Improved inter-subject alignment of the lumbosacral cord for group-level in vivo gray and white matter assessments: A scan-rescan MRI study at 3T.

INTRODUCTION: Magnetic resonance imaging (MRI) enables the investigation of pathological changes in gray and white matter at the lumbosacral enlargement (LSE) and conus medullaris (CM). However, conducting group-level analyses of MRI metrics in the lumbosacral spinal cord is challenging due to variability in CM length, lack of established image-based landmarks, and unknown scan-rescan reliability. This study aimed to improve inter-subject alignment of the lumbosacral cord to facilitate group-level analyses of MRI metrics. Additionally, we evaluated the scan-rescan reliability of MRI-based cross-sectional area (CSA) measurements and diffusion tensor imaging (DTI) metrics. METHODS: Fifteen participants (10 healthy volunteers and 5 patients with spinal cord injury) underwent axial T2*-weighted and diffusion MRI at 3T. We assessed the reliability of spinal cord and gray matter-based landmarks for inter-subject alignment of the lumbosacral cord, the inter-subject variability of MRI metrics before and after adjusting for the CM length, the intra- and inter-rater reliability of CSA measurements, and the scan-rescan reliability of CSA measurements and DTI metrics. RESULTS: The slice with the largest gray matter CSA as an LSE landmark exhibited the highest reliability, both within and across raters. Adjusting for the CM length greatly reduced the inter-subject variability of MRI metrics. The intra-rater, inter-rater, and scan-rescan reliability of MRI metrics were the highest at and around the LSE (scan-rescan coefficient of variation <3% for CSA measurements and <7% for DTI metrics within the white matter) and decreased considerably caudal to it. CONCLUSIONS: To facilitate group-level analyses, we recommend using the slice with the largest gray matter CSA as a reliable LSE landmark, along with an adjustment for the CM length. We also stress the significance of the anatomical location within the lumbosacral cord in relation to the reliability of MRI metrics. The scan-rescan reliability values serve as valuable guides for power and sample size calculations in future longitudinal studies.

Detrusor Sphincter Dyssynergia.

Detrusor sphincter dyssynergia (DSD) is defined as a detrusor contraction concurrent with an involuntary contraction of the urethral and/or periurethral striated muscles typically occurring in a patient with a spinal cord lesion above the sacral cord. Consequently, high urethral closure pressures during the detrusor contraction leads to high intravesical voiding pressure and large postvoid residuals, which can lead to significant complications in up to 50% of patients if DSD is not treated and followed-up regularly. DSD treatment options are centered around symptomatic management rather that addressing the underlying causative mechanisms.

Summary of the 2024 Update of the European Association of Urology Guidelines on Neurourology.

BACKGROUND AND OBJECTIVE: Most patients with neurourological disorders require lifelong medical care. The European Association of Urology (EAU) regularly updates guidelines for diagnosis and treatment of these patients. The objective of this review is to provide a summary of the 2024 updated EAU guidelines on neurourology. METHODS: A structured literature review covering the timeframe 2021-2023 was conducted for the guideline update. A level of evidence and a strength rating were assigned for each recommendation on the basis of the literature data. KEY FINDINGS AND LIMITATIONS: Neurological conditions significantly affect urinary, sexual, and bowel function, and lifelong management is required for neurourological patients to maintain their quality of life and prevent urinary tract deterioration. Early diagnosis and effective treatment are key, and comprehensive clinical assessments, including urodynamics, are crucial. Management should be customised to individual needs and should involve a multidisciplinary approach and address sexuality and fertility. Lifelong monitoring and follow-up highlight the importance of continuous care for neurourological patients. CONCLUSIONS AND CLINICAL IMPLICATIONS: The 2024 EAU guidelines on neurourology provide an up-to-date overview of available evidence on diagnosis, treatment, and follow-up for neurourological patients. PATIENT SUMMARY: Neurological disorders very frequently affect the lower urinary tract and sexual and bowel function and patients need lifelong management. We summarise the updated European Association of Urology guidelines on neurourology to provide patients and caregivers with the latest insights for optimal health care support.

Impact of cfDNA Reference Materials on Clinical Performance of Liquid Biopsy NGS Assays.

BACKGROUND: Liquid biopsy enables the non-invasive analysis of genetic tumor variants in circulating free DNA (cfDNA) in plasma. Accurate analytical validation of liquid biopsy NGS assays is required to detect variants with low variant allele frequencies (VAFs). METHODS: Six types of commercial cfDNA reference materials and 42 patient samples were analyzed using a duplex-sequencing-based liquid biopsy NGS assay. RESULTS: We comprehensively evaluated the similarity of commercial cfDNA reference materials to native cfDNA. We observed significant differences between the reference materials in terms of wet-lab and sequencing quality as well as background noise. No reference material resembled native cfDNA in all performance metrics investigated. Based on our results, we established guidelines for the selection of appropriate reference materials for the different steps in performance evaluation. The use of inappropriate materials and cutoffs could eventually lead to a lower sensitivity for variant detection. CONCLUSION: Careful consideration of commercial reference materials is required for performance evaluation of liquid biopsy NGS assays. While the similarity to native cfDNA aids in the development of experimental protocols, reference materials with well-defined variants are preferable for determining sensitivity and precision, which are essential for accurate clinical interpretation.

Neuro-Urology and Biobanking: An Integrated Approach for Advancing Research and Improving Patient Care.

Understanding the molecular mechanisms underlying neuro-urological disorders is crucial for the development of targeted therapeutic interventions. Through the establishment of comprehensive biobanks, researchers can collect and store various biological specimens, including urine, blood, tissue, and DNA samples, to study these mechanisms. In the context of neuro-urology, biobanking facilitates the identification of genetic variations, epigenetic modifications, and gene expression patterns associated with neurogenic lower urinary tract dysfunction. These conditions often present as symptoms of neurological diseases such as Alzheimer's disease, multiple sclerosis, Parkinson's disease, spinal cord injury, and many others. Biobanking of tissue specimens from such patients is essential to understand why these diseases cause the respective symptoms and what can be done to alleviate them. The utilization of high-throughput technologies, such as next-generation sequencing and gene expression profiling, enables researchers to explore the molecular landscape of these conditions in an unprecedented manner. The development of specific and reliable biomarkers resulting from these efforts may help in early detection, accurate diagnosis, and effective monitoring of neuro-urological conditions, leading to improved patient care and management. Furthermore, these biomarkers could potentially facilitate the monitoring of novel therapies currently under investigation in neuro-urological clinical trials. This comprehensive review explores the synergistic integration of neuro-urology and biobanking, with particular emphasis on the translation of biobanking approaches in molecular research in neuro-urology. We discuss the advantages of biobanking in neuro-urological studies, the types of specimens collected and their applications in translational research. Furthermore, we highlight the importance of standardization and quality assurance when collecting samples and discuss challenges that may compromise sample quality and impose limitations on their subsequent utilization. Finally, we give recommendations for sampling in multicenter studies, examine sustainability issues associated with biobanking, and provide future directions for this dynamic field.

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.

How should prospective research be designed to legitimately assess the value of urodynamic studies in female urinary incontinence?

AIMS: Since formal evidence demonstrating the value of urodynamic studies (UDS) in functional urology remains elusive, we aimed to consider how best to design robust research for this purpose in female urinary incontinence. METHODS: An expert group was convened to debate the following considerations: (a) precedents for formally proving the value of a gold standard diagnostic test, (b) key research principles, (c) defining a study population, (d) selecting endpoints, (e) defining interventional and controls arms, (f) blinding, (g) powering the study, and (h) duration of follow-up. In each case, we considered the strengths and weaknesses of different approaches in terms of scientific validity, ethical acceptability, practicality, and likelihood of bias. RESULTS: We agreed that unlike evaluating therapies, attempting to judge the value of a diagnostic test based on eventual treatment success is conceptually flawed. Nonetheless, we explored the design of a hypothetical randomized controlled trial for this purpose, agreeing that: (1) the study population must sufficiently reflect its real-world counterpart; (2) clinical endpoints should include not only continence status but also other lower urinary tract symptoms and risks of management; (3) participants in the interventional arm should receive individualized management based on their UDS findings; (4) the most scientifically valid approach to the control arm-empiric treatment-is ethically problematic; (5) sufficient statistical power is imperative; and (6) ≥ 2 years' follow-up is needed to assess the long-term impact of management. CONCLUSIONS: Although a perfect protocol does not exist, we recommend careful consideration of our observations when reflecting on past studies or planning new prospective research.

Development of a Sham Protocol to Investigate Transcutaneous Tibial Nerve Stimulation in Randomised, Sham-Controlled, Double-Blind Clinical Trials.

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

Enhancing bacteriophage therapeutics through in situ production and release of heterologous antimicrobial effectors.

Bacteriophages operate via pathogen-specific mechanisms of action distinct from conventional, broad-spectrum antibiotics and are emerging as promising alternative antimicrobials. However, phage-mediated killing is often limited by bacterial resistance development. Here, we engineer phages for target-specific effector gene delivery and host-dependent production of colicin-like bacteriocins and cell wall hydrolases. Using urinary tract infection (UTI) as a model, we show how heterologous effector phage therapeutics (HEPTs) suppress resistance and improve uropathogen killing by dual phage- and effector-mediated targeting. Moreover, we designed HEPTs to control polymicrobial uropathogen communities through production of effectors with cross-genus activity. Using phage-based companion diagnostics, we identified potential HEPT responder patients and treated their urine ex vivo. Compared to wildtype phage, a colicin E7-producing HEPT demonstrated superior control of patient E. coli bacteriuria. Arming phages with heterologous effectors paves the way for successful UTI treatment and represents a versatile tool to enhance and adapt phage-based precision antimicrobials.

Engineered reporter phages for detection of Escherichia coli, Enterococcus, and Klebsiella in urine.

The rapid detection and species-level differentiation of bacterial pathogens facilitates antibiotic stewardship and improves disease management. Here, we develop a rapid bacteriophage-based diagnostic assay to detect the most prevalent pathogens causing urinary tract infections: Escherichia coli, Enterococcus spp., and Klebsiella spp. For each uropathogen, two virulent phages were genetically engineered to express a nanoluciferase reporter gene upon host infection. Using 206 patient urine samples, reporter phage-induced bioluminescence was quantified to identify bacteriuria and the assay was benchmarked against conventional urinalysis. Overall, E. coli, Enterococcus spp., and Klebsiella spp. were each detected with high sensitivity (68%, 78%, 87%), specificity (99%, 99%, 99%), and accuracy (90%, 94%, 98%) at a resolution of ≥103 CFU/ml within 5 h. We further demonstrate how bioluminescence in urine can be used to predict phage antibacterial activity, demonstrating the future potential of reporter phages as companion diagnostics that guide patient-phage matching prior to therapeutic phage application.

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.

Abnormal Resting-State Network Presence in Females with Overactive Bladder.

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

Prediction of Lower Urinary Tract, Sexual, and Bowel Function, and Autonomic Dysreflexia after Spinal Cord Injury.

Spinal cord injury (SCI) produces damage to the somatic and autonomic pathways that regulate lower urinary tract, sexual, and bowel function, and increases the risk of autonomic dysreflexia. The recovery of these functions has a high impact on health, functioning, and quality of life and is set as the utmost priority by patients. The application of reliable models to predict lower urinary tract, sexual, and bowel function, and autonomic dysreflexia is important for guiding counseling, rehabilitation, and social reintegration. Moreover, a reliable prediction is essential for designing future clinical trials to optimize patients' allocation to different treatment groups. To date, reliable and simple algorithms are available to predict lower urinary tract and bowel outcomes after traumatic and ischemic SCI. Previous studies identified a few risk factors to develop autonomic dysreflexia, albeit a model for prediction still lacks. On the other hand, there is an urgent need for a model to predict the evolution of sexual function. The aim of this review is to examine the available knowledge and models for the prediction of lower urinary tract, sexual, and bowel function, and autonomic dysreflexia after SCI, and critically discuss the research priorities in these fields.

Urodynamics Are Essential to Predict the Risk for Upper Urinary Tract Damage after Acute Spinal Cord Injury.

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

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.

Bacterial species and antimicrobial resistance differ between catheter and non-catheter-associated urinary tract infections: Data from a national surveillance network.

Objective: To investigate clinically relevant microbiological characteristics of uropathogens and to compare patients with catheter-associated urinary tract infections (CAUTIs) to those with non-CAUTIs. Methods: All urine cultures from the calendar year 2019 of the Swiss Centre for Antibiotic Resistance database were analyzed. Group differences in the proportions of bacterial species and antibiotic-resistant isolates from CAUTI and non-CAUTI samples were investigated. Results: Data from 27,158 urine cultures met the inclusion criteria. Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis together represented 70% and 85% of pathogens identified in CAUTI and non-CAUTI samples, respectively. Pseudomonas aeruginosa was significantly more often detected in CAUTI samples. The overall resistance rate for the empirically often-prescribed antibiotics ciprofloxacin (CIP), norfloxacin (NOR), and trimethoprim-sulfamethoxazole (TMP-SMX) was between 13% and 31%. Except for nitrofurantoin, E. coli from CAUTI samples were more often resistant (P ≤ .048) to all classes of antibiotics analyzed, including third-generation cephalosporines used as surrogate for extended-spectrum ß-lactamase (ESBL). Significanty higher resistance proportions in CAUTI samples versus non-CAUTI samples were observed for CIP (P = .001) and NOR (P = .033) in K. pneumoniae, for NOR (P = .011) in P. mirabilis, and for cefepime (P = .015), and piperacillin-tazobactam (P = .043) in P. aeruginosa. Conclusion: CAUTI pathogens were more often resistant to recommended empirical antibiotics than non-CAUTI pathogens. This finding emphasizes the need for urine sampling for culturing before initiating therapy for CAUTI and the importance of considering therapeutic alternatives.

Neuro-Urology: Call for Universal, Resource-Independent Guidance.

Neurogenic lower urinary tract dysfunction (NLUTD), the abnormal function of the lower urinary tract in the context of neurological pathology, has been the subject of multiple efforts worldwide for the development of clinical practice guidelines. These guidelines are based on the same body of evidence, and are therefore subject to the same gaps. For example, sexual and bowel dysfunction in the context of NLUTD, optimal renal function assessment in those who are non-ambulatory or with low muscle mass, optimal upper tract surveillance timing, and modification of diagnostic and treatment modalities for low-resource nations and communities are inadequately addressed. In addition, many aspects of the conclusions and final recommendations of the guidelines are similar. This duplicative work represents a large expenditure of time and effort, which we believe could be focused instead on evidence gaps. Here, we call for a global unified approach to create a single, resource-independent, comprehensive guidance on NLUTD, neurogenic sexual, and neurogenic bowel dysfunction. Targeted research addressing the evidence gaps should be called for and pursued. This will allow for focus to shift to filling the gaps in the evidence for future guidelines.

Not revenge, but change is sweet: Experimental evidence of how offender change and punishment play independent roles in victims' sense of justice.

What positive effects do victims gain by punishing their offenders? Previous research suggests that punishment increases victims' justice-related satisfaction only when the offender indicates that they changed their moral attitude and behaviour. However, offender change may increase justice-related satisfaction independently of punishment. So far, it is empirically unclear whether punishment affects satisfaction beyond offender change (e.g. by producing the change), and whether punishment has positive effects on victims that are independent of offender change, specifically how it empowers victims. In two studies, we use a full experimental design to test the unique influence of punishment and offender change on victims' justice-related satisfaction and empowerment. In a third study, we extend the design and additionally test for the effects of assigned versus self-selected punishment. Across three studies (N = 824) with different methodological approaches, we consistently found that offender change alone increased victims' justice-related satisfaction-and this effect was not moderated by punishment. Study 2, but not Study 3, showed that punishment alone empowered victim-and this effect was not moderated by offender change. This indicates that offender change and punishment have independent roles in producing positive effects on victims. Overall, it was offender change and not punishment that made victims feel that justice has been done.

Mapping the Iceberg of Autonomic Recovery: Mechanistic Underpinnings of Neuromodulation following Spinal Cord Injury.

Spinal cord injury leads to disruption in autonomic control resulting in cardiovascular, bowel, and lower urinary tract dysfunctions, all of which significantly reduce health-related quality of life. Although spinal cord stimulation shows promise for promoting autonomic recovery, the underlying mechanisms are unclear. Based on current preclinical and clinical evidence, this narrative review provides the most plausible mechanisms underlying the effects of spinal cord stimulation for autonomic recovery, including activation of the somatoautonomic reflex and induction of neuroplastic changes in the spinal cord. Areas where evidence is limited are highlighted in an effort to guide the scientific community to further explore these mechanisms and advance the clinical translation of spinal cord stimulation for autonomic recovery.

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.