Model matters: Differential outcomes in traumatic optic neuropathy pathophysiology between blunt and blast-wave mediated head injuries.

Over 3 million people in the United States live with long-term disability because of a traumatic brain injury (TBI). The purpose of this study was to characterize and compare two different animal models of TBI (blunt head trauma and blast TBI) to determine common and divergent characteristics of these models. With recent literature reviews noting the prevalence of visual system injury in animal models of TBI, coupled with clinical estimates of 50-75% of all TBI cases, we decided to assess commonalities, if they existed, through visual system injury. A unilateral (left directed) blast and repeat blast model injury with coup-contra-coup injury patterns were compared to a midline blunt injury. Injuries were induced in adult male mice to observe and quantify visual deficits. Retinal ganglion cell loss and axonal degeneration in the optic tract, superior colliculus, and lateral geniculate nuclei were examined to trace injury outcomes throughout major vision-associated areas. Optokinetic response, immunohistochemistry, and western blots were analyzed. Where a single blunt injury produces significant visual deficits a single blast injury appears to have less severe visual consequences. Visual deficits after repeat blasts are similar to a single blast. Single blast injury induces contralateral damage to the right optic chiasm and tract whereas bilateral injury follows a single blunt TBI. Repeat blast injuries are required to see degeneration patterns in downstream regions similar to the damage seen in a single blunt injury. This finding is further supported by amyloid precursor protein (APP) staining in injured cohorts. Blunt injured groups present with staining 1.2 mm ahead of the optic nerve, indicating axonal breakage closer to the optic chiasm. In blast groups, APP was identifiable in a bilateral pattern only in the geniculate nucleus. Evidence for unilateral neuronal degeneration in brain tissue with bilateral axonal ruptures are pivotal discoveries in this model differentiation. Analysis of the two injury models suggests that there is a significant difference in the histological outcomes dependent on injury type, though visual system injury is likely present in more cases than are currently diagnosed clinically.

Concern for Increased Prevalence of Heyde's Syndrome in Patients on Hemodialysis.

The association between aortic stenosis and increased gastrointestinal arteriovenous malformations is known as Heyde's syndrome. An acquired von Willebrand deficiency mediates the connection between these two seemingly dispersed pathologies. As von Willebrand factor passes through a stenosed aorta, it is broken down and can no longer inhibit angiogenesis, leading to angiodysplasias. Heyde's syndrome can manifest with chronic, refractory anemia requiring multiple hospitalizations for symptomatic gastrointestinal bleeding and transfusion. Hitherto, Heyde's syndrome has been considered exceptionally rare, with 1-3% of populations with aortic stenosis. However, given that 31.7% of patients with gastrointestinal angioplasty have aortic stenosis and gastrointestinal arteriovenous malformations are not screened for in patients without anemia, the prevalence of Heyde's syndrome is most likely higher than currently reflected in the literature. Also, the prevalence of Heyde's syndrome in populations who are predisposed to angiodysplasias, such as those on hemodialysis, is understudied. We aim to impart a need for increased research on the prevalence of Heyde's syndrome, especially in high-risk patients. This case report presents a patient with severe Heyde's syndrome on hemodialysis, showing an unconsidered risk factor for Heyde's syndrome in need of further research.

Women in Irish urology: An examination of female representation amongst attendees of the Irish Society of Urology annual meeting (2008-2020).

BACKGROUND: There is underrepresentation of women at surgical conferences. We examine the representation of women in Irish urology by looking at gender balance within the Irish Society of Urology (ISU) conference. AIMS: ISU programmes over thirteen years from 2008 to 2020 were assessed and female representation in session chairs, guest speakers, poster and oral presentations identified. Gender distributions of authors for each year was examined. To investigate changes in female representation temporally, the period of this study (2008-2020) was subdivided and compared: 2008-2013 and 2014-2020. RESULTS: 76 sessions were presided over by 138 chairs, of which 6 (4.3%) were female. Eight conferences had zero female chairs. 62 guest lectures were given, 6 (9.6%) by women. Of total 340 poster and 434 oral presentations, women delivered 24.9% (0-47.5%) of posters and 31.6% (10.3-59.4%) of oral presentations. We found no significant difference in the percentage of female poster presentations between the time periods 2008-2013 (m = 18.2, sd = 13.7) and 2014-2020 (m = 34.3, sd = 17.8), t(11) = -1.4, p > 0.05. However, we found a significant difference in the percentage of female oral presentations between the periods 2008-2013 (m = 18.7, sd = 14.2) and 2014-2020 (m = 40.6, sd = 14.5), t(11) = -2.8, p < 0.05. CONCLUSIONS: Our study is the second to examine female representation in Irish urology. Session chairs and guest speakers were grossly overrepresented by males as were oral and poster presentations. Despite lacking female influence overall, in more recent years there was an increased representation of women. Societies should strive to increase female representation, as this perpetuates a positive feedback loop, encouraging future female trainees to pursue urological surgery.

Does instillation of lidocaine gel following flexible cystoscopy decrease the severity of post procedure symptoms? A randomised controlled trial assessing the efficacy of lidocaine gel post flexible cystoscopy.

OBJECTIVE: To assess whether instillation of lidocaine gel both before and after flexible cystoscopy is more effective at reducing post procedural symptoms than instillation of lidocaine gel pre flexible cystoscopy alone. We hypothesise that inadequate urethral dwell time and dilution of lidocaine gel by the irrigation fluid during flexible cystoscopy limits its anaesthetic efficacy. Only one other study has attempted to reduce bothersome urinary symptoms through an intervention after flexible cystoscopy. METHODS: This was a randomised controlled trial in which patients were randomised 1:1 to receive lidocaine gel pre and post flexible cystoscopy (treatment) or lidocaine gel pre flexible cystoscopy only (control). Patient-reported outcome measures were used to assess symptoms and quality of life prior to cystoscopy, on day 2 and day 7 post cystoscopy. RESULT: Fifty patients were divided equally between the treatment and control groups. There were no significant differences in baseline characteristics between the groups (p = 1.000). An overall symptoms variable was measured, though no significant difference was found in the distribution of responses between the groups at baseline, 2 or 7 days after the flexible cystoscopy (p = 0.423, 0.651,0.735). In the treatment group, 1 patient (4.0%) presented to a doctor for review following flexible cystoscopy, and 4 patients (16.0%) presented in the control group (p = 0.349). CONCLUSION: Initial study results suggest that post-operative lidocaine does not significantly limit the exacerbation of urinary symptoms following flexible cystoscopy; however, our results are not powered to detect a small difference. We do not recommend a change in practice based on our results.

The Canadian Neuromuscular Disease Registry 2010-2019: A Decade of Facilitating Clinical Research Througha Nationwide, Pan-NeuromuscularDisease Registry.

We report the recruitment activities and outcomes of a multi-disease neuromuscular patient registry in Canada. The Canadian Neuromuscular Disease Registry (CNDR) registers individuals across Canada with a confirmed diagnosis of a neuromuscular disease. Diagnosis and contact information are collected across all diseases and detailed prospective data is collected for 5 specific diseases: Amyotrophic Lateral Sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), Myotonic Dystrophy (DM), Limb Girdle Muscular Dystrophy (LGMD), and Spinal Muscular Atrophy (SMA). Since 2010, the CNDR has registered 4306 patients (1154 pediatric and 3148 adult) with 91 different neuromuscular diagnoses and has facilitated 125 projects (73 academic, 3 not-for-profit, 3 government, and 46 commercial) using registry data. In conclusion, the CNDR is an effective and productive pan-neuromuscular registry that has successfully facilitated a substantial number of studies over the past 10 years.

The Management of Incidental Prostate Cancer Following TURP

Aims The aim of this study was to assess the incidence, management and outcomes of incidentally diagnosed prostate cancer following TURP. Methods A retrospective review was performed using the histopathological departments' database of all patients who underwent a TURP across two university teaching hospitals over a ten year period. Results During the study period, a total of 826 patients underwent a TURP. 72 (10.3%) had an incidental diagnosis of CaP following TURP. 46 (63.9%) were managed expectantly while 26 (36.1%) underwent active treatment. Overall mortality was 29.2% (n=21) while cancer specific mortality was 6.9% (n=5). All these patients were in the hormonal treatment sub-group. Conclusion Our study demonstrates an expectant approach is favourable in low risk disease. Curative treatment does need to be considered for younger patients with a long life expectancy or patients with higher risk disease.

Optimising the biocompatibility of 3D printed photopolymer constructs in vitro and in vivo.

3D printing is a rapid and accessible fabrication technology that engenders creative custom design solutions for cell scaffolds, perfusion systems and cell culture systems for tissue engineering. Critical to its success is the biocompatibility of the materials used, which should allow long-term tissue culture without affecting cell viability or inducing an inflammatory response for in vitro and in vivo applications. Polyjet 3D printers offer arguably the highest resolution with the fewest design constraints of any commercially available 3D printing systems. Although widely used for rapid-prototyping of medical devices and 3D anatomical modelling, polyjet printing has not been adopted by the tissue engineering field, largely due to the cytotoxicity of leachates from the printed parts. Biocompatibility in the context of cell culture is not commonly addressed for polyjet materials, as they tend to be optimised for their ability to fabricate complex structures. In order to study the potential issues surrounding the leaching of toxins, we prepared cell culture substrates using the commercially available MED610 photopolymer. The substrates were cleaned using either the manufacturer-specified 'biocompatible' washing procedures, or a novel protocol incorporating a sonication in isopropanol and water step. We then compared the effectiveness of these both in vitro and in vivo. Using primary mouse myoblast cultures, the manufacturer's protocol led to inconsistent and poorer cell viability when compared to the sonication protocol (p = 0.0002 at 48 h after indirect exposure). Subdermal implantation of MED610 into nude rats demonstrated a significant foreign body response with a greater number of giant cells (p = 0.0161) and foreign bodies (p = 0.0368) when compared to the sonication protocol, which was comparable to the control (sham) groups. These results present an improved, cytocompatible cleaning protocol of printable photopolymers to facilitate creative 3D-printed custom designs for cell culture systems for both in vitro and in vivo tissue engineering applications.

Long-term outcomes of saline boluses in very preterm infants.

BACKGROUND: Normal saline bolus is commonly used in clinical practice for treating hypotension in very preterm infants during resuscitation at an early age despite the paucity of high quality evidence supporting this practice. OBJECTIVES: To determine the effects of early (<7 days after birth) saline boluses given to very preterm infant (VPI) from 23 to 31 weeks GA. METHOD: This is a population-based cohort analysis of the use of normal saline boluses given to VPI. The outcomes were extracted from the Perinatal Follow-Up Program Database which included all VPI from Halifax County admitted to the NICU at the IWK Health Centre, Halifax, Nova Scotia, Canada between January 2006 to December 2010. We excluded infants with major congenital anomalies and those not offered resuscitation in the delivery room. Our primary outcome was the composite of death or disability by 18-36 months while secondary outcomes were neonatal death, BPD, CP, IVH, PVL, ROP, BSITD III (Bayley Scales of Infant and Toddler Development®, Third Edition) Cognitive, Motor and Language score. RESULTS: Death or disability in those who received saline bolus occurred in 15 (53.6%) compared with 9 (32.1%) in non saline group. Significantly higher rates of CP (p = 0.04), lower scores on the BSITDIII for motor (p = 0.04) and language scales (p = 0.03) were noted for infants who received saline boluses. Cognitive scores approached significance (p = 0.05) with lower scores in the saline bolus group. CONCLUSION: Significant differences were found between the two groups in terms of long term neurodevelopmental outcome and one of the short-term outcome (i.e. BPD). Given the limitations of this retrospective study and the small sample size, a larger cohort from Canadian Neonatal Network database is warranted to evaluate the effects of using normal saline boluses during early life on neurodevelopmental.

The CanPain SCI Clinical Practice Guidelines for Rehabilitation Management of Neuropathic Pain after Spinal Cord: introduction, methodology and recommendation overview

"STUDY DESIGN: Clinical practice guidelines. OBJECTIVES: The objective was to develop the first Canadian clinical practice guidelines for the management of neuropathic pain in people with spinal cord injury (SCI). SETTING: The guidelines are relevant for inpatient and outpatient SCI rehabilitation settings in Canada. METHODS: The guidelines were developed in accordance with the Appraisal of Guidelines for Research and Evaluation II tool. A Steering Committee and Working Group reviewed the relevant evidence on neuropathic pain management (encompassing screening and diagnosis, treatment and models of care) after SCI. The quality of evidence was scored using Grading of Recommendations Assessment, Development and Evaluation (GRADE). A consensus process was followed to achieve agreement on recommendations and clinical considerations. RESULTS: The Working Group developed 12 recommendations for screening and diagnosis, 12 recommendations for treatment and 5 recommendations for models of care. Important clinical considerations accompany each recommendation. CONCLUSIONS: The Working Group recommendations for the management of neuropathic pain after SCI should be used to inform practice."

The CanPain SCI Clinical Practice Guidelines for Rehabilitation Management of Neuropathic Pain after Spinal Cord: introduction, methodology and recommendation overview.

STUDY DESIGN: Clinical practice guidelines. OBJECTIVES: The objective was to develop the first Canadian clinical practice guidelines for the management of neuropathic pain in people with spinal cord injury (SCI). SETTING: The guidelines are relevant for inpatient and outpatient SCI rehabilitation settings in Canada. METHODS: The guidelines were developed in accordance with the Appraisal of Guidelines for Research and Evaluation II tool. A Steering Committee and Working Group reviewed the relevant evidence on neuropathic pain management (encompassing screening and diagnosis, treatment and models of care) after SCI. The quality of evidence was scored using Grading of Recommendations Assessment, Development and Evaluation (GRADE). A consensus process was followed to achieve agreement on recommendations and clinical considerations. RESULTS: The Working Group developed 12 recommendations for screening and diagnosis, 12 recommendations for treatment and 5 recommendations for models of care. Important clinical considerations accompany each recommendation. CONCLUSIONS: The Working Group recommendations for the management of neuropathic pain after SCI should be used to inform practice.

The CanPain SCI Clinical Practice Guidelines for Rehabilitation Management of Neuropathic Pain after Spinal Cord: Recommendations for treatment.

STUDY DESIGN: Clinical practice guidelines. OBJECTIVES: To develop the first Canadian clinical practice guidelines for treatment of neuropathic pain in people with spinal cord injury (SCI). SETTING: The guidelines are relevant for inpatient and outpatient SCI rehabilitation settings in Canada. METHODS: The CanPainSCI Working Group reviewed the evidence for different treatment options and achieved consensus. The Working Group then developed clinical considerations for each recommendation. Recommendations for research are also included. RESULTS: Twelve recommendations were developed for the management of neuropathic pain after SCI. The recommendations address both pharmacologic and nonpharmacologic treatment modalities. CONCLUSIONS: An expert Working Group developed recommendations for the treatment of neuropathic pain after SCI that should be used to inform practice.

The CanPain SCI Clinical Practice Guideline for Rehabilitation Management of Neuropathic Pain after Spinal Cord: recommendations for model systems of care.

STUDY DESIGN: Clinical practice guidelines. OBJECTIVES: The project objectives were to develop the first Canadian recommendations on a model of care for the management of at- and below-level neuropathic pain in people with spinal cord injury (SCI). SETTING: The guidelines are relevant for inpatient and outpatient SCI rehabilitation settings in Canada. METHODS: On the basis of a review of the Accreditation Canada standards, the Steering Committee developed questions to guide the CanPainSCI Working Group when developing the recommendations. The Working Group agreed on recommendations through a consensus process. RESULTS: The Working Group developed five recommendations for the organization of neuropathic pain rehabilitation care in people with SCI. CONCLUSIONS: The Working Group recommendations for a model of care for at- and below-level neuropathic pain after SCI should be used to inform clinical practice.

The CanPain SCI Clinical Practice Guidelines for Rehabilitation Management of Neuropathic Pain after Spinal Cord: screening and diagnosis recommendations.

STUDY DESIGN: Clinical practice guidelines. OBJECTIVES: To develop the first Canadian clinical practice guidelines for screening and diagnosis of neuropathic pain in people with spinal cord injury (SCI). SETTING: The guidelines are relevant for inpatient and outpatient SCI rehabilitation settings in Canada. METHODS: The CanPainSCI Working Group reviewed evidence to address clinical questions regarding screening and diagnosis of neuropathic pain after SCI. A consensus process was followed to achieve agreement on recommendations and clinical considerations. RESULTS: Twelve recommendations, based on expert consensus, were developed for the screening and diagnosis of neuropathic pain after SCI. The recommendations address methods for assessment, documentation tools, team member accountability, frequency of screening and considerations for diagnostic investigation. Important clinical considerations accompany each recommendation. CONCLUSIONS: The expert Working Group developed recommendations for the screening and diagnosis of neuropathic pain after SCI that should be used to inform practice.

OC-14 - Baseline D-dimer levels are predictive of recurrent venous thromboembolism (VTE) at 6 months in cancer patients with VTE treated with tinzaparin.

INTRODUCTION: VTE is a major complication in cancer patients. Despite treatment with low molecular weight heparin (LMWH), 9% will have recurrent VTE within 6 months. Measurement of plasma biomarkers in cancer patients receiving LMWH may be predictive of recurrent VTE or overall survival (OS). AIM: We conducted a single arm phase 2 study to evaluate the efficacy and safety of once daily tinzaparin for the initial treatment and extended prophylaxis of VTE in cancer patients. The study included a prospective analysis of plasma biomarkers D-dimer and IL-6 to assess whether these were predictive of recurrent VTE or OS. MATERIALS AND METHODS: Consecutive patients with active cancer diagnosed with a pulmonary embolism (PE) and/or proximal deep venous thrombosis (DVT) at the University of Southern California Norris Comprehensive Cancer Center, Los Angeles County Medical Center, or New York Presbyterian - Weill Cornell Medical Center were invited to participate in this study with a target enrollment of 100 patients. Key eligibility criteria included: age ≥18, ECOG score ≤2, adequate organ function, and ≥6 month estimated survival. Patients were treated with daily subcutaneously tinzaparin 175 U/kg for 6 months on study. Tinzaparin could be continued ≤1 year at the discretion of the treating physician. All patients who received ≥1 dose were evaluable for efficacy and safety. Primary study endpoints were recurrent VTE or major bleeding. Secondary outcome measures included OS and plasma biomarkers. Biomarkers were measured at baseline, 7 days, 1 month and 6 months after tinzaparin initiation. Patients who had baseline and 1 week or 1 month samples collected were included in the biomarker analysis. RESULTS: 97 patients were enrolled. 2 patients were ineligible. 8 patients did not have baseline or follow-up biomarkers completed. 87 patients were included in the analysis. 28 (32%) of patients completed≥6 months of tinzaparin. Major bleeding occurred in 2 patients. 11 patients had recurrent VTE at 6 months (3 PE, 7 DVT, 1 central venous thrombosis not associated with a catheter). Median baseline D-dimer level was 2759 ng/mL (range: 375-37,591). Median baseline IL-6 level was 9.4 pg/mL (range: 0.8-20.9). Baseline D-dimer>median was predictive of VTE recurrence at 6 months (p=.006). Baseline IL-6>median was not predictive of VTE recurrence at 6 months. Neither 1 month D-dimer or IL-6 levels were predictive of VTE recurrence at 6 months. D-dimer and IL-6 at baseline and at 1 month were not predictive of OS. CONCLUSIONS: In patients with active cancer and VTE treated with tinzaparin, baseline D-dimer levels above the median value were predictive of VTE recurrence at 6 months.