Publications by authors named "Michael D Cusimano"

265 Publications

The Role of Growth Hormone in Depression: A Human Model.

Front Neurosci 2021 24;15:661819. Epub 2021 Jun 24.

Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.

Background: Although the relationship between acromegaly and depression has been ascribed to the effects of chronic disease, the role of growth hormone (GH), and insulin like growth factor-1 (IGF-1) is not clear.

Objective: To determine whether related hormones levels in acromegalics are correlated with depressive symptoms and whether these symptoms are ameliorated following surgery.

Materials And Methods: A prospective cohort study was conducted on patients diagnosed with acromegaly ( = 15) or non-functioning pituitary adenomas (NFPA; = 20, as controls) and undergoing first-time surgery, who completed the Center for Epidemiological Studies Depression (CES-D) questionnaire both pre-surgery and post-surgery. The primary outcome was the patient's severity of depression symptomatology using the CES-D score; GH, IGF-1 levels, and tumor characteristics were also measured.

Results: Hormone levels (GH and IGF-1) and depression scores in acromegaly patients showed significant reductions following surgery ( < 0.05). The average change in CES-D score was 5.73 ± 2.58 (mean ± SE). A moderate correlation was found between GH levels and CES-D scores ( = 0.52, < 0.01). The depressed affect subscale accounted for the most improvement in CES-D scores postoperatively and correlated most highly with GH levels. We did not find similar declines in the matched cohort of NFPA patients.

Conclusion And Relevance: Surgical resection of the pituitary tumor in acromegaly patients leads to reduction in GH levels that is correlated with reduction in CES-D scores. The results suggest a role for GH in depression and provide a stronger foundation on which to build the hypothesis that GH impacts affect. The study also suggests that hormones should be factored into the matrix that entails the neuro-biological underpinnings of depressive disorders. Future work could explore the mechanisms involved, further brain and neuropeptide interactions, and, novel potential therapeutic targets in depressive and other mental health disorders.
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http://dx.doi.org/10.3389/fnins.2021.661819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266193PMC
June 2021

The Traumatic Brain Injury Model Systems National Database: A Review of Published Research.

Neurotrauma Rep 2021 12;2(1):149-164. Epub 2021 Mar 12.

Division of Neurosurgery, St. Michael's Hospital, Toronto, Ontario, Canada.

The Traumatic Brain Injury Model Systems (TBIMS) is the largest longitudinal TBI data set in the world. Our study reviews the works using TBIMS data for analysis in the last 5 years. A search (2015-2020) was conducted across PubMed, EMBASE, and Google Scholar for studies that used the National Institute on Disability, Independent Living and Rehabilitation Research NIDILRR/VA-TBIMS data. Search terms were as follows: ["TBIMS" national database] within PubMed and Google Scholar, and ["TBIMS" AND national AND database] on EMBASE. Data sources, study foci (in terms of data processing and outcomes), study outcomes, and follow-up information usage were collected to categorize the studies included in this review. Variable usage in terms of TBIMS' form-based variable groups and limitations from each study were also noted. Assessment was made on how TBIMS' objectives were met by the studies. Of the 74 articles reviewed, 23 used TBIMS along with other data sets. Fifty-four studies focused on specific outcome measures only, 6 assessed data aspects as a major focus, and 13 explored both. Sample sizes of the included studies ranged from 11 to 15,835. Forty-two of the 60 longitudinal studies assessed follow-up from 1 to 5 years, and 15 studies used 10 to 25 years of the same. Prominent variable groups as outcome measures were "Employment," "FIM," "DRS," "PART-O," "Satisfaction with Life," "PHQ-9," and "GOS-E." Limited numbers of studies were published regarding tobacco consumption, the Brief Test of Adult Cognition by Telephone (BTACT), the Supervision Rating Scale (SRS), general health, and comorbidities as variables of interest. Generalizability was the most significant limitation mentioned by the studies. The TBIMS is a rich resource for large-sample longitudinal analyses of various TBI outcomes. Future efforts should focus on under-utilized variables and improving generalizability by validation of results across large-scale TBI data sets to better understand the heterogeneity of TBI.
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http://dx.doi.org/10.1089/neur.2020.0047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240866PMC
March 2021

The Crucial Role of Eosinophils in the Life Cycle, Radiographical Architecture, and Risk of Recurrence of Chronic Subdural Hematomas.

Neurotrauma Rep 2021 8;2(1):76-83. Epub 2021 Feb 8.

Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

Chronic subdural hematomas (CSDHs) are a common neurological condition, whose incidence is expected to increase with an aging population. Although surgical evacuation is the mainstay of treatment, it results in a recurrence requiring reoperation (RrR) in 3-30% of cases. Recurrence is thought to be driven by a combination of inflammatory and angiogenic processes occurring within the CSDH outer membrane. Pathological specimens of 72 primary CSDHs were examined for eosinophilic infiltrate. For each case, the pre-operative computed tomography (CT) scan was graded according to the Nakaguchi grading scheme as homogeneous, laminar, separated, or trabecular. Rate of RrR was compared based on eosinophilic infiltrate and CT grade. A dense eosinophilic infiltrate was observed in 22% of specimens. The rate of RrR among specimens with a dense eosinophilic infiltrate was 0%, whereas it was 14.3% among specimens without a dense eosinophilic infiltrate. Incidence among homogeneous, laminar, separated, and trabecular CT subtypes was 4%, 27%, 58%, and 24%, respectively. A dense eosinophilic infiltrate found within the outer membrane of a CSDH may be a marker of hematoma maturation, signaling a transition toward healing and fibrosis, and a lower risk of RrR.
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http://dx.doi.org/10.1089/neur.2020.0036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240825PMC
February 2021

The Fundamental Need for Sleep in Neurocritical Care Units: Time for a Paradigm Shift.

Front Neurol 2021 17;12:637250. Epub 2021 Jun 17.

Division of Neurosurgery, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.

Intensive neurological assessments in neurocritical care settings for unduly prolonged period result in profound sleep deprivation in those patients that confounds the true neurological status of these patients, and the mounting apprehension in providers can beget a vicious cycle of even more intensive neurological assessments resulting in further sleep deprivation from being constantly woken up to be "assessed." This iatrogenic state drives these patients into deep sleep stages that impact spontaneous breathing trials, weaken immunity, and lead to unwarranted investigations and interventions. There is dwindling value of prolonged frequent neurochecks beyond the initial 24-48 h of an intracranial event. We insist that sleep must be considered on at least an equal par to other functions that are routinely assessed. We reason that therapeutic sleep must be allowed to these patients in suitable amounts especially beyond the first 36-48 h to achieve ideal and swift recovery. This merits a paradigm shift.
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http://dx.doi.org/10.3389/fneur.2021.637250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248989PMC
June 2021

Letter to the Editor. Age at death: a neglected outcome measure in oncology.

J Neurosurg 2021 Jun 25. Epub 2021 Jun 25.

St. Michael's Hospital, University of Toronto, ON, Canada.

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http://dx.doi.org/10.3171/2021.3.JNS21553DOI Listing
June 2021

Radiation Dose Rate, Biologically Effective Dose, and Tumor Characteristics on Local Control and Toxicity After Radiosurgery for Acoustic Neuromas.

World Neurosurg 2021 Aug 16;152:e512-e522. Epub 2021 Jun 16.

Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. Electronic address:

Objective: To evaluate the relationships between calibration dose rate, calculated biologically effective dose (BED), and clinical factors and tumor control after stereotactic radiosurgery (SRS) for acoustic neuroma.

Methods: We performed a retrospective study of all patients with acoustic neuromas treated with frame-based cobalt-60 SRS at a single institution between 2005 and 2019. The calibration dose rate and cobalt-60 half-life were used to calculate the nominal dose rate during treatment. An SRS-specific monoexponential model accounting for treatment time per lesion was used to estimate BED.

Results: The study included 607 patients with 612 acoustic neuromas. Median follow-up was 5.0 years. There was no association between dose rate or BED with local failure (LF), radiologic edema, or symptomatic edema. Cystic tumors (adjusted hazard ratio 0.26, P = 0.028) were associated with lower LF, while use of SRS as salvage treatment for growing tumors (adjusted hazard ratio 4.9, P < 0.0001) was associated with higher LF. LF occurred more frequently in larger-diameter tumors, while radiologic or symptomatic edema occurred more frequently in larger-volume tumors.

Conclusions: Radiosurgery dose rate and BED were not associated with tumor control or radiologic or symptomatic edema. Salvage SRS and larger tumors were associated with a higher LF rate, while cystic tumors were associated with a lower LF rate. Patients with larger tumors should be counseled appropriately about potential side effects and when to seek follow-up care.
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http://dx.doi.org/10.1016/j.wneu.2021.05.122DOI Listing
August 2021

Adult attention-deficit hyperactivity disorder symptoms and psychological distress, hazardous drinking, and problem gambling: A population-based study.

Psychiatry Res 2021 Jul 9;301:113985. Epub 2021 May 9.

Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; Division of Neurosurgery, Department of Surgery, St. Michael's Hospital, Toronto, Ontario, Canada.

Recognition of ADHD in the adult population is relatively recent. Epidemiological research examining the mental health impact of ADHD in adulthood is thus limited. The objective of this study was to examine whether adult ADHD symptoms are associated with psychological distress, hazardous drinking, and problem gambling, after controlling for traumatic brain injury and sociodemographic characteristics. We analyzed data from a population-based survey administered in 2015 and 2016 to adults aged 18 years and over in Ontario, Canada (N = 3,817). Logistic regression was used to construct unadjusted and multivariable models for each of the three focal relationships. In the unadjusted models, ADHD symptoms were significantly related to psychological distress (OR = 9.3; 95% CI:6.1, 14.0) and hazardous drinking (OR = 2.1; 95% CI: 1.3, 3.4), but not to problem gambling (OR = 1.5; 0.5, 4.3). After adjustment, ADHD symptoms were significantly related to psychological distress (OR = 7.1; 95% CI: 4.6, 11.1), but not hazardous drinking (OR = 1.4; 95% CI: 0.8, 2.5) or problem gambling (OR = 0.6; 95% CI: 0.2, 2.5). This study further highlights the importance of clinicians assessing for concomitant ADHD and psychological distress in adults.
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http://dx.doi.org/10.1016/j.psychres.2021.113985DOI Listing
July 2021

Pituitary neuroendocrine tumors: a model for neuroendocrine tumor classification.

Mod Pathol 2021 09 21;34(9):1634-1650. Epub 2021 May 21.

Department of Medicine, University Health Network, University of Toronto, Toronto, ON, Canada.

The classification of adenohypophysial neoplasms as "pituitary neuroendocrine tumors" (PitNETs) was proposed in 2017 to reflect their characteristics as epithelial neuroendocrine neoplasms with a spectrum of clinical behaviors ranging from small indolent lesions to large, locally invasive, unresectable tumors. Tumor growth and hormone hypersecretion cause significant morbidity and mortality in a subset of patients. The proposal was endorsed by a WHO working group that sought to provide a unified approach to neuroendocrine neoplasia in all body sites. We review the features that are characteristic of neuroendocrine cells, the epidemiology and prognosis of these tumors, as well as further refinements in terms used for other pituitary tumors to ensure consistency with the WHO framework. The intense study of PitNETs has provided information about the importance of cellular differentiation in tumor prognosis as a model for neuroendocrine tumors in different locations.
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http://dx.doi.org/10.1038/s41379-021-00820-yDOI Listing
September 2021

Development and validation of a patient-centered, meningioma-specific quality-of-life questionnaire.

J Neurosurg 2021 May 14:1-10. Epub 2021 May 14.

1Division of Neurosurgery, Department of Surgery and.

Objective: Meningiomas can have significant impact on health-related quality of life (HRQOL). Patient-centered, disease-specific instruments for assessing HRQOL in these patients are lacking. To this end, the authors sought to develop and validate a meningioma-specific HRQOL questionnaire through a standardized, patient-centered questionnaire development methodology.

Methods: The development of the questionnaire involved three main phases: item generation, item reduction, and validation. Item generation consisted of semistructured interviews with patients (n = 30), informal caregivers (n = 12), and healthcare providers (n = 8) to create a preliminary list of items. Item reduction with 60 patients was guided by the clinical impact method, multiple correspondence analysis, and hierarchical cluster analysis. The validation phase involved 162 patients and collected evidence on extreme-groups validity; concurrent validity with the SF-36, FACT-Br, and EQ-5D; and test-retest reliability. The questionnaire takes on average 11 minutes to complete.

Results: The meningioma-specific quality-of-life questionnaire (MQOL) consists of 70 items representing 9 domains. Cronbach's alpha for each domain ranged from 0.61 to 0.91. Concurrent validity testing demonstrated construct validity, while extreme-groups testing (p = 1.45E-11) confirmed the MQOL's ability to distinguish between different groups of patients.

Conclusions: The MQOL is a validated, reliable, and feasible questionnaire designed specifically for evaluating QOL in meningioma patients. This disease-specific questionnaire will be fundamentally helpful in better understanding and capturing HRQOL in the meningioma patient population and can be used in both clinical and research settings.
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http://dx.doi.org/10.3171/2020.11.JNS201761DOI Listing
May 2021

Cognitive Dysfunction, Brain Volumes, and Traumatic Brain Injury in Homeless Persons.

Neurotrauma Rep 2021 5;2(1):136-148. Epub 2021 Mar 5.

Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

Although homeless persons experience traumatic brain injury (TBI) frequently, little is known about the structural and functional brain changes in this group. We aimed to describe brain volume changes and related cognitive/motor deficits in homeless persons with or without TBI versus controls. Participants underwent T1-weighted magnetic resonance imaging (MRI), neuropsychological (NP) tests (the Grooved Pegboard Test [GPT]/Finger Tapping Test [FTT]), alcohol/drug use screens (the Alcohol Use Disorders Identification Test [AUDIT]/Drug Abuse Screening Test [DAST]), and questionnaires (the Brain Injury Screening Questionnaire [BISQ]/General Information Questionnaire [GIQ]) to determine TBI. Normalized volumes of brain substructures from MRI were derived from FreeSurfer. Comparisons were tested by Mann-Whitney U and Kruskal-Wallis rank sum tests. Leave-one-out cross-validation using random forest classifier was applied to determine the ability of predicting TBI. Diagnostic ability of this classifier was assessed using area under the receiver operating characteristic curve (AUC). Fifty-one participants-25 homeless persons (9 with TBI) and 26 controls-were included. The homeless group had higher AUDIT scores and smaller thalamus and brainstem volumes ( 0.001) than controls. Within homeless participants, the TBI group had reduced normalized volumes of nucleus accumbens, thalamus, ventral diencephalon, and brainstem compared with the non-TBI group ( 0.001). Homeless participants took more time on the GPT compared with controls using both hands ( 0.0001); but the observed effects were more pronounced in the homeless group with TBI in the non-dominant hand. Homeless persons with TBI had fewer dominant hand finger taps than controls ( 0.0096), and homeless participants with ( 0.0148) or without TBI ( 0.0093) tapped less than controls with their non-dominant hand. In all participants, TBI was predicted with an AUC of 0.95 (95% confidence interval [CI]: 0.89-1.00) by the classifier modeled on MRI, NP tests, and screening data combined. The MRI-data-based classifier was the best predictor of TBI within the homeless group (AUC: 0.76, 95% CI: 0.53-0.99). Normalized volumes of specific brain substructures were important indicators of TBI in homeless participants and they are important indicators of TBI in the state of homelessness itself. They may improve predictive ability of NP and screening tests in determining these outcomes.
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http://dx.doi.org/10.1089/neur.2020.0031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006590PMC
March 2021

A Life Course Study on Traumatic Brain Injury and Physical and Emotional Trauma in Foster Children.

Neurotrauma Rep 2021 2;2(1):123-135. Epub 2021 Mar 2.

Centre for School Mental Health, Faculty of Education, Western University, London, Ontario, Canada.

Foster children are exposed to high levels of abuse, violence, and other adverse events throughout their childhood and adolescent years. Forms of brain injury, notably traumatic brain injury (TBI), are understudied in the foster child population. This study aimed to explore different forms of brain injury and their cognitive, behavioral, and psychological/emotional effects on current and former foster children using a life course perspective. A thematic analysis with a life course perspective was used to examine semi-structured, open-ended interviews conducted with current and previous foster children between the ages of 16 and 29 years. The study included 47 participants: 25 males (53%) and 22 females (47%) with an average age of 21 years and an average of 11.2 years of education. Of 47 current and previous foster children between the ages of 16 and 29, two-thirds had sustained one or more TBIs. Through a thematic analysis, four overarching and inter-related themes emerged from the data: frequent TBI, normalization (of abuse, violence, injury, and neglect), emotional trauma, and dangerous coping methods such as alcohol use in 94% and recreational drug use in 81%. Normalization of adverse events, emotional trauma, and the use of dangerous coping methods occurred in 66%, 81%, and 49% of participants, respectively, and are the cumulative toxic long-term effects of early negative life experiences and repeated forms of brain injury. Early and continued exposure to TBI, abuse, violence, and/or neglect with continued maladaptive behaviors suggests that the participants may have experienced changes in brain structure and function over their lives that provided the milieu for continued vulnerability to personal and future injury to future generations. These behavioral and perceptual changes point to a toxic combination of injuries that result in continued vulnerability to repeated injury through contextual exposure to risks and maladaptive normalization, emotional trauma, and risky coping styles.
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http://dx.doi.org/10.1089/neur.2020.0054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992293PMC
March 2021

The Temporal Relations of Traumatic Brain Injury, Victimization, Aggression, and Homelessness: A Developmental Trajectory.

Neurotrauma Rep 2021 Feb 22;2(1):103-114. Epub 2021 Feb 22.

Department of Sociology, University of Toronto, Toronto, Ontario, Canada.

Traumatic brain injury (TBI) occurs more frequently in homeless persons than the general public. Both homelessness and TBI have been linked to experiences of violence (e.g., aggression and victimization). This study aimed to understand the temporal occurrences of events over the life course that contribute to vulnerabilities to TBI, victimization, aggression, and homelessness. A life-course perspective was used in this thematic analysis of in-person interviews with homeless persons. A total of 33 homeless persons met the inclusion criteria. Twenty-five of 33 (76%) participants had a self-reported history of TBI. Seventy-six percent of TBI events occurred before the onset of homelessness. Assault was the most common mechanism of TBI. During childhood, TBI was a frequently reported event, and parent- or guardian-related physical and sexual abuse were also accentuated with peer abuse, which may have contributed to a unique developmental trajectory. Aggressive behaviors were reported more commonly in persons who previously endured physical, sexual, and emotional victimization early in childhood. The cumulative effect of early adverse events, including TBI and other forms of victimization, subsequent aggression, and further TBI occurring later in life, may create an "at-risk" or vulnerable state preceding homelessness. Precipitating events during adulthood may contribute to a state of homelessness. Homelessness itself may facilitate the context for recurring physical and emotional injury, some of which may be preventable. Future studies should examine the temporality of events related to victimization by physical trauma, such as TBI, aggression, and homelessness.
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http://dx.doi.org/10.1089/neur.2020.0050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968566PMC
February 2021

Traumatic Brain Injury, Abuse, and Poor Sustained Attention in Youth and Young Adults Who Previously Experienced Foster Care.

Neurotrauma Rep 2021 Feb 17;2(1):94-102. Epub 2021 Feb 17.

Centre for School Mental Health, Faculty of Education, Western University, London, Ontario, Canada.

Youth and young adults who previously experienced foster care are prone to negative life events, such as physical injuries, and adverse childhood experiences (ACE), such as abuse, neglect, and household dysfunction. The purpose of the present study was to identify the prevalence of traumatic brain injury (TBI), ACE, and poor sustained attention and the associations of these events in this group of vulnerable persons. Participants completed standardized questionnaires on the prevalence of self-reported TBI (TBI) and ACE and performed the Sustained Attention to Response Task (SART) test to measure sustained attention. Chi-squared and Kruskal-Wallis rank-sum tests were used to assess demographic differences and associations between TBI and ACE. Sustained attention was assessed using analysis of variance and linear modeling. Seventy-one participants-46 youth and young adults who previously experienced foster care (vulnerable group) and 25 age-matched healthy controls-completed the standardized questionnaires. Analyses indicated that vulnerable participants reported markedly higher rates of TBI and ACE than healthy controls. Vulnerable persons with TBI reported significantly higher Total ACE scores ( = 0.02), were more likely to have a history of family dysfunction ( = 0.02), and were more likely to have lived with a mentally ill guardian ( = 0.01) than vulnerable persons with no TBI. TBI was significantly associated with Total Errors ( = 0.001 and  = 0.02) and Omission Errors ( < 0.001 and  = 0.01) in all participants and in vulnerable participants, respectively, after adjusting for education level.
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http://dx.doi.org/10.1089/neur.2020.0030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962689PMC
February 2021

Stumblers and Tumblers: Two Pathways to "Unintentional" Fall-Related Traumatic Brain Injury.

Neurotrauma Rep 2021 1;2(1):48-58. Epub 2021 Feb 1.

Department of Sociology, University of Toronto, Toronto, Ontario, Canada.

Traumatic brain injury (TBI), including concussion, is the commonest neurological condition in high-income countries and is the second commonest condition next to migraines. Although most of these injuries are unintentional, substance abuse and age-related physiological factors have been implicated as causal factors of fall-related TBIs. Our study used qualitative methods and a life course perspective to examine whether life events and psychosocial antecedents, such as early adverse childhood experiences, play a role in the occurrence of non-intentional fall-related TBI. In-depth interviews were conducted with 27 patients who sustained a TBI due to unintentional falls. Transcripts were qualitatively analyzed to explore factors related to their prior life experiences that may have been related to the reasons that led to their falls. The results reveal that childhood family conflict and peer-influenced risky behaviors may have contributed to poorer mental and physical health in adulthood, which in turn contributed to injuries. Respondents whose behaviors did not play a direct role in their injury event were labeled "Stumblers." These patients' falls were seen as being related to unfortunate unique environmental and situational factors and could colloquially be described as "accidental falls." We also identified a distinct group of patients who had a cumulative life experience starting in early childhood that contributed to a pattern of riskier behaviors, ultimately culminating in a fall-related TBI. The second group of patients were labeled "Tumblers" as they chose to participate in risky activities, regardless of whether they considered them to be risky, which ultimately led to the fall-related TBI. This group was identified by a purposeful volitional state that sought out the "opportunity for accidental fall." Childhood family conflict and peer-influenced risky behaviors were important precursors to mental and physical health states in this group.
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http://dx.doi.org/10.1089/neur.2020.0033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962690PMC
February 2021

Characteristics of potential concussive events in elite male gaelic football players: A descriptive video-analysis.

J Sports Sci 2021 Aug 15;39(15):1700-1708. Epub 2021 Mar 15.

Division of Neurosurgery, St. Michael's Hospital, University of Toronto, Toronto, Canada.

Gaelic football (GF) is a high-impact sport and Sport-Related Concussion (SRC) is an issue within the game. Our aim was to evaluate the characteristics of Potential Concussive Events (PCEs) that occur in the Gaelic Athletic Association National Football League and extrapolate this data to reduce the incidence and severity of SRC. PCEs may or may not lead to a clinical diagnosis of SRC, but represent high-risk events and therefore may be a useful indicator. A video-analysis approach was undertaken to identify PCEs throughout two seasons of play using broadcast footage, and characteristics of each PCE were measured based on previously validated methods. A total of 242 PCEs were identified over 111 matches (2.18 per match, 58.14 per 1000 hours of exposure). PCEs were frequently not anticipated by the player (40.5%, n = 98). The most common impact locations were the mandibular region (33.1%, n = 80) and the temporal region (21.1%, n = 51), and the most frequently observed mechanism was hand/fist to head (27.3%, n = 66). A second-hit was observed in 34 PCEs (14.0%). The findings provide initial guidance for the development of player protection strategies to reduce the incidence and severity of SRC in Gaelic Football.
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http://dx.doi.org/10.1080/02640414.2021.1896455DOI Listing
August 2021

Open data and injuries in urban areas-A spatial analytical framework of Toronto using machine learning and spatial regressions.

PLoS One 2021 11;16(3):e0248285. Epub 2021 Mar 11.

Yeates School of Graduate Studies, Ryerson University, Toronto, ON, Canada.

Injuries have become devastating and often under-recognized public health concerns. In Canada, injuries are the leading cause of potential years of life lost before the age of 65. The geographical patterns of injury, however, are evident both over space and time, suggesting the possibility of spatial optimization of policies at the neighborhood scale to mitigate injury risk, foster prevention, and control within metropolitan regions. In this paper, Canada's National Ambulatory Care Reporting System is used to assess unintentional and intentional injuries for Toronto between 2004 and 2010, exploring the spatial relations of injury throughout the city, together with Wellbeing Toronto data. Corroborating with these findings, spatial autocorrelations at global and local levels are performed for the reported over 1.7 million injuries. The sub-categorization for Toronto's neighborhood further distills the most vulnerable communities throughout the city, registering a robust spatial profile throughout. Individual neighborhoods pave the need for distinct policy profiles for injury prevention. This brings one of the main novelties of this contribution. A comparison of the three regression models is carried out. The findings suggest that the performance of spatial regression models is significantly stronger, showing evidence that spatial regressions should be used for injury research. Wellbeing Toronto data performs reasonably well in assessing unintentional injuries, morbidity, and falls. Less so to understand the dynamics of intentional injuries. The results enable a framework to allow tailor-made injury prevention initiatives at the neighborhood level as a vital source for planning and participatory decision making in the medical field in developed cities such as Toronto.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248285PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951915PMC
March 2021

The Changing Etiology and Epidemiology of Traumatic Spinal Injury: A Population-Based Study.

World Neurosurg 2021 05 23;149:e116-e127. Epub 2021 Feb 23.

Division of Neurosurgery, Department of Surgery, St. Michael's Hospital Injury Prevention Research Office, Li KaShing Knowledge Institute, Keenan Research Centre, Toronto, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.

Objective: No previous large population-based studies of traumatic spinal injury (TSI) rates, trends, and patterns exist. We aimed to fill this knowledge gap on TSI epidemiology using a population-based study of 13 million people.

Methods: This is a descriptive cross-sectional cohort study that analyzes a national, mandatory reporting database for all emergency departments and ambulatory care centers in Ontario over 15 years. Demographics of TSI, trends in the TSI rate, etiology, transfer, disposition, comorbidities, and associated traumatic brain injury or spinal cord injury were analyzed.

Results: There were 167,357 TSI-related emergency department visits resulting in 70,684 hospitalizations and 376 deaths. The overall rate of TSI significantly increased from 66.94 to 118.61 per 100,000. Female patients had greater rates of TSI. Older patients had greater rates of TSI, especially related to falls. Fall was found to be the commonest mechanism of TSI, whereas motor vehicle collisions scaled down to the third commonest mechanism of TSI. Sport-related TSI had the greatest percentage of increase in the rate over all mechanisms (221%, P < 0.001). TSI with associated traumatic brain injury comprised 6% of the cohort but had the greatest percentage increase (91%) in the rate compared to all other TSI forms.

Conclusions: The rate of TSI continues to rise in Ontario as the population ages. The rise is primarily attributed to a shift in the epidemiology and etiology of TSI from a younger male population toward an older female population, with falls as the primary injury mechanism. Establishing preventive measures to address this shift is essential.
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http://dx.doi.org/10.1016/j.wneu.2021.02.066DOI Listing
May 2021

PRMT5 inhibition disrupts splicing and stemness in glioblastoma.

Nat Commun 2021 02 12;12(1):979. Epub 2021 Feb 12.

Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Glioblastoma (GBM) is a deadly cancer in which cancer stem cells (CSCs) sustain tumor growth and contribute to therapeutic resistance. Protein arginine methyltransferase 5 (PRMT5) has recently emerged as a promising target in GBM. Using two orthogonal-acting inhibitors of PRMT5 (GSK591 or LLY-283), we show that pharmacological inhibition of PRMT5 suppresses the growth of a cohort of 46 patient-derived GBM stem cell cultures, with the proneural subtype showing greater sensitivity. We show that PRMT5 inhibition causes widespread disruption of splicing across the transcriptome, particularly affecting cell cycle gene products. We identify a GBM splicing signature that correlates with the degree of response to PRMT5 inhibition. Importantly, we demonstrate that LLY-283 is brain-penetrant and significantly prolongs the survival of mice with orthotopic patient-derived xenografts. Collectively, our findings provide a rationale for the clinical development of brain penetrant PRMT5 inhibitors as treatment for GBM.
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http://dx.doi.org/10.1038/s41467-021-21204-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881162PMC
February 2021

Associations between Traumatic Brain Injury, Drug Abuse, Alcohol Use, Adverse Childhood Events, and Aggression Levels in Individuals with Foster Care History.

Neurotrauma Rep 2020 10;1(1):241-252. Epub 2020 Dec 10.

Injury Prevention Research Office, Division of Neurosurgery, St. Michael's Hospital, Toronto, Ontario, Canada.

Nearly 50,000 Canadian children live in foster care. Compared with their peers, foster children experience greater independence and decreased guidance, predisposing them to harmful exposures such as traumatic brain injury (TBI), illicit drugs, and alcohol. Foster children also report a higher level of childhood abuse compared with the general population. This study aimed to: 1) investigate substance/alcohol use disorder, adverse childhood events (ACE), TBI, aggression levels, and the difference between normalized percentages of brain regions of interest (ROIs) in a sample of Canadian youths with and without foster care history; 2) determine the prevalence of substance/alcohol use disorder, ACE, and aggression levels within individuals with foster care history when stratified by likelihood of TBI; and 3) determine the significant correlates of elevated aggression levels within this population. Participants completed standardized questionnaires that measured the prevalence of TBI, substance and alcohol use disorder, ACE, and aggression. Magnetic resonance imaging (MRI) was used to measure differences in brain ROI. Regression and network analysis were used to study interactions between variables. Seventy-four participants (51 individuals with foster care history and 23 age-matched controls from the general population) completed standardized questionnaires. Fifty-five of these individuals (39 foster participants and 16 controls) underwent brain MRI. Foster participants had higher prevalence of substance use disorder ( < 0.001), alcohol use disorder ( = 0.003), ACE ( < 0.001), and elevated aggression levels ( < 0.001) than healthy controls. No significant difference was found among brain ROI. The prevalence of TBI in foster participants was 65%. Foster participants with moderate or high likelihood of TBI exposure had higher levels of drug use and aggression than those with no or low likelihood of exposure. Brain volumes were not associated with substance/alcohol use disorder or ACE. No significant associations were found between aggression levels and the studied variables.
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http://dx.doi.org/10.1089/neur.2020.0032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774879PMC
December 2020

Setting standards of performance expected in neurosurgery residency: A study on entrustable professional activities in competency-based medical education.

Am J Surg 2021 02 8;221(2):388-393. Epub 2020 Dec 8.

Injury Prevention Research Office, St. Michael's Hospital, Toronto, Ontario, Canada; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, Canada.

Background: Competency-based medical education requires evaluations of residents' performances of tasks of the discipline (ie. entrustable professional activities (EPAs)). Using neurosurgical Faculty perspectives, this study investigated whether a sample of neurosurgical EPAs accurately reflected the expectations of general neurosurgical practice.

Method: A questionnaire was sent to all Canadian neurosurgery Faculty using a SurveyMonkey® platform.

Results: The proportion of respondents who believed the EPAs were representative of general neurosurgery competences varied significantly across all EPAs [47%-100%] (p < 0.0001). For 9/15 proposed EPAs, ≥75% agreed they were appropriate for general neurosurgery training and expected residents to attain the highest standard of performance. However, a range of 27-53% of the respondents felt the other six EPAs would be more appropriate for fellowship training and thus, require a lower standard of performance from graduating residents.

Conclusion: The shift towards subspecialization in neurosurgery has implications for curriculum design, delivery and certification of graduating residents.
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http://dx.doi.org/10.1016/j.amjsurg.2020.12.014DOI Listing
February 2021

Resident evaluations in the age of competency-based medical education: faculty perspectives on minimizing burdens.

J Neurosurg 2020 Dec 11:1-6. Epub 2020 Dec 11.

1Injury Prevention Research Office, St. Michael's Hospital, Toronto.

Objective: Competency-based medical education (CBME), an outcomes-based approach to medical education, continues to be implemented across many postgraduate medical education programs worldwide, including a recent introduction into Canadian neurosurgical training programs (July 2019). The success of this educational paradigm shift requires frequent faculty observation and evaluation of residents performing defined tasks of the specialty. A main challenge involves providing residents with frequent performance evaluations and feedback that are feasible for faculty to complete. This study aims to define what is currently happening and what changes are needed to make CBME successful for the certification of neurosurgeons' competence.

Methods: A 55-item questionnaire was emailed nationwide to survey Canadian neurosurgical faculty.

Results: Fifty-two complete responses were received and achieved a distribution highly correlated with the number of faculty neurosurgeons practicing in each Canadian province (Pearson's r = 0.94). Two-thirds (35/52) of faculty reported currently taking a median of 10 minutes to complete evaluation forms at the end of a resident's rotation block. Regardless of the faculty's province of practice (p = 0.50) or years of experience (p = 0.06), they reported 3 minutes (minimum 1 minute, maximum 10 minutes, interquartile range [IQR] 3 minutes) as a feasible amount of time to spend completing an evaluation form following an observation of a resident's performance of an entrustable professional activity (EPA). If evaluation forms took 3 minutes to complete, 85% of respondents (44/52) would complete EPA evaluations weekly or daily. The faculty recommended 5 minutes as a feasible amount of time to provide oral feedback (minimum 1 minute, maximum 20 minutes, IQR 3.25 minutes), which was significantly higher (p = 0.00099) than their recommended amount of time for completing evaluation forms. The majority of faculty (71%) stated they would prefer to access resident evaluation forms through a mobile application compared to a paper form (12%), an evaluation website (8%), or through a URL link sent via email (10%; p = 0.0032).

Conclusions: To facilitate the successful implementation of CBME into a neurosurgical training curriculum, resident EPA assessment forms should take 3 minutes or less to complete and be accessible through a mobile application.
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http://dx.doi.org/10.3171/2020.7.JNS201688DOI Listing
December 2020

Gene Expression Signatures Identify Biologically Homogenous Subgroups of Grade 2 Meningiomas.

Front Oncol 2020 5;10:541928. Epub 2020 Nov 5.

Division of Neurosurgery, Department of Surgery, St. Michael's Hospital, Toronto, ON, Canada.

Introduction: Meningiomas are the most common brain tumor, with prevalence of approximately 3%. Histological grading has a major role in determining treatment choice and predicting outcome. While indolent grade 1 and aggressive grade 3 meningiomas exhibit relatively homogeneous clinical behavior, grade 2 meningiomas are far more heterogeneous, making outcome prediction challenging. We hypothesized two subgroups of grade 2 meningiomas which biologically resemble either World Health Organization (WHO) grade 1 or WHO grade 3. Our aim was to establish gene expression signatures that separate grade 2 meningiomas into two homogeneous subgroups: a more indolent subtype genetically resembling grade 1 and a more aggressive subtype resembling grade 3.

Methods: We carried out an observational meta-analysis on 212 meningiomas from six distinct studies retrieved from the open-access platform Microarray data was analyzed with systems-level gene co-expression network analysis. Fuzzy C-means clustering was employed to reclassify 34 of the 46 grade 2 meningiomas (74%) into a benign "grade 1-like" (13/46), and malignant "grade 3-like" (21/46) subgroup based on transcriptomic profiles. We verified shared biology between matching subgroups based on meta-gene expression and recurrence rates. These results were validated further using an independent RNA-seq dataset with 160 meningiomas, with similar results.

Results: Recurrence rates of "grade 1-like" and "grade 3- like" tumors were 0 and 75%, respectively, statistically similar to recurrence rates of grade 1 (17%) and 3 (85%). We also found overlapping biological processes of new subgroups with their adjacent grades 1 and 3.

Conclusion: These results underpin molecular signatures as complements to histological grading systems. They may help reshape prediction, follow-up planning, treatment decisions and recruitment protocols for future and ongoing clinical trials.
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http://dx.doi.org/10.3389/fonc.2020.541928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674612PMC
November 2020

Sinonasal Chondrosarcoma Presenting With Isolated Severe Vision Loss.

J Neuroophthalmol 2020 Oct 27. Epub 2020 Oct 27.

Department of Ophthalmology and Vision Sciences (MTBN, JAM), University of Toronto, Toronto, Ontario, Canada; Faculty of Medicine (AF), University of Toronto, Toronto, Ontario, Canada; Department of Pathology and Laboratory Medicine (BCD), Mount Sinai Hospital; Department of Laboratory Medicine and Pathobiology (BCD), University of Toronto, Toronto, Ontario, Canada; Department of Otolaryngology-Head and Neck Surgery (JML), St. Michael's Hospital, Toronto, Ontario, Canada; Department of Otolaryngology-Head and Neck Surgery (JML), University of Toronto, Toronto, Ontario, Canada; Division of Neurosurgery (MDC), Department of Surgery, St. Michael's Hospital, Toronto, Ontario, Canada; Department of Surgery (MDC), University of Toronto, Toronto, Ontario, Canada; Radiation Medicine Program (DST), Princess Margaret Cancer Centre, University Health Network; Department of Radiation Oncology (DST), University of Toronto, Toronto, Ontario, Canada; Division of Neurology (JAM), Department of Medicine, University of Toronto, Toronto, Ontario, Canada; and Department of Ophthalmology (JAM), St. Michael's Hospital, Toronto, Ontario, Canada.

A 24-year-old man presented with a 2-month history of progressive, painless vision loss in the right eye, with no history of headache, nasal congestion, rhinorrhea, or epistaxis. His visual acuity was counting fingers at 1 ft in the right eye and 20 of 20 in the left eye with a right relative afferent pupillary defect and mild temporal optic disc pallor. MRI of the brain and orbits showed a mass involving bilateral ethmoid and sphenoid sinuses and right nasal cavity. He underwent urgent extended endoscopic endonasal transsphenoidal approach for resection of the sinonasal skull base tumor and photon radiation therapy. Pathology revealed a well-differentiated cartilaginous neoplasm with focal areas of entrapped native bone, consistent with a chondrosarcoma WHO grade I/III. At 6-month follow-up after surgery, he had a visual acuity of 20/40 in the right eye and 20/20 in the left eye. Malignant tumors from the sinonasal area should be kept in the differential diagnosis for compressive optic neuropathies and may present with vision loss even in the absence of nasal or sinus symptoms.
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http://dx.doi.org/10.1097/WNO.0000000000001130DOI Listing
October 2020

Meta-gene markers predict meningioma recurrence with high accuracy.

Sci Rep 2020 10 22;10(1):18028. Epub 2020 Oct 22.

Division of Neurosurgery, Department of Surgery, St. Michael's Hospital, Toronto, ON, Canada.

Meningiomas, the most common adult brain tumors, recur in up to half of cases. This requires timely intervention and therefore accurate risk assessment of recurrence is essential. Our current practice relies heavily on histological grade and extent of surgical excision to predict meningioma recurrence. However, prediction accuracy can be as poor as 50% for low or intermediate grade tumors which constitute the majority of cases. Moreover, attempts to find molecular markers to predict their recurrence have been impeded by low or heterogenous genetic signal. We therefore sought to apply systems-biology approaches to transcriptomic data to better predict meningioma recurrence. We apply gene co-expression networks to a cohort of 252 adult patients from the publicly available genetic repository Gene Expression Omnibus. Resultant gene clusters ("modules") were represented by the first principle component of their expression, and their ability to predict recurrence assessed with a logistic regression model. External validation was done using two independent samples: one merged microarray-based cohort with a total of 108 patients and one RNA-seq-based cohort with 145 patients, using the same modules. We used the bioinformatics database Enrichr to examine the gene ontology associations and driver transcription factors of each module. Using gene co-expression analysis, we were able predict tumor recurrence with high accuracy using a single module which mapped to cell cycle-related processes (AUC of 0.81 ± 0.09 and 0.77 ± 0.10 in external validation using microarray and RNA-seq data, respectively). This module remained predictive when controlling for WHO grade in all cohorts, and was associated with several cancer-associated transcription factors which may serve as novel therapeutic targets for patients with this disease. With the easy accessibility of gene panels in healthcare diagnostics, our results offer a basis for routine molecular testing in meningioma management and propose potential therapeutic targets for future research.
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http://dx.doi.org/10.1038/s41598-020-74482-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582964PMC
October 2020

Traumatic brain injuries and problem gambling in youth: Evidence from a population-based study of secondary students in Ontario, Canada.

PLoS One 2020 2;15(10):e0239661. Epub 2020 Oct 2.

Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Traumatic brain injury (TBI) is characterized by a change in brain function after an external force or sudden movement to the head. TBI is associated with risk-taking, impulsivity, psychological distress, substance abuse, and violent crime. Previous studies have also linked problem gambling to TBI, but these studies have not controlled for possible confounding variables such as mental health problems and hazardous drinking which are also linked to TBI. This study examines the relationship between problem gambling and TBI among adolescents. Data were obtained from the 2011, 2013 and 2015 cycles of the OSDUHS, a biennial cross-sectional school-based study of children in grades 7 to 12 (N = 9,198). Logistic regression was used to estimate adjusted odds ratios (AOR) in controlled and uncontrolled analyses. Adjusting for sex and grade only, problem gambling was associated with a history of TBI (AOR = 2.8). This association remained significant after adjusting for hazardous drinking and suicidality (AOR = 2.0). In addition, problem gambling had a statistically significant relationship with being male (AOR = 4.7), hazardous drinking (AOR = 4.5), and suicidality (AOR = 3.1). This study provides further data to suggest a link between TBI and problem gambling. However, research is needed on the causal relationship between these variables and the potential implications for treatment and prevention.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239661PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531994PMC
November 2020

A population-based study of fall-related traumatic brain injury identified in older adults in hospital emergency departments.

Neurosurg Focus 2020 10;49(4):E20

4Injury Section, Centre for Surveillance and Applied Research, Public Health Agency of Canada, Ottawa, Ontario, Canada.

Objective: The purpose of this study was to examine the population-based trends and factors associated with hospitalization of patients with traumatic brain injury (TBI) treated in the Emergency Department (ED) among those 65 years and older. The implications of these trends for neurosurgery and the broader society are discussed.

Method: With a national, mandatory reporting system of ED visits, the authors used Poisson regression controlling for age and sex to analyze trends in fall-related TBI of those aged 65 years and older between 2002 and 2017.

Results: The overall rate of ED visits for TBI increased by 78%-from 689.51 per 100,000 (95% CI 676.5-702.8) to 1229 per 100,000 (95% CI 1215-1243) between 2002 and 2017. Females consistently experienced higher rates of fall-related TBI than did males. All age groups 65 years and older experienced significant increases in fall-related TBI rate over the study period; however, the highest rates occurred among the oldest individuals (90+ and 85-89 years). The hospital admission rate increased with age and Charlson Comorbidity Index. Males experienced both a higher admission rate and a greater percentage change in admission rate than females.

Conclusions: Rates of ED visits for fall-related TBI, hospitalization, and in-ED mortality in those aged 65 years and older are increasing for both sexes. The increasing hospital admission rate is related to more advanced comorbidities, male sex, and increasing age. These findings have significant implications for neurosurgical resources; they emphasize that health professionals should work proactively with patients, families, and caregivers to clarify goals of care, and they also outline the need for more high-level and, preferably, randomized evidence to support outcomes-based decisions. Additionally, the findings highlight the urgent need for improved population-based measures for prevention in not only this age demographic but in younger ones, and the need for changes in the planning of health service delivery and long-term care.
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http://dx.doi.org/10.3171/2020.7.FOCUS20520DOI Listing
October 2020

Frequent but limited assessment of potentially concussed players in Gaelic Football: an opportunity to learn from other sports.

Ir J Med Sci 2021 May 30;190(2):787-792. Epub 2020 Sep 30.

Division of Neurosurgery, St. Michael's Hospital, University of Toronto, 30 Bond St, Toronto, ON, M5B 1W8, USA.

Background: Sport-related concussion (SRC) is a potential issue within Gaelic Football. Therefore, it is essential that concussion management guidelines are adhered to.

Hypothesis/purpose: The aim of this study is to determine if potential concussive events (PCEs) in the Gaelic Athletic Association (GAA) National Football League (NFL) are assessed in accordance with GAA concussion guidelines and compare this to other sports.

Methods: A descriptive video analysis approach was undertaken to identify PCEs throughout two seasons of play. Subsequent assessment, return to play (RTP) decisions, and signs of concussion were evaluated.

Results: A total of 242 PCEs were identified over 111 matches. Most PCEs (87.2%, n = 211) were assessed by medical personnel. However, 187 (88.6%) of assessments were under 2 min in duration. Of the 242 PCEs, 189 (78.1%) returned to play after on-pitch assessment, and 12 (5.0%) were removed following a PCE. Sixty-one (25.2%) players sustaining a PCE demonstrated one or more signs of concussion, of which 9 (14.8%) were removed from play.

Conclusion: In the GAA NFL, PCEs are often briefly assessed but rarely result in player removal. Introduction of video incident analysis and concussion substitutions, as in other sports, may reduce the long-term burden of SRC on Gaelic Football players.
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http://dx.doi.org/10.1007/s11845-020-02390-5DOI Listing
May 2021

Determining the unmet needs of patients with intracranial meningioma-a qualitative assessment.

Neurooncol Pract 2020 Mar 29;7(2):228-238. Epub 2019 Oct 29.

Injury Prevention Research Office, St. Michael's Hospital, Division of Neurosurgery, Toronto, Ontario, Canada.

Background: Meningiomas are the most common primary benign brain neoplasms, but despite their commonality, the supportive needs of this patient population have been overlooked. The aim of this study is to identify unmet needs of meningioma patients, caregivers, and health care providers.

Methods: We adopted a patient-centered approach by using qualitative interviewing with patients diagnosed with a meningioma who have undergone treatment in the last 10 years since the date of their interview. Informal caregivers (family and/or friends) of the patient population and health care providers who are normally involved in the management and care of meningioma patients were also interviewed. Interview transcripts were subjected to thematic analysis.

Results: Of the 50 participants interviewed, there were 30 patients, 12 caregivers, and 8 health care professionals. Thematic analysis revealed 4 overarching themes: (1) access to targeted postoperative care, (2) financial struggles for patients and their families, (3) lack of information specific to meningiomas and postsurgical management, and (4) lack of psychosocial support.

Conclusion: This study identified supportive needs specific to the meningioma patient population, which predominantly falls within the postoperative phase. The postoperative journey of this patient population could potentially extend to the rest of the patient's life, which necessitates resources and information directed to support postoperative recovery and management. The development of directly relevant supportive resources that support meningioma patients in their postoperative recovery is necessary to improve the health-related quality of life in this patient population.
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http://dx.doi.org/10.1093/nop/npz054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318855PMC
March 2020

Considerations for a surgical RCT for diffuse low-grade glioma: a survey.

Neurooncol Pract 2020 Jun 12;7(3):338-343. Epub 2019 Nov 12.

Division of Neurosurgery, St. Michael's Hospital, Toronto, Ontario, Canada.

Background: Diffuse low-grade gliomas (DLGGs) are heterogeneous tumors that inevitably differentiate into malignant entities, leading to disability and death. Recently, a shift toward up-front maximal safe resection of DLGGs has been favored. However, this transition is not supported by randomized controlled trial (RCT) data. Here, we sought to survey the neuro-oncology community on considerations for a surgical RCT for DLGGs.

Methods: A 21-question survey focusing on a surgical RCT for DLGGs was developed and validated by 2 neurosurgeons. A sample case of a patient for whom management might be debatable was presented to gather additional insight. The survey was disseminated to members of the Society for Neuro-Oncology (SNO) and responses were collected from March 16 to July 10, 2018.

Results: A total of 131 responses were collected. Sixty-three of 117 (54%) respondents thought an RCT would not be ethical, 39 of 117 (33%) would consider participating, and 56 of 117 (48%) believed an RCT would be valuable for determining the differing roles of biopsy, surgery, and observation. This was exemplified by an evenly distributed selection of the latter management options for our sample case. Eighty-three of 120 (69.2%) respondents did not believe in equipoise for DLGG patients. Quality of life and overall survival were deemed equally important end points for a putative RCT.

Conclusions: Based on our survey, it is evident that management of certain DLGG patients is not well defined and an RCT may be justified. As with any surgical RCT, logistic challenges are anticipated. Robust patient-relevant end points and standardization of perioperative adjuncts are necessary if a surgical RCT is undertaken.
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http://dx.doi.org/10.1093/nop/npz058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274180PMC
June 2020

Landscape of immune cell gene expression is unique in predominantly WHO grade 1 skull base meningiomas when compared to convexity.

Sci Rep 2020 06 3;10(1):9065. Epub 2020 Jun 3.

Division of Neurosurgery, Department of Surgery, St. Michael's Hospital, Toronto, ON, Canada.

Modulation of tumor microenvironment is an emerging frontier for new therapeutics. However in meningiomas, the most frequent adult brain tumor, the correlation of microenvironment with tumor phenotype is scarcely studied. We applied a variety of systems biology approaches to bulk tumor transcriptomics to explore the immune environments of both skull base and convexity (hemispheric) meningiomas. We hypothesized that the more benign biology of skull base meningiomas parallels the relative composition and activity of immune cells that oppose tumor growth and/or survival. We firstly applied gene co-expression networks to tumor bulk transcriptomics from 107 meningiomas (derived from 3 independent studies) and found immune processes to be the sole biological mechanism correlated with anatomical location while correcting for tumour grade. We then derived tumor immune cell fractions from bulk transcriptomics data and examined the immune cell-cytokine interactions using a network-based approach. We demonstrate that oncolytic Gamma-Delta T cells dominate skull base meningiomas while mast cells and neutrophils, known to play a role in oncogenesis, show greater activity in convexity tumors. Our results are the first to suggest the importance of tumor microenvironment in meningioma biology in the context of anatomic location and immune landscape. These findings may help better inform surgical decision making and yield location-specific therapies through modulation of immune microenvironment.
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http://dx.doi.org/10.1038/s41598-020-65365-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270140PMC
June 2020
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