Thunder Bay Regional Research Institute

SARS-CoV-2 is now endemic and expected to remain a health threat, with new variants continuing to emerge and the potential for vaccines to become less effective. While effective vaccines and natural immunity have significantly reduced hospitalisations and the need for critical care, outpatient treatment options remain limited, and real-world evidence on their clinical and cost-effectiveness is lacking. In this paper, we present the design of the Canadian Adaptive Platform Trial of Treatments for COVID in Community Settings (CanTreatCOVID). By evaluating multiple treatment options in a pragmatic adaptive platform trial, this study will generate high-quality, generalisable evidence to inform clinical guidelines and healthcare decision-making. CanTreatCOVID is an open-label, individually randomised, multicentre, national adaptive platform trial designed to evaluate the clinical and cost-effectiveness of therapeutics for non-hospitalised SARS-CoV-2 patients across Canada. Eligible participants must present with symptomatic SARS-CoV-2 infection, confirmed by PCR or rapid antigen testing (RAT), within 5 days of symptom onset. The trial targets two groups that are expected to be at higher risk of more severe disease: (1) individuals aged 50 years and older and (2) those aged 18-49 years with one or more comorbidities. CanTreatCOVID uses numerous approaches to recruit participants to the study, including a multifaceted public communication strategy and outreach through primary care, outpatient clinics and emergency departments. Participants are randomised to receive either usual care, including supportive and symptom-based management, or an investigational therapeutic selected by the Canadian COVID-19 Outpatient Therapeutics Committee. The first therapeutic arm evaluates nirmatrelvir/ritonavir (Paxlovid), administered two times per day for 5 days. The second therapeutic arm investigates a combination antioxidant therapy (selenium 300 µg, zinc 40 mg, lycopene 45 mg and vitamin C 1.5 g), administered for 10 days. The primary outcome is all-cause hospitalisation or death within 28 days of randomisation. The CanTreatCOVID master protocol and subprotocols have been approved by Health Canada and local research ethics boards in the participating provinces across Canada. The results of the study will be disseminated to policy-makers, presented at conferences and published in peer-reviewed journals to ensure that findings are accessible to the broader scientific and medical communities. This study was approved by the Unity Health Toronto Research Ethics Board (#22-179) and Clinical Trials Ontario (Project ID 4133). NCT05614349.

Objective.This article explores a new graphics processing unit (GPU)-based techniques for efficient image reconstruction in organ-targeted positron emission tomography (PET) scanners with planar detectors.Approach.GPU-based reconstruction is applied to the Radialis low-dose organ-targeted PET technology, developed to overcome the issues of high exposure and limited spatial resolution inherent in traditional whole-body PET/CT (Computed Tomography) scans. The Radialis planar detector technology is based on four-side tileable sensor modules that can be seamlessly combined into a sensing area of the needed size, optimizing the axial field-of-view for specific organs, and maximizing geometric sensitivity. The article explores the transition from central processing unit-based maximum likelihood expectation maximization algorithms to a GPU-based counterpart, demonstrating a tenfold overall speedup in image reconstruction with a hundredfold improvement in iteration speed.Main results.Through standardized PET performance tests and clinical image analysis, this work demonstrates that GPU-based image reconstruction maintains diagnostic image quality while significantly reducing reconstruction times. The application of this technology, particularly in breast imaging using the Radialis low-dose positron emission mammography, significantly reduces exam times thus improving patient comfort and throughput in clinical settings.Significance.This study represents an important advancement in the clinical workflow of PET imaging, providing insights into optimizing reconstruction algorithms to effectively leverage the parallel processing capabilities of GPUs.

Holmium laser enucleation of the prostate (HoLEP) is known to have a steep learning curve. The top-down technique was introduced to lessen the number of procedures required to master HoLEP. We aimed to present the experiences of two successive clinical fellows with the top-down HoLEP learning curve and compare their performance with the supervisor. We conducted a prospective study of 40 patients who underwent top-down HoLEP performed by two successive fellows at our institution from September 2020 to November 2022. Before data collection, each learner observed three top-down HoLEP procedures and assisted with seven additional cases before independently performing top-down HoLEP under supervision. We collected data from each fellow's first 20 consecutive top-down HoLEP procedures. The learners' cases were grouped according to chronological order (Cases 1-10 and 11-20). The primary outcome was defined as the number of cases before the fellow could independently complete all steps of top-down HoLEP without any major intraoperative complications. The secondary outcomes included the intraoperative and postoperative outcomes of both groups. The fellows' 40 cumulative cases were then compared against retrospective data from 148 procedures conducted by their supervisor. There were no significant differences in patient demographics for both clinical fellows. Each learner performed the first 20 cases independently without needing the supervisor to intervene. No major intraoperative complications were recorded, and there were no statistically significant differences in intraoperative and postoperative outcomes between fellows' cases. There was a statistically significant difference between the fellows and their supervisor in terms of operative efficiency and enucleation efficiency (p < 0.001). We did not find a significant difference between the fellows and the supervisor regarding intraoperative complications, major postoperative complications, or postoperative subjective and objective parameters. Top-down HoLEP shows promising and reproducible results in shortening HoLEP's learning curve. Larger comparative and multi-institutional studies are warranted.

Studies of lithogeochemical dispersion haloes of rare metal pegmatites, particularly those of economic interest, are known to display strong development of haloes of rare alkali elements (Li–Rb–Cs), in particular lithium, into country rocks. The use of these haloes in exploration for pegmatites has had apparently little application in an Australian context, where it has the potential to assist exploration undercover by expanding the known ‘footprint’ of these mineral systems. Dispersion haloes have two parts: proximal (typically of centimetres to metres thickness), characterised by visible changes to mineralogy relating to metasomatism, and distal, where there are typically cryptic geochemical changes, but no changes in host mineralogy. Collation of global data have shown that the lithogeochemical haloes of large rare metal pegmatites can extend laterally at least 200 m, with a few localities giving indications extending several kilometres along strike. Lithium displays the largest haloes, with Rb and Cs typically being less extensive; other elements are mostly localised close to the pegmatite wallrock interface. These haloes are more extensive in mafic host rocks than other host-rock types. Mafic host rocks also provide the best geochemical contrast for rare alkali elements. Of the 22 datasets reviewed here, many are simply ‘proof of concept’ studies based on single sample lines and may not have had their outer limits defined. The actual distribution of these haloes is likely to be controlled by anisotropies that control host-rock permeability in the host units, with fluids emanating from the rare metal pegmatites being commonly channelled into structures or exploiting foliation or bedding. Regional-scale structures are likely to control kilometre-scale haloes. Sheet silicates and amphiboles are the most important hosts for these elements, which consequently accumulate in units or structures rich in these minerals. The actual distributions of these elements are, in most cases, likely to be irregular and complex anomalies of varying three-dimensional shapes, and thus ‘vectoring’ based on systematic changes in concentration away from a source should be treated with caution. It is important to note that given anomaly types do not indicate the presence of particular minerals, such as spodumene. The presence of these haloes in Australian Archean cratons is supported by dispersion haloes in saprolite and saprock units in deep weathering profiles and is potentially applicable to lag sampling over near fresh or unweathered host-rock units in exposed terranes.

This study determined the impact of pre-operative abdominal MRI on all-cause mortality for patients with resected PDAC. All adult (≥18 years) PDAC patients who underwent pancreatectomy between January 2011 and December 2022 in Ontario, Canada, were identified for this population-based cohort study (ICD-O-3 codes: C250, C251, C252, C253, C257, C258). Patient demographics, comorbidities, PDAC stage, medical and surgical management, and survival data were sourced from multiple linked provincial administrative databases at ICES. All-cause mortality was compared between patients with and without a pre-operative abdominal MRI after controlling for multiple covariates. A cohort of 4579 patients consisted of 2432 men (53.1%) and 2147 women (46.9%) with a mean age of 65.2 years (standard deviation: 11.2 years); 2998 (65.5%) died while 1581 (34.5%) survived. Median follow-up duration post-resection was 22.4 months (interquartile range: 10.8-48.8 months), and median survival post-pancreatectomy was 25.9 months (95% confidence interval [95% CI]: 24.8, 27.5). Patients who underwent a pre-operative abdominal MRI had a median survival of 33.1 months (95% CI: 30.7, 37.2) compared to 21.1 months (95% CI: 19.8, 22.6) for all others. A total of 2354/4579 (51.4%) patients underwent a pre-operative abdominal MRI, which was associated with a 17.2% (95% CI: 11.0, 23.1) decrease in the rate of all-cause mortality, with an adjusted hazard ratio (aHR) of 0.828 (95% CI: 0.769, 0.890). Pre-operative abdominal MRI was associated with improved overall survival for PDAC patients who underwent pancreatectomy, possibly due to better detection of liver metastases than CT. Northern Ontario Academic Medicine Association (NOAMA) Clinical Innovation Fund.

Molecular magnetic resonance imaging (MRI) is an emerging field that is set to revolutionize our perspective of disease diagnosis, treatment efficacy monitoring, and precision medicine in full concordance with personalized medicine. A wide range of hyperpolarized (HP) 129Xe biosensors have been recently developed, demonstrating their potential applications in molecular settings, and achieving notable success within in vitro studies. The favorable nuclear magnetic resonance properties of 129Xe, coupled with its non-toxic nature, high solubility in biological tissues, and capacity to dissolve in blood and diffuse across membranes, highlight its superior role for applications in molecular MRI settings. The incorporation of reporters that combine signal enhancement from both hyperpolarized 129Xe and chemical exchange saturation transfer holds the potential to address the primary limitation of low sensitivity observed in conventional MRI. This review provides a summary of the various applications of HP 129Xe biosensors developed over the last decade, specifically highlighting their use in MRI. Moreover, this paper addresses the evolution of in vivo applications of HP 129Xe, discussing its potential transition into clinical settings.