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MacSphere is McMaster University's Institutional Repository. MacSphere brings together the institution's scholarly works under one umbrella to preserve and provide ongoing open access to them. MacSphere works have been selected and deposited by members of the McMaster community as part of our collective committment to sharing our knowledge with the world.

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Recent Submissions

TSLP Mediated Regulation of Airway Inflammation: Associations of Genetic Polymorphisms with Clinical Heterogeneity in Respiratory Diseases
(2026) Ranjbar Maral; Gauvreau, Gail; Medicine
Airway epithelial cells are key regulators of immune responses in respiratory disease through the release of alarmin cytokines, including thymic stromal lymphopoietin (TSLP). As an upstream mediator of type 2 inflammation, TSLP is elevated in asthma and inducible during viral respiratory infections. Genetic variation within the TSLP locus has been associated with asthma susceptibility; however, how these variants influence epithelial inflammatory responses across disease contexts remains unclear. This thesis investigated whether TSLP polymorphisms are associated with variation in airway epithelial inflammation during viral infection, asthma severity, and allergen-induced responses. Associations between TSLP genetic variants (rs2289276, rs3806933, rs1837253) and systemic inflammation were first examined in SARS-CoV-2 infection. Genotype frequencies did not differ by infection status or disease severity. However, minor alleles of rs2289276 and rs3806933 were associated with lower circulating TSLP levels, suggesting a modulatory role in epithelial responses to viral infection, although not a major determinant of COVID-19 severity. In asthma cohorts, rs2289276 and rs3806933 were associated with reduced odds of asthma. rs2289276 carriers were more likely to have mild rather than moderate–severe disease and exhibited lower long-form TSLP expression and reduced sputum TSLP protein levels, alongside decreased eosinophilic inflammation. Sex-stratified analyses revealed lower TSLP levels in female carriers. In an allergen challenge model, variant carriers demonstrated attenuated inflammatory responses, including reduced IL-5, IL-4, and eosinophilia, as well as improved lung function recovery. RNA sequencing further showed that rs3806933 was associated with reduced expression of genes involved in epithelial–immune signaling and cytokine pathways following allergen exposure. Collectively, these findings demonstrate that TSLP polymorphisms are associated with context-dependent variation in airway inflammation, linking genetic regulation of epithelial responses to molecular, cellular, and physiologic features of asthma.
Prognostic role of a preoperative troponin elevation in patients undergoing urgent or emergency noncardiac surgery: a pooled analysis
(2026) Maiorano Silvia; Borges, Flavia; Clinical Health Sciences (Health Research Methodology)
Background 10% of the surgeries performed worldwide each year are urgent/emergency surgeries, with 3-fold higher mortality than elective procedures. Preoperative troponin elevation is a well-established risk marker in elective surgery, but prognostic value in urgent/emergency surgeries remains poorly defined. Purpose We aimed to determine the relationship between baseline preoperative troponin and composite outcome of death, MINS, heart failure, atrial fibrillation, and non-fatal cardiac arrest at 30-days. Additionally, we assessed the relationship between time from troponin measurement to surgery and composite outcome. Methods We performed a pooled individual participant data analysis of VISION-1 and POISE-3, including patients >45years-old who had urgent/emergency noncardiac surgery and at least one preoperative troponin measurement. We used multivariable Cox proportional hazards models to determine if preoperative troponin elevation predicted the primary outcome. We assessed time from troponin measurement to surgery based on troponin status in POISE-3 (physicians not always aware of preoperative troponin values in VISION-1). Mediation analysis assessed whether time from troponin measurement to surgery mediated the association of preoperative troponin with cardiovascular outcomes. Results Among 5,275 patients, 1,080 had preoperative troponin measured, of whom 242 (22.4%, 95%CI 20.1–25%) were elevated. The primary outcome occurred in 47.5% (95%CI 41.3–53.8) with preoperative troponin elevation versus 11.1% (95%CI 9.1–13.4) without. Increasing age (aHR1.03,95%CI1.02-1.05), preoperative troponin elevation (aHR3.67,95%CI 2.65–5.09), and vascular surgery (aHR1.77,95%CI1.05–2.97) predicted the primary outcome. Preoperative troponin elevation was associated with longer time to surgery (median 22 vs. 18.6 hours) in POISE-3, but mediation analysis indicated that only 3.3% of the association between preoperative troponin elevation and cardiovascular outcomes was mediated by delayed time to surgery (95%CI 2.5–12.4,P=0.277). Conclusions Preoperative troponin elevation is independently associated with an increased risk of death or cardiovascular complications after emergency/urgent surgery. Although patients with preoperative troponin elevation had delayed time to surgery, it did not mediate worse cardiovascular outcomes.
A Health Technology Assessment of Medical Cannabis: Clinical and Economic Effectiveness for Chronic Non-Cancer Pain and Policy Relevant Evidence From Canada
(2026) Jeddi Haron Mark; Tarride, Jean-Eric; Clinical Health Sciences (Health Research Methodology)
Chronic non-cancer pain affects many Canadians and is commonly treated with opioids, despite well-known risks such as dependence and overdose. Medical cannabis is increasingly used as an alternative, but uncertainty remains about its effectiveness, safety, and economic value through three studies. The first study indicated that opioids and medical cannabis produced small, comparable reductions in pain relief. However, opioids were associated with higher rates of treatment discontinuation due to adverse events. In the second study, which took an economic lens, medical cannabis was found to be cost-neutral relative to opioids, with comparable quality of life. The third study showed that medical cannabis users differ meaningfully from non-medical and dual users, exhibiting more frequent but less problematic consumption patterns. Overall, the results of these three studies provided evidence to inform clinical decision-making and reimbursement policy regarding medical cannabis for chronic pain in Canada.
Membrane-Coated CNT-Based Chemiresistive Sensors for Ion Detection in Water
(2026) Maryam Darestani-Farahani; Peter, Kruse; Chemistry and Chemical Biology
Development and Validation of a Risk Prediction Score for Patients with ST-Elevation Myocardial Infarction and Multivessel Disease
(2026) Mehdi Madanchi; Mehta, Shamir R.; Health Research Methodology
Background: Patients with ST-elevation myocardial infarction (STEMI) and multivessel disease (MVD) are at a significantly higher risk of subsequent cardiovascular death (CV death) and recurrent myocardial infarction (MI). Although complete revascularization improves outcomes, baseline risk may differ significantly according to individual differences in clinical and anatomical characteristics. Currently available risk prediction tools were not optimized for this population. The goal of this study was to synthesize and internally validate a basic, point-based risk score that would predict 3-year cardiovascular events and guide treatment decisions in this high-risk population. Methods: Based on data from the COMPLETE trial (n=3,738 participants), we first screened potential clinical and angiographic variables for inclusion in the score using univariate. Key predictors of cardiovascular death or myocardial infarction over 3 years of follow-up were identified using a multivariate Cox proportional hazards model. Regression coefficients (β-coefficients) were converted into integer values. Model performance was evaluated by Harrell’s C-statistic for discrimination and by calibration plots to assess model fit. Results We identified the following six predictors for CV death or MI: age (≥65), sex, diabetes, chronic kidney disease (CKD), Killip class ≥2, and percentage diameter stenosis ≥80% of the non-culprit lesion (NCL) by visual estimation. The total score ranged from 0 to 30. The model demonstrated average discriminant performance, with a C-statistic of 0.60 when applied to the full cohort. Conclusions: We derived and internally validated a point-based risk score to risk stratify STEMI patients with MVD. However, further refinements to the model, including the use of a larger development cohort and external validation, are necessary to improve its performance and confirm its generalizability across a broader population of patients with STEMI and MVD.

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