Vancouver Spine Surgery Institute

Neurogenic lower urinary tract dysfunction (NLUTD) is a major cause of morbidity and reduced quality of life after spinal cord injury (SCI). In pre-clinical research, small and large animal models such as rats, dogs, and minipigs have been used to investigate NLUTD through urodynamic studies (UDS) such as conventional filling cystometry. Although filling cystometry is currently considered the gold standard for bladder monitoring in pre-clinical research, this approach has several well-recognized limitations. The aim of this study was to develop and evaluate the feasibility of an implantable, radiotelemetric system for monitoring bladder pressure in a Yucatan minipig model of SCI. The transmitter was surgically implanted in the dome of the bladder and several UDS experiments were conducted to evaluate the system's effectiveness at measuring pressure compared to conventional UDS equipment. We observed a strong correlation and agreement between the transmural telemetry sensor and the UDS system. There was no significant difference between bladder compliance and baseline bladder pressure between the two sensor systems. However, the telemetry system recorded significantly lower voiding and non-voiding contraction pressure amplitudes as well as lower voiding threshold pressures and detrusor after-contraction measured with the telemetry system. The telemetry system appeared to be a reliable and accurate method for assessing bladder pressure and allowed for an evaluation of urodynamics in a pig model of SCI for several months. The application of this method could enable a more detailed in vivo evaluation of NLUTD after SCI and a better understanding of micturition behavior during natural-filling, ambulatory urodynamics.

Rotation of the cervical spine beyond its normal range of motion is a leading cause of fall-related spinal cord injuries (SCIs) in older adults. This rotation is constrained, in part, by the spinal ligaments. The experimentally measured properties of these ligaments are tabulated in literature, including sex- specific properties; however, their influence on the rotation kinematics of the cervical spine has not been compared. We examined how different mechanical properties of spinal ligaments, including sex- specific properties, affected the rotational kinematics of the cervical spine using finite element analysis (FEA). Ligament properties most influenced the rotation of the lower cervical spine, with increased ligament stiffness reducing rotation. Ligament deformation remained mostly in the toe region of their force-displacement curves, emphasizing the need to incorporate non-linear ligament behavior in FEA. Predictions made using one set of experimental properties (Property 1) better-matched experimental kinematic data. Using sex-specific properties had a moderate effect (6% in extension, − 3% in flexion) on rotation, with a greater impact on extension. Ligament properties also affected the segmental distribution of rotation, causing a variability of 3–21% at different levels. We emphasized the need to incorporate tailored approaches to FEA to obtain clinically relevant results when modeling flexion/extension rotation.

Frailty is associated with an increased risk of postoperative adverse events (AEs) within the surgical spine population. Multiple frailty tools have been reported in the surgical spine literature. However, the applicability of these tools remains unclear. Primary objective is to appraise the construct, feasibility, objectivity, and clinimetric properties of frailty tools reported in the surgical spine literature. Secondary objectives included determining the applicability and the most sensitive surgical spine population for each tool. Systematic Review. Studies reporting the use of a clinical frailty tool with a defined methodology in the adult surgical population (age ≥18 years). Postoperative adverse events (AEs) including mortality, major and minor morbidity, length of stay (LOS), unplanned readmission and reoperation, admission to the Intensive Care Unit (ICU), and adverse discharge disposition; postoperative patient-reported outcomes (health-related quality of life (HRQoL), functional, cognitive, and symptomatic); radiographic outcomes; and postoperative frailty trajectory. This systematic review was registered with PROSPERO: CRD42019109045. Publications from January 1950 to December 2020 were identified by a comprehensive search of PubMed, Ovid, and Embase, supplemented by manual screening. Studies reporting and validating a frailty tool in the surgical spine population with a measurable outcome were included. Each tool and its clinimetric properties were evaluated using validated criteria and definitions. The applicability of each tool and its most sensitive surgical spine population was determined by panel consensus. Bias was assessed using the Newcastle-Ottawa Scale. 47 studies were included in the final qualitative analysis. A total of 14 separate frailty tools were identified, in which 9 tools assessed frailty according to the cumulative deficit definition, while 4 instruments utilized phenotypic or weighted frailty models. One instrument assessed frailty according to the comprehensive geriatric assessment (CGA) model. Twelve measures were validated as risk stratification tools for predicting postoperative AEs, while 1 tool investigated the effect of spine surgery on postoperative frailty trajectory. The modified frailty index (mFI), 5-item mFI, adult spinal deformity frailty index (ASD-FI), FRAIL Scale, and CGA had the most positive ratings for clinimetric properties assessed. The assessment of frailty is important in the surgical decision-making process. Cumulative deficit and weighted frailty instruments are appropriate risk stratification tools. Phenotypic tools are sensitive for capturing the relationship between spinal pathology, spine surgery, and prehabilitation on frailty trajectory. CGA instruments are appropriate screening tools for identifying health deficits susceptible to improvement and guiding optimization strategies. Studies are needed to determine whether spine surgery and prehabilitation are effective interventions to reverse frailty.

Study DesignSurvey.IntroductionAO Spine Research Objectives and Common Data Elements for Degenerative Cervical Myelopathy (AO Spine RECODE-DCM) is an international initiative that aims to accelerate knowledge discovery and improve outcomes by developing a consensus framework for research. This includes defining the top research priorities, an index term and a minimum data set (core outcome set and core data elements set – core outcome set (COS)/core data elements (CDE)).ObjectiveTo describe how perspectives were gathered and report the detailed sampling characteristics.MethodsA two-stage, electronic survey was used to gather and seek initial consensus. Perspectives were sought from spinal surgeons, other healthcare professionals and people with degenerative cervical myelopathy (DCM). Participants were allocated to one of two parallel streams: (1) priority setting or (2) minimum dataset. An email campaign was developed to advertise the survey to relevant global stakeholder individuals and organisations. People with DCM were recruited using the international DCM charity Myelopathy.org and its social media channels. A network of global partners was recruited to act as project ambassadors. Data from Google Analytics, MailChimp and Calibrum helped optimise survey dissemination.ResultsSurvey engagement was high amongst the three stakeholder groups: 208 people with DCM, 389 spinal surgeons and 157 other healthcare professionals. Individuals from 76 different countries participated; the United States, United Kingdom and Canada were the most common countries of participants.ConclusionAO Spine RECODE-DCM recruited a diverse and sufficient number of participants for an international PSP and COS/CDE process. Whilst PSP and COS/CDE have been undertaken in other fields, to our knowledge, this is the first time they have been combined in one process.

There is an increasing need to develop approaches that will not only improve the clinical management of neurogenic lower urinary tract dysfunction (NLUTD) after spinal cord injury (SCI), but also advance therapeutic interventions aimed at recovering bladder function. Although pre-clinical research frequently employs rodent SCI models, large animals such as the pig may play an important translational role in facilitating the development of devices or treatments. Therefore, the objective of this study was to develop a urodynamics protocol to characterize NLUTD in a porcine model of SCI. An iterative process to develop the protocol to perform urodynamics in female Yucatan minipigs began with a group of spinally intact, anesthetized pigs. Subsequently, urodynamic studies were performed in a group of awake, lightly restrained pigs, before and after a contusion-compression SCI at the T2 or T9-T11 spinal cord level. Bladder tissue was obtained for histological analysis at the end of the study. All anesthetized pigs had bladders that were acontractile, which resulted in overflow incontinence once capacity was reached. Uninjured, conscious pigs demonstrated appropriate relaxation and contraction of the external urethral sphincter during the voiding phase. SCI pigs demonstrated neurogenic detrusor overactivity and a significantly elevated post-void residual volume. Relative to the control, SCI bladders were heavier and thicker. The developed urodynamics protocol allows for repetitive evaluation of lower urinary tract function in pigs at different time points post-SCI. This technique manifests the potential for using the pig as an intermediary, large animal model for translational studies in NLUTD.

Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of CSF and serum samples from 111 acute SCI patients and, in parallel, a large animal (porcine) model of SCI. We develop protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at six months with an AUC of 0.91, and validate these in an independent cohort. Through cross-species proteomic analyses, we dissect evolutionarily conserved and divergent aspects of the SCI response, and establish the CSF abundance of glial fibrillary acidic protein (GFAP) as a biochemical outcome measure in both humans and pigs. Our work opens up new avenues to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.

# Presentation CPSS1: Spinal insufficiency fracture in the geriatric pediatric spine {#article-title-2} Regular corticosteroid has become standard for slowing disease progression in Duchenne muscular dystrophy (DMD). However, patients must contend with the insidious side effect of osteopenia and

Recently identified prognostic variables among patients undergoing surgery for cervical spondylotic myelopathy (CSM) are limited to two large international data sets. To optimally inform shared clinical decision-making, the authors evaluated which preoperative clinical factors are significantly associated with improvement on the modified Japanese Orthopaedic Association (mJOA) scale by at least the minimum clinically important difference (MCID) 12 months after surgery, among patients from the Canadian Spine Outcomes and Research Network (CSORN). The authors performed an observational cohort study with data that were prospectively collected from CSM patients at 7 centers between 2015 and 2017. Candidate variables were tested using univariable and multiple binomial logistic regression, and multiple sensitivity analyses were performed to test assumptions about the nature of the statistical models. Validated mJOA MCIDs were implemented that varied according to baseline CSM severity. Among 205 patients with CSM, there were 64 (31%) classified as mild, 86 (42%) as moderate, and 55 (27%) as severe. Overall, 52% of patients achieved MCID and the mean change in mJOA score at 12 months after surgery was 1.7 ± 2.6 points (p < 0.01), but the subgroup of patients with mild CSM did not significantly improve (mean change 0.1 ± 1.9 points, p = 0.8). Univariate analyses failed to identify significant associations between achieving MCID and sex, BMI, living status, education, smoking, disability claims, or number of comorbidities. After adjustment for potential confounders, the odds of achieving MCID were significantly reduced with older age (OR 0.7 per decade, 95% CI 0.5-0.9, p < 0.01) and higher baseline mJOA score (OR 0.8 per point, 95% CI 0.7-0.9, p < 0.01). The effects of symptom duration (OR 1.0 per additional month, 95% CI 0.9-1.0, p = 0.2) and smoking (OR 0.4, 95% CI 0.2-1.0, p = 0.06) were not statistically significant. Surgery is effective at halting the progression of functional decline with CSM, and approximately half of all patients achieve the MCID. Data from the CSORN confirmed that older age is independently associated with poorer outcomes, but novel findings include that patients with milder CSM did not experience meaningful improvement, and that symptom duration and smoking were not important. These findings support a nuanced approach to shared decision-making that acknowledges some prognostic uncertainty when weighing the various risks, benefits, and alternatives to surgical treatment.

Abstract Chronic high-thoracic and cervical spinal cord injury (SCI) results in a complex phenotype of cardiovascular consequences, including impaired left-ventricular contractility. Here, we sought to determine whether such dysfunction manifests immediately post-injury, and if so, whether correcting impaired contractility can improve spinal cord oxygenation (SCO2), blood flow (SCBF) and metabolism. Using a porcine model of SCI, we demonstrate that high-thoracic SCI acutely impairs cardiac contractility and causes substantial reductions in intraparenchymal SCO2 and SCBF within the first hours post-injury. Utilizing the same model, we next show that treating the reduced contractile function with the β-agonist dobutamine is more efficacious at increasing SCO2 and SCBF than the current clinical standard of vasopressor therapy, whilst also mitigating increased anaerobic metabolism and hemorrhage in the injured cord. Our data provide compelling evidence that cardio-centric hemodynamic management represents a novel and advantageous alternative to the current clinical standard of vasopressor therapy for acute traumatic SCI.