Identification of brain functional connectivity during acute transcutaneous tibial nerve stimulation: A 3T fMRI study.

OBJECTIVES: A feasibility proof-of-concept study was conducted to assess the effects of acute tibial nerve stimulation (TNS) on the central nervous system in healthy volunteers using functional magnetic resonance imaging (fMRI). MATERIALS AND METHODS: Fourteen healthy volunteers were included in a prospective, single-site study conducted on a clinical 3T MRI scanner. Four scans of functional MRI, each lasting 6 min, were acquired: two resting-state fMRI scans (prior and following the TNS intervention) and in-between two fMRI scans, both consisting of alternating rest periods and noninvasive acute transcutaneous TNS (TTNS). Whole brain seed-based functional connectivity (FC) correlation analysis was performed comparing TTNS stimulation with rest periods. Cluster-level familywise error (FWE) corrected p and a minimal cluster size of 200 voxels were used to explore FC patterns. RESULTS: Increased FC is reported between inferior frontal gyrus, posterior cingulate gyrus, and middle temporal gyrus with the precuneus as central receiving node. In addition, decreased FC in the cerebellum, hippocampus, and parahippocampal areas was observed. CONCLUSIONS: Altered FC is reported in areas which have been described to be also involved in lower urinary tract control. Although conducted with healthy controls, the assumption that the underlying therapeutic effect of TNS involves the central nervous system is supported and has to be further examined in patients with incomplete spinal cord injury.

Percutaneous Tibial Nerve Stimulation in the Treatment of Refractory Idiopathic Overactive Bladder Syndrome: A Retrospective Cohort Study.

BACKGROUND: Overactive bladder (OAB) is a syndrome defined as urinary urgency, accompanied by increased frequency and nocturia with or without urge incontinence, in the absence of urinary tract infection or other obvious pathology. The standard therapies are anticholinergic agents, selective beta-3 adrenoreceptor agonists, or intradetrusor injections of botulinum toxin (BTX-A). For patients with contraindications for BTX-A or drug therapies, percutaneous tibial nerve stimulation (PTNS) may be used. PTNS shows fewer side effects than anticholinergic drugs and costs less than BTX-A. The primary outcome of this study was to assess the efficacy of PTNS in women with refractory OAB. METHODS: Women with refractory OAB undergoing PTNS at our tertiary referral center from 2017 to 2019 were included. The validated German Female Pelvic Floor Questionnaire and a micturition protocol were filled out before and after PTNS. PTNS was applied weekly for 12 weeks. RESULTS: Improvements in OAB symptoms were seen in daily micturition frequency, urgency, and urgency incontinence from pre- to post-PTNS (p < 0.006). Impairments to quality of daily life were significantly (p < 0.0002) less severe after PTNS. There was a significant reduction in daytime voiding frequency from a median of nine to five (p < 0.0001). CONCLUSIONS: Substantial reductions in OAB symptoms, daily micturition frequency, urgency, and urgency incontinence were found in patients with refractory OAB after PTNS.

Immune Status of Individuals with Traumatic Spinal Cord Injury: A Systematic Review and Meta-Analysis.

Individuals with spinal cord injury (SCI) have higher infection rates compared to those without SCI. In this review, the immune status difference between individuals with and without traumatic SCI is investigated by examining their peripheral immune cells and markers. PubMed, Cochrane, EMBASE, and Ovid MEDLINE were searched without language or date restrictions. Studies reporting peripheral immune markers' concentration and changes in functional capabilities of immune cells that compared individuals with and without SCI were included. Studies with participants with active infection, immune disease, and central nervous system (CNS) immune markers were excluded. The review followed the PRISMA guidelines. Effect estimates were measured by Weighted Mean Difference (WMD) using a random-effects model. Study quality was assessed using the National Heart, Lung, and Blood Institute Quality Assessment Tool. Fifty-four studies (1813 with SCI and 1378 without SCI) contributed to the meta-analysis. Leukocytes (n = 23, WMD 0.78, 95% CI 0.17; 1.38, I2 83%), neutrophils (n = 11, WMD 0.76, 95% CI 0.09; 1.42, I2 89%), C-reactive protein (CRP) (n = 12, WMD 2.25, 95% CI 1.14; 3.56, I2 95%), and IL6 (n = 13, WMD 2.33, 95% CI 1.20; 3.49, I2 97%) were higher in individuals with SCI vs. without SCI. Clinical factors (phase of injury, completeness of injury, sympathetic innervation impairment, age, sex) and study-related factors (sample size, study design, and serum vs. plasma) partially explained heterogeneity. Immune cells exhibited lower functional capability in individuals with SCI vs. those without SCI. Most studies (75.6%) had a moderate risk of bias. The immune status of individuals with SCI differs from those without SCI and is clinically influenced by the phase of injury, completeness of injury, sympathetic innervation impairment, age, and sex. These results provide information that is vital for monitoring and management strategies to effectively improve the immune status of individuals with SCI.

Impact of Defined Risk Factors on Degree of Urinary Stress Incontinence and Sling Outcome: A Retrospective Cohort Analysis.

Urinary stress incontinence is a distressing condition that has a severe impact on quality of life for most affected women. The insertion of the suburethral tension-free vaginal tape (TVT) is regarded as the gold-standard surgical treatment option. It is unclear whether all women with severe SUI benefit equally from TVT. Thus, the aim of our study was to identify risk factors for severe SUI and determine whether successful the resolution of incontinence after a TVT procedure was different in women with a higher degree of SUI. In total, 168 women were included in this retrospective cohort study. Women with severe SUI showed a significantly lower maximum urethral closure pressure (MUCP) (median 53 cmH2O in moderate vs. 39 cmH2O in severe, p = 0.001) and higher BMI (median 26.1 kg/m2 in moderate vs. 28.5 kg/m2 in severe, p = 0.045). Sonographic bladder neck funneling was detected significantly more often in women with severe SUI (27% in moderate vs. 57% in severe, p = 0.004). Lower MUCP and higher BMI were identified as significant predictors of severe SUI (p < 0.032). There was no difference in parity, age, functional urethral length and negative urethral stress pressure. Overall postoperative continence after the insertion of TVT was 91.9%. We found no significant difference in postoperative continence between women with severe vs. moderate SUI, suggesting that in our cohort the success of TVT was not significantly affected by the severity of SUI. In our cohort, low MUCP and high BMI were shown to be significant predictors of SUI severity. Nevertheless, treatment success of SUI with TVT did not differ substantially in women with more severe SUI.

Satisfaction with Homeopathic Service and Care for Persons with Spinal Cord Injury.

BACKGROUND: The aim of the study was to investigate the satisfaction of individuals with spinal cord injury (SCI) with a homeopathic service at an SCI rehabilitation center. PATIENTS AND METHODS: A cross-sectional questionnaire study was performed at an SCI rehabilitation center in Switzerland. It included patients with chronic SCI who presented themselves to a homeopathic service offered by the hospital in a 12-months period. The participants filled in standardized questionnaires in German: "Measure Yourself Medical Outcome Profile" (MYMOP), Treatment Satisfaction Questionnaire for Medication (TSQM-9), the European Project on Patient Evaluation of General Practice Care (EUROPEP) questionnaire, and a self-administered questionnaire. RESULTS: The data of 14 patients were analyzed. Symptom severity as well as bother by the symptoms that led to homeopathic treatment decreased under homeopathic treatment (severity: from 4.3 to 3.3; bother: from 4.2 to 2.9) and remained lower over time (severity: 2.6; bother: 2.7), suggesting a sustained effect. Irrespective of the test instrument used, satisfaction rates were higher for homeopathic service than for homeopathic medication, which was rated as successful by 50% of the participants. CONCLUSION: Persons with SCI suffering from secondary complications of SCI who accessed homeopathic care reported high satisfaction rates with the service. Therefore, homeopathic service can be considered as an additive measure in persons with SCI suffering from recurrent symptoms.Evaluierung der Zufriedenheit von Personen mit Querschnittlähmung (QSL) mit einer homöopathischen Betreuung an einem Rehabilitationszentrum für QSL.An einem Rehabilitationszentrum für QSL in der Schweiz wurde eine Querschnittserhebung mittels Fragebögen durchgeführt. Eingeschlossen wurden Personen mit chronischer QSL, die sich in einer von der Klinik angebotenen homöopathischen Sprechstunde in einem 12-Monats-Intervall vorstellten. Die Teilnehmenden füllten standardisierte Fragebogen in deutscher Sprache aus: "Measure Yourself Medical Outcome Profile" (MYMOP), Treatment Satisfaction Questionnaire for Medication (TSQM-9), den "European Project on Patient Evaluation of General Practice Care (EUROPEP)" Fragebogen sowie einen selbst-erstellten Fragebogen.Die Daten von 14 Teilnehmenden wurden ausgewertet. Der Schweregrad der Symptome sowie die Belastung durch die Symptome die zur homöopathischen Behandlung geführt haben, wurden unter der homöopathischen Therapie geringer (Schweregrad: von 4.3 auf 3.3; Belastung: von 4.2 auf 2.9) und blieben über den Untersuchungszeitraum geringer (Schweregrad: 2.6; Belastung 2.7), was einen anhaltenden Effekt nahelegt. Unabhängig von dem verwendeten Testinstrument waren die Zufriedenheitsraten für die homöopathische Betreuung höher als diejenigen für die homöopathische Medikation, die von 50% der Teilnehmenden als erfolgreich bewertet wurde.Personen mit QSL, die wegen Sekundärkomplikationen eine homöopathische Sprechstunde aufsuchten, berichteten eine hohe Zufriedenheit mit dieser Betreuung. Daher kann eine homöopathische Betreuung als zusätzliche Massnahme bei Personen mit QSL mit persistierender Symptomatik in Betracht gezogen werden.

Prevalence of an insufficient vitamin D status at the onset of a spinal cord injury - a cross-sectional study.

STUDY DESIGN: A cross-sectional study. OBJECTIVE: This study aimed to investigate the vitamin D status after acute spinal cord injury (SCI) onset. SETTING: Specialized SCI rehabilitation center in Switzerland. METHODS: Patients admitted to the center after an acute SCI onset were included. The prevalence of a deficient (25(OH)D ≤ 50 nmol/l), insufficient (50 < 25(OH)D ≤ 75 nmol/l) and sufficient (25(OH)D > 75 nmol/l) vitamin D status were determined after admission. Vitamin D status was compared between different patient groups based on demographic and SCI characteristics. The occurrence of bed rest, falls and pressure injuries were also assessed. RESULTS: In total, 87 patients (median (interquartile range); 53 (39-67) years, 25 females, 66 traumatic SCI, 54 paraplegia) were included. Assessed a median of 15 (9-22) days after SCI onset, median vitamin D status was 41 (26-57) (range 8-155) nmol/l. The majority of patients had a deficient (67%, 95% confidence interval (95% CI) 0.56-0.76) or insufficient (25%, 95% CI 0.17-0.36) vitamin D status. A moderate negative correlation was found between vitamin D status and body mass index (p = 0.003). A moderate positive correlation was found between vitamin D and calcium status (p = 0.01). CONCLUSION: A deficient or insufficient vitamin D status directly after SCI onset is highly prevalent. Vitamin D status should be carefully observed during acute SCI rehabilitation. We recommend that all patients with recent SCI onset should receive vitamin D supplementation with a dosage depending on their actual vitamin D status.

One-year follow-up of the CAPSID randomized trial for high-dose convalescent plasma in severe COVID-19 patients.

BACKGROUNDResults of many randomized trials on COVID-19 convalescent plasma (CCP) have been reported, but information on long-term outcome after CCP treatment is limited. The objectives of this extended observation of the randomized CAPSID trial are to assess long-term outcome and disease burden in patients initially treated with or without CCP.METHODSOf 105 randomized patients, 50 participated in the extended observation. Quality of life (QoL) was assessed by questionnaires and a structured interview. CCP donors (n = 113) with asymptomatic to moderate COVID-19 were included as a reference group.RESULTSThe median follow-up of patients was 396 days, and the estimated 1-year survival was 78.7% in the CCP group and 60.2% in the control (P = 0.08). The subgroup treated with a higher cumulative amount of neutralizing antibodies showed a better 1-year survival compared with the control group (91.5% versus 60.2%, P = 0.01). Medical events and QoL assessments showed a consistent trend for better results in the CCP group without reaching statistical significance. There was no difference in the increase in neutralizing antibodies after vaccination between the CCP and control groups.CONCLUSIONThe trial demonstrated a trend toward better outcome in the CCP group without reaching statistical significance. A predefined subgroup analysis showed a significantly better outcome (long-term survival, time to discharge from ICU, and time to hospital discharge) among those who received a higher amount of neutralizing antibodies compared with the control group. A substantial long-term disease burden remains after severe COVID-19.Trial registrationEudraCT 2020-001310-38 and ClinicalTrials.gov NCT04433910.FundingBundesministerium für Gesundheit (German Federal Ministry of Health).

A Prediction Model for Various Treatment Pathways of Upper Extremity in Tetraplegia.

Upper extremity function is essential for the autonomy in patients with cervical spinal cord injuries and consequently a focus of the rehabilitation and treatment efforts. Routinely, an individualized treatment plan is proposed to the patient by an interprofessional team. It dichotomizes into a conservative and a surgical treatment pathway. To select an optimal pathway, it is important to define predictors that substantiate the treatment strategy. Apart from standard assessments (Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), the manual muscle test (MRC), and lower motoneuron integrity of key actuators for hand function performed by motor point (MP) mapping might serve as a possible predictor. Type of damage (upper motor neuron (UMN) or lower motor neuron (LMN) lesion) influences hand posture and thus treatment strategy as positioning and splinting of fingers, hands, arms, and surgical reconstructive procedures (muscle-tendon or nerve transfers) in choice and timing of intervention. For this purpose, an analysis of a database comprising 220 patients with cervical spinal cord injury is used. It includes ISNCSCI, MRC, and MP mapping of defined muscles at selected time points after injury. The ordinal regression analysis performed indicates that MP and ASIA impairment scale (AIS) act as predictors of muscle strength acquisition. In accordance with the innervation status defined by MP, electrical stimulation (ES) is executed either via nerve or direct muscle stimulation as a supplementary therapy to the traditional occupational and physiotherapeutic treatment methods. Depending on the objective, ES is applied for motor learning, strengthening, or maintenance of muscle contractile properties. By employing ES, hand and arm function can be predicted by MP and AIS and used as the basis for providing an individualized treatment plan.

Multidisciplinary and standardized management of patients with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

BACKGROUND: The appropriate management of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) remains uncertain. We aimed to evaluate the effect of implementing a standardized protocol for detection and management of DCI after aSAH on cerebral infarction and functional outcome. METHODS: We studied two cohorts of aSAH patients, one before (pre-implementation cohort: January 2012 to August 2014) and one after (post-implementation cohort: January 2016 to July 2018) implementation of a multidisciplinary approach, with standardized neurological and radiological assessment and risk-based medical treatment of DCI. We assessed the presence of new hypodensities on CT within 6 weeks after aSAH and categorized cerebral infarction into overall and DCI-related infarctions (hypodensities not within 48 h after IA repair and not attributable to aneurysm occlusion or intraparenchymal hematoma). Functional outcome was assessed at 3 months using the extended Glasgow outcome scale (eGOS), dichotomized into unfavorable (eGOS: 1-5) and favorable (eGOS: 6-8). We calculated odds ratios (OR) with corresponding 95% confidence intervals (CI's), and adjusted for age, WFNS grade, Fisher score, and treatment modality (aOR). RESULTS: In the post-implementation (n = 158) versus the pre-implementation (n = 143) cohort the rates for overall cerebral infarction were 29.1% vs 46.9% (aOR: 0.41 [0.24-0.69]), for DCI-related cerebral infarction 17.7% vs. 31.5% (aOR: 0.41 [0.23-0.76]), and for unfavorable functional outcome at 3 months 37.3% vs. 53.8% (aOR: 0.30 [0.17-0.54]). For patients with DCI, the rates for unfavorable functional outcomes at 3 months in the post-implementation versus the pre-implementation cohort were 42.3% vs. 77.8% (aOR: 0.1 [0.03-0.27]). CONCLUSIONS: A multidisciplinary approach with more frequent and standardized neurological assessment, standardized CT and CT perfusion monitoring, as well as tailored application of induced hypertension and invasive rescue therapy strategies, is associated with a significant reduction of cerebral infarction and unfavorable functional outcome after aneurysmal aSAH.

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.

Osteomyelitis and antibiotic treatment in patients with grade IV pressure injury and spinal cord lesion-a retrospective cohort study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To analyze characteristics and treatment of osteomyelitis (OM) in the treatment of grade IV pressure injury (PI) in patients with spinal cord injury/disorder (SCI/D) following the Basel Decubitus Concept. SETTING: Acute care and rehabilitation clinic specialized in SCI/D. METHODS: Patients with SCI/D were admitted for grade IV PI treatment between 1st January 2010 and 28th February 2015. Patients, SCI/D, and PI characteristics were collected from chart reviews. Descriptive statistics and differences between groups with and without OM were evaluated. RESULTS: In total, 117 patients (87 male, 30 female) with 130 PI grade IV were included. In 95 patients (81%), OM was diagnosed histologically. In 87 cases, more than one bacterial species was involved. Out of 49 different bacterial species, Enterococcus faecalis and Staphylococus aureus were most frequently observed. Amoxicillin/clavulanic acid and ciprofloxacin were the most frequently used out of 24 different antibiotics. Length of antibiotic treatment varied between <8 days and >91 days with 31 patients receiving antibiotics for about 8 weeks. Complications occurred in all groups of antibiotic duration. Having a paraplegia, no OM and sacral PI was associated with increased complication rates, but the number of patients did not allow comprehensive risk factor analysis. CONCLUSION: Because the variety of patients concerning SCI/D, PI, and OM characteristics did not show a conclusive relation between length of antibiotic treatment and complication rates, the development of a subgroup specific treatment concept for PI in patients with SCI/D would be favorable to further optimize antibiotic treatment.

Impact of sacrocolpopexy for the management of pelvic organ prolapse on voiding dysfunction and uroflowmetry parameters: a prospective cohort study.

PURPOSE: Voiding difficulties in the context of pelvic organ prolapse are often neglected or underestimated. To date, there are heterogeneous data available on the outcome of a surgical correction of pelvic organ prolapse and the impact on concomitant voiding dysfunction. The primary aim of this study was to evaluate whether laparoscopic sacrocolpopexy would resolve preoperative voiding dysfunction and the impact on objective uroflowmetry parameters. METHODS: Data from 103 women undergoing sacrocolpopexy for prolapse stage ≥ II with concurrent objective and/or subjective voiding dysfunction were prospectively evaluated. All women underwent full urogynecological examination, and completed a validated questionnaire pre- and postoperatively. Objective uroflowmetry parameters and subjective outcome data regarding voiding functions were compared pre- and postoperatively. RESULTS: All points of the POP-Q system improved significantly pre- to postoperatively (p < 0.001). Preoperatively, 42 of 103 women showed a postvoid residual ≥ 100 ml, whereas only six women had a relevant postvoid residual postoperatively. In total, the postoperative postvoid residual in all women decreased significantly (p < 0.001). Voiding time decreased significantly postoperatively (p < 0.001) with no significant change in the voided volume (p = 0.352). The maximum flow rate increased postoperatively, reaching no statistically significant change (p = 0.132). Subjective outcome measurements (weak or prolonged stream, incomplete bladder emptying, and straining to void) improved significantly (p < 0.001 for all the questions). CONCLUSION: Our prospective study demonstrates that sacrocolpopexy to correct pelvic organ prolapse can successfully resolve voiding dysfunction, as both objective and subjective parameters improved significantly after surgery.

Ground truth labels challenge the validity of sepsis consensus definitions in critical illness.

BACKGROUND: Sepsis is the leading cause of death in the intensive care unit (ICU). Expediting its diagnosis, largely determined by clinical assessment, improves survival. Predictive and explanatory modelling of sepsis in the critically ill commonly bases both outcome definition and predictions on clinical criteria for consensus definitions of sepsis, leading to circularity. As a remedy, we collected ground truth labels for sepsis. METHODS: In the Ground Truth for Sepsis Questionnaire (GTSQ), senior attending physicians in the ICU documented daily their opinion on each patient's condition regarding sepsis as a five-category working diagnosis and nine related items. Working diagnosis groups were described and compared and their SOFA-scores analyzed with a generalized linear mixed model. Agreement and discriminatory performance measures for clinical criteria of sepsis and GTSQ labels as reference class were derived. RESULTS: We analyzed 7291 questionnaires and 761 complete encounters from the first survey year. Editing rates for all items were > 90%, and responses were consistent with current understanding of critical illness pathophysiology, including sepsis pathogenesis. Interrater agreement for presence and absence of sepsis was almost perfect but only slight for suspected infection. ICU mortality was 19.5% in encounters with SIRS as the "worst" working diagnosis compared to 5.9% with sepsis and 5.9% with severe sepsis without differences in admission and maximum SOFA. Compared to sepsis, proportions of GTSQs with SIRS plus acute organ dysfunction were equal and macrocirculatory abnormalities higher (p < 0.0001). SIRS proportionally ranked above sepsis in daily assessment of illness severity (p < 0.0001). Separate analyses of neurosurgical referrals revealed similar differences. Discriminatory performance of Sepsis-1/2 and Sepsis-3 compared to GTSQ labels was similar with sensitivities around 70% and specificities 92%. Essentially no difference between the prevalence of SIRS and SOFA ≥ 2 yielded sensitivities and specificities for detecting sepsis onset close to 55% and 83%, respectively. CONCLUSIONS: GTSQ labels are a valid measure of sepsis in the ICU. They reveal suspicion of infection as an unclear clinical concept and refute an illness severity hierarchy in the SIRS-sepsis-severe sepsis spectrum. Ground truth challenges the accuracy of Sepsis-1/2 and Sepsis-3 in detecting sepsis onset. It is an indispensable intermediate step towards advancing diagnosis and therapy in the ICU and, potentially, other health care settings.

Risk factors for hospital acquired pressure injury in patients with spinal cord injury during first rehabilitation: prospective cohort study.

STUDY DESIGN: Prospective observational cohort study. OBJECTIVES: First, describe pressure injury (PI) and associated risk factors in individuals with spinal cord injury/disorder (SCI/D) during first rehabilitation. Second, evaluate a prediction model for hospital acquired PI (HAPI) development. SETTING: Acute care and rehabilitation clinic specialized in SCI/D. METHODS: Patients ≥18 years of age with SCI/D were included during first rehabilitation between 08/2018 and 12/2019. We performed a systematic literature search to identify risk factors for PI development. Patients were classified according to HAPI developed. Between group differences of patients' characteristics and risk factors were analyzed using descriptive statistics. Logistic predictive models were performed to estimate HAPI development and receiver operator characteristic (ROC) curve was used to test the model. RESULTS: In total, 94 patients were included, 48 (51.1%) developed at least one HAPI and in total 93 were observed, mainly stage I and stage II HAPI according to the European Pressure Ulcer Advisory Panel. We found nine significantly associated risk factors: completeness of SCI/D, pneumonia, sedative medications, autonomic dysreflexia, Braden ≤12 points, SCIPUS ≥9 points, lower admission SCIM and lower admission FIM-cognition, longer length of stay (LOS) (p ≤ 0.0005). In a predictive model, none of the risk factors was associated with HAPI development (AUC = 0.5). CONCLUSION: HAPIs in patients with SCI/D during first rehabilitation are a frequent and complex condition and associated with several risk factors. No predictive model exists but with the identified risk factors of this study, larger studies can create a tailored and flexible HAPI risk prediction model.

An instrument for assessing quality of life in persons with neurogenic lower urinary tract dysfunction: validation of the German short-form Qualiveen questionnaire.

STUDY DESIGN: Prospective validation study. OBJECTIVES: To validate and evaluate the measurement properties of the German Qualiveen short-form (SF) questionnaire in individuals with chronic neurogenic lower urinary tract dysfunction (NLUTD) resulting from spinal cord injury (SCI). SETTING: Tertiary neuro-urologic referral center in Switzerland. METHODS: Fifty individuals with chronic (>12 months) NLUTD resulting from SCI presenting for a urodynamic follow-up examination were enrolled to complete both the full version Qualiveen and the SF-Qualiveen questionnaires twice within three weeks. The criterion validity and test-retest reliability were evaluated by calculating the interclass correlation coefficients. Internal consistency was evaluated by calculating Cronbach's alpha. Finally, the cross-sectional construct validity was evaluated using Spearman's rank correlations between the scores of the two questionnaires for bladder evacuation, urinary continence, and urinary tract infection sub-groups. RESULTS: The mean age of the evaluated individuals was 53 years. The median duration of NLUTD was 14.9 years. The SF-Qualiveen showed good to excellent criterion validity with correlation coefficients greater than 0.8. Internal consistency was good overall and in the domains "bother with limitations" as well as "feelings" (>0.75). However, internal consistency in the domains "frequency of limitations" and "fears" was moderate-poor (0.68-0.37). The test-retest reliability was excellent with correlation coefficients greater than 0.9. Finally, the cross-sectional construct validity ranged from moderate to excellent (0.60-0.97). CONCLUSIONS: The German SF-Qualiveen has shown excellent reliability and validity and variable internal consistency. Its brevity will increase compliance, and we therefore recommend to include the SF-Qualiveen in urologic assessments.

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.

Inhalationally Administered Semifluorinated Alkanes (SFAs) as Drug Carriers in an Experimental Model of Acute Respiratory Distress Syndrome.

Aerosol therapy in patients suffering from acute respiratory distress syndrome (ARDS) has so far failed in improving patients' outcomes. This might be because dependent lung areas cannot be reached by conventional aerosols. Due to their physicochemical properties, semifluorinated alkanes (SFAs) could address this problem. After induction of ARDS, 26 pigs were randomized into three groups: (1) control (Sham), (2) perfluorohexyloctane (F6H8), and (3) F6H8-ibuprofen. Using a nebulization catheter, (2) received 1 mL/kg F6H8 while (3) received 1 mL/kg F6H8 with 6 mg/mL ibuprofen. Ibuprofen plasma and lung tissue concentration, bronchoalveolar lavage (BAL) fluid concentration of TNF-α, IL-8, and IL-6, and lung mechanics were measured. The ibuprofen concentration was equally distributed to the dependent parts of the right lungs. Pharmacokinetic data demonstrated systemic absorption of ibuprofen proofing a transport across the alveolo-capillary membrane. A significantly lower TNF-α concentration was observed in (2) and (3) when compared to the control group (1). There were no significant differences in IL-8 and IL-6 concentrations and lung mechanics. F6H8 aerosol seemed to be a suitable carrier for pulmonary drug delivery to dependent ARDS lung regions without having negative effects on lung mechanics.

Changes in Bacterial Spectrum and Resistance Patterns Over Time in the Urine of Patients with Neurogenic Lower Urinary Tract Dysfunction Due to Spinal Cord Injury.

INTRODUCTION: Urinary tract infections (UTI) are among the most common complications in persons with neurogenic lower urinary tract dysfunction (NLUTD) due to spinal cord injury (SCI). As both asymptomatic bacteriuria and UTI are frequently treated with antibiotics, concerns about multidrug resistance arise. Therefore, we analyzed the bacterial spectrum in the urine and the resistance patterns of the strains over time in patients with NLUTD due to SCI. METHODS: In a systematic chart review, we identified all microbiologic urine test results including resistance patterns of persons with SCI in a tertiary referral hospital at 2 time periods (2010-2011 and 2017-2018). We assessed the frequency of the bacterial strains, the resistance patterns of the 5 most frequent bacteria, and the use of antibiotics for in- as well as for outpatients. RESULTS: From 2010 to 2011, 1,308 (outpatients) and 2,479 (inpatients) bacterial strains were detected in the urinalyses performed; these numbers rose to 3,162 and 6,112 during 2017-2018, respectively. The most frequently detected bacteria during both time periods were Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae/variicola, Streptococcus viridans, Pseudomonas aeruginosa, and coagulase negative Staphylococci. Fluoroquinolones were the most frequently used antibiotics during both time periods. Despite its frequent use, no relevant increase in resistance against fluoroquinolones was detected. The most prominent increase in resistance appeared in E. coli against amocixillin/clavulanic acid in inpatients (from 26.0 to 38.5%). DISCUSSION AND CONCLUSIONS: Although fluoroquinolones were used frequently, we did not observe an increased resistance against these antibiotics over time in the urine of patients with SCI.

Outcome of perineoplasty and de-adhesion in patients with vulvar Lichen sclerosus and sexual disorders.

OBJECTIVE: Vulvar Lichen sclerosus (LS) is a chronic inflammatory disease in which architectural changes and symptoms like itching, soreness, pain and dyspareunia can affect quality of life and sexual activity. Perineoplasty has been shown to be effective as a supportive surgical treatment in women with refractory dyspareunia in addition to the standard topical immunosuppressive treatment. The aim of this study was to evaluate retrospectively general complaints, patient satisfaction concerning sexual activity, reduction of dyspareunia/apareunia, orgasm ability and recurrence of LS after perineoplasty. STUDY DESIGN: This study is a retrospective monocentric observational study, in which patients with vulvar LS who had undergone perineoplasty were invited to fill out a standardized questionnaire during the follow-up time. The main outcome measure is the overall patient satisfaction after surgical therapy of vulvar LS. RESULTS: Forty-one of the 70 invited patients with a median age at surgery of 58 years (18-74 years) and a median 60 years (19-76 years) at the last follow-up were evaluated. The median follow-up time was 2.3 years (1-5 years). There was a significant (p < 0.001) reduction in general complaints after surgery. Twenty-two patients were very satisfied, 15 were satisfied and 3 were not satisfied with the outcome of the surgery. Only 2 patients would not recommend the surgery. Although, there was a significant (p = 0.02) reduction in dyspareunia after surgery, 10 patients still felt pain during sexual intercourse. CONCLUSION: This is one of the largest studies reporting on long-term results of perineoplasty. It showed that perineoplasty is a safe surgical treatment option with a high satisfaction rate in patients with dyspareunia due to LS and a desire to regain sexual activity. Perineoplasty can improve sexual activity and achieve overall satisfaction in selected patients even though the recurrence rate of LS in sexually active patients remains high.