Browsing by Author "Winston, Brent W"

Now showing 1 - 6 of 6
  • Thumbnail Image
    ItemOpen Access
    Bacterial DNA patterns identified using paired-end Illumina sequencing of 16S rRNA genes from whole blood samples of septic patients in the emergency room and intensive care unit
    (2018-07-25) Faria, Monica M P; Winston, Brent W; Surette, Michael G; Conly, John M
    Abstract Background Sepsis refers to clinical presentations ranging from mild body dysfunction to multiple organ failure. These clinical symptoms result from a systemic inflammatory response to pathogenic or potentially pathogenic microorganisms present systemically in the bloodstream. Current clinical diagnostics rely on culture enrichment techniques to identify bloodstream infections. However, a positive result is obtained in a minority of cases thereby limiting our knowledge of sepsis microbiology. Previously, a method of saponin treatment of human whole blood combined with a comprehensive bacterial DNA extraction protocol was developed. The results indicated that viable bacteria could be recovered down to 10 CFU/ml using this method. Paired-end Illumina sequencing of the 16S rRNA gene also indicated that the bacterial DNA extraction method enabled recovery of bacterial DNA from spiked blood. This manuscript outlines the application of this method to whole blood samples collected from patients with the clinical presentation of sepsis. Results Blood samples from clinically septic patients were obtained with informed consent. Application of the paired-end Illumina 16S rRNA sequencing to saponin treated blood from intensive care unit (ICU) and emergency department (ED) patients indicated that bacterial DNA was present in whole blood. There were three clusters of bacterial DNA profiles which were distinguished based on the distribution of Streptococcus, Staphylococcus, and Gram-negative DNA. The profiles were examined alongside the patient’s clinical data and indicated molecular profiling patterns from blood samples had good concordance with the primary source of infection. Conclusions Overall this study identified common bacterial DNA profiles in the blood of septic patients which were often associated with the patients’ primary source of infection. These results indicated molecular bacterial DNA profiling could be further developed as a tool for clinical diagnostics for bloodstream infections.
  • Thumbnail Image
    ItemOpen Access
    Integration of metabolic and inflammatory mediator profiles as a potential prognostic approach for septic shock in the intensive care unit
    (Critical Care, BioMed Central, 2015-01-15) Mickiewicz, Beata; Tam, Patrick; Jenne, Craig N; Leger, Caroline; Wong, Josee; Winston, Brent W; Doig, Christopher; Kubes, Paul; Vogel, Hans J
    Introduction Septic shock is a major life-threatening condition in critically ill patients and it is well known that early recognition of septic shock and expedient initiation of appropriate treatment improves patient outcome. Unfortunately, to date no single compound has shown sufficient sensitivity and specificity to be used as a routine biomarker for early diagnosis and prognosis of septic shock in the intensive care unit (ICU). Therefore, the identification of new diagnostic tools remains a priority for increasing the survival rate of ICU patients. In this study, we have evaluated whether a combined nuclear magnetic resonance spectroscopy-based metabolomics and a multiplex cytokine/chemokine profiling approach could be used for diagnosis and prognostic evaluation of septic shock patients in the ICU. Methods Serum and plasma samples were collected from septic shock patients and ICU controls (ICU patients with the systemic inflammatory response syndrome but not suspected of having an infection). 1H Nuclear magnetic resonance spectra were analyzed and quantified using the targeted profiling methodology. The analysis of the inflammatory mediators was performed using human cytokine and chemokine assay kits. Results By using multivariate statistical analysis we were able to distinguish patient groups and detect specific metabolic and cytokine/chemokine patterns associated with septic shock and its mortality. These metabolites and cytokines/chemokines represent candidate biomarkers of the human response to septic shock and have the potential to improve early diagnosis and prognosis of septic shock. Conclusions Our findings show that integration of quantitative metabolic and inflammatory mediator data can be utilized for the diagnosis and prognosis of septic shock in the ICU.
  • Thumbnail Image
    ItemOpen Access
    Metabolomics Study of the Diagnosis and Prognosis of Severe Traumatic Brain Injury (sTBI)
    (2020-11-30) Banoei, Mohammad Mehdi; Winston, Brent W; Habibi, Hamid R; Lewis, Ian A; Couillard, Phillippe; Debert, Chantel T; Fraser, Douglas D;
    Traumatic brain injury (TBI) is defined as neurologic injury resulting from an external mechanical force, which is associated with long-term neurological and cognitive disability and affects individuals of all ages, ethnicities, and socioeconomic characteristics. TBI severe enough to cause hospitalization occurs in over 10 million people each year worldwide. TBI is the most common cause of death and long-term disability in children and young adults in developed countries. Currently, clinical assessment and neuroimaging (e.g. CT and MRI) are the most reliable techniques used for the diagnosis and prognosis of TBI. Unfortunately, this approach has considerable shortcomings when considering sensitivity and specificity of TBI diagnosis and prognosis. Disease stratification and the prediction of outcomes and are key problems for the management of severe TBI (sTBI).This study showed that metabolomics can be applied for the diagnosis and prognosis of sTBI using nuclear magnetic resonance (NMR) spectroscopy and direct infusion tandem mass spectrometry (DI-MS/MS). The results are promising for the diagnose sTBI when compared to orthopedic injury (OI) controls and for the prognostication sTBI outcomes at 3, 6, and 12-months post-injury particularly in predicting poor outcomes from the good outcome. We also investigated the metabolomics on animal models for sTBI. Using the cortical controlled impact (CCI) mouse model of sTBI demonstrated a difference in metabolic profiles of CCI and CCI mice receiving a plastic CAP to cover the skull in the craniotome area (CCI+CAP) mice when compared to sham controls. Our result revealed that the highest degree of metabolic alterations occurs at 8 hours post-injury and that the CCI+CAP mice have a prolonged brain injury compared to CCI mice (assessed at 7 days post-injury).
  • Thumbnail Image
    ItemOpen Access
    National Preclinical Sepsis Platform: developing a framework for accelerating innovation in Canadian sepsis research
    (2021-03-19) Mendelson, Asher A; Lansdell, Casey; Fox-Robichaud, Alison E; Liaw, Patricia; Arora, Jaskirat; Cailhier, Jean-François; Cepinskas, Gediminas; Charbonney, Emmanuel; dos Santos, Claudia; Dwivedi, Dhruva; Ellis, Christopher G; Fergusson, Dean; Fiest, Kirsten; Gill, Sean E; Hendrick, Kathryn; Hunniford, Victoria T; Kowalewska, Paulina M; Krewulak, Karla; Lehmann, Christian; Macala, Kimberly; Marshall, John C; Mawdsley, Laura; McDonald, Braedon; McDonald, Ellen; Medeiros, Sarah K; Muniz, Valdirene S; Osuchowski, Marcin; Presseau, Justin; Sharma, Neha; Sohrabipour, Sahar; Sunohara-Neilson, Janet; Vázquez-Grande, Gloria; Veldhuizen, Ruud A W; Welsh, Donald; Winston, Brent W; Zarychanski, Ryan; Zhang, Haibo; Zhou, Juan; Lalu, Manoj M
    Abstract Despite decades of preclinical research, no experimentally derived therapies for sepsis have been successfully adopted into routine clinical practice. Factors that contribute to this crisis of translation include poor representation by preclinical models of the complex human condition of sepsis, bias in preclinical studies, as well as limitations of single-laboratory methodology. To overcome some of these shortcomings, multicentre preclinical studies—defined as a research experiment conducted in two or more research laboratories with a common protocol and analysis—are expected to maximize transparency, improve reproducibility, and enhance generalizability. The ultimate objective is to increase the efficiency and efficacy of bench-to-bedside translation for preclinical sepsis research and improve outcomes for patients with life-threatening infection. To this end, we organized the first meeting of the National Preclinical Sepsis Platform (NPSP). This multicentre preclinical  research collaboration of Canadian sepsis researchers and stakeholders was established to study the pathophysiology of sepsis and accelerate movement of promising therapeutics into early phase clinical trials. Integrated knowledge translation and shared decision-making were emphasized to ensure the goals of the platform align with clinical researchers and patient partners. 29 participants from 10 independent labs attended and discussed four main topics: (1) objectives of the platform; (2) animal models of sepsis; (3) multicentre methodology and (4) outcomes for evaluation. A PIRO model (predisposition, insult, response, organ dysfunction) for experimental design was proposed to strengthen linkages with interdisciplinary researchers and key stakeholders. This platform represents an important resource for maximizing translational impact of preclinical sepsis research.
  • Thumbnail Image
    ItemOpen Access
    Plasma lipid profiling for the prognosis of 90-day mortality, in-hospital mortality, ICU admission, and severity in bacterial community-acquired pneumonia (CAP)
    (2020-07-27) Banoei, Mohammad M; Vogel, Hans J; Weljie, Aalim M; Yende, Sachin; Angus, Derek C; Winston, Brent W
    Abstract Introduction Pneumonia is the most common cause of mortality from infectious diseases, the second leading cause of nosocomial infection, and the leading cause of mortality among hospitalized adults. To improve clinical management, metabolomics has been increasingly applied to find specific metabolic biopatterns (profiling) for the diagnosis and prognosis of various infectious diseases, including pneumonia. Methods One hundred fifty bacterial community-acquired pneumonia (CAP) patients whose plasma samples were drawn within the first 24 h of hospital admission were enrolled in this study and separated into two age- and sex-matched cohorts: non-survivors (died ≤ 90 days) and survivors (survived > 90 days). Three analytical tools, 1H-NMR spectroscopy, GC-MS, and targeted DI-MS/MS, were used to prognosticate non-survivors from survivors by means of metabolic profiles. Results We show that quantitative lipid profiling using DI-MS/MS can predict the 90-day mortality and in-hospital mortality among patients with bacterial CAP compared to 1H-NMR- and GC-MS-based metabolomics. This study showed that the decreased lysophosphatidylcholines and increased acylcarnitines are significantly associated with increased mortality in bacterial CAP. Additionally, we found that decreased lysophosphatidylcholines and phosphatidylcholines (> 36 carbons) and increased acylcarnitines may be used to predict the prognosis of in-hospital mortality for bacterial CAP as well as the need for ICU admission and severity of bacterial CAP. Discussion This study demonstrates that lipid-based plasma metabolites can be used for the prognosis of 90-day mortality among patients with bacterial CAP. Moreover, lipid profiling can be utilized to identify patients with bacterial CAP who are at the highest risk of dying in hospital and who need ICU admission as well as the severity assessment of CAP.
  • Thumbnail Image
    ItemOpen Access
    Plasma metabolomics for the diagnosis and prognosis of H1N1 influenza pneumonia
    (2017-04-19) Banoei, Mohammad M; Vogel, Hans J; Weljie, Aalim M; Kumar, Anand; Yende, Sachin; Angus, Derek C; Winston, Brent W
    Abstract Background Metabolomics is a tool that has been used for the diagnosis and prognosis of specific diseases. The purpose of this study was to examine if metabolomics could be used as a potential diagnostic and prognostic tool for H1N1 pneumonia. Our hypothesis was that metabolomics can potentially be used early for the diagnosis and prognosis of H1N1 influenza pneumonia. Methods 1H nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry were used to profile the metabolome in 42 patients with H1N1 pneumonia, 31 ventilated control subjects in the intensive care unit (ICU), and 30 culture-positive plasma samples from patients with bacterial community-acquired pneumonia drawn within the first 24 h of hospital admission for diagnosis and prognosis of disease. Results We found that plasma-based metabolomics from samples taken within 24 h of hospital admission can be used to discriminate H1N1 pneumonia from bacterial pneumonia and nonsurvivors from survivors of H1N1 pneumonia. Moreover, metabolomics is a highly sensitive and specific tool for the 90-day prognosis of mortality in H1N1 pneumonia. Conclusions This study demonstrates that H1N1 pneumonia can create a quite different plasma metabolic profile from bacterial culture-positive pneumonia and ventilated control subjects in the ICU on the basis of plasma samples taken within 24 h of hospital/ICU admission, early in the course of disease.