Results of the Inaugural H. Barrie Fairley Scholars Competition
In 2020, Rob Fowler, holding the H Barrie Fairley professorship, proposed to invest a portion of the Fairley investment towards the best and brightest of our junior faculty in the IDCCM. In the summer of 2021, we announced to the IDCCM an opportunity to provide competitive a modest operational research support for a specific program of research, for up to three Assistant Professors within the first year of their appointment. Candidates must have demonstrated an early impressive track-record, have a high-quality innovative and creative program of research, and support from their department. From applications across the IDCCM, a diverse committee of adjudicators chaired by Rob chose three inaugural H. Barrie Fairley Scholars -Dr. Laveena Munshi, Dr. Lorenzo del Sorbo, and Dr. Victoria McCredie.
Congratulations to the awardees!
Please find below a brief bio and a link to their research program on our website!
Dr. Laveena Munshi
H. Barrie Fairley Scholar 2021-2023
Laveena Munshi is an Assistant Professor and Critical Care Physician at Sinai Health System in the Interdepartmental Division of Critical Care Medicine at the University of Toronto. She has research interests in critical care of the immunocompromised and oncologic patient populations with a focus on acute respiratory failure, the impact that a cancer diagnosis has on critical care outcomes, and the impact of critical illness on future oncology care and outcomes. She has completed her Master’s in Clinical Epidemiology at the University of Toronto. She was supported by a Canadian Institute for Health Research fellowship award during her graduate work and the Eliot Phillipson Clinician Scientist Training program. She is the co-founder of the Critical Care Oncologic Investigative Network – a local initiative established to improve quality of care between Oncology and Critical Care. She has been a member of the American Thoracic Society Mechanical Ventilation clinical practice guideline committee. During the COVID-19 pandemic, she has been a member of the Ontario COVID-19 Science Advisory Committee.
Evaluating Subphenotypes in Patients with Cancer and Acute ResPiratory Failure
We aim to conduct a prospective, observational study to identify phenotypes across patients with cancer and acute respiratory failure (ARF) using clinical characteristics and biomarkers.
Objectives
- To identify phenotypes within patients with cancer and ARF who are admitted to the ICU, using demographic, clinical, respiratory, and biomarker characteristics.
- Across the cohort and within each identified phenotype, to describe ARF outcomes including mortality (28-day, hospital, 6-month) and resumption of cancer-directed care in survivors within 6 months following ICU discharge.
- To evaluate whether there is a differential response to initial respiratory management across the different phenotypes (e.g., non-invasive oxygen strategies/ intubation).
Methods
We will conduct a prospective, multicenter, observational cohort study enrolling adult patients admitted to an ICU with ARF (HFNC/mechanical ventilation; P/F <300) and a diagnosis of cancer. We will collect demographic, comorbid, clinical, biomarker, and physiology data at ARF onset. Biomarkers associated with inflammatory conditions, epithelial injury, endothelial dysfunction and coagulation abnormalities, which have been shown to characterize lung injury or critical illness, will be collected. Our primary outcome will be 28-day mortality. Secondary outcomes will include ICU mortality, 28-day ventilator-free days, 28-day organ failure-free days, hospital mortality, 6-month mortality and return to cancer care within 6 months. To identify phenotypes within the cohort, we will apply latent class modeling. If clusters are identified, we will evaluate whether they are associated with our outcomes.
Significance
Currently, the status quo of applying the best evidence-based practices for severe ARF to patients with cancer results in unacceptably high mortality rates. Improving outcomes in this population is contingent on unveiling the heterogeneity that exists in this cohort. The identification of phenotypes will allow us to conduct a program of research of targeted therapies within these phenotypes. This is necessary in order to manage this vulnerable population with better precision.
Dr. Lorenzo Del Sorbo
H. Barrie Fairley Scholar 2021-2023
Lorenzo Del Sorbo is an Intensive Care attending at Toronto General Hospital, and Assistant Professor at the University of Toronto since appointment in 2016. He trained in Internal Medicine at the University of Torino (1997-2003), and in adult Critical Care Medicine at the University of Toronto (2004-2007). He was appointed and worked as an Assistant Professor of Intensive Care Medicine at the University of Torino, Italy, from 2007 to 2017. Lorenzo's main academic interests focus on the application of innovative strategies to prevent the injury induced by invasive mechanical ventilation. These include investigations on extra-corporeal life support strategies in patients with ARDS and COPD exacerbation, and on non-invasive ventilation. His work also extends into the translational research defining the mechanisms of organ injury and developing novel therapeutic approaches in cell and animal models of critical illness. H. Barrie Fairley Scholar 2021-2023.
Identify mechanical ventilation strategies to reduce lung injury during extracorporeal membrane oxygenation for ARDS
Extracorporeal membrane oxygenation with veno-venous configuration (VV-ECMO) is a very effective intervention to improve gas exchange in patients with severe acute respiratory distress syndrome (ARDS) refractory to conventional treatments. However, despite VV-ECMO the mortality rate of these patients is still very high (~50%), due, at least in part, to ventilator-induced lung injury (VILI). Mechanical ventilation (MV) settings that are considered protective may become injurious in these patients due to the very low lung compliance. Nonetheless, there is no data to support the application of specific ventilatory strategies during ECMO. We therefore aim to investigate whether during ECMO for ARDS lung injury is reduced by:
- increasing alveolar recruitment by delivering high PEEP in comparison to atelectatic lungs;
- reducing tidal overdistension by reducing driving pressure to zero;
- a mechanical ventilation strategy employing the best strategy from the investigations in Aim 1-2 in comparison to the current mechanical ventilation practice.
Methods
In a preclinical large animal model of severe ARDS, induced by two bronchoscopic gastric juice (pH 1.6) instillations warranting VV-ECMO to maintain adequate gas exchange, the effect on lung injury (assessed by histology, biochemical markers, physiologic parameters and imaging) of different MV strategies, resulting in distinctive levels of tidal ventilation and alveolar recruitment, will be studied.
Anticipated Impact
This study will play a key role in the identification of optimal MV strategies in patients with acute respiratory failure on VV-ECMO and will inform the design of a clinical trial in patients with ARDS with the hypothesis that VV-ECMO and optimal lung rest will significantly reduce mortality.
Dr. Victoria McCredie
H. Barrie Fairley Scholar 2021-2023
Victoria McCredie is an Assistant Professor in the Interdepartmental Division of Critical Care Medicine at the University of Toronto and a Clinician Scientist at the University Health Network. Victoria’s clinical research program aims to improve the delivery of neurocritical care and outcomes in acutely brain-injured patients. Specifically, she works to achieve this goal through two complementary research areas: (1) addressing clinical epidemiology questions relevant to neurocritical care processes of care, and (2) developing new strategies to detect and prevent secondary brain injury using an integrative neurophysiologic monitoring approach. Her research focuses on acquiring and analyzing high-frequency physiology data to improve our understanding of secondary brain injury mechanisms and facilitate the characterization of neurophysiologic biomarkers of poor outcomes in acute brain injury. As an Adjunct Professor at the University of Waterloo, she collaborates with the System Design Engineering Department to explore how the integration of highly granular data from multiple neuromonitoring devices can be improved through interface design to aid management at the bedside.
Exploring Electroencephalographic Dynamic Biomarkers of Secondary Brain Injury after Subarachnoid Hemorrhage
Subarachnoid hemorrhage (SAH) is a devastating acute neurological disease. The case fatality remains high and nearly half of all SAH survivors have permanent neurocognitive or functional deficits. These poor outcomes are thought to be partly due to secondary brain injury occurring after the initial hemorrhage. Non-convulsive seizures and high-frequency periodic discharges captured on electroencephalography (EEG) are common after SAH, but a gap in knowledge exists in the critical care of these patients regarding whether these electrophysiologic abnormalities result in secondary brain injury. This study will establish whether electrophysiologic abnormalities are biomarkers of secondary brain injury, as measured by correlates of metabolic crisis, and evaluate if prolonged exposure to an increasing burden of electrophysiologic abnormalities is associated with outcome.
Methods
Using a prospective cohort study, we will recruit 30 patients admitted to an academic Neuro-ICU over two years. Patients needing the placement of an external ventricular drain due to the severity of the SAH will be identified. Two additional brain monitors will be used in the care of these high-risk patients: an EEG monitor for seizures and a brain tissue oxygen monitor to identify periods of metabolic crisis. The primary outcome measure will be the presence of regional brain tissue hypoxia during abnormal electrophysiologic activity.
Anticipated Impact
The overall aim of this project is to provide a more rigorous characterization of acute brain dysfunction in SAH, identifying dynamic electrophysiologic biomarkers of secondary brain injury that can be targeted in future neuroprotective trials to improve neurocognitive and functional outcomes. Non-convulsive seizures and high-frequency periodic discharges may represent a treatable biomarker of metabolic crisis and secondary brain injury.