Publications by authors named "Douglas D Fraser"

Background: Pulmonary infections, ranging from mild respiratory issues to severe multiorgan failure, pose a major global health threat. The immune response in community-acquired pneumonia (CAP) and COVID-19 influences disease severity and outcomes, but molecular pathogenesis differs across pathogens. Comparisons of plasma cytokine profiles between CAP and COVID-19 are limited.

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Objectives: Inhaled anesthetics may reduce alveolar and systemic inflammation in surgical and critically ill patients. This study aimed to perform a systematic review and meta-analysis comparing the effect of inhaled volatile and IV anesthetics on alveolar and plasma cytokines in patients with surgical or medical acute lung injury.

Data Sources: Medline, Embase, and Cochrane CENTRAL databases from 2000 to July 2021.

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Introduction: Altered metabolic pathways are critical in the progression of traumatic brain injury (TBI). Identifying differentially abundant metabolites (DAMs) from specific cell types can offer valuable diagnostic and prognostic insights.

Objective: This study aimed to characterize the metabolomic profile of injured human brain microvascular endothelial cells (hBMEC) at 2-, 12-, 24-, and 48 h post-injury.

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Understanding the interplay among clinical variables-such as demographics, symptoms, and laboratory results-and their relationships with disease outcomes is critical for advancing diagnostics and understanding mechanisms in complex diseases. Existing methods fail to capture indirect or directional relationships, while existing Bayesian network learning methods are computationally expensive and only infer general associations without focusing on disease outcomes. Here we introduce random walk- and genetic algorithm-based network inference (RAMEN), a method for Bayesian network inference that uses absorbing random walks to prioritize outcome-relevant variables and a genetic algorithm for efficient network refinement.

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Knowledge regarding the pediatric immune response to SARS-CoV-2 infection and/or vaccination remains limited, particularly for the variants of concern (VOC). Our objective was to evaluate the neutralizing antibody response against SARS-CoV-2 VOC in the naturally infected and/or vaccinated pediatric population. Participants aged 5-12 years who presented to either an outpatient clinic or emergency room were eligible for participation in this study.

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In vitro cell culture experiments play an important role in medical research. Various cellular mechanisms and signaling pathways have been identified with in vitro experimental techniques. Unfortunately, the clinical and translational impact of these studies is often limited due to their inability to closely resemble physiological or pathophysiological milieus in cell culture and the use of unrealistic experimental conditions.

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Investigations on some innate immunity proteins can yield misleading information, as investigators often rely on static measurements and assume a direct correlation to function. As protein function is often not directly proportional to protein abundance, and mechanistic pathways are interconnected and under constant feedback regulatory control, functional analysis is required. In this study, we used functional mass spectrometry to measure anti-protease and complement activity in plasma obtained from coronavirus disease 2019 (COVID-19) patients.

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Background: In children with type 1 diabetes (T1D), diabetic ketoacidosis (DKA) triggers a significant inflammatory response; however, the specific effector proteins and signaling pathways involved remain largely unexplored. This pediatric case-control study utilized plasma proteomics to explore protein alterations associated with severe DKA and to identify signaling pathways that associate with clinical variables.

Methods: We conducted a proteome analysis of plasma samples from 17 matched pairs of pediatric patients with T1D; one cohort with severe DKA and another with insulin-controlled diabetes.

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Sepsis is a major cause of morbidity and mortality worldwide. Among the various types of end-organ damage associated with sepsis, hepatic injury is linked to significantly higher mortality rates compared to dysfunction in other organ systems. This study aimed to investigate potential biomarkers of hepatic injury in sepsis patients through a multi-center, case-control approach.

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Background: Diabetic ketoacidosis (DKA) is a serious complication of type 1 diabetes (T1D), arising from relative insulin deficiency and leading to hyperglycemia, ketonemia, and metabolic acidosis. Early detection and treatment are essential to prevent severe outcomes. This pediatric case-control study utilized plasma metabolomics to explore metabolic alterations associated with DKA and to identify predictive metabolite patterns.

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Article Synopsis
  • COVID-19 leads to systemic inflammation that stimulates adrenal glands, causing elevated cortisol levels without necessarily increasing ACTH, which can result in "pseudo-Cushing's syndrome."
  • The disease also shows characteristics of endocrine resistance, with varying signaling pathways activated in mild versus severe cases, impacting survival factors and receptor signaling.
  • Understanding these mechanisms could reveal potential therapeutic targets in the endocrine system to enhance outcomes for COVID-19 patients.
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Background: Severe COVID-19 is associated with neutrophilic inflammation and immunothrombosis. Several members of the IL-17 cytokine family have been associated with neutrophilic inflammation and activation of the endothelium. Therefore, we investigated whether these cytokines were associated with COVID-19.

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Objective: This study aims to identify key characteristics of hyperglycemic emergencies in pediatric patients and those at risk for acute neurologic dysfunction during transport.

Methods: We conducted a retrospective chart review of pediatric patients during interfacility transport by Ornge, Ontario's critical care transport service, from January 1, 2009, to December 31, 2019. Data were extracted from electronic patient care records and included demographic, clinical, and transport-specific variables.

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Importance: Blood-based biomarkers may clarify underlying neuropathology and potentially assist in clinical management of adolescents with sport-related concussion (SRC).

Objective: To investigate the association between SRC and plasma biomarkers in adolescents.

Design, Setting, And Participants: Prospective cohort study in Canadian sport and clinic settings (Surveillance in High Schools and Community Sport to Reduce Concussions and Their Consequences study; September 2019 to November 2022).

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Article Synopsis
  • The study investigates the proteome changes in critically ill COVID-19 patients to understand susceptibility, symptoms, and treatment markers by analyzing the plasma proteins of various patient groups using machine learning.
  • A case-control study compared 2000 plasma proteins among COVID-19 patients, non-COVID-19 sepsis controls, and healthy individuals, leading to the identification of a 28-protein model that effectively differentiates these groups.
  • Key findings include a subset of 9 proteins linked to important clinical factors, with no significant changes over time in the COVID-19 cohort, and a multi-system expression pattern, particularly in the digestive and nervous systems.
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Background: The Multi-System Inflammatory Syndrome in Children (MIS-C) can develop several weeks after SARS-CoV-2 infection and requires a distinct treatment protocol. Distinguishing MIS-C from SARS-CoV-2 negative sepsis (SCNS) patients is important to quickly institute the correct therapies. We performed targeted proteomics and machine learning analysis to identify novel plasma proteins of MIS-C for early disease recognition.

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Background: Sepsis is a dysregulated systemic inflammatory response triggered by infection, resulting in organ dysfunction. A major challenge in clinical pediatrics is to identify sepsis early and then quickly intervene to reduce morbidity and mortality. As blood biomarkers hold promise as early sepsis diagnostic tools, we aimed to measure a large number of blood inflammatory biomarkers from pediatric sepsis patients to determine their predictive ability, as well as their correlations with clinical variables and illness severity scores.

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Article Synopsis
  • - SARS-CoV-2 infection triggers intense immune responses, which can lead to severe COVID-19 in some people, but the detailed mechanisms behind these excessive responses are not fully understood.
  • - The study analyzed blood samples from patients with or without sepsis and healthy individuals, revealing significant changes in protein and phosphoprotein profiles during COVID-19 that could differentiate between disease stages.
  • - The researchers found that SARS-CoV-2 reprograms immune signaling pathways, impairing the function of immune cells and leading to excessive inflammation, while also pinpointing potential new therapeutic targets for COVID-19 treatment.
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  • The study aimed to evaluate the impact of an early rehabilitation program on critically ill children’s functioning, health-related quality of life (HRQL), and parental stress after they leave the Pediatric Intensive Care Unit (PICU).
  • Conducted at two hospitals in Ontario, Canada, the intervention involved a rehabilitation bundle including pain management, delirium prevention, and early mobilization for children expecting to stay in the PICU for 48 hours.
  • The results showed that after the rehabilitation bundle was implemented, there was no significant improvement in children’s recovery or decreased parental stress, with many children still experiencing functional decline and low HRQL at discharge and follow-ups.
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  • Annexin A5 is a protein that helps reduce inflammation, prevent blood clotting, and avoid cell death, showing promise in improving organ function in sepsis models.
  • A clinical trial tested a recombinant version of annexin A5 (SY-005) for severe COVID-19, with patients receiving low (50 μg/kg) or high (100 μg/kg) doses or placebo over 7 days.
  • Results indicated that SY-005 was quickly cleared from the body without significant changes in blood coagulation or kidney function, suggesting it was safe and well-tolerated in the participants.
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  • The study aimed to implement an early rehabilitation bundle in two Canadian Pediatric Intensive Care Units (PICUs), focusing on improving patient care through specific interventions.
  • Key components of the intervention included prioritizing pain management, monitoring for delirium, and promoting early mobilization among children under 18 admitted to the PICU.
  • While the implementation improved compliance and reduced certain sedative use without compromising patient safety or comfort, it did not have a significant impact on overall clinical outcomes like delirium rates or PICU length of stay.
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  • Acute and chronic kidney diseases are serious conditions that lead to significant health challenges, yet there are limited reliable biomarkers for predicting kidney dysfunction.
  • This study analyzed blood and urine samples from healthy individuals, COVID-19 patients with acute kidney injury, and chronic kidney disease patients, using a new multiplex panel to assess 21 proteins.
  • The results revealed distinct biomarker profiles that can differentiate between healthy controls, patients with acute kidney injury, and those with end-stage kidney disease, highlighting correlations between these biomarkers and clinical data.
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Background: The COVID-19 a pandemic changed the world. Public health directives to socially distance with stay-at-home orders altered injury risk factor exposure, resulting injury patterns and conducting injury prevention (IP). The objective of this study was to determine the impact the COVID-19 pandemic on injury and IP at North American trauma centers (TC).

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Importance: Advancing research on fluid biomarkers associated with sport-related concussion (SRC) highlights the importance of detecting low concentrations using ultrasensitive platforms. However, common statistical practices may overlook replicate errors and specimen exclusion, emphasizing the need to explore robust modeling approaches that consider all available replicate data for comprehensive understanding of sample variation and statistical inferences.

Objective: To evaluate the impact of replicate error and different biostatistical modeling approaches on SRC biomarker interpretation.

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