Browsing by Author "Brindle, Mary"

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    Cytokines and Chemokines in Pediatric Appendicitis: A Multiplex Analysis of Inflammatory Protein Mediators
    (2019-02-21) Naqvi, S. Ali; Thompson, Graham C.; Joffe, Ari R.; Blackwood, Jaime; Martin, Dori-Ann; Brindle, Mary; Barkema, Herman W.; Jenne, Craig N.
    Objectives. We aimed to demonstrate the potential of precision medicine to describe the inflammatory landscape present in children with suspected appendicitis. Our primary objective was to determine levels of seven inflammatory protein mediators previously associated with intra-abdominal inflammation (C-reactive protein—CRP, procalcitonin—PCT, interleukin-6 (IL), IL-8, IL-10, monocyte chemoattractant protein-1—MCP-1, and serum amyloid A—SAA) in a cohort of children with suspected appendicitis. Subsequently, using a multiplex proteomics approach, we examined an expansive array of novel candidate cytokine and chemokines within this population. Methods. We performed a secondary analysis of targeted proteomics data from Alberta Sepsis Network studies. Plasma mediator levels, analyzed by Luminex multiplex assays, were evaluated in children aged 5-17 years with nonappendicitis abdominal pain (NAAP), acute appendicitis (AA), and nonappendicitis sepsis (NAS). We used multivariate regression analysis to evaluate the seven target proteins, followed by decision tree and heat mapping analyses for all proteins evaluated. Results. 185 children were included: 83 with NAAP, 79 AA, and 23 NAS. Plasma levels of IL-6, CRP, MCP-1, PCT, and SAA were significantly different in children with AA compared to those with NAAP (). Expansive proteomic analysis demonstrated 6 patterns in inflammatory mediator profiles based on severity of illness. A decision tree incorporating the proteins CRP, ferritin, SAA, regulated on activation normal T-cell expressed and secreted (RANTES), monokine induced by gamma interferon (MIG), and PCT demonstrated excellent specificity (0.920) and negative predictive value (0.882) for children with appendicitis. Conclusions. Multiplex proteomic analyses described the inflammatory landscape of children presenting to the ED with suspected appendicitis. We have demonstrated the feasibility of this approach to identify potential novel candidate cytokines/chemokine patterns associated with a specific illness (appendicitis) amongst those with a broad ED presentation (abdominal pain). This approach can be modelled for future research initiatives in pediatric emergency medicine.
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    Intrapleural Dornase and Tissue Plasminogen Activator in pediatric empyema (DTPA): a study protocol for a randomized controlled trial
    (2017-06-24) Livingston, Michael H; Mahant, Sanjay; Ratjen, Felix; Connolly, Bairbre L; Thorpe, Kevin; Mamdani, Muhammad; Maclusky, Ian; Laberge, Sophie; Giglia, Lucy; Walton, J. M; Yang, Connie L; Roberts, Ashley; Shawyer, Anna C; Brindle, Mary; Parsons, Simon J; Stoian, Cristina A; Cohen, Eyal
    Abstract Background A randomized controlled trial of adults with empyema recently demonstrated decreased length of stay in hospital in patients treated with intrapleurally administered dornase alfa and fibrinolytics compared to fibrinolytics alone. Whether this treatment strategy is safe and effective in children remains unknown. Methods/design This study protocol is for a superiority, placebo-controlled, parallel-design, multicenter randomized controlled trial. The participants are previously well children admitted to a children’s hospital with a diagnosis of empyema requiring chest tube insertion and fibrinolytics administered intrapleurally. Children will be randomized after the treating physician has decided that pleural drainage is required but prior to chest tube insertion. After chest tube insertion, participants in the treatment group will receive intrapleurally administered tissue plasminogen activator (tPA) 4 mg followed by dornase alfa 5 mg. Participants in the placebo group will receive tPA 4 mg followed by normal saline. Study treatments will be administered once daily for 3 days. All participants, parents or caregivers, clinicians, and research personnel will remain blinded. The primary outcome is length of stay from chest tube insertion to discharge from hospital. Secondary outcomes include time to meeting discharge criteria, chest tube duration, fever duration, need for additional procedures, adverse events, hospital readmission, cost of hospitalization, and mortality. Discussion This multicenter randomized controlled trial will assess the safety, effectiveness, and cost-effectiveness of combined treatment with dornase alfa and fibrinolytics compared to fibrinolytics alone for the treatment of empyema in children. Trial registration ClinicalTrials.gov: NCT01717742 . Registered on 8 October 2012.
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    National Surgical Quality Improvement Program: A Scoping Review of the Literature and Real-World Application Among Radical Cystectomy Patients
    (2022-05-09) Mardinger, Cynthia; Kortbeek, John; Hyndman, Eric; Brindle, Mary; Yergens, Dean; Hee Lee, Chel; Fraulin, Frankie; Austen, Lea
    Introduction: The National Surgical Quality Improvement Program (NSQIP) is a validated database designed to measure risk-adjusted 30-day surgical outcomes for national and international benchmarking. De-identified, anonymized datasets can be abstracted from submitting NSQIP hospitals. The purpose of this scoping review is to describe the breadth of studies in the NSQIP literature. Methods: A comprehensive electronic literature search was performed using PubMed, MEDLINE, Web of Knowledge and Scopus to capture all NSQIP articles published between January 1, 2000 and December 31, 2020. Two reviewers independently reviewed articles to determine their relevance using predefined inclusion criteria. Articles were included if they were about NSQIP or used NSQIP data. References were imported into a literature review application, Synthesis®, to semi-automate data management. Extracted data included the domain of surgery, study type, and year of publication. Results: Of the 4,661 NSQIP articles included, 77.9% were published within the last 5 years. Outcomes (46.7%) and Association (41.7%) were the most common types of NSQIP-related articles. The most common surgical domains of NSQIP articles were general surgery and orthopedic surgery, representing 35.7% and 24.0% of the articles, respectively. Overall, 52 (1.1%) articles could not be categorized. Conclusion: This scoping review provides an overview of the diversity of articles in the NSQIP literature. Mapping the NSQIP database identified areas where systematic reviews might be feasible or relevant and identified opportunities for future research.