A new study by University Health Network (UHN)’s Princess Margaret Cancer Centre (PM) found that the COVID-19 pandemic caused more patients with cancer to die at home and led to less receipt of specialized palliative care. The pandemic also amplified socioeconomic disparities in death at home and delivery of end-of-life care.
“Studies suggest that most patients with advanced cancer prefer to receive end-of-life care at home and to die at home,” says Dr. Camilla Zimmermann, Senior Scientist at PM and senior author of the study.
“When cancer patients can receive specialized palliative care and follow their preference to die at home, they usually enjoy a better quality of life at the end of their life and a better quality of death.”
Although the COVID-19 pandemic had a significant impact on the delivery of cancer care, less is known about its influence on the place of death, delivery of specialized palliative care, and disparities in these outcomes due to socioeconomic status.
Dr. Zimmermann’s team set out to determine whether the end-of-life experience is equitable across socioeconomic statuses and whether the pandemic played a role in increasing inequities.
“We analyzed data from a pool of over 170,000 Ontario patients who died with cancer from 2015 to 2021 to determine whether there was a change in home deaths and specialized palliative care delivery before and during the pandemic, using patient socioeconomic status as subgroups,” says Dr. Javaid Iqbal, Doctoral Student at PM and first author of the study.
“We found that both before and during the pandemic, patients with the lowest socioeconomic status were least likely to die at home and to receive palliative care at the end of life,” adds Dr. Iqbal.
Despite a substantial surge of patients who died at home during COVID, the home death increase in the lowest socioeconomic group was less marked than in other groups.
In addition, although the pandemic disrupted overall access to palliative care, this was more evident in the lowest socioeconomic group. Unlike the other groups where the surge in home death occurred both in patients receiving and not receiving palliative care, low socioeconomic patients had a significant home death increase only in those without this care.
These findings indicate that the pandemic increased socioeconomic disparities in end-of-life care and identify a need to deliver this care more broadly and equitably in the future.
“Future research should focus on the mechanisms of these disparities to develop interventions that ensure equitable and consistent access to palliative care,” concludes Dr. Zimmermann.
This work was supported by the Canadian Institutes of Health Research, Canada Graduate Scholarship, the Peterborough KM Hunter Charitable Foundation, and The Princess Margaret Cancer Foundation. Dr. Camilla Zimmermann is a Professor of Medicine at the University of Toronto.
Co-author Dr. Krzyzanowska reported being a principal investigator for trials with Eli Lilly, Exelixis, and Novartis and receiving advisory board fees from Ipsen. Co-author Dr. Lau received funding from the Health Canada Health Care Policy and Strategies Program.
Iqbal J, Moineddin R, Fowler RA, Krzyzanowska MK, Booth CM, Downar J, Lau J, Le LW, Rodin G, Seow H, Tanuseputro P, Earle CC, Quinn KL, Hannon B, Zimmermann C. Socioeconomic Status, Palliative Care, and Death at Home Among Patients With Cancer Before and During COVID-19. JAMA Netw Open. 2024 Feb 5;7(2):e240503. doi: 10.1001/jamanetworkopen.2024.0503
The Government of Canada has announced that the Canada Foundation for Innovation (CFI) will be investing more than $515 million to support researchers across Canada through essential research facilities and equipment.
UHN researchers were awarded $6.3 million in funding for four projects, including two led by UHN and two led by collaborating institutions.
The following UHN-led teams received funding for large-scale infrastructure to support research projects on advanced organ transplantation strategies and retinal disease assessment and therapeutics:
● Drs. Marcelo Cypel and Atul Humar, Senior Scientists at Toronto General Hospital Research Institute and the Ajmera Transplant Centre, received $2.8 million for a project to develop advanced strategies for modifying organs outside of the body—ultimately increasing the pool of available donor organs and improving outcomes for patients. The team will also develop customized donor organs to help improve long-term organ acceptance by the recipient. Dr. Cypel is a Professor of Surgery at the University of Toronto (U of T) and Dr. Humar is a Professor in the Department of Medicine at U of T. Team members include Drs. Sarah Crome, Siba Haykal, Stephen Juvet, Shaf Keshavjee, Deepali Kumar, Sonya MacParland, Trevor Reichman and Markus Selzner.
● Drs. Valerie Wallace and Philippe Monnier, Senior Scientists at the Krembil Research Institute’s Donald K. Johnson Eye Institute, received $2.5 million to develop a facility for assessing degenerative eye diseases and developing therapeutics. Their multidisciplinary research team with expertise in retinal biology, stem cell biology and regenerative medicine will resolve the mechanisms underlying retinal connectivity and disease to preserve and restore vision. Dr. Wallace is a Professor in the Department of Laboratory Medicine and Pathobiology at U of T and Dr. Monnier is a Professor in the Department of Physiology at U of T. The team also includes Drs. Brian Ballios, Michael Reber, Karun Singh, Jeremy Sivak as well as investigators from U of T and The Hospital for Sick Children.
Two other UHN teams received a total of $1 million in funding through projects led by other institutions: one to automate the high-throughput imaging of structural features in biological samples (led by Sinai Health System) and the other to establish a Diagnostic Horizons Lab to accelerate the development of diagnostic tests, initially for sepsis and heart failure (led by U of T). UHN researchers on these teams include Drs. Gary Bader, Ana Konvalinka, Marianne Koritzinksy, Sonya MacParland, Valerie Wallace, Bo Wang, Phyllis Billia, Azadeh Yadollahi and Heather Ross.
Congratulations to all award recipients at UHN!
To see the full press release, click here.
Researchers at UHN’s Schroeder Arthritis Institute have deciphered the immunological signature of flares in systemic lupus erythematosus (SLE), paving the way for improved prognosis and treatment.
SLE is a chronic autoimmune disease that affects many body systems. SLE can be a complex puzzle for clinicians because it can present very differently in patients. Additionally, in approximately 80% of patients, SLE is marked by intermittent flares in disease activity, interspersed with symptom-free periods.
“Managing SLE can be quite challenging due to the unpredictable nature of the condition. Pre-empting flares is important for preventing tissue damage, but we have a limited arsenal of tools to predict whether a given patient will experience a flare and when it will happen,” explains Dr. Joan Wither, a Senior Scientist at the Schroeder Arthritis Institute and senior author of the study.
“A major goal for researchers today is to determine the immune processes that drive changes in SLE activity to allow clinicians to closely monitor high-risk patients and offer pre-emptive treatments.”
To accomplish this, Dr. Wither’s team examined the immune cells present in blood samples from men and women with or without SLE. The team grouped people with similar immunological profiles and tracked immune changes at six-month and 12-month follow-up visits.
The team studied 47 distinct cell populations in samples from 46 patients experiencing flares, 25 patients not experiencing flares and 16 healthy controls.
The study revealed a spectrum of immunologic profiles linked to SLE activity. Based on their profiles, participants fit into five clusters, each characterized by unique clinical phenotypes—or observable disease features.
Levels of certain immune cells, such as age-associated B cells and T peripheral helper cells, predicted SLE activity one year later. For example, patients with higher levels of B cell activity were more likely to experience flares at their initial clinic visit and, if B cell activation continued or subsequently developed, have sustained or recurrent high disease activity over the subsequent year.
Conversely, patients who had elevated levels of T helper cells in the absence of changes in B cell activity, or those with elevated levels of type 1 helper cells and innate immune cells, typically transitioned to a symptom-free state during the follow-up period.
These findings underscore the role of dysregulated immune responses in driving SLE flares and suggest that age-associated B and T peripheral helper cells could serve as biomarkers for ongoing or recurrent flares.
When the immune system is activated by a pathogen, distinct cell populations interact to mount a response. In SLE and other autoimmune diseases, immune cells mistakenly attack the body’s own tissues.
Dr. Kieran Manion, a former postdoctoral researcher in Dr. Wither’s lab and the first author of the study, emphasizes the clinical significance of the team’s findings: "Our study uncovered distinct immunological profiles in SLE patients that are associated with different ways the disease can manifest. By using these profiles to stratify patients, we can improve their prognosis and offer more personalized therapies to mitigate flares and improve their long-term outcomes.”
This work was supported by the Canadian Institutes of Health Research, the Pfizer Chair Research Award, the Arthritis Centre of Excellence, the Schroeder Arthritis Institute and UHN Foundation. Dr. Wither is a Professor in the Department of Immunology at the University of Toronto.
Manion K, Muñoz-Grajales C, Kim M, Atenafu E, Faheem Z, Gladman DD, Urowitz M, Touma Z, Wither JE. Different Immunologic Profiles Are Associated With Distinct Clinical Phenotypes in Longitudinally Observed Patients With Systemic Lupus Erythematosus. Arthritis Rheumatol. 2023 Dec 10. doi: 10.1002/art.42776.
In a recent study, a UHN KITE Research Institute scientist delves into the vital connection between individual capabilities, neighbourhood walkability, and outdoor walking habits among older adults—shedding light on strategies to promote healthy aging.
As the population ages, maintaining mobility and well-being becomes increasingly crucial for preserving independence, reducing the risk of injury, and promoting quality of life. Walking outdoors is a particularly effective way to achieve these benefits.
“Navigating outdoor environments presents unique challenges for seniors compared to walking indoors: ability and confidence to manage uneven terrain, traffic, and weather conditions can impact their willingness to engage in outdoor walking,” explains Dr. Nancy Salbach, KITE Senior Scientist and co-author of the study. “Understanding these factors is critical to promote healthy aging.”
Dr. Salbach and researchers from the University of Manitoba analyzed data from 205 older adults participating in an outdoor walking program to understand the individual and environmental factors impacting outdoor walking habits.
Factors such as balance, leg strength, walking confidence, speed, endurance, income, and car access were closely linked with outdoor walking habits—highlighting the importance of physical well-being and financial status. In particular, individuals with better walking capacity and greater confidence were more likely to engage in outdoor walking.
Environmental factors like the design of neighbourhoods, availability of sidewalks, and safety of streets indirectly influenced outdoor walking habits.
“Seniors with better physical ability and higher income were found to live in more walkable neighbourhoods that were perceived as safe with low traffic and attractive buildings and landscaping,” explains Dr. Salbach.
The implications of these findings are profound. Interventions aimed at improving balance, walking capacity and self-confidence could increase outdoor walking among older adults. Community-based physiotherapists and other rehabilitation professionals can play an important role in leading walking programs for older adults that enhance individual factors such as balance and walking endurance, while considering how environmental factors like neighbourhood walkability can influence the ability to walk outdoors.
“Our research offers a roadmap for tailoring interventions that address individual capabilities, and account for socioeconomic status and environmental factors,” says Dr. Salbach. “Empowering older adults to overcome physical limitations and creating supportive environments can help promote active living. We need to create programs that are accessible to people regardless of income.”
Looking forward, the research team is interested in partnering with community organizations to implement supervised outdoor walking programs to promote healthy active living for seniors.
As societies explore and overcome the challenges faced by aging populations, this research offers invaluable insights into promoting health and well-being among older adults.
This work was supported by the Visual and Automated Disease Analytics Graduate Training Program of Natural Science and Engineering Research, the Canadian Institutes of Health Research, and UHN Foundation. Dr. Nancy Salbach is a Professor in the Department of Physical Therapy at the University of Toronto and holds the Toronto Rehabilitation Institute Chair at the University of Toronto.
Liu Y, Salbach NM, Webber SC, Barclay R. Individual and environmental variables related to outdoor walking among older adults: Verifying a model to guide the design of interventions targeting outdoor walking. PLoS One. 2024 Jan 10. doi: 10.1371/journal.pone.0296216.
Researchers at UHN’s Donald K. Johnson Eye Institute (DKJEI) have shed light on the molecular processes underlying the neuroprotective effects of lipoxins, paving the way for novel therapies for neurodegenerative diseases.
Lipoxins are small lipid molecules that are known to protect the nervous system from damage caused by inflammation.
DKJEI Senior Scientist Dr. Jeremy Sivak previously discovered that these molecules are produced in the retina—the neural tissue that lines the back of the eye—and showed that they protect neurons in an experimental model of retinal degeneration.
“An important step towards using lipoxins as targeted treatments for neurodegenerative diseases is determining how they protect against excessive inflammation,” explains Dr. Sivak, the senior author of the study.
Dr. Sivak’s team set out to determine the mechanisms by which two lipoxins dampen inflammation using an experimental model of posterior uveitis—retinal inflammation which can cause vision loss.
"We were particularly interested in how lipoxins interact with glial cells, which are critical for maintaining the immune response in the nervous system,” explains Dr. Izhar Livne-Bar, a research associate in Dr. Sivak’s lab and the first author of the study.
The team discovered that the lipoxins act on glial cells—namely astrocytes and microglia—to interrupt a cascade of cellular events that drive inflammation.
The lipoxins reduced retinal cells’ production of key signalling proteins called chemokines and cytokines, which typically initiate inflammatory processes.
Interestingly, the glial cell changes initiated by lipoxins depended on when they were administered—before or after the onset of inflammation. When lipoxins were delivered before the onset of inflammation, they primarily reduced the activity of astrocytes and initiated anti-inflammatory processes. In contrast, when they were delivered after inflammation began, they primarily reduced microglia activation and initiated processes that resolved the inflammation.
This finding prompts further investigations, as it has implications for developing lipoxin-based treatments for neurodegeneration.
“Discovering how lipoxins are involved in distinct processes that prevent and resolve inflammation brings us a step closer to determining how we can translate the actions of these molecules as treatments for a wide range of neurodegenerative diseases,” concludes Dr. Livne-Bar.
This work was supported by the Canadian Institutes of Health Research, the National Institutes of Health, and UHN Foundation. Dr. Jeremy Sivak holds the Graham Trope Chair in Glaucoma Research and is an Associate Professor in the Department of Ophthalmology and Vision Sciences at the University of Toronto.
Drs. Izhar Livne-Bar and Jeremy Sivak hold a US patent for the use of lipoxins to treat neurodegeneration.
Livne-Bar I, Maurya S, Gronert K, Sivak JM. Lipoxins A4 and B4 inhibit glial cell activation via CXCR3 signaling in acute retinal neuroinflammation. J Neuroinflammation. 2024 Jan 11. doi: 10.1186/s12974-024-03010-0.
Researchers at University Health Network (UHN)’s Princess Margaret Cancer Centre (PM) have developed a method to distinguish between different types of pediatric brain cancers. These findings are important for pediatric neurosurgery, as they could assist surgeons in determining the most suitable and personalized treatment strategies.
Classifying cancers into subtypes has become a key tool for determining diagnoses, prognoses, and treatment decisions. Intraoperative consultations—analysis of cancer samples during surgery— can utilize the differences in shape and structure between cancer cells and healthy cells to guide decision-making. This is often done by microscopic analysis of sections of tissue and can take up to 30 minutes to complete.
In addition, important subtypes of brain cancer have recently been identified at the molecular level. These subtypes influence prognosis and treatment decisions, prompting the need for a diagnostic strategy that considers the shape, structure, and molecular makeup of these brain tumours.
“Identifying specific molecular subtypes of brain cancer remains a challenge with existing intraoperative pathology consultation techniques,” says Dr. Arash Zarrine-Afsar, Senior Scientist at PM and senior author of the study. “These techniques do not rapidly provide molecular information during surgery to inform surgical decisions in real-time.”
A technique called Picosecond InfraRed Laser mass spectrometry (PIRL-MS) that can analyze the molecular composition of a small amount of tissue, was previously developed at UHN by Dr. Zarrine-Afsar’s lab. PIRL-MS consists of a handheld probe that uses a laser beam to vaporize tumour tissue. Mass spectrometry analysis— sorting particles by mass and charge— can then identify the sample’s components in up to 10 seconds.
“In this study, we examined the utility of PIRL-MS as a rapid method for differentiating major pediatric brain cancer types of medulloblastoma, pilocytic astrocytoma, and ependymoma,” says Dr. Michael Woolman, former Doctoral Student in Dr. Zarrine-Afsar’s lab and first author of the study. “We analyzed the lipid (fat molecule) profile of patient tissue from previous surgeries and identified a range of molecular markers involved in tumour classification.”
The researchers found that PIRL-MS could identify specific molecular features unique to each cancer type, enabling precise classification. Based on this, they propose a protocol for a 10-second classification of seven types of pediatric brain cancers.
Additionally, based on a retrospective analysis of prognoses and treatments for pediatric brain cancer, the team further identified situations where PIRL-MS analysis could influence the aggressiveness of surgical intervention in a manner that could benefit the patient’s overall survival.
These findings have significant implications for pediatric neurosurgery and treatment decisions and could ultimately improve patient outcomes.
Highlighting the collaborative nature of this research, Dr. Zarrine-Afsar adds, “Without the support of Dr. James Rutka and Dr. Michael D. Taylor at the Arthur and Sonia Labatt Brain Tumour Research Centre (BTRC) and The Hospital for Sick Children, this study would not have been possible.”
Future research will further collaborative efforts between Toronto area hospitals and involve evaluating the utility of PIRL-MS in prospective patient trials.
This work was supported by the Canadian Institutes of Health Research, Canadian Cancer Society and The Princess Margaret Cancer Foundation. Dr. Arash Zarrine-Afsar is an Associate Professor at the University of Toronto.
Dr. Zarrine-Afsar, Dr. Howard Ginsberg, and Dr. Michael Woolman are inventors of PIRL-MS and are consultants with financial interest in Point Surgical Inc.
Woolman M, Kiyota T, Belgadi SA, Fujita N, Fiorante A, Ramaswamy V, Daniels C, Rutka JT, McIntosh C, Munoz DG, Ginsberg HJ, Aman A, Zarrine-Afsar A. Lipidomic-Based Approach to 10 s Classification of Major Pediatric Brain Cancer Types with Picosecond Infrared Laser Mass Spectrometry. Anal Chem. 2024 Jan 23;96(3):1019-1028. doi: 10.1021/acs.analchem.3c03156.
In neurosurgery, doctors often need to quickly (under 30 minutes) decide how much of a tumour to remove and assess the risks involved. (Getty images)
A new Toronto General Hospital Research Institute (TGHRI) study has shed light on how cells in blood vessels communicate with each other, paving the way for new treatments for cardiovascular diseases like atherosclerosis—the build-up of fats, cholesterol, and other substances on the artery wall. Atherosclerosis can cause arteries to narrow, blocking blood flow and potentially lead to conditions such as heart attack or stroke.
Endothelial cells (ECs) line the inner surface of blood vessels, including arteries. Dysfunctional endothelium—changes to EC structure and function—is often the earliest disruption in numerous cardiovascular diseases. ECs communicate by releasing small packages called extracellular vesicles (EVs), which carry essential molecules like proteins capable of influencing the biological activities of recipient cells.
“We know that ECs release vesicles that contain different components when they are activated versus inactivated. EC activation can happen due to stimuli such as inflammation in conditions like atherosclerosis. Despite ECs residing between the bloodstream and vessel wall, it remains uncertain whether they release vesicles in a directional manner to convey specific messages to these parts,” says Dr. Kathryn Howe, Scientist at TGHRI, Vascular Surgeon at the Peter Munk Cardiac Centre, and senior author of the study.
To determine this, the researchers isolated EVs from human aortic endothelial cells and analyzed their contents. They found that when these cells were activated, as occurs in conditions like atherosclerosis, they released more EVs containing molecules linked to the disease such as regulators of inflammation.
These vesicles talk to immune cells (monocytes) and muscle cells found in the blood and vessel walls, causing changes to their genetic instructions which then impact cell behaviour.
“Importantly, we discovered that endothelial cells predominantly release more vesicles from the side facing the bloodstream, known as the apical side, compared to the side facing the vessel wall, known as the basolateral side. This pattern increased with activation,” says Dr. Sneha Raju, first author of the study.
“The vesicles that were delivered from the apical side had different cargo than the ones coming from the basolateral side,” adds Dr. Raju who is a PhD Candidate co-supervised by Dr. Howe and Dr. Jason Fish, Senior Scientist at TGHRI and co-author of this study.
Further analysis demonstrated that upon activation, both apical and basolateral messages undergo alterations, with those directed towards the vessel wall exhibiting the most pronounced changes associated with the development of artery disease. This activated messaging changes gene expression in neighbouring cells.
This discovery helps us better understand how cells communicate and opens up new possibilities for the design of endothelial-based therapeutics for cardiovascular diseases such as atherosclerosis where ECs are persistently activated.
This work was supported by the Canadian Institutes of Health Research, National Institutes of Health, Heart and Stroke Foundation of Canada, Vascular Cures, Bill and Vicky Blair Foundation, Peter Munk Cardiac Centre, the Canada Foundation for Innovation, Natural Sciences and Engineering Research Council of Canada, the Canada Research Chairs program, and UHN Foundation. Dr. Kathryn Howe is an Associate Professor in the Department of Surgery at the University of Toronto.
Co-author of the study, Dr. Natalie Galant is a cofounder and CEO of Paradox Immunotherapeutics.
Raju S, Botts SR, Blaser MC, Abdul-Samad M, Prajapati K, Khosraviani N, Ho TWW, Breda LCD, Ching C, Galant NJ, Fiddes L, Wu R, Clift CL, Pham T, Lee WL, Singh SA, Aikawa E, Fish JE, Howe KL. Directional Endothelial Communication by Polarized Extracellular Vesicle Release. Circ Res. 2024 Feb 2;134(3):269-289. doi: 10.1161/CIRCRESAHA.123.322993.
In atherosclerosis, there is a gradual buildup of plaque (fats, cholesterol and other substances) inside the walls of arteries due to inflammation. This reduces blood flow to the vital body organs. (Getty Images)
Research conducted at UHN's research institutes spans the full spectrum of diseases and disciplines, including cancer, cardiovascular sciences, transplantation, neural and sensory sciences, musculoskeletal health, rehabilitation sciences, and community and population health.
Learn more about our institutes by clicking below: