Publications by authors named "Bryan Lo"

Background: Digital Health Literacy (DHL) is crucial in navigating digital health environments, yet few studies focus on older adults.

Objective: Explore the associations of digital health information and resource utilization, IT-related social support, and barriers/enhancers to digital health service usage with DHL among older adults.

Methods: A cross-sectional study was conducted from January 2022 to April 2023, involving 417 individuals over the age of 60 who were interviewed using an instrument for collecting data on DHL, social support, barriers/enhancers influencing use of digital health resources and personal/demographic data.

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Prior studies indicate donor age-recipient age (DA-RA) difference may be of prognostic value in adolescents, although not adults. We aim to analyze the relationship between DA-RA difference and long-term survival of young adult heart transplantation (HTx) recipients. First-time, single-organ HTx recipients aged 18-30 who underwent HTx between 2010 and 2020 were analyzed from the United Network for Organ Sharing (UNOS) registry.

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Genome-based testing in oncology is a rapidly expanding area of health care that is the basis of the emerging area of precision medicine. The efficient and considered adoption of novel genomic medicine testing is hampered in Canada by the fragmented nature of health care oversight as well as by lack of clear and transparent processes to support rapid evaluation, assessment, and implementation of genomic tests. This article provides an overview of some key barriers and proposes approaches to addressing these challenges as a potential pathway to developing a national approach to genomic medicine in oncology.

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Tumor-agnostic testing for NTRK1-3 gene rearrangements is required to identify patients who may benefit from TRK inhibitor therapies. The overarching objective of this study was to establish a high-quality pan-TRK immunohistochemistry (IHC) screening assay among 18 large regional pathology laboratories across Canada using pan-TRK monoclonal antibody clone EPR17341 in a ring study design. TRK-fusion positive and negative tumor samples were collected from participating sites, with fusion status confirmed by panel next-generation sequencing assays.

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The detection of gene fusions by RNA-based next-generation sequencing (NGS) is an emerging method in clinical genetic laboratories for oncology biomarker testing to direct targeted therapy selections. A recent Canadian study (CANTRK study) comparing the detection of gene fusions on different NGS assays to determine subjects' eligibility for tyrosine kinase TRK inhibitor therapy identified the need for recommendations for best practices for laboratory testing to optimize RNA-based NGS gene fusion detection. To develop consensus recommendations, representatives from 17 Canadian genetic laboratories participated in working group discussions and the completion of survey questions about RNA-based NGS.

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The Canadian NTRK (CANTRK) study is an interlaboratory comparison ring study to optimize testing for neurotrophic receptor tyrosine kinase (NTRK) fusions in Canadian laboratories. Sixteen diagnostic laboratories used next-generation sequencing (NGS) for NTRK1, NTRK2, or NTRK3 fusions. Each laboratory received 12 formalin-fixed, paraffin-embedded tumor samples with unique NTRK fusions and two control non-NTRK fusion samples (one ALK and one ROS1).

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Context.—: Penile squamous cell carcinomas (PSCCs) are divided into tumors that are human papillomavirus (HPV) associated and those that are non-HPV associated. HPV and non-HPV PSCCs each display unique pathogenic mechanisms, histologic subtypes, and clinical behaviors.

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Next-generation sequencing (NGS) of tumor genomes has changed and improved cancer treatment over the past few decades. It can inform clinicians on the optimal therapeutic approach in many of the solid and hematologic cancers, including non-small lung cancer (NSCLC). Our study aimed to determine the costs of NGS assays for NSCLC diagnostics.

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Article Synopsis
  • The study investigates the extent and significance of neuroendocrine (NE) differentiation in basaloid squamous cell carcinomas (B-SqCC) compared to poorly differentiated squamous cell carcinomas (PD-SqCC).
  • It evaluates various samples from patients and uses gene expression analysis to identify differentially expressed genes associated with NE differentiation.
  • Results show that B-SqCC has unique molecular characteristics and poorer disease-free survival, suggesting they are biologically different from other squamous cell carcinomas and share traits with small cell lung cancer.
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Objectives: In precision medicine, where oncologic management is tailored to the individual's clinical and genetic profiles, advanced diagnostic testing provides prognostic information and guides management in a growing number of malignancies. There is a need to capture the work pathologists perform to meet this demand by providing medically relevant, timely, and accurate testing results. This work includes not only direct patient consults (interpretation of results and issuing reports) but the administrative and medical oversight as well as the research needed to provide the necessary quality assurance, quality control, direction, and framework for the laboratory.

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Background: Systemic therapy prolongs overall survival (OS) in advanced non-small cell lung cancer (NSCLC), but diagnostic tests, staging and molecular profiling take time, and this can delay therapy initiation. OS approximates first-order kinetics.

Methods: We used OS of chemo-naive NSCLC patients on a placebo/best supportive care trial arm to estimate % of patients dying while awaiting therapy.

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Increasingly, systemic treatment decisions in nonsmall cell lung cancer require the determination of predictive biomarkers on biopsy or surgical specimens. Although currently these have their major role in the advanced setting, these tumor-specific treatments are increasingly moving into earlier stage disease. As part of the multidisciplinary team managing those with nonsmall cell lung cancer, thoracic surgeons need to be aware of these biomarkers and in particular of the need for adequate biopsy specimens containing sufficient tissue to perform the necessary analyses that guide treatment selection.

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Molecular variants including single nucleotide variants (SNVs), copy number variants (CNVs) and fusions can be detected in the clinical setting using deep targeted sequencing. These assays support low limits of detection using little genomic input material. They are gaining in popularity in clinical laboratories, where sample volumes are limited, and low variant allele fractions may be present.

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Introduction: Genotyping circulating tumor DNA (ctDNA) is a promising noninvasive clinical tool to identify the T790M resistance mutation in patients with advanced NSCLC with resistance to EGFR inhibitors. To facilitate standardization and clinical adoption of ctDNA testing across Canada, we developed a 2-phase multicenter study to standardize T790M mutation detection using plasma ctDNA testing.

Methods: In phase 1, commercial reference standards were distributed to participating clinical laboratories, to use their existing platforms for mutation detection.

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Background: The use of Next-Generation Sequencing (NGS) has recently allowed significant improvements in cancer treatment. Foundation Medicine (FM) provides a genomic profiling test based on NGS for a variety of cancers. However, it is unclear if the Foundation Medicine test would result in a better outcome than the standard on-site molecular testing.

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WNT9B plays a key role in the development of the mammalian urogenital system. It is essential for the induction of mesonephric and metanephric tubules, the regulation of renal tubule morphogenesis, and the regulation of renal progenitor cell expansion and differentiation. To our knowledge, WNT9B has not been associated with renal defects in humans; however, WNT9B mice have renal agenesis/hypoplasia and reproductive tract abnormalities.

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Background: In high grade serous ovarian cancer (HGSOC), there is a spectrum of sensitivity to first line platinum-based chemotherapy. This study molecularly characterizes HGSOC patients from two distinct groups of chemotherapy responders (good vs. poor).

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Purpose: Mutations in BRAF are the most prominent activating mutations in melanoma and are increasingly recognized in other cancers. There is currently no accepted treatment regimen for patients with mutant BRAF melanoma, and the study of melanoma driven by BRAF mutations at the 601 locus is lacking due to a paucity of cellular model systems. Therefore, we sought to better understand the treatment and clinical approach to patients with mutant BRAF melanoma and subsequently develop a novel personalized oncology platform for rare or treatment-refractory cancers.

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Brain metastases are observed in more than 40% of all patients with stage 4 melanoma. In recent years, more extensive use of stereotactic radiation (STRT) and the advent of immune checkpoint inhibitors have positively impacted outcomes in patients with metastatic melanoma.brain metastases.

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In critically ill patients with coronavirus disease 2019, there has been considerable debate about when to intubate patients with acute respiratory failure. Early expert recommendations supported early intubation. However, as we learned more about this disease, the risks versus benefits of early intubation are less clear.

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Background: Treating cancer depends in part on identifying the mutations driving each patient's disease. Many clinical laboratories are adopting high-throughput sequencing for assaying patients' tumours, applying targeted panels to formalin-fixed paraffin-embedded tumour tissues to detect clinically-relevant mutations. While there have been some benchmarking and best practices studies of this scenario, much variant calling work focuses on whole-genome or whole-exome studies, with fresh or fresh-frozen tissue.

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Over 95% of hip fractures in older adults are caused by falls, yet only 1% to 2% of falls result in hip fracture. Our current understanding of the types of falls that lead to hip fracture is based on reports by the faller or witness. We analyzed videos of real-life falls in long-term care to provide objective evidence on the factors that separate falls that result in hip fracture from falls that do not.

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Tumor DNA sequencing data can be interpreted by computational methods that analyze genomic heterogeneity to infer evolutionary dynamics. A growing number of studies have used these approaches to link cancer evolution with clinical progression and response to therapy. Although the inference of tumor phylogenies is rapidly becoming standard practice in cancer genome analyses, standards for evaluating them are lacking.

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