D PC MRI) has been introduced for spatiotemporal evaluation of intracranial hemodynamics in various cerebrovascular diseases. However, it still lacks validation with standards of reference. Our goal was to compare blood flow quantification derived from 4D PC MRI with transcranial ultrasound and 2D PC MRI. METHODS: Velocity measurements within large intracranial arteries [internal carotid artery (ICA), basilar artery (BA), and middle cerebral artery (MCA)] were obtained in 20 young healthy volunteers with 4D and 2D PC MRI, transcranial Doppler sonography (TCD), and transcranial color-coded duplex sonography (TCCD). Maximum velocities at peak systole (PSV) and end diastole (EDV) were compared using regression analysis and Bland-Altman plots. RESULTS: Correlation of 4D PC MRI measured velocities was higher in comparison with TCD (r = 0.49-0.66) than with TCCD (0.35-0.44) and 2D PC MRI (0.52-0.60). In mid-BA and ICA C7 segment, a significant correlation was found with TCD (0.68-0.81 and 0.65-0.71, respectively). No significant correlation was found in carotid siphon. On average over all volunteers, PSVs and EDVs in MCA were minimally underestimated compared with TCD/TCCD. Minimal overestimation of velocities was found compared to TCD in mid-BA and ICA C7 segment. CONCLUSION: 4D PC MRI appears as valid alternative for intracranial velocity measurement consistent with previous reference standards, foremost with TCD. Spatiotemporal averaging effects might contribute to vessel size-dependent mild underestimation of velocities in smaller (MCA), and overestimation in larger-sized (BA and ICA) arteries, respectively. Complete spatiotemporal flow analysis may be advantageous in anatomically complex regions (e.g. carotid siphon) relative to restrictions of ultrasound techniques.

Management of uncomplicated urinary tract infection in the post-antibiotic era: select non-antibiotic approaches.

BACKGROUND: Given the high frequency of patients presenting with urinary tract infections (UTIs) and the ensuing high degree of antibiotic prescription, UTI is a critical point of intervention for non-antibiotic treatments to curb the further development of antimicrobial resistance and provide risk-appropriate care for patients. OBJECTIVES: To highlight several select non-antibiotic therapies for the treatment of uncomplicated UTI and relevant indications (prevention and complicated UTI) from recent literature. SOURCES: PubMed, Google Scholar, and clinicaltrials.gov were searched for clinical trials published in the English language corresponding to non-antibiotic treatments for UTI. CONTENT: The focus of this narrative review centres on a limited number of non-antibiotic therapies for the treatment of UTI based on (a) herbal extracts or (b) antibacterial strategies (e.g. bacteriophage therapy and D-mannose). The experience of treatment with non-steroidal anti-inflammatory drugs is also used to fuel discussion on the risk of developing pyelonephritis without antibiotics-compared with the projected harms of continuing their widespread use. IMPLICATIONS: Non-antibiotic treatment strategies for UTI have shown varying results in clinical trials, and the current evidence does not yet indicate a clear, better alternative to antibiotics. However, the collective experience with non-antibiotic treatments suggests that there is a need to weigh the actual benefits/risks of unfettered, non-culture-confirmed antibiotic use in uncomplicated UTI. Given the different mechanisms of action of proposed alternatives, more in-depth knowledge on microbiological and pathophysiological factors influencing UTI susceptibility and prognostic indicators are highly needed to stratify patients most likely to benefit. The feasibility of alternatives in clinical practice should also be considered.