Immunomodulation for primary prevention of urinary tract infections in patients with spinal cord injury during primary rehabilitation: protocol for a randomized placebo-controlled pilot trial (UROVAXOM-pilot).

BACKGROUND Urinary tract infections (UTIs) are common in individuals with neurogenic lower urinary tract dysfunction (NLUTD) following spinal cord injury (SCI). They are not only a great burden for affected individuals, but also cause considerable health costs. Furthermore, recurrent antibiotic treatments of UTIs contribute to the growing problem of bacterial resistance to antimicrobial compounds. Even though there is a multitude of different measures to prevent UTIs in individuals with NLUTD, no clear evidence exists for any of these. Oral immunomodulation with UTI-relevant Escherichia coli lysate may be a promising preventative measure with a good safety profile in individuals with NLUTD. However, currently available data are sparse. METHODS This is a randomized, quasi-blinded, placebo-controlled, mono-centric pilot trial investigating the feasibility of a main trial regarding the effects of a lyophilized lysate of E. coli strains for oral application (Uro-Vaxom®, OM Pharma SA, Meyrin, Switzerland). There will be two parallel groups of 12 participants each. Individuals with acute SCI (duration SCI ≤ 56 days) from 18 to 70 years of age admitted for primary rehabilitation will be eligible. Blood and urine samples will be taken prior to intervention start, at the end of the intervention, and 3 months after intervention termination. The trial intervention will last 90 days. The participants will not be informed regarding the treatment allocation (quasi-blinded). The nursing staff will prepare the daily dose of the allocated treatment from the original packaging. The trial personnel and the biostatistician will be blinded. Feasibility (e.g., recruitment rate, patient attrition), clinical (e.g., number of symptomatic UTIs), and laboratory parameters (e.g., urinary culture, urinary proteo- and microbiome, blood cell counts) as well as adverse events will be collected. DISCUSSION Effective and efficient measures for the prevention of UTIs in individuals with NLUTD are urgently needed. If the conclusion of this pilot is positive regarding feasibility, the effects of oral immunomodulation with a E. coli lysate will be investigated in a larger, sufficiently powered, multi-center trial. TRIAL REGISTRATION ClinicalTrials.gov NCT04049994 . Registered on 8 August 2019

Early Changes in Androgen Levels in Individuals with Spinal Cord Injury: A Longitudinal SwiSCI Study.

We aimed to explore longitudinal changes in androgen levels in individuals with spinal cord injury (SCI) within initial inpatient rehabilitation stay and identify clinical/injury characteristics associated with hormone levels. Linear regression analysis was applied to explore the association between personal/injury characteristics and androgen hormones (total testosterone, free testosterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEA-S)) at admission to rehabilitation. Longitudinal changes in androgen levels were studied using linear mixed models. Analyses were stratified by sex and by injury type. We included 70 men and 16 women with SCI. We observed a non-linear association between age, time since injury, and androgens at baseline. At admission to initial rehabilitation, mature serum SHBG (full-length, protein form which lacks the N-terminal signaling peptide) was higher, while DHEA and DHEA-S were lower among opioid users vs. non-users. Serum levels of total testosterone and DHEA-S increased over rehabilitation period [β 3.96 (95%CI 1.37, 6.56), p = 0.003] and [β 1.77 (95%CI 0.73, 2.81), p = 0.01], respectively. We observed no significant changes in other androgens. Restricting our analysis to men with traumatic injury did not materially change our findings. During first inpatient rehabilitation over a median follow up of 5.6 months, we observed an increase in total testosterone and DHEA-S in men with SCI. Future studies need to explore whether these hormonal changes influence neurological and functional recovery as well as metabolic parameters during initial rehabilitation stay

External Urethral Sphincter Pressure Measurement: An Accurate Method for the Diagnosis of Detrusor External Sphincter Dyssynergia?

Combined pelvic floor electromyography (EMG) and videocystourethrography (VCUG) during urodynamic investigation are the most acceptable and widely agreed methods for diagnosing detrusor external sphincter dyssynergia (DESD). Theoretically, external urethral sphincter pressure (EUSP) measurement would provide enough information for the diagnosis of DESD and could simplify the urodynamic investigation replacing combined pelvic floor EMG and VCUG. Thus, we evaluated the diagnostic accuracy of EUSP measurement for DESD. PATIENTS #ENTITYSTARTX00026;A consecutive series of 72 patients (36 women, 36 men) with neurogenic lower urinary tract dysfunction able to void spontaneously was prospectively evaluated at a single university spinal cord injury center. Diagnosis of DESD using EUSP measurement (index test) versus combined pelvic floor EMG and VCUG (reference standard) was assessed according to the recommendations of the Standards for Reporting of Diagnostic Accuracy Initiative.Using EUSP measurement (index test) and combined pelvic floor EMG and VCUR (reference standard), DESD was diagnosed in 10 (14%) and in 41 (57%) patients, respectively. More than half of the patients presented discordant diagnosis between the index test and the reference standard. Among 41 patients with DESD diagnosed by combined pelvic floor EMG and VCUR, EUSP measurement identified only 6 patients. EUSP measurement had a sensitivity of 15% (95% CI 5%-25%), specificity of 87% (95% CI 76%-98%), positive predictive value of 60% (95% CI 30%-90%), and negative predictive value of 56% (95% CI 44%-68%) for the diagnosis of DESD.For diagnosis of DESD, EUSP measurement is inaccurate and cannot replace combined pelvic floor EMG and VCUR

Management of stress urinary incontinence in female patients with spinal cord injury by autologous fascial sling: time for a revival?

STUDY DESIGN This study is a retrospective chart analysis. OBJECTIVES Surgical treatment of stress urinary incontinence (SUI) in women with neurogenic lower urinary tract dysfunction (NLUTD) is a challenge, as minimally invasive procedures do not seem to be effective, whereas synthetic implants are associated with substantial risks. Thus, we evaluated the results of an autologous sling procedure in this group of patients SETTING: This study was performed at a spinal cord injury rehabilitation center in Switzerland. METHODS In this retrospective analysis, we evaluated the objective, subjective, and urodynamic results in women undergoing autologous sling insertion for SUI due to NLUTD at our institution. RESULTS The data of 17 women who underwent fascial sling surgery were analyzed. After a median follow-up of 40 months, 8 women (47%) were continent, and another 8 patients (47%) significantly improved (1 pad/day). Median video-urodynamic parameters remained unchanged after sling insertion, but two women developed de novo detrusor overactivity. Postoperative complications occurred in 6 of the 17 patients (35.3%), which required surgical interventions in 2 women (12%) (urethral erosion by the sling and complete occlusion of the urethra after removal of the catheter), which could be resolved without loss of continence. CONCLUSION In our case series, autologous fascial slings were effective in the treatment of SUI in women with NLUTD. As they are more effective than minimally invasive procedures, are associated with fewer complications than AUS, and seem to omit possible severe long-term consequences of synthetic slings, they are an excellent treatment option in this group of patients. Urodynamic controls are recommended, as de novo detrusor overactivity may occur after sling insertion

Bladder management in individuals with spinal cord injury or disease during and after primary rehabilitation: a retrospective cohort study.

PURPOSE The purpose of this study was to investigate the course of bladder evacuation and the predictors of intermittent self-catheterization (ISC) in individuals with neurogenic lower urinary tract dysfunction (NLUTD) during and after primary rehabilitation. METHODS The patient database of a single spinal cord injury rehabilitation center was screened for patients with NLUTD admitted for primary rehabilitation. Patient characteristics and bladder evacuation details were collected during and after rehabilitation. Binary logistic regression analysis was used to evaluate predictors of ISC: sex, age > 65 years, injury severity, and bladder capacity ≥ 400 ml. RESULTS Data of 255 men (74.3%) and 88 women (25.7%) with a mean age of 54 ± 19 years were analyzed. Early in rehabilitation, 21.6% of the evaluated individuals used ISC. In 17.8%, the bladder was evacuated by transurethral catheterization (TUC). The proportion of TUC decreased during rehabilitation and dropped below 2% at the last follow-up. In contrast, the proportion of ISC and suprapubic catheterization (SPC) increased to 28% and 12.8%, respectively, during rehabilitation. These proportions increased further thereafter and reached 37.7% and 18.6% for ISC and SPC, respectively. Age and injury severity were significant (p ≤ 0.041) negative predictors, whereas male sex and above-average bladder capacity were positive predictors of ISC. CONCLUSIONS There is a shift toward bladder evacuation by ISC and SPC during and after primary rehabilitation. Bladder evacuation by ISC, regarded as the gold standard, is less common in individuals > 65 years or with high-level tetraplegia. The optimal bladder evacuation method needs to be established individually, considering all medical and psychosocial factors rather than simply following a guideline

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

PURPOSE We investigated prevalence of asymptomatic bacteriuria and incidence of symptomatic urinary tract infections (UTI) in patients with neurogenic lower urinary tract dysfunction (NLUTD) undergoing urodynamics and assessed predictors for symptomatic UTI. PATIENTS AND METHODS A prospective consecutive series of 317 patients (106 women, 211 men) with NLUTD was evaluated. Of them, 111 (35%) voided spontaneously, 141 (44%) relied on intermittent self-catheterization and 65 (21%) on an indwelling catheter. Before urodynamics, urine samples were collected by sterile catheterization for dipstick testing and urine culture. We assessed the association between patient characteristics and the occurrence of symptomatic UTIs following urodynamics in patients with asymptomatic bacteriuria and developed a prediction model based on the most important risk factors. RESULTS Urine cultures before urodynamics were negative in 123 (39%) and positive in 194 (61%) patients. (32%) and e (18%) were the most frequent bacteria. Of 194 patients with positive culture, 35 (18%) had at least one symptomatic UTI. In patients with a history of previous UTIs, the overall estimated probability of a symptomatic UTI was 45%, irrespective of the underlying neurological disorder. CONCLUSIONS About one out of five patients with asymptomatic bacteriuria will develop a symptomatic UTI in the follow-up year. This rather low overall probability precludes routine antibiotic prophylaxis or treatment in patients with NLUTD having asymptomatic bacteriuria as 4 out of 5 patients would be overtreated. However, in patients with a history of previous symptomatic UTIs antibiotic prescription might be justified

Effects of onabotulinumtoxinA on cardiac function following intradetrusor injections

OnabotulinumtoxinA intradetrusor injections are considered a highly effective localized therapy for refractory detrusor overactivity. However, despite evidence for distant systemic effects of onabotulinumtoxinA, little is known on potential systemic side effects following intradetrusor injections. Given that onabotulinumtoxinA is a highly potent toxin this is an important safety issue specifically with regard to repeat injections and parallel treatments with botulinum toxin. Hence, it was the purpose of this prospective study to investigate, using heart rate variability (HRV) analysis, whether onabotulinumtoxinA causes systemic effects on cardiac function following intradetrusor injections. Patients with neurogenic detrusor overactivity (NDO) and age-matched healthy controls were recruited. Concomitant medication and diseases affecting the cardio-vascular system were exclusion criteria. A 3-channel resting electrocardiogram (ECG) was recorded in supine position for 15min during four consecutive visits: 1) 2weeks prior onabotulinumtoxinA intradetrusor injections, 2) 10min prior injections, 3) 30min after injections, and 4) 6weeks after injections. NDO patients received intradetrusor injections (300units Botox®) between visits 2 and 3. The control group had no intervention. Short-term (5min) HRV analysis included assessment of frequency and time domain parameters. Statistical analysis was performed using ANOVA with repeated measures and the t-test. Due to multiple comparisons, α was corrected to 0.0125 (Bonferroni method). Twelve healthy volunteers (5♀, 7♂; 46±12years old) and 12 NDO patients (5♀, 7♂; 46±13years old) completed all measurements. Comparing both groups, resting heart rate was significantly higher in the patients group at visit 4 only. No further significant differences in time and frequency domain parameters were discovered. Within the NDO group, standard deviation of the normal to normal intervals (SDNN) in the ECG demonstrated a significant decrease (1.70 to 1.53ms, p=0.003) from visit 3 to 4, whereas the total power (TP) significantly increased (3.05 to 3.29ms(2), p=0.009) from visit 2 to 3. This increase subsided until visit 4. STUDY LIMITATIONS: single treatment investigation under resting conditions only. In conclusion, onabotulinumtoxinA intradetrusor injections do not seem to affect resting state cardiac function. Short-term changes such as total power might rather result from natural cardio-vascular responses to the procedure itself (e.g. discomfort, stress). Further detailed investigations also under physical stress and repeated injections are necessary to fully exclude systemic cardiac side effects of onabotulinumtoxinA intradetrusor injections

Risk Factors for Pulmonary Embolism in Patients with Paralysis and Deep Venous Thrombosis

Background. Venous thromboembolism is a frequent complication and an important cause of death in patients with paralysis. We aimed to investigate predictors of pulmonary embolism (PE) and the impact of PE on the survival of patients with paralysis in comparison to those with deep venous thrombosis or thrombophlebitis (DVT). Methods: Patients were selected by screening the German nationwide inpatient sample (2005–2017) for paralysis, and were stratified for venous thromboembolism (VTE) and the VTE-sub-entity PE (ICD-code I26). Impact of PE on mortality and predictors for PE were analyzed. Results: Overall, 7,873,769 hospitalizations of patients with paralysis were recorded in Germany 2005–2017, of whom 1.6% had VTE and 7.0% died. While annual hospitalizations increased (2005: 520,357 to 2017: 663,998) (β 12,421 (95% CI 10,807 to 14,034), p < 0.001), in-hospital mortality decreased from 7.5% to 6.7% (β −0.08% (95% CI −0.10% to −0.06%), p < 0.001). When focusing on 82,558 patients with paralysis hospitalized due to VTE (51.8% females; 58.3% aged ≥ 70 years) in 2005–2017, in-hospital mortality was significantly higher in patients with paralysis and PE than in those with DVT only (23.8% vs. 6.3%, p < 0.001). Cancer (OR 2.18 (95% CI 2.09–2.27), p < 0.001), heart failure (OR 1.83 (95% CI 1.76–1.91), p < 0.001), COPD (OR 1.63 (95% CI 1.53–1.72), p < 0.001) and obesity (OR 1.42 (95% CI 1.35–1.50), p < 0.001) were associated with PE. PE (OR 4.28 (95% CI 4.07–4.50), p < 0.001) was a strong predictor of in-hospital mortality. Conclusions: In Germany, annual hospitalizations of patients with paralysis increased in 2005–2017, in whom VTE and especially PE substantially affected in-hospital mortality. Cancer, heart failure, COPD, obesity and acute paraplegia were risk factors of PE

Improving component cleanliness during laser remote ablation processes with high-power lasers by optimized emission blower and suction strategies

Laser remote processing with high-performance laser sources enables materials such as metals or fiber composites to be cut, welded or ablated flexibly and quickly. All these manufacturing processes produce process and material specific particulate as well as gaseous emissions. This must be recorded quantitatively and qualitatively in order to implement appropriate protective measures with regard to occupational health and safety as well as to minimize the crosscontamination of the component to be treated. Ideally, an additional cleaning step should be avoided by optimizing the arrangement of the process suction and blower. Particle distributions as well as gas phase analyses during the remote ablation process were recorded during ablation tests on metals or carbon-based composites. The structure quality and the contamination of the sample surface after laser material processing as well as after the additional cleaning process were determined. Subsequently, the samples were thermally joined to evaluate the influences

An 8 French transurethral reusable microtip dual sensor microtransducer catheter (Unisensor AG, Attikon, Switzerland) was used to simultaneously measure the intravesical and urethral pressure.

<p>The microtransducers were positioned in the bladder (a) and the external urethral sphincter (b) under the guidance of continuous pressure monitoring and fluoroscopy ensuring correct position during the urodynamic investigation.</p