Synthetic versus non-synthetic slings for female stress and mixed urinary incontinence: A systematic review and meta-analysis.

OBJECTIVE: To systematically review objective and subjective success, and surgical outcomes of sub-urethral sling surgery for female patients with stress or mixed urinary incontinence (SUI, MUI) using synthetic vs. non-synthetic material with corresponding surgical approach (retropubic, RP or transobturator, TO). DATA SOURCES: We systematically searched Medline, Embase, EBM Reviews, ClinicalTrials.gov and Web of Science Core Collection using standardized medical subject headings, no date restrictions (Prospero registered). We double-screened studies and used backward citation chaining. STUDY ELIGIBILITY: We included peer-reviewed randomized controlled trials and prospective or retrospective comparative studies examining outcomes of RP or TO synthetic vs non-synthetic (autologous, allograft, xenograft) slings for female SUI or MUI, with available English or French full text. We excluded minislings (single insertion point). We allowed slings for recurrent SUI or MUI, and slings concomitant with prolapse surgery, with at least 6 weeks of postoperative follow-up. We excluded systematic reviews, meta-analyses, review studies, case-control studies, case reports, studies that did not describe surgical approach or material, and studies of combination slings. STUDY APPRAISAL: We evaluated study quality using the Cochrane Risk of Bias Tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies. We used pooled relative risk (RR) with 95% confidence intervals (CI) to estimate effect of sling material type on each outcome through meta-analysis and meta-regression as appropriate. RESULTS: We screened 4341 abstracts, assessed 104 full-texts and retained 35 manuscripts (30 separate studies). For RP synthetic vs non-synthetic, there was no difference in number of objectively or subjectively continent patients. Reoperation for SUI and overall was higher for non-autologous RP slings compared to synthetic. RP synthetic vs autologous slings were associated with higher subjective continence in populations with ≥ 25% recurrent SUI (RR 1.27, 95% CI 1.12-1.43). For TO synthetic vs non-synthetic, there were no differences in continence. Subjective satisfaction was better in the TO synthetic group compared to autologous (RR 1.42, 95% CI 1.03;1.94). CONCLUSIONS: Synthetic and non-synthetic slings have comparable objective and subjective success, with differences in operative outcomes and complications generally in favour of synthetic material.

Vascular-Cognitive Impairment following High-Thoracic Spinal Cord Injury Is Associated with Structural and Functional Maladaptations in Cerebrovasculature.

Individuals living with chronic spinal cord injury (SCI) often exhibit impairments in cognitive function, which impede their rehabilitation and transition into the community. Although a number of clinical studies have demonstrated the impact of impaired cardiovascular control on cognitive impairment, the mechanistic understanding of this deleterious relationship is still lacking. The present study investigates whether chronic disruption of cardiovascular control following experimental SCI results in cerebrovascular decline and vascular cognitive impairment. Fourteen weeks following a high thoracic SCI (at the third thoracic segment), rats were subjected to a battery of in vivo and in vitro physiological assessments, cognitive-behavioral tests, and immunohistochemical approaches to investigate changes in cerebrovascular structure and function in the middle cerebral artery (MCA). We show that in the MCA of rats with SCI, there is a 55% (SCI vs. control: 13.4 ± 1.9% vs. 29.63 ± 2.8%, respectively) reduction in the maximal vasodilator response to carbachol, which is associated with reduced expression of endothelial marker cluster of differentiation 31 (CD31) and transient receptor potential cation channel 4 (TRPV 4) channels. Compared with controls, MCAs in rats with SCI were found to have 50% (SCI vs. control: 1.5 ± 0.2 vs. 1 ± 0.1 a.u., respectively) more collagen 1 in the media of vascular wall and 37% (SCI vs. control: 30.5 ± 2.9% vs. 42.0 ± 4.0%, respectively) less distensibility at physiological intraluminal pressure. Further, the cerebral blood flow (CBF) in the hippocampus was reduced by 32% in the SCI group (SCI vs. control: 44.3 ± 4.5 mL/100 g/min vs. 65.0 ± 7.2 mL/100 g/min, respectively) in association with impairment of short-term memory based on a novel object recognition test. There were no changes in the sympathetic innervation of the vasculature and passive structure in the SCI group. Chronic experimental SCI is associated with structural alterations and endothelial dysfunction in cerebral arteries that likely contribute to significantly reduced CBF and vascular cognitive impairment.

Diverse cognitive impairment after spinal cord injury is associated with orthostatic hypotension symptom burden.

This study: 1) compared cognitive functioning between individuals with chronic (>1 year) spinal cord injury (SCI) and non-injured controls and, 2) assessed associations between symptoms of autonomic dysreflexia and orthostatic hypotension with cognitive functioning in SCI participants with a history of unstable blood pressure (BP). Thirty-two individuals with SCI (C4-L2, American Spinal Injury Association Impairment Scale A-D) and thirty age, sex-matched non-injured controls participated in this study. Participants completed a motor-free neuropsychological test battery assessing 1) memory, 2) attention/concentration/psychomotor speed and, 3) executive function. Nineteen participants with SCI who had injuries ≥T6 and a history of unstable BP also completed the Autonomic Dysfunction Following Spinal Cord Injury (ADFSCI) questionnaire. Cognitive function was significantly lower in people with SCI across measures of memory and executive function compared to non-injured controls. Significant, moderate-to-large associations were observed between cumulative (frequency x severity) orthostatic hypotension and total BP instability symptoms scores, with measures of attention/concentration/psychomotor speed and executive function. These data demonstrate a 10 - 65% reduced performance across specific realms of cognitive functioning in individuals with SCI relative to non-injured controls. Furthermore, cumulative subjective scores for symptoms of unstable BP were associated with diverse cognitive deficits. These findings, in individuals without co-occurring traumatic brain injury, imply cardiovascular dysregulation plays a role in cognitive deficits observed in this population.

Reliability of Cognitive Measures in Individuals With a Chronic Spinal Cord Injury.

BACKGROUND: Following spinal cord injury (SCI), up to 64% of individuals experience cognitive deficit. However, the reliability of commonly used neuropsychological tests is currently unknown in this population. OBJECTIVES: To evaluate the test-retest reliability of cognitive measures in individuals with SCI. DESIGN: Cross-sectional study. SETTING: Vancouver General Hospital. PARTICIPANTS: Individuals with a chronic (>2 years) SCI (n = 22). METHODS: Across three visits (separated by ~16 days), 22 participants with chronic SCI completed a neuropsychological battery evaluating memory (Rey Auditory-Verbal Learning Test [RAVLT]), attention/concentration/psychomotor speed (Digit Span Task, Stroop Test), and executive function (Trail Making Test A&B, Symbol Digit Modalities Test, Controlled Oral Word Association Test). Coefficients of variation (CVintra ) and intraclass correlation coefficients (ICCs) were calculated to determine the reliability of each test between visits. Linear regressions were performed to assess the associations between variability (CVintra ) and participant characteristics, such as age or highest education level attained. Repeated-measures, one-way analysis of variance (ANOVA) was conducted to determine any significant practice effects, and smallest real differences (SRDs) were calculated. MAIN OUTCOME MEASUREMENTS: Repeated scores on aforementioned neuropsychological tests. RESULTS: ICCs ranged from 0.77 to 0.93, with the exception of RAVLT recognition score (ICC = 0.27). Age showed a moderate association with CVintra in RAVLT interference recall scores (r = 0.43, P = .047), but was not a confounding factor for other measures. Education was not associated with CVintra . Significant practice effects were noted for most of the cognitive tests assessed. CONCLUSIONS: Other than the RAVLT recognition score, these cognitive measures demonstrated good-to-excellent reliability. Although this is encouraging, test-retest variability should be considered when interpreting the efficacy of various cognitive training strategies to mitigate cognitive decline in this population. Thus, the SRD values presented herein will allow researchers and clinicians to identify "true" changes in cognitive function with repeated testing. LEVEL OF EVIDENCE: III.

Transient Hypertension after Spinal Cord Injury Leads to Cerebrovascular Endothelial Dysfunction and Fibrosis.

We aimed to create a clinically relevant pre-clinical model of transient hypertension, and then evaluate the pathophysiological cerebrovascular processes resulting from this novel stimulus, which has recently been epidemiologically linked to cerebrovascular disease. We first developed a clinically relevant model of transient hypertension, secondary to induced autonomic dysreflexia after spinal cord injury and demonstrated that in both patients and rats, this stimulus leads to drastic acute cerebral hyperperfusion. For this, iatrogenic urodynamic filling/penile vibrostimulation was completed while measuring beat-by-beat blood pressure and cerebral blood flow (CBF) in patients. We then developed a rodent model mimicking the clinical reality by performing colorectal distention (to induce autonomic dysreflexia) using pre-clinical beat-by-beat blood pressure and CBF assessments. We then performed colorectal distension in rats for four weeks (6x/day) to evaluate the long-term cerebrovascular consequences of transient hypertension. Outcome measures included middle cerebral artery endothelial function, remodeling, profibrosis and perivascular innervation; measured via pressure myography, immunohistochemistry, molecular biology, and magnetic resonance imaging. Our model demonstrates that chronic repetitive cerebral hyperperfusion secondary to transient hypertension because of autonomic dysreflexia: (1) impairs cerebrovascular endothelial function; (2) leads to profibrotic cerebrovascular stiffening characterized by reduced distensibility and increased collagen deposition; and (3) reduces perivascular sympathetic cerebrovascular innervation. These changes did not occur concurrent to hallmark cerebrovascular changes from chronic steady-state hypertension, such as hypertrophic inward remodeling, or reduced CBF. Chronic exposure to repetitive transient hypertension after spinal cord injury leads to diverse cerebrovascular impairment that appears to be unique pathophysiology compared with steady-state hypertension in non-spinal cord injured models.

Neurovascular coupling in humans: Physiology, methodological advances and clinical implications.

Neurovascular coupling reflects the close temporal and regional linkage between neural activity and cerebral blood flow. Although providing mechanistic insight, our understanding of neurovascular coupling is largely limited to non-physiologicalex vivopreparations and non-human models using sedatives/anesthetics with confounding cerebrovascular implications. Herein, with particular focus on humans, we review the present mechanistic understanding of neurovascular coupling and highlight current approaches to assess these responses and the application in health and disease. Moreover, we present new guidelines for standardizing the assessment of neurovascular coupling in humans. To improve the reliability of measurement and related interpretation, the utility of new automated software for neurovascular coupling is demonstrated, which provides the capacity for coalescing repetitive trials and time intervals into single contours and extracting numerous metrics (e.g., conductance and pulsatility, critical closing pressure, etc.) according to patterns of interest (e.g., peak/minimum response, time of response, etc.). This versatile software also permits the normalization of neurovascular coupling metrics to dynamic changes in arterial blood gases, potentially influencing the hyperemic response. It is hoped that these guidelines, combined with the newly developed and openly available software, will help to propel the understanding of neurovascular coupling in humans and also lead to improved clinical management of this critical physiological function.

Neurovascular coupling of the posterior cerebral artery in spinal cord injury: a pilot study.

PURPOSE: To compare neurovascular coupling in the posterior cerebral artery (PCA) between those with spinal cord injury (SCI) and able bodied (AB) individuals. METHODS: A total of seven SCI and seven AB were matched for age and sex. Measures included PCA velocity (PCAv), beat-by-beat blood pressure and end-tidal carbon dioxide. Posterior cerebral cortex activation was achieved by 10 cycles of (1) 30 s eyes closed (pre-stimulation), (2) 30 s reading (stimulation). RESULTS: Blood pressure was significantly reduced in those with SCI (SBP: 100 ± 13 mmHg; DBP: 58 ± 13 mmHg) vs. AB (SBP: 121 ± 12 mmHg; DBP: 74 ± 9 mmHg) during both pre-stimulation and stimulation, but the relative increase was similar during the stimulation period. Changes in PCAv during stimulation were mitigated in the SCI group (6% ± 6%) vs. AB (29% ± 12%, P < 0.001). Heart rate and end-tidal carbon dioxide responded similarly between groups. CONCLUSIONS: Clearly, NVC is impaired in those with SCI. This study may provide a link between poor perfusion of the posterior cerebral region (containing the medullary autonomic centres) and autonomic dysfunction after SCI.