Lab Research

Translation of Novel Intestinal Injury Biomarkers to Clinical Application

Title: Translation of Novel Intestinal Injury Biomarkers to Clinical Application

Research Ethics Board#: Pro00025429

Principal Investigator: Dr. Rachel Khadaroo

Funding Source: Department of Critical Care Medicine Research Grant

Project #: RES0016824

Objective: Our primary objective is to measure novel serum biomarkers and the urine metabolite profile for the early detection of acute intestinal ischemia. Our secondary objectives include characterization of high risk features for development of post-operative intestinal ischemia, describing the complications associated with post-operative intestinal ischemia (i.e. acute lung injury [ALI], acute kidney injury [AKI], multiple organ dysfunction [MOD]), and describing the post-operative natural history and clinical outcomes associated with intestinal ischemia.

Study Design and Setting: A prospective observational cohort study in the University of Alberta Hospital in Edmonton, Canada. Study Protocol: We propose to sample serial blood and urine specimens for biomarkers/metabolites starting pre-operatively (at enrollment), immediately pre-operatively and post-operatively, then at 24 h post-operatively. Data will be collected on demographics, acute physiology, peri-operative diagnostic tests and interventions, clinical course and outcomes. Serum samples Blood samples will be drawn from existing arterial lines or at the same time as routine blood samples. Sterile urine is to be collected from the side port of each patient's indwelling urinary catheter. The plasma and urine samples will be assessed for biomarkers and metabolomics.

Study Outcomes: The primary outcome will be the predictive value of novel biomarkers (I-FABP, sPLA2)/urine metabolite concentration for the diagnosis of intestinal ischemia compared to traditional markers (lactate, WBC). Intestinal ischemia will be diagnosed either by colonoscopy or surgery with a gold standard pathological confirmation. Secondary outcomes will be: 1) post-operative surgical morbidity and/or need for re-operation; 2) post-operative organ injury (i.e. ALI, AKI, MOD) and/or sepsis; 3) lengths of ICU and hospital; and, 4) 30-day mortality.

Summary: The proposed study constitutes a ‘bench to bedside’ translation of our laboratory findings to the clinical setting. This study represents a significant opportunity in developing new modalities in the diagnosis of early intestinal ischemia and may allow for more rapid intervention to mitigate devastating complication.

Establishing Clinically Relevant Biomarkers to Diagnosis NEC

Title: Establishing clinically relevant biomarkers for the early diagnosis of necrotizing enterocolitis

Research Ethics Board #: Pro00031854

Principal Investigator: Dr. Rachel Khadaroo

Co-Investigators: Dr. Bryan Dicken, Dr. Po-Yin Cheung

Funding Source: Women and Children’s Health Research Institute, Innovation Grant

Project #: RES0018666

Background: Necrotizing enterocolitis (NEC) is a major medical condition afflicting premature neonates. It is associated with significant risks of morbidity and mortality, and can result in lifelong health consequences. Earlier detection and diagnosis would result in earlier initiation of treatment and possible prevention of long term complications. A novel set of biomarkers will be tested to determine the accuracy and specificity of these tests in detecting NEC.

Study design: A prospective, observational cohort study in the NICU of the Royal Alexandra Hospital and Stollery Children‘s Hospital in Edmonton, Alberta. Inclusion Criteria: All neonates with modified Bell clinical stage I (suspected NEC), stage II (definite NEC), or stage III (advanced NEC) as determined by two independent neonatologists. Exclusion Criteria: Refusal of parental consent, Absence of clinical and/or laboratory data, Major congenital or chromosomal abnormality Outcome Measures

Study Outcomes: The primary outcome will be the diagnosis of NEC in the group of neonates with suspected NEC diagnoses. By convention, case definitions will define confirmed NEC diagnoses as Stage II or III NEC on the modified Bell clinical staging system. Secondary outcomes will include: 30-day mortality, length of NICU and hospital stay, development of sepsis, requirement for surgical intervention.

Summary: The proposed study constitutes a ‘bench to bedside’ translation of these findings to the clinical setting. Only FABP has been studied to a limited degree in the diagnosis of NEC. The use of sPLA2 and metabolomics has never been examined in this setting. The new diagnostic modalities proposed in this study have potential in the early diagnosis of intestinal injury in a high-risk neonatal population. The lack of information available in the current literature represents a major opportunity to develop novel techniques that can dramatically improve the level of clinical care in NEC.