Canadian Centers Research Articles

765. PATTERNS, TIMING, AND SURVIVAL OF RECURRENCE FOLLOWING SURGERY FOR ESOPHAGEAL ADENOCARCINOMA IN THE EUROPEAN MULTICENTRE ENSURE STUDY

Abstract Background After surgery for esophageal cancer approximately half of patients will develop disease recurrence. A more accurate and detailed understanding of the pattern, timing, treatment and prognosis of initial recurrence sites can guide improvements in surveillance and therapy. Therefore, the aim of this study was to accurately describe the pattern and timing of esophageal cancer recurrence, and to assess the distinct survival patterns of these recurrence locations. Methods This study included all patients who underwent surgical resection for esophageal and junctional adenocarcinoma registered in the ENSURE study. ENSURE was an international multicenter study of consecutive patients undergoing surgery for esophageal and esophagogastric junction cancers between 2009 and 2015 across 20 centers in Europe and Canada (NCT03461341). The first recurrence site was recorded and recurrence-free survival (RFS) was estimated using Kaplan-Meier curves. Sites of first recurrence were stratified into different groups and survival outcomes post recurrence detection were estimated using Kaplan-Meier curves. Results Of 3397 eligible patients, 1310 patients had disease recurrence with comprehensive follow-up data available (median RFS of 12.1 months). First recurrence was detected at multiple distant sites (n=469; 37.3%) or at a single distant site (n=463; 33.7%), while isolated local recurrence occurred in 189 (14.4%) patients. Liver-only recurrence occurred significantly earlier (median 9.0 months), while lung-only (15.2 months) and local-only occurred later (17.8 months). Patients with multiple-sites and liver-only recurrence had significant worse median post recurrence survival (7.4 and 8.3 months, respectively) when compared with lung- or local-only recurrence (10.4 and 15.9 months, respectively). Conclusion This study demonstrates that specific recurrence locations of esophageal cancer possess distinct RFS curves. Furthermore, specific recurrence locations result in different post recurrence survival outcomes. This information can help guide improvements in surveillance after esophageal cancer surgery and decisions regarding treatment of esophageal cancer recurrence.

Impact of Dyspnea on Adults With Respiratory Symptoms Without a Defined Diagnosis

BackgroundWe investigated dyspnea, its associated risk factors, and its impact on healthcare utilization, quality of life, and work productivity in adults with undiagnosed respiratory symptoms. Research QuestionWhat is the impact of dyspnea in adults with undiagnosed respiratory symptoms? Study Design and MethodsThis population-based study included 2857 adults who were experiencing respiratory symptoms. These individuals had not been previously diagnosed with any lung conditions and were recruited from 17 Canadian centers using random digit-dialing. Each participant underwent spirometry testing both before and after using a bronchodilator to determine if they met the diagnostic criteria for COPD, asthma, Preserved Ratio Impaired Spirometry (PRISm), or if their spirometry results were normal. An age-matched control group (n= 231) was similarly recruited using random-digit dialing. A dyspnea impact assessment score from 0 to 100 was produced using questions from the COPD Assessment Test and St. George’s Respiratory Questionnaire. ResultsIndividuals with PRISm (n=172) reported more impactful dyspnea (mean score 63.0, 95% CI: 59.5- 66.4) than those with undiagnosed asthma (n=265, mean score 56.6, 95% CI: 53.9-59.3) or undiagnosed COPD (n=330, mean score 57.5, 95% CI: 55.1-59.9). All groups reported significantly more impactful dyspnea compared to controls (mean score 13.8, 95% CI:11.8-15.7). Subject-specific risk factors including age, sex, BMI, smoking, and comorbidities explained 20.6% of the variation in dyspnea. An additional 12.4% of the variation was explained by disease classification and another 1.7% by the severity of lung function impairment assessed with spirometry. After adjusting for age, sex, and BMI, greater dyspnea impact was associated with increased healthcare utilization, lower quality of life, and reduced work productivity. InterpretationIn community-based adults with undiagnosed respiratory symptoms, those identified with PRISm experienced the greatest impact of dyspnea. Dyspnea imposes burdens on the healthcare system and is associated with impaired quality of life and work productivity.

Relationship Between Baseline Infarct and Clinical Outcome in Pediatric Large‐Vessel Occlusion Ischemic Stroke

Background In adults with large‐vessel occlusion stroke, the extent of the baseline infarct measured using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) predicts outcome and is used during patient selection for mechanical thrombectomy. The relationship between ASPECTS and clinical outcome is unknown in pediatric large‐vessel occlusion stroke. Methods Secondary analysis of a retrospective multicenter case–control study assessing mechanical thrombectomy versus medical management alone for pediatric large‐vessel occlusion stroke across 5 centers in Australia and Canada from 2011 to 2022. ASPECTS was measured on baseline computed tomography or magnetic resonance imaging–diffusion‐weighted imaging while blinded to clinical outcome and treatment status. The relationship between ASPECTS and pediatric modified Rankin scale scores at 3 months following stroke was assessed using ordinal logistic regression. Results In total, n = 24 thrombectomy patients (F = 10, mean age, 11.3 years [SD, 4.36]) and n = 24 control patients (F = 10, mean age, 10.2 years [SD, 4.32) were included. Mean ASPECTS was 6.3 (SD, 2.37) in the thrombectomy group and 6.1 (SD, 2.64) in the control group. In patients undergoing thrombectomy, baseline ASPECTS significantly correlated with pediatric modified Rankin scale scores at 3 months (odds ratio, 1.58 [95% CI, 1.10–2.27]; P = 0.013). In control patients, there was no significant correlation (odds ratio, 1.17 [95% CI, 0.87–1.55]; P = 0.298). Six of 7 thrombectomy patients with a large baseline infarct (ASPECTS <6) had a pediatric modified Rankin scale score of 0 to 2 at final follow‐up. Conclusion Baseline ASPECTS was significantly associated with clinical outcome in pediatric patients with large‐vessel occlusion stroke who received mechanical thrombectomy. Thrombectomy patients with low ASPECTS demonstrated favorable long‐term outcomes, suggesting ASPECTS alone should not be used to exclude pediatric patients from receiving thrombectomy.

Anastomotic metabolic and bariatric surgeries with same-day discharge: 30-day outcomes of a cohort from a high-volume center in Canada

BackgroundOn the basis of our extensive experience in same-day discharge (SDD) sleeve gastrectomy, we extended this management strategy to anastomotic metabolic and bariatric surgeries (MBS). ObjectivesTo retrospectively analyze early outcomes (≤30 d) after anastomotic MBS with planned SDD (≤12 hr). SettingUniversity Hospital, Canada; Public Practice. MethodsSDD anastomotic MBS were proposed with strict preoperative criteria and included single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S), Roux-en-Y gastric bypass (RYGB), one-anastomosis gastric bypass (OAGB), and single-anastomosis sleeve ileal bypass (SASI). Enhanced recovery after bariatric surgery protocols and post-anesthesia care unit criteria were followed. Unplanned overnight stay, emergency department (ED) visit, readmission, morbidity-mortality, and reintervention rates were analyzed. ResultsSince 2021, 208 patients (191 female and 17 male) have undergone SDD anastomotic MBS, with 76% conversion procedures: 92 SADI-S, 72 RYGB, 35 OAGB, and 9 SASI (mean age = 41.4 yr and mean preoperative body mass index = 41.9 kg/m2). Unplanned overnight stays and ED visits were 4.8% and 4.3%, respectively. Readmission rate was 5.8% (5 SADI-S, 5 RYGB, 1 OAGB, and 1 SASI). Overall morbidity rate was 14.9%, including 3.9% major complications. Within 30 days postoperatively, there were 2 duodenal leaks, 1 intrabdominal collection, 1 common bile duct stenosis, and 1 acute appendicitis in the SADI-S group. There were 2 occlusions on the jejunojejunal anastomosis and 1 bleeding on the gastrojejunal anastomosis in the RYGB group. Five (2.4%) required reintervention with no mortality. ConclusionsWe report low and acceptable rates of unplanned overnight stay, readmission, and reintervention. Early outcomes suggest that SDD anastomotic MBS seems safe and feasible with an experienced team, selective criteria, and appropriate postoperative follow-up.

Structural characterisation of Eastern Canada’s old industrial masonry buildings via typological analysis: part II – building database analysis

The typological analysis conducted in the companion paper is further expanded within this work through the critical analysis of a new extensive building database specifically conceived for old industrial masonry buildings in Eastern Canada. The identification of recurrent unreinforced masonry (URM) building archetypes in this low-to-moderate seismic region is essential to decrease uncertainties currently prevalent in the analysis of local old URM structures, often targeted for adaptive reuse. The database assembled herein comprises various heritage designated buildings across Eastern Canada and was compiled harmonising existing repositories at the federal, provincial and municipal level with an unprecedented focus on structural features. The characteristics of these resources are quantitatively analysed and applied to a case study of the city of Montréal, one of the most important industrial centres in nineteenth and twentieth century Canada. Outcomes from this study will guide practitioners and researchers involved in the structural and seismic assessment and retrofit of old industrial URM constructions, enable more and less invasive rational retrofit designs and inform the new Existing Structures provisions to be included in the 2030 National Building Code of Canada.

Treatment patterns and outcomes in KRASG12C‐positive advanced NSCLC patients previously treated with immune checkpoint inhibitors: A Canada-wide real-world, multi-center, retrospective cohort study

ObjectivesKRAS mutations, particularly KRASG12C, are prevalent in non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICIs) have been a frontline treatment, but recently developed KRASG12C-selective inhibitors, such as sotorasib, present new therapeutic options. We conducted a multi-center retrospective cohort study to gain insights into real-world treatment patterns and outcomes in patients with KRASG12C-positive advanced NSCLC receiving systemic therapy post-ICI treatment. MethodsFrom the CAnadian CAncers With Rare Molecular Alterations-Basket Real-world Observational Study (CARMA-BROS), a cohort of 102 patients with KRASG12C-positive advanced NSCLC across 9 Canadian centers diagnosed between 2015 and 2021 was analyzed. Clinico-demographic and treatment data were obtained from electronic health records. Survival outcomes were assessed using Kaplan-Meier curves and Cox proportional hazards models. ResultsThe patients (median age 66 years; 58 % female; 99 % current/former tobacco exposure; 59 % PD-L1 ≥ 50 %), exhibited heterogeneous treatment patterns post-ICI. Most patients received ICIs as a first-line therapy, with varying subsequent lines including chemotherapy and targeted therapy. In patients receiving systemic therapy post-ICI, median overall survival was 12.6 months, and real-world progression-free survival was 4.7 months. KRASG12C-selective targeted therapy post-ICI (n = 20) showed longer real-world progression-free survival compared to single-agent chemotherapy (aHR = 0.39, p = 0.012). ConclusionThis study contributes valuable real-world data on KRASG12C-positive advanced NSCLC post-ICI treatment. The absence of a standard treatment sequencing post-ICI underscores the need for further investigation and consensus-building in the evolving landscape of KRASG12C-targeted therapies.

Impact of Positive Resection Margins on Recurrence and Survival Following Resection and Adjuvant Chemotherapy in Pancreatic Cancer: Results of the PRODIGE 24-CCTG PA-6 Randomized Controlled Trial.

This study investigated the correlation between positive resection margins and outcomes in patients with pancreatic ductal adenocarcinoma who underwent surgery and adjuvant chemotherapy according to the pivotal trial PRODIGE 24-CCTG PA-6. The primary focus is on elucidating the prognostic significance of specific resection margins, including those associated with the superior-mesenteric vein (SMV), medial, and posterior pancreas. The analysis involved 400 patients across multiple centers in France and Canada. Surgical resection and subsequent adjuvant chemotherapy were core interventions. This study assessed the prognostic impact of resection margins, highlighting the significance of standardized pathology assessments. Additionally, the influence of chemotherapy regimen choice, comparing gemcitabine to mFOLFIRINOX, on the implications of positive resection margins was examined. Only three margins, SMV (HR=1.48 95% CI [1.11;1.96], P<.001), medial (HR=1.92 95% CI [1.36;2.73], P<.001) and posterior (HR=1.65 95% CI [1.21;2.24], P=.002), had a significant prognostic impact on disease-free survival and were sufficient compared with the seven recommended margins (Kappa=0.90 95% CI [0.87; 0.94]). R1 status was significant independent prognostic factor for poorer survival in gemcitabine-treasted patients (HR=1.97 95% CI [1.23;3.16], P=.005) but lost its significance with mFOLFIRINOX (HR=1.46 95% CI [0.91;2.35], P=.114). All efforts should be made to evaluate the three margins of the highest prognostic value, with the others being secondary. A key finding of this study is the likely effect of mFOLFIRINOX on local invasion in operated patients, which seems to correct the impairment related to margin involvement, probably explaining the improvements in DFS and OS.

Epidemiology of carbapenemase-producing Enterobacterales carriage in a paediatric tertiary health care centre of Ontario, Canada

Introduction: The epidemiology of carbapenemase-producing Enterobacterales (CPE) in hospitalized children in low endemicity settings is not well known. We aim to describe it in a large tertiary paediatric health care centre in Canada. Methods: A repeated point-prevalence study including all inpatients was conducted at the Hospital for Sick Children, Toronto, for surveillance purposes over 3 days serially in April 2017, April 2019, and April 2022. Patients in the emergency department and medical day units were excluded. Stools or rectal swabs were analyzed for CPE identification, with confirmatory testing at the provincial reference laboratory. Results: We detected CPE colonization in 0.4% (1/242), 0.7% (2/278), and 0.9% (2/220) of inpatients in 2017, 2019, and 2022, respectively. Identified CPE included OXA-48-like and NDM beta-lactamases in Escherichia coli and Klebsiella pneumoniae. All patients with CPE colonization had a history of travel or hospitalization outside of Canada, including in the Middle East and Asia. Discussion: CPE colonization in children hospitalized in this Canadian hospital was detected. A history of prolonged travel or hospitalization outside of Canada are risk factors that should be considered in targeted screening programs.

Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema (DELTA 1 and DELTA 2): results from multicentre, randomised, controlled, double-blind, phase 3 trials

Chronic hand eczema is a fluctuating, inflammatory, pruritic, often painful disease of hands and wrists that strongly impacts quality of life and occupational capabilities of patients. The aim of phase 3 DELTA 1 and DELTA 2 was to assess the efficacy and safety of twice-daily applications of the topical pan-Janus kinase inhibitor delgocitinib cream 20 mg/g versus cream vehicle in adults with moderate to severe chronic hand eczema. Both trials were randomised, double-blinded, and vehicle-controlled, with DELTA 1 being conducted at 53 trial centres in Canada, France, Germany, Italy, Poland, and the UK and DELTA 2 at 50 trial centres in Belgium, Canada, Denmark, Germany, the Netherlands, Poland, and Spain. Adults (aged ≥18 years) with moderate to severe chronic hand eczema were randomly assigned 2:1 to twice-daily delgocitinib cream 20 mg/g or cream vehicle for 16 weeks. The primary endpoint was Investigator's Global Assessment for Chronic Hand Eczema (IGA-CHE) treatment success at week 16, defined as IGA-CHE score of 0 (clear) or 1 (almost clear, defined as only barely perceptible erythema). Efficacy and safety were assessed in all patients who were exposed to trial treatment. These trials are registered with ClinicalTrials.gov, NCT04871711 and NCT04872101. Between May 10, 2021, and Oct 31, 2022, 487 patients (181 male and 306 female) were enrolled in DELTA 1; between May 25, 2021, and Jan 6, 2023, 473 patients (161 male and 312 female) were enrolled in DELTA 2. 325 patients in DELTA 1 and 314 in DELTA 2 were assigned to delgocitinib cream; 162 patients in DELTA 1 and 159 in DELTA 2 were assigned to cream vehicle. At week 16, a greater proportion of delgocitinib-treated patients versus cream vehicle patients had IGA-CHE treatment success (64 [20%] of 325 vs 16 [10%] of 162 in DELTA 1 and 91 [29%] of 313 vs 11 [7%] of 159 in DELTA 2; both trials p≤0·0055). The proportion of patients who reported adverse events was similar with delgocitinib (147 [45%] of 325 in DELTA 1 and 143 [46%] of 313 in DELTA 2) and the cream vehicle (82 [51%] of 162 in DELTA 1 and 71 [45%] of 159 in DELTA 2). Most frequent adverse events occurring in at least 2% of patients were similar in both treatment groups and included COVID-19 and nasopharyngitis. Overall, delgocitinib cream showed superior efficacy versus cream vehicle and was well tolerated over 16 weeks. These results support the clinical benefit of delgocitinib cream as a potential treatment option for patients with moderate to severe chronic hand eczema, who are unable to adequately control their disease with basic skin care practices and topical corticosteroids. LEO Pharma.

A Canadian Retrospective Chart Review Evaluating Concomitant Methotrexate De-escalation Patterns in Patients with Rheumatoid Arthritis Treated with Biologic or Targeted Synthetic DMARDs.

Rheumatoid arthritis (RA) guidelines recommend methotrexate (MTX)-anchored therapy with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs); however, tolerability issues often lead to non-adherence. Canadian data on MTX tapering and/or withdrawal following b/tsDMARD initiation are minimal. This chart review assessed frequency of MTX tapering or withdrawal following b/tsDMARD initiation and the impact on disease status in Canadian adults with RA. Eligible patients had received MTX for ≥ 3months before b/tsDMARD initiation. The b/tsDMARD was prescribed continuously for ≥ 18months. Patients taking > 10mg/day oral prednisone or equivalent were excluded. Eight hundred eighty-nine patients (mean baseline MTX dose 19.0mg/week) prescribed b/tsDMARDs (tumor necrosis factor inhibitor 52.1%, Janus kinase inhibitor 18.3%, interleukin-6 inhibitor [IL-6i] 11.9%, other 17.7%) were evaluated at 22 Canadian centers. Within 2years of b/tsDMARD initiation, MTX was tapered in 123 (13.8%) patients and discontinued in 147 (16.5%), most commonly due to planned tapering (36.6%) and patient decision (27.2%), respectively, and most commonly with IL-6i use (34.9%). The MTX dose was unchanged for 582 (65.5%) patients and increased for 37 (4.2%). Missing data limit interpretations of MTX dose effects on some secondary endpoints and challenge the assertion that a disease activity measure-based treat-to-target approach is routinely used in Canadian rheumatology practice. Methotrexate tapering or withdrawal occurred in 30.4% of Canadians with RA within 2years following b/tsDMARD initiation. Baseline disease activity measures were missing from many medical records. However, for patients with baseline assessments, MTX tapering or discontinuation did not worsen disease activity.

Masculinities in Immigration Detention Centres

A great tool to grow an empire, detention camps have been historically used and abused as a subordination tactic by all of the most powerful empires, most notably by Germany’s Nazi Regime in the Second World War. Commonly thought to have been born and died in history, they are a mostly forgotten piece of the past. Many would be shocked to discover that there is a secret world of institutions that disregard international human rights law in order to prioritize their national goals, where refugees, asylum seekers and migrants are the primary victims. Systems for migrancy and immigration detention have emerged in the wake of globalization, seeking asylum from conflicts, natural disasters or financial insecurity, or simply searching for better economic opportunities, education or reunion with family. Multicultural liberal democracies use detention centres to enforce their racialized and gendered penal power and establish a national hierarchy where poor, young men of colour are the most marginalized. This paper critically examines the victimization of male refugees, asylum seekers and migrants by neo-colonial masculinities in Canadian, American and British immigration detention centres and how these experiences create offenders through the victim-offender overlap.

Assessing Cardiovascular Health in Paediatric Hypertrophic Cardiomyopathy Using the CANHEART Health Index

BackgroundPaediatric hypertrophic cardiomyopathy (HCM) is associated with sudden cardiac death, often resulting in restriction of strenuous physical activity. High levels of inactivity and a rise in youth obesity may increase risk of poor cardiovascular (CV) health in these patients. We aim to compare the CV disease risk profile of paediatric patients with HCM to Canadian youth. MethodsPatients with HCM (10-19 years) were recruited from 10 paediatric cardiac centres in Canada. The CV disease risk profile was determined using the Healthy Hearts School Program questionnaire and Cardiovascular Health in Ambulatory Care Research Team (CANHEART) health index. Poisson regressions were used to assess associations between the CV disease risk profile of paediatric patients with HCM and the overall CANHEART health score. ResultsA total of 56 subjects were enrolled (71% male, median age: 15.5 years [interquartile range: 13.8-16.8], median body mass index: 23.3 [interquartile range: 19.5-27.7]). Results of the CANHEART health index revealed that 89% of participants with HCM never tried smoking, 52% had a healthy body mass index, 39% consumed ≥5 fruits/vegetables per day, and 50% engaged in ≥60 minutes of walking or 20 minutes of running/jogging per day. When CANHEART intermediate and poor health index scores were combined, similar proportions were obtained for each group (HCM 82.1% vs Canadian youth 83.4%; P = 0.724). ConclusionsMany paediatric patients with HCM in Canada have intermediate or poor CV health as determined by the CANHEART health score, with high rates of obesity and low physical activity levels driving these trends. Interventions should be developed to promote positive CV health behaviours among patients with HCM.

Availability and Use of Methods To Limit Cross-Contamination of Gluten-Free Foods in Restaurants in a Large Urban Centre in Canada

Availability and Use of Methods To Limit Cross-Contamination of Gluten-Free Foods in Restaurants in a Large Urban Centre in Canada

Longitudinal biomarker evaluation in Fabry disease patients receiving lentivirus-mediated gene therapy

Aim: In 2016, a team of Canadian researchers initiated the world’s first gene therapy clinical trial for Fabry disease. The study, aiming to determine the safety and toxicity of lentivirus α-galactosidase A transduced autologous CD34+ cells in adult males with Fabry disease (n = 5), was conducted at three Canadian centers. The objective of the present work was to evaluate a profile of Fabry disease-related biomarkers in five participants during a 5-year surveillance period, as part of the evaluation of this novel therapy. Methods: Sixteen globotriaosylceramide (Gb3) isoforms and eight globotriaosylsphingosine (lyso-Gb3) analogues were measured by LC-MS/MS in plasma and urine at numerous time points before and after gene therapy. Plasma and peripheral blood leukocyte α-galactosidase A activity were also measured. Results: Levels of urine and plasma lyso-Gb3 and analogues, and urine Gb3 were lower after gene therapy and while treated with enzyme replacement therapy (ERT) compared to baseline (before gene therapy) in participants treated with ERT only. Three participants chose to cease ERT treatment at some point after gene therapy. Two of these patients had lower levels of urine and plasma lyso-Gb3 and analogues compared to baseline, whereas one participant had higher levels of these biomarkers compared to baseline. An increase in urine Gb3 was observed when ERT treatment ceased after gene therapy (P &lt; 0.05) in all three participants. Conclusion: The evaluation of this complete glycosphingolipid biomarker profile was useful in monitoring the biochemical response to gene therapy in this cohort of five patients with Fabry disease.

LGG-50. POOR RESPONSE TO MEKI RE-INITIATION IN PEDIATRIC LOW-GRADE GLIOMA AFTER TREATMENT DISCONTINUATION. A PLGG TASKFORCE STUDY

Abstract BACKGROUND Pediatric low-grade gliomas (pLGG) exhibit dramatic objective response to treatment with MEKi (Mitogen-Activated Protein Kinase inhibitors). Although the initial response to MEKi is promising, it is unknown whether it is safe to stop MEKi therapy and if the response to re-initiating MEKi would have the same impact. The study objective was to compare the first and second response to MEKi in patients with pLGG who stopped therapy and had further tumor progression. METHODS PLGG identified at neurooncology centers in Canada, Australia, and US, which were treated twice with MEKi were included. Second therapy was defined as MEKi upon progression for tumors where treatment was stopped. Response to MEKi between 2 treatments (MEKi1, MEKi2) were analyzed by using RANO criteria. RESULTS Mature data on 19 patients reveals a median patient age of 13 years (range 7–24), and the most common tumor location is hypothalamic/chiasmatic (89%). PLGG alterations include KIAA1549:BRAF fusion in 69%, NF1 in 21%, and other alterations in 10%. The overall response (minor and partial) to MEKi1 was 63% compared to 26% in MEKi2 (p=0.04). Furthermore, upon restarting MEKi2, 11% had further growth on therapy in contrast to none at MEKi1. MEKi1 resulted in average of 37% size decrease (range, 3%-98%), including 6 PLGG with over 50% response. In contrast, the average decrease to MEKi2 was 10% (range, 6%-40%, p=0.005), and none had &amp;gt;50% size reduction. Comparing each patient MEKi1 to MEKi2 revealed that initial response was superior to the second one in all PLGG. CONCLUSION These data suggest that the second response to MEKi is inferior when compared to initial therapy. Expansion of this cohort and biomarker correlates are ongoing. Biological insights are required for this observation, and careful consideration should be made for stopping MEKi, especially in strategic locations such as the optic pathway.

Delayed cold-stored vs. room temperature stored platelet transfusions in bleeding adult cardiac surgery patients—a randomized multicentre pilot study (PLTS-1)

BackgroundPlatelets stored at 1–6 °C are hypothesized to be more hemostatically active than standard room temperature platelets (RTP) stored at 20–24 °C. Recent studies suggest converting RTP to cold-stored platelets (Delayed Cold-Stored Platelets, DCSP) may be an important way of extending platelet lifespan and increasing platelet supply while also activating and priming platelets for the treatment of acute bleeding. However, there is little clinical trial data supporting the efficacy and safety of DCSP compared to standard RTP.MethodsThis protocol details the design of a multicentre, two-arm, parallel-group, randomized, active-control, blinded, internal pilot trial to be conducted at two cardiac surgery centers in Canada. The study will randomize 50 adult (≥ 18 years old) patients undergoing at least moderately complex cardiac surgery with cardiopulmonary bypass and requiring platelet transfusion to receive either RTP as per standard of care (control group) or DCSP (intervention group). Patients randomized to the intervention group will receive ABO-identical, buffy-coat, pathogen-reduced, platelets in platelet additive solution maintained at 22 °C for up to 4 days then placed at 4 °C for a minimum of 24 h, with expiration at 14 days after collection. The duration of the intervention is from the termination of cardiopulmonary bypass to 24 h after, with a maximum of two doses of DCSP. Thereafter, all patients will receive RTP. The aim of this pilot is to assess the feasibility of a future RCT comparing the hemostatic effectiveness of DCSP to RTP (defined as the total number of allogeneic blood products transfused within 24 h after CPB) as well as safety. Specifically, the feasibility objectives of this pilot study are to determine (1) recruitment of ≥ 15% eligible patients per center per month); (2) appropriate platelet product available for ≥ 90% of patients randomized to the cold-stored platelet group; (3) Adherence to randomization assignment (> 90% of patients administered assigned product).DiscussionDCSP represents a promising logistical solution to address platelet supply shortages and a potentially more efficacious option for the management of active bleeding. No prospective clinical studies on this topic have been conducted. This proposed internal pilot study will assess the feasibility of a larger definitive study.Trial registrationNCT 06147531 (clinicaltrials.gov).

The Blastulation Rate Is Negatively Associated With Euploid Rate

ObjectivesTo study the association between the blastulation rate, the presence of 1 pronucleus (1PN) zygotes, and the ploidy of the cohort of blastocysts. MethodsA cross-sectional study using the existing databases of 2 university fertility centres in Canada. We included 345 cycles from 235 couples who underwent next-generation sequencing preimplantation genetic testing for the detection of aneuploidy in the study. ResultsA total of 1456 blastocysts were biopsied. In multivariate analysis, only female age and the number of 1PN/2PN embryos showed a negative association with euploid ratio. Surprisingly, when the analysis was limited to cycles with no delayed blastulation, the blastulation rate was also negatively associated with the euploid ratio. ConclusionsThis study sheds some light on the stages of early embryo development. Further study on the mechanisms governing embryo development and the different cell cycle checkpoints in embryo development is warranted.

The Association of Ethnicity and Oncologic Outcomes for Oral Cavity Squamous Cell Carcinoma (OSCC).

(1) Background: To compare oncologic outcomes of South Asian (SA) patients treated for oral squamous cell carcinoma (OSCC) to the general population. (2) Methods: Adult patients who underwent surgical resection of OSCC +/- adjuvant treatment between 2009 and 2022 (N = 697) at a regional cancer centre in Canada were included. SA patients, identified using a validated method, were compared to non-SA patients. Kaplan-Meier methods were used to compare the primary outcomes, disease-specific survival (DSS) and recurrence-free survival (RFS) across baseline univariate characteristics, including betel nut consumption. Median follow-up time was 36.4 months. Cox proportional hazard models were used to identify independent predictors of survival with significance set at p < 0.05. (3) Results: SA patients (9% of cohort, N = 64) were significantly younger and had lower rates of smoking and alcohol consumption compared to non-SA patients (p < 0.05). SA patients had a two-fold higher risk of recurrence and significantly worse disease-specific survival, even after adjusting for stage and high-risk features [RFS: HR 2.01 (1.28-3.14), DSS: HR 1.79 (1.12-2.88)]. The consumption of betel nut was not associated with outcomes. (4) Conclusions: SA patients had significantly worse oncologic outcomes, even after controlling for known predictors of poor prognosis. These findings are novel and can inform personalized treatment decisions and influence public health policies when managing patients with different ethnic backgrounds.

Extracorporeal Membrane Oxygenation for Acute Lung Injury in Idiopathic Inflammatory Myopathies-A Potential Lifesaving Intervention.

Idiopathic inflammatory myopathies (IIM) can present with acute IIM-related lung injury and respiratory failure, leading to a high mortality risk in intensive care units (ICU). Extracorporeal membrane oxygenation (ECMO) in acute respiratory distress syndrome can be lifesaving. We aimed to report a case series of IIM patients that received ECMO. Patients with IIM from tertiary care centers in Belgium, Canada, Denmark, United States, and Sweden who underwent ECMO were reviewed to describe clinical characteristics, disease outcomes and hospitalization course. Clinical characteristics at admission and during ICU stay including ECMO complications and mortality causes were summarized. The study included 22 patients (50% female, mean±SD age at admission 47 ± 12 years) with anti-MDA5 positive dermatomyositis (68%), anti-synthetase syndrome (14%), polymyositis (9%), overlap myositis (5%) and non-MDA5 dermatomyositis (5%). Patients had low comorbidity scores and 46% had received immunosuppression before their ICU admission. Eight (36%) patients died in the ICU, six (27%) were bridged to recovery and eight (36%) were bridged to transplant. When comparing patients bridged to recovery and those who died in the ICU, those who died were older (p= 0.03) and had higher median Charlson comorbidity index scores (p= 0.05). Both groups had similar frequencies of ECMO-related complications (33% vs 50%, p= 0.94). In the patients exposed to ECMO in this case series, 14 were successfully bridged to recovery or transplant, while 8 died in the ICU. Large studies are needed to collect data on clinical outcomes in patients with IIM-ILD exposed to ECMO to identify the best candidates for the intervention.

P.139 The use of tranexamic acid in craniotomy: a Canadian survey and literature review

Background: There is growing evidence supporting the intraoperative use of an antifibrinolytic agent, tranexamic acid (TXA) to limit blood loss; however, use of TXA has not been widely adopted in cranial procedures. We aimed to determine the practice pattern regarding the use of TXA in craniotomy in Canada, and review the literature. Methods: A survey was conducted among the Canadian centres on TXA use during elective craniotomy. Online databases were searched for randomized controlled trials reporting the use of TXA in craniotomy for tumors. The results included the estimated blood loss and the dose used. Results: TXA was not routinely used in elective craniotomy but used selectively in 6 of 15 centres based on risk, intraoperative bleeding, or surgeon preference. The dose was 1 g with or without infusion. 6 studies were identified through literature search. The dose varied between 10–20 mg/kg bolus and 1 mg/kg/hr infusion, or a 2 g bolus alone. All studies reported a significant reduction in blood loss with TXA. Conclusions: We found widely divergent indications for intraoperative TXA use in elective craniotomy throughout Canada. This is in keeping with limited evidence in the literature. Further studies are needed to inform the decision regarding TXA use.