Background: The complement C5 inhibitor (C5IT), ravulizumab, is approved in Canada for the treatment of anti-acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG). Updated effectiveness and safety results from the ongoing MG SPOTLIGHT Registry (NCT04202341) are reported. Methods: MGFA classification and MG-ADL total scores were assessed in patients who received ravulizumab only (ravu-only) or transitioned from eculizumab to ravulizumab (ecu-to-ravu), with data available prior to C5IT initiation (“pre-C5IT”) and ≥1 assessment post-initiation (“post-ravu”). Results: Of 52 patients with 2 post-ravu assessments, average treatment duration was 10.4 months at last assessment (LA). Mean±SD MG-ADL scores improved (pre-C5IT: 7.6±3.6; LA: 3.4±3.3), as did the proportions of patients with minimal symptom expression (MSE, MG-ADL≤1) (pre-C5IT: 1/52 [2%]; LA: 17/52 [33%]) and MGFA classification 0-II (pre-C5IT: 18/45 [40%]; LA: 40/45 [89%]). In the ravu-only subgroup, outcomes improved (pre-C5IT vs LA): MG-ADL, 6.3±3.0 vs 4.0±3.4; MGFA 0-II, 9/14 [64%] vs 12/14 [86%]. The ecu-to-ravu subgroup sustained continued gradual improvement from last eculizumab assessment to LA: MG-ADL, 4.4±4.2 vs 3.0±2.8; MGFA 0-II, 19/21 [90%] vs 20/21 [95%]. Ravulizumab was well tolerated; no meningococcal infections were reported. Conclusions: These results demonstrate the long-term effectiveness and safety of ravulizumab in routine clinical practice in patients with gMG.

Background: Ischemic stroke is a major cause of morbidity and mortality in Canada. Since 2015, mechanical thrombectomy has been the standard of care for eligible large vessel occlusions (LVOs), though anesthetic strategies remain variable. Methods: We conducted a single-center retrospective review of patients undergoing mechanical thrombectomy for anterior circulation LVOs between 2021 and 2023. Patients were categorized by anesthetic strategy (general anesthesia vs. conscious sedation), and outcomes, including time to recanalization, angiographic results (mTICI), and 90-day functional status (mRS), were compared. Statistical analyses included Student’s t-test, Mann-Whitney U-test, and Fisher’s exact test. Results: Among 226 patients, 177 (78%) received general anesthesia and 49 (22%) underwent conscious sedation. Baseline characteristics including sex, age, NIHSS, ASPECTS, collaterals, and laterality were similar between groups. Conscious sedation was associated with a statistically significant shorter time from arrival to the angiography suite to groin puncture (p=0.007), but no differences in time to recanalization (p=0.893), angiographic outcomes (p=0.987), or 90-day functional status (p=0.795) were observed. Conclusions: Conscious sedation led to faster procedural initiation, though no difference in clinical or radiographic outcome was observed. Anesthetic choice should be individualized based on patient and physician factors in acute mechanical thrombectomy.

Background: The WHO grade of meningioma was updated in 2021 to include homozygous deletions of CDKN2A/B and TERT promotor mutations. Previous work including the recent cIMPACT-NOW statement have discussed the potential value of including chromosomal copy number alterations to help refine the current grading system. Methods: Chromosomal copy number profiles were inferred from from 1964 meningiomas using DNA methylation. Regularized Cox regresssion was used to identify CNAs independenly associated with post-surgical and post-RT PFS. Outcomes were stratified by WHO grade and novel CNAs to assess their potential value in WHO critiera. Results: Patients with WHO grade 1 tumours and chromosome 1p loss had similar outcomes to those with WHO grade 2 tumours (median PFS 5.83 [95% CI 4.36-Inf] vs 4.48 [4.09-5.18] years). Those with chromosome 1p loss and 1q gain had similar outcomes to those with WHO grade 3 cases regardless of initial grade (median PFS 2.23 [1.28-Inf] years WHO grade 1, 1.90 [1.23-2.25] years WHO grade 2, compared to 2.27 [1.68-3.05] years in WHO grade 3 cases overall). Conclusions: We advocate for chromosome 1p loss being added as a criterion for a CNS WHO grade of 2 meningioma and addition of 1q gain as a criterion for a CNS WHO grade of 3.

Background: Meningiomas exhibit considerable heterogeneity. We previously identified four distinct molecular groups (immunogenic, NF2-wildtype, hypermetabolic, proliferative) which address much of this heterogeneity. Despite their utility, the stochasticity of clustering methods and the requirement of multi-omics data limits the potential for classifying cases in the clinical setting. Methods: Using an international cohort of 1698 meningiomas, we constructed and validated a machine learning-based molecular classifier using DNA methylation alone. Original and newly-predicted molecular groups were compared using DNA methylation, RNA sequencing, whole exome sequencing, and clinical outcomes. Results: Group-specific outcomes in the validation cohort were nearly identical to those originally described, with median PFS of 7.4 (4.9-Inf) years in hypermetabolic tumors and 2.5 (2.3-5.3) years in proliferative tumors (not reached in the other groups). Predicted NF2-wildtype cases had no NF2 mutations, and 51.4% had others mutations previously described in this group. RNA pathway analysis revealed upregulation of immune-related pathways in the immunogenic group, metabolic pathways in the hypermetabolic group and cell-cycle programs in the proliferative group. Bulk deconvolution similarly revealed enrichment of macrophages in immunogenic tumours and neoplastic cells in hypermetabolic/proliferative tumours. Conclusions: Our DNA methylation-based classifier faithfully recapitulates the biology and outcomes of the original molecular groups allowing for their widespread clinical implementation.

Discretionary foods that are energy-dense and nutrient-poor contribute to over one third of total energy intake in Australian children and adults, and the typical portion sizes of many discretionary foods have increased significantly in the last two decades(1). The portion size norms (described as a typical perception of how much of a given food people choose to eat at a single eating occasion) are likely to have increased concurrently, with larger sizes now being considered the new normal(2). Public health interventions are urgently needed to reduce the portion size norms and consumption of discretionary foods(3), but the acceptability of such interventions remains unknown. Therefore, this qualitative study aimed to gain insights into consumers’ attitudes towards potential interventions targeted at promoting portion control of discretionary foods. Four online focus group sessions were conducted via Zoom with healthy Australian adults who regularly consume discretionary foods. A question guide was developed to gather participants’ perspectives around four potential public health interventions; reduction of the default serving sizes, increasing serving size options, changes to package sizes, and improving serving size labelling. A female facilitator moderated all focus groups, with a second moderator present to capture other relevant details. Collected data were analysed using a hybrid approach combining deductive and inductive thematic analyses. A total of 35 participants completed the study (19 females, mean age 38 ± 14 years). Participants identified the current food environment as promoting overconsumption; larger serving sizes were reported to be more ubiquitous and better value for money than smaller size options. An overall positive attitude towards the proposed interventions was noted. Out of the four proposed interventions, participants considered the most acceptable intervention to be providing a wider range of serving size options while maintaining a consistent unit price. Other acceptable interventions included reducing the default serving sizes with concurrent price reduction; education and clear guidance around portion size selection (for example, the involvement of health professionals to promote portion control, along with relevant recommendations of appropriate portion sizes from health authorities); more practical on-pack serving size suggestions; and innovative package designs that enable better portion control without contributing to food and plastic waste. In conclusion, participants identified a need for and were in support of interventions aimed at the portion control of discretionary foods. Further research should focus on examining the feasibility and effectiveness of the potential interventions to reduce the purchasing and consumption of large serving sizes. More efforts from public health authorities are required to develop practical and tailored recommendations for consumers around appropriate portion sizes for discretionary foods. Collaboration with the food industry and policy makers is also necessary for implementing public health interventions to reduce the excessive intake of discretionary foods.

Objectives: Activities that require active thinking, like occupations, may influence cognitive function and its change over time. Associations between retirement and dementia risk have been reported, however the role of retirement age in these associations is unclear. We assessed associations of occupation and retirement age with cognitive decline in the US community-based Atherosclerosis Risk in Communities (ARIC)cohort.

Methods: We included 14,090 ARIC participants, followed for changes in cognition during up to 21 years. Information on current or most recent occupation was collected at ARIC baseline (1987–1989; participants aged 45–64 years) and categorized according to the 1980 US Census protocols and the Nam-Powers-Boyd occupational status score. Follow-up data on retirement was collected during 1999–2007 and classified as retired versus not retired at age 70. Trajectories of global cognitive factor scores from ARIC visit 2 (1990–1992) to visit 5 (2011–2013) were presented, and associations with occupation and age at retirement were studied using generalized estimating equation models, stratified by race and sex, and adjusted for demographics andcomorbidities.

Results: Mean age (SD) at first cognitive assessment was 57.0 (5.72) years. Higher occupational status and white- collar occupations were significantly associated with higher cognitive function at baseline. Occupation was associated with cognitive decline over 21 years only in women, and the direction of the effect on cognitive function differed between black and white women: in white women, the decline in cognitive function was greater in homemakers and low status occupations, whereas in black women, less decline was found in homemakers and low (compared to high) occupational status. Interestingly, retirement on or before age 70 was associated with less 21-year cognitive decline in all race-sex strata, except for blackwomen.

Conclusions: Associations between occupation, retirement age and cognitive function substantially differed by race and sex. Further research should explore reasons for the observed associations and race-sex differences.

To improve transitions in care, a new patient navigation (PN) program was introduced to support older adults with complex care needs transition from hospital to home. The patient navigator is a community social worker embedded in the hospital’s care teams. A cohort observational design was used to conduct the study by analysing the patient navigator’s clinical notes and hospital’s administrative data to describe the characteristics of patients, scope of the patient navigator’s activities, and patient outcomes. Ninety patients were assigned to the patient navigator’s caseload (November 2019–November 2021) in which the average age was 78.9 (range 55–95). The most frequent PN intervention types were referrals to community services (66%, n = 59) and discharge planning (61%, n = 55). The patient navigator supported 66% patients (n = 59) in returning home and provided follow-up care for 74 days (average). This study provides important insights into the patient navigator’s role to guide decision makers in implementing PN programs for older adults in a hospital setting.

Background: Hyperacute stroke care demands rapid, coordinated care. Traditional metrics like Door-to-Needle time are pivotal but insufficient for capturing the complexity of endovascular stroke interventions. The SMILES collaboration aims to standardize and optimize protocols for door-to-intervention times, incorporating Crew Resource Management (CRM). Methods: The multidisciplinary initiative integrates both hospitals, ED, neurology, and QI teams. We employed a comprehensive approach: stakeholder engagement, simulation-based learning, process mapping, and literature review. Emphasis was placed on enhancing situational awareness, triage and prioritization, cognitive load management, role clarity, effective communication, and debriefing. Results: The collaboration led to PDSA cycles and development of refined stroke protocols. Interventions included: 1) A ’zero point survey’ for team pre-arrival briefings, enhancing situational awareness and role clarity; 2) Streamlined patient registration to reduce cognitive load and improve triage efficiency; 3) Direct transfer of patients to imaging. Additionally, digital tools were implemented to facilitate communication. Simulation sessions reinforced CRM principles, leading to improved team cohesion and operational performance. Conclusions: The SMILES initiative is grounded in CRM principles by standardizing protocols and emphasizing non-technical skills crucial for high-stakes environments. This improves outcomes but also fosters a culture of safety and efficiency. Future directions include an evaluation of these protocols’ impact on patient factors.

Background: The fragility index (FI) is the minimum number of patients whose status would have to change from a nonevent to an event to turn a statistically significant result to a non-significant result. We used this to measure the robustness of trials comparing carotid endarterectomy (CEA) to carotid artery stenting (CAS). Methods: A search was conducted in MEDLINE, Embase, and PubMed on RCTs comparing CEA to CAS. The trials need to have statistically significant results and dichotomous primary endpoints to be included. Results: Our literature search identified 10 RCTs which included 9382 patients (4734 CEA, 4648 CAS). The primary end points of all included trials favoured CEA over CAS. The median FI was 9.5 (interquartile range 2.25 - 21.25). All of the studies that reported lost-to-follow-up (LTFU) had LTFU greater than its fragility index, which raises concern that the missing data could change the results of the trial from statistically significant to statistically insignificant. Conclusions: A small number of events (FI, median 9.5) were required to render the results of carotid artery stenosis RCTs comparing CEA to CAS statistically insignificant. All of the studies that reported LTFU had LTFU greater than its fragility index.

Background: Basilar fenestration is a rare congenital anomaly. When present, it is commonly found at the proximal portion of the artery near the vertebrobasilar junction. Methods: This is a case report of a ruptured basilar fenestration aneurysm in a 47-year-male successfully treated with endovascular coiling. Results: A 47-year-old male presented with sudden onset headache, neck pain, blurry vision, nausea, vomiting, and diaphoresis. Cerebral angiogram revealed a saccular basilar fenestration aneurysm located at the vertebrobasilar junction measuring 3.1 x 2.6 x 3.4 mm with a 2.3 mm neck. Multiple coils were placed including Target 360 Nano 2mm x 4 cm (Stryker, Kalamazoo, MI, US), Target 360 Nano 1.5 mm x 2 cm (Stryker, Kalamazoo, MI, US), and Target Helical Nano 1.5 mm x 1 cm (Stryker, Kalamazoo, MI, US). A repeat angiogram revealed complete exclusion of the aneurysm with preservation of both vertebral arteries. Conclusions: A literature review was conducted on basilar fenestration aneurysms which included 158 patients from 39 studies. Overall, complete exclusion of the aneurysm was achieved in 75.8% of cases, with 22.4% of cases having residual flow and 1.8% of cases with unreported exclusion status.

The great demographic pressure brings tremendous volume of beef demand. The key to solve this problem is the growth and development of Chinese cattle. In order to find molecular markers conducive to the growth and development of Chinese cattle, sequencing was used to determine the position of copy number variations (CNVs), bioinformatics analysis was used to predict the function of ZNF146 gene, real-time fluorescent quantitative polymerase chain reaction (qPCR) was used for CNV genotyping and one-way analysis of variance was used for association analysis. The results showed that there exists CNV in Chr 18: 47225201-47229600 (5.0.1 version) of ZNF146 gene through the early sequencing results in the laboratory and predicted ZNF146 gene was expressed in liver, skeletal muscle and breast cells, and was amplified or overexpressed in pancreatic cancer, which promoted the development of tumour through bioinformatics. Therefore, it is predicted that ZNF146 gene affects the proliferation of muscle cells, and then affects the growth and development of cattle. Furthermore, CNV genotyping of ZNF146 gene was three types (deletion type, normal type and duplication type) by Real-time fluorescent quantitative PCR (qPCR). The association analysis results showed that ZNF146-CNV was significantly correlated with rump length of Qinchuan cattle, hucklebone width of Jiaxian red cattle and heart girth of Yunling cattle. From the above results, ZNF146-CNV had a significant effect on growth traits, which provided an important candidate molecular marker for growth and development of Chinese cattle.