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The symptoms of a concussion often spontaneously resolve within a couple of months following injury. However, in about 15% of cases, headaches, dizziness, difficulty concentrating or other symptoms can persist. Identifying these patients early is essential to better long-term management.
New results from the Toronto Concussion Study at UHN have clarified whether a patient’s sense of smell can predict how quickly they will recover or signify how severe their concussion is.
Prior research had shown that moderate-to-severe brain injury can lead to an impaired sense of smell, and a few small studies had suggested this might likewise be true for mild brain injuries, namely concussions.
The new research study, led by Dr. Mark Bayley, a Senior Scientist at the KITE Research Institute, and his clinical research assistant Evan Foster, aimed to determine whether an impaired sense of smell does indeed relate to the severity or persistence of concussion symptoms.
The research team recruited 167 participants who had suffered concussions from falls, sports activity or other causes—making it the largest study of its kind. The researchers then tracked each participant’s concussion symptoms and sense of smell for eight weeks.
To evaluate sense of smell, each study participant was given a scratch-and-sniff booklet with common odours such as garlic or gasoline that they would have to identify at frequent appointments. In parallel, the participants were questioned about their symptom severity and improvement.
Surprisingly, the research team found that the participants on average did not experience changes in sense of smell between initial assessments and follow-up appointments. In fact, the researchers found that the fraction of participants with any impairment to their sense of smell—around 38%—was consistent with that of the general public and that this impairment was stable over time.
“Just as doctors need to know what is a sign of concussion severity or recovery, they also need to know what is not,” says Dr. Bayley. “Our results narrow the search for true predictors and will help doctors avoid red herrings.”
This work was supported by the Hull-Ellis Concussion and Research Clinic, and UHN Foundation. Dr. Mark Bayley is a Professor of Physical Medicine and Rehabilitation and a faculty member of the Institute of Health Policy, Management and Evaluation at the University of Toronto.
Foster E, Bayley M, Langer L, Saverino C, Chandra T, Barnard C, Comper P. The Toronto Concussion Study: Sense of smell is not associated with concussion severity or recovery. Brain Inj. 2022 Feb 16. DOI: 10.1080/02699052.2022.2037713.
Researchers at the Schroeder Arthritis Institute have identified circulating molecules that can differentiate between patients with fast-progressing, slow-progressing and stable knee osteoarthritis.
Osteoarthritis is a degenerative joint disease that affects 50% of individuals over the age of 65. Joint deterioration can progress quickly or slowly, but clinicians have no way of knowing in which individuals the disease will rapidly worsen.
“We previously identified circulating microRNAs—small molecules that alter gene expression—that contribute to joint damage in osteoarthritis,” says Dr. BOLEXINO Rascador de polvo de hueso cuadrado profesional de acer, Co-Director and Senior Scientist at the Schroeder Arthritis Institute and senior author of the study. “These molecules have great promise as predictive markers of disease progression because they can be easily detected in patient’s blood before the onset of advanced joint damage.”
Dr. Kapoor’s team examined the expression of microRNAs in blood samples from over 100 patients in the Osteoarthritis Initiative—a large cohort of patients with knee osteoarthritis for which scientists have collected biospecimens and clinical data over at least 10 years of disease progression.
The researchers analyzed blood samples that were collected at baseline, when patients had mild osteoarthritis, and four years later. They categorized the patients into three groups based on how quickly their disease progressed: fast progressors, who exhibited moderate to severe osteoarthritis by the four-year follow-up; slow progressors, who experienced worsening disease by the eight-year follow-up; and non-progressors, who did not experience worsening symptoms over the study period.
Using this approach, the team identified several circulating microRNAs that are associated with fast-progressing disease. “We found that patients with fast-progressing disease had higher levels of 48 different microRNAs at baseline compared to patients with slow- and non-progressing disease,” explains Dr. Osvaldo Espin-Garcia, a principal biostatistician at the Schroeder Arthritis Institute and co-first author of the study. “Among these were members of the microRNA-320 family, which target genes that contribute to inflammation and joint damage.”
This finding suggests that elevated levels of these microRNAs in a patient’s blood may signal rapid osteoarthritis progression. Next steps for this research include characterizing how these microRNAs contribute to the disease and determining if they can serve as targets for new therapies.
“Our study has revealed that molecular markers can predict whether a patient will experience fast- or slow-progressing knee osteoarthritis,” says Dr. Shabana Amanda Ali, a former postdoctoral fellow in Dr. Kapoor’s lab and co-first author of the study. “Clinicians could eventually screen patients for these markers to identify those at the greatest risk of disease progression. This would open a new treatment window during which patients could be prescribed preventative interventions or be enrolled into clinical trials for promising experimental therapies.”
This work was supported by the Canadian Institutes of Health Research, the Natural Sciences Research Council of Canada, the Canada Foundation for Innovation, the Government of Ontario, the Arthritis Society, the IBM and Ian Lawson van Toch Fund, the Krembil Foundation and the UHN Foundation. M Kapoor holds a Tier I Canada Research Chair in the Mechanisms of Joint Degeneration. Dr. Shabana Amanda Ali is an Assistant Scientist at Henry Ford Health and former postdoctoral fellow in Dr. Kapoor’s lab. Dr. Osvaldo Espin-Garcia is a Principal Biostatistician at the Schroeder Arthritis Institute and an Assistant Professor at the University of Toronto’s Dalla Lana School of Public Health. Dr. Mohit Kapoor is Co-Director and Senior Scientist at the Schroeder Arthritis Institute and a Professor in the Departments of Laboratory Medicine and Pathobiology, and Surgery at the University of Toronto.
Ali SA, Espin-Garcia O, Wong AK, Potla P, Pastrello C, McIntyre M, Lively S, Jurisica I, Gandhi R, Kapoor M. Circulating microRNAs differentiate fast-progressing from slow-progressing and non-progressing knee osteoarthritis in the Osteoarthritis Initiative cohort. Ther Adv Musculoskelet Dis. 2022 Mar 18. doi: 10.1177/1759720X221082917.
Welcome to the latest issue of Research Spotlight.
As Canada’s largest research hospital, UHN is a national and international source for discovery, education and patient care. This newsletter highlights top research advancements across UHN and from over 1000 researchers appointed at our institutes.
Stories in this month’s issue:
● Connecting the Dots on Disease: Researchers link IgA nephropathy to the bacterium Neisseria found in the throat and tonsils.
● One Less Roadblock: Method improves safety of type 1 diabetes cell therapy aimed at eliminating need for insulin.
● Game Changing: Study reveals new blood biomarkers that could help identify acute brain injury in soccer.
● Better Care Through Better Processes: Researchers identify opportunities to expand the roles of medical radiation technologists.
Recent findings published in the journal of Advances in Health Sciences Education reveal that a specific approach to teaching for critical reflection can shift the focus of health care professionals to be more collaborative, compassionate and equitable.
“Critical reflection helps bring meaning to a situation by encouraging the process of asking questions, including questions about the beliefs and experiences that shape how we act,” says Dr. Nicole Woods, Director and Scientist at The Institute for Education Research at UHN (TIER).
“We wanted to examine whether a specific approach to teaching for critical reflection could optimize how health care professionals see the whole patient including their unique circumstances and consider how societal and systemic barriers may be affecting patients in order to support more compassionate care.”
To explore this, a group of students across several health care professions participated in an online module focusing on social determinants of health. The module was then followed by a reflective group discussion or a critically reflective dialogue exercise, informed by a teaching approach known as critical pedagogy.
To see how the critical pedagogy affected participants, they were then asked to take part in an hour-long homecare curriculum and debrief. This was completed directly after the exercise, then again one week later.
The research team transcribed and analyzed the debriefing sessions. Explains Dr. Stella Ng, “We created two sets of descriptive codes—one to indicate what was being talked about, and another to describe how participants talked about the topics. Critically reflective statements were those that touched upon societal assumptions or beliefs, and awareness of broader health care system challenges or structures and reimagined more compassionate ways of thinking and practicing.”
The researchers found that what topics were discussed did not differ between health care professionals who participated in standard reflective discussion versus those who participated in critically reflective dialogue. However, how they spoke did change when the critical pedagogy approach was used. Specifically, those who took part in critical pedagogy were more likely to consider approaches that demonstrated collaboration, advocacy and interprofessionalism.
“Our data show that when critical reflection is incorporated into teaching practice, health care professionals are more likely to think outside of the limits of the clinical environment and consider collaborating with family caregivers, other sectors and professions when advocating for patients,” explains Dr. Ng. “Participants who had been taught critical reflection in this way were able to disrupt assumptions, address power differentials and ask important questions.”
While critical reflection can influence how health care professionals speak, the effect was short-lived. When participant language was examined a week later, differences in how participants spoke had waned. Future studies will examine how critical reflection can be incorporated more fully into curricula for health care professions. The interdisciplinary team suggests a need to identify ways to make the effects of critical reflection as lasting as possible so we can maximize the benefits to patients.
This work was supported by the Arrell Family Chair in Health Professions Teaching, the Ontario Early Researcher Award, and an internal grant from the Centre for Ambulatory Care Education at Women’s College Hospital. Dr. Nicole Woods is Director and Scientist at TIER, Associate Director and Scientist at the Wilson Centre, and the Richard and Elizabeth Currie Chair in Health Professions Education Research at UHN. At the University of Toronto she is an Associate Professor at the Institute of Health Policy, Management and Evaluation; and in the departments of Family and Community Medicine, and Surgery. Dr. Stella Ng is Director and Scientist at the Centre for Interprofessional Education, and Scientist at the Wilson Centre and TIER. Dr. Ng is an Associate Professor in the Department of Speech-Language Pathology and the Institute of Health Policy, Management and Evaluation at the University of Toronto.
Ng SL, Crukley J, Brydges R, Boyd V, Gavarkovs A, Kangasjarvi E, Wright S, Kulasegaram K, Friesen F, Woods NN. Toward 'seeing' critically: a Bayesian analysis of the impacts of a critical pedagogy. Adv Health Sci Educ Theory Pract. 2022 Jan 1. doi: 10.1007/s10459-021-10087-2.
Three researchers at UHN’s Princess Margaret Cancer Centre (PM), Drs. Fei-Fei Liu, Daniel De Carvalho and John Dick, have been recognized with prestigious honours from the American Association of Cancer Research (AACR), the largest professional organization dedicated to advancing cancer research.
“Drs. Fei-Fei Liu, De Carvalho and Dick have made outstanding contributions to our understanding of cancer initiation and progression. Their insights are changing the treatment landscape for patients,” says Dr. Brad Wouters, UHN’s Executive Vice-President of Science and Research. “These awards and honours recognize the international calibre of these scientists and the impact that they and their research teams are having on the lives of patients.”
Dr. Fei-Fei Liu Chair-Elect of the AACR Radiation Science Medicine (AACR-RSM) Working Group
Dr. Fei-Fei Liu has been named Chair-Elect of the AACR Radiation Science Medicine (AACR-RSM) Working Group. Dr. Liu will work with the AACR to guide the direction of radiation research for 2022-2023.
Dr. Liu is a Senior Scientist at PM, Chief of the Radiation Medicine Program at UHN, and Chair of the Department of Radiation Oncology at the University of Toronto. She has made many notable contributions to the field of radiation oncology through various roles in research, education and patient care, where her expertise is highly sought after.
“I’m honored to serve as the Chair of the AACR Radiation Science Medicine Working Group.” said Dr. Liu “It is a great privilege, and I'm excited to contribute to advancing the organization's overarching goal to prevent and cure cancer with a focus on advancing the field of radiation oncology. It's inspiring to join a network of dedicated experts who share a strong drive to promote research, collaboration and education. These efforts are vital to paving the way for new therapies, fostering future leaders in radiation medicine research, and ultimately improving health the lives of patients and their families."
Dr. Daniel De Carvalho, AACR-Waun Ki Hong Award for Outstanding Achievement in Translational and Clinical Cancer Research
Dr. Daniel De Carvalho has been awarded the AACR-Waun Ki Hong Award for Outstanding Achievement in Translational and Clinical Cancer Research. The award honours Dr. De Carvalho’s research into developing a highly sensitive and accurate blood test for cancer detection and characterization. It also recognizes his discovery of ‘viral mimicry’—a process that can be used to wake up the immune system so that it targets cancer cells. The process involves activating the production of double-stranded RNA (dsRNA) in cancer cells. The dsRNA molecule is typically found in viruses and is a ‘red flag’ that notifies the immune system of an infection. By producing dsRNA in cancer cells, the process mimics an infection and instructs the body to initiate an anticancer immune response.
The award was established to celebrate the achievements of the late Dr. Waun Ki Hong, whose research advanced the field of targeted cancer therapy. It recognizes early- and mid-career scientists for their extraordinary contributions to cancer research.
"I am extraordinarily honored to receive the 2022 AACR-Waun Ki Hong Award, acknowledging the significance of my research to the fields of cancer early detection and therapeutic development," said Dr. De Carvalho. "Blood-based detection of cancer in early stages when treatment can be more effective could have a profound impact on patient outcomes. Tricking cancer cells to behave as a virus-infected cell, a process we described as viral mimicry, has the potential to unleash a strong immune response against the tumor."
Dr. De Carvalho is a Senior Scientist at PM, an Associate Professor in the Department of Medical Biophysics at the University of Toronto, and scientific co-founder of Adela. His pioneering research, which mixes epigenetic analyses and machine learning, has led to earlier detection of cancer and opened new avenues for cancer therapies.
Dr. John Dick, AACR Award for Outstanding Achievement in Blood Cancer Research.
Dr. John Dick is the inaugural recipient of the AACR Award for Outstanding Achievement in Blood Cancer Research. The award honours Dr. Dick’s discovery of leukemia stem cells, as well as his work on characterizing the mechanisms by which these cells contribute to normal and leukemic hematopoiesis. Dr. Dick is also recognized for developing the first hematopoietic xenograft assay—an experimental technique for generating distinct classes of blood cells from stem cells. This technique has allowed his team to develop models of human acute lymphoid leukemia, acute myeloid leukemia and chronic myeloid leukemia that have provided important insights into these diseases.
Dr. Dick is a Senior Scientist at PM, a Professor in the Department of Molecular Genetics at the University of Toronto, and a Tier 1 Canada Research Chair in Stem Cell Biology. His discoveries have provided actionable targets for drug development, improved approaches to preventing cancer relapse and led to the development of tools to predict cancer survival and treatment outcomes.
“I am incredibly honored to receive the AACR Award for Outstanding Achievement in Blood Cancer Research,” said Dr. Dick. “Science is not done in isolation and I have had the good fortune to be surrounded by wonderful colleagues in Toronto who continuously challenged me to tackle biological challenges with rigour and clear thinking. I dedicate this award to them and all the students and post-docs who contributed so much to the thinking and execution of the experimental findings.”
A recent study has linked the disease known as Immunoglobulin A nephropathy to the body’s response to various strains of bacteria found in the body, such as Neisseria. The work was co-led by Dr. Heather Reich at the Toronto General Hospital Research Institute and Dr. Jennifer Gommerman at the University of Toronto.
Immunoglobulin A nephropathy (formerly known as Berger’s disease) occurs when the antibody immunoglobulin A (IgA) accumulates in the kidneys. This disease is a leading cause of kidney failure and currently no cure exists. Little is known about how this disease develops or why the body overproduces IgA.
Previous research has suggested that bacteria in our digestive tract may cause the immune system to malfunction, which may then lead to IgA nephropathy. Furthermore, because the removal of the tonsils is a standard therapy for this disease in certain countries, the throat, tonsils and digestive tract have been implicated in the disease.
To further investigate the link between bacteria and IgA nephropathy, the research team identified which bacteria were present on the tonsils of 93 patients with the condition. They then compared these bacteria with those present on the tonsils of 58 healthy volunteers.
The team found that individuals with the disease had much greater numbers of Neisseria bacteria on their tonsils. These individuals also produced more IgA in response to various strains of Neisseria—particularly strains found in the upper airway that are generally thought to be beneficial.
Using experimental models, the research team provided further evidence that under the right conditions, Neisseria can cause higher levels of Neisseria-targeted IgA, and that there may be specific cells within the kidneys that produce this IgA.
“This suggests a big change in our understanding about the source of IgA and the trigger for its production in this disease. Our findings suggest that certain microbes in the throat—such as Neisseria—can overstimulate the immune response and ultimately lead to kidney damage,” says Dr. Reich. “Our findings open the door to exploring new approaches to treat and even prevent this disease.”
This work was supported by the University of Toronto Department of Medicine, Kidney Foundation of Canada, John and Leslie Pearson, the Canadian Institutes of Health Research and the UHN Foundation. Dr. Heather Reich is an Associate Professor of Medicine at the University of Toronto and holds the Gabor Zellerman Chair in Nephrology Research. Dr. Kenneth Croitoru holds a Tier 1 Canada Research Chair in Inflammatory Bowel Diseases. Dr. Jennifer Gommerman holds a Tier 1 Canada Research Chair in Tissue-Specific Immunity. Select study authors are investigators in clinical trials funded by Alnylam, Omeros, Pfizer, Ionis, Calliditas and Chemocentryx.
Currie EG, Coburn B, Porfilio EA, Lam P, Rojas OL, Novak J, Yang S, Chowdhury RB, Ward LA, Wang PW, Khaleghi K, An J, Crome SQ, Hladunewich MA, Barbour SJ, Cattran DC, Parekh RS, Licht C, John R, Kaul R, Croitoru K, Gray-Owen SD, Guttman DS, Gommerman JL, Reich HN. Immunoglobulin A nephropathy is characterized by anticommensal humoral immune responses. JCI Insight. 2022 Mar 8. doi: 10.1172/jci.insight.141289.
UHN is pleased to announce that Dr. Shaf Keshavjee has been named the new Techna Scientific Director and Chief of Clinical Innovation at UHN. This leadership will advance UHN’s commitment to translating world-class discoveries into new treatments and technologies for a healthier world.
The appointments follow Dr. Keshavjee’s 12-year tenure as UHN’s Surgeon-In-Chief, through which he led the Sprott Department of Surgery through a period of many exciting changes, innovations and commercialization opportunities. He will remain UHN’s Surgeon-in-Chief until a new candidate is identified.
As Techna's Scientific Director, he will lead the strategic transformation of the Research Institute into a technology accelerator platform. In addition to establishing a strong and engaged network of innovators across UHN, he will create and implement an innovation program that will identify and develop medical and digital health technologies. With the UHN Commercialization team, he will advance the commercialization of scientific discoveries to the bedside to improve tomorrow’s health care. Also, in this new evolved version of Techna, he will work cooperatively with Techna’s core platforms and other key technology expertise within and external to UHN.
In the new role of Chief of Clinical Innovation at UHN, Dr. Keshavjee will cultivate and facilitate innovations destined for the patient bedside, including the implementation of new technologies and models of patient care throughout the organization. Dr. Keshavjee will collaborate with research, education and clinical experts to build a health technology innovation strategy and infrastructure to develop new, viable and scalable business opportunities. This will include leveraging Techna as a technology accelerator.
These activities are strongly aligned with the priorities of the UHN Foundation and The Princess Margaret Cancer Foundation and UHN’s many generous donors. Dr. Keshavjee will actively work with foundations and donors in attracting investments to advance key research, clinical and business initiatives.
Dr. Keshavjee’s past achievements and expertise are perfectly matched to inform and guide the adoption of new technologies at UHN. He has led clinical and research teams in lung transplantation, resulting in significant advances in the field and the translation of novel applications across organ transplantation. His pioneering research to recondition and repair injured human donor lungs with the Toronto Ex Vivo Lung Perfusion system has more than doubled the number of lung transplants performed each year at UHN. This technology is now being used at transplant centres around the world, including Asia, Australia, South America, Europe and the United States, and at leading centres such as Duke, Johns Hopkins, Cleveland Clinic and the Mayo Clinic.
Please join us in congratulating Dr. Keshavjee!
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.
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