The life of a laboratory requisition form: Patient compliance with clinical laboratory testing in a Canadian primary care health region.

Objective: To examine patient laboratory testing compliance by tracking time to submission of laboratory requisitions in Southern Alberta, Canada as part of a quality improvement initiative.

Methods: Data was collected retrospectively from patients from the Chinook Primary Care Network in Alberta, Canada, who received a laboratory requisition consisting of a complete blood count (CBC) test order between September 1, 2016 and August 31, 2017. To allow for all laboratory requisitions created to be submitted within one year, the study collection period was from September 1, 2016 to August 31, 2018.

Dataset of test volume and tests repeated for complete blood count and electrolyte panels from hospitals in a Canadian province in 2018.

All laboratory tests performed within the province of Alberta in Canada are captured by three Laboratory Information Systems (LIS; Millennium, Sunquest and Meditech), which comprise the provincial Consolidated Laboratory Data Repository (CLDR). The following secondary laboratory data for electrolyte panel (EP) and complete blood count (CBC) test panels performed in emergency room (ER) and inpatient settings were collected from January 1 - December 31, 2018: total test panel volume, total number of test panels repeated, number of test panels repeated within the 24 hour period, test result, date of testing, time of test, and patient Provincial Health Number (PHN). Patient PHN were used as a linking variable to match subsequent tests performed on the same patient.

Inappropriate repeat testing of complete blood count (CBC) and electrolyte panels in inpatients from Alberta, Canada.

Introduction: The avoidance of repeat chemistry testing such as Complete Blood Count (CBC) and Electrolyte Panel (EP) on clinically stable patients was identified as important utilization goals by Choosing Wisely Canada. The purpose of this study was to assess the volume of overutilization of CBC and EP in an inpatient setting in Alberta, Canada, and provide an estimated cost assessment of unnecessary testing.

Methods: The total laboratory testing volumes of two common test panels were collected retrospectively for one-year from January to December 2018.

Differential role of TIMP2 and TIMP3 in cardiac hypertrophy, fibrosis, and diastolic dysfunction.

Aims: Tissue inhibitor of metalloproteinases (TIMPs) can mediate myocardial remodelling, hypertrophy, and fibrosis in heart disease. We investigated the impact of TIMP2 vs. TIMP3 deficiency in angiotensin II (Ang II)-induced myocardial remodelling and cardiac dysfunction.

Loss of Apelin exacerbates myocardial infarction adverse remodeling and ischemia-reperfusion injury: therapeutic potential of synthetic Apelin analogues.

Background: Coronary artery disease leading to myocardial ischemia is the most common cause of heart failure. Apelin (APLN), the endogenous peptide ligand of the APJ receptor, has emerged as a novel regulator of the cardiovascular system.

Methods And Results: Here we show a critical role of APLN in myocardial infarction (MI) and ischemia-reperfusion (IR) injury in patients and animal models.

TIMP3 is the primary TIMP to regulate agonist-induced vascular remodelling and hypertension.

Aims: Hypertension is accompanied by structural remodelling of vascular extracellular matrix (ECM). Tissue inhibitor of metalloproteinases (TIMPs) inhibits matrix metalloproteinases (MMPs) that degrade the matrix structural proteins. In response to a hypertensive stimulus, the balance between MMPs and TIMPs is altered.

Loss of Timp3 gene leads to abdominal aortic aneurysm formation in response to angiotensin II.

Aortic aneurysm is dilation of the aorta primarily due to degradation of the aortic wall extracellular matrix (ECM). Tissue inhibitors of metalloproteinases (TIMPs) inhibit matrix metalloproteinases (MMPs), the proteases that degrade the ECM. Timp3 is the only ECM-bound Timp, and its levels are altered in the aorta from patients with abdominal aortic aneurysm (AAA).

Lack of tissue inhibitor of metalloproteinases 2 leads to exacerbated left ventricular dysfunction and adverse extracellular matrix remodeling in response to biomechanical stress.

Background: Remodeling of the extracellular matrix (ECM) is a key aspect of myocardial response to biomechanical stress and heart failure. Tissue inhibitors of metalloproteinases (TIMPs) regulate the ECM turnover through negative regulation of matrix metalloproteinases (MMPs), which degrade the ECM structural proteins. Tissue inhibitor of metalloproteinases 2 is unique among TIMPs in activating pro-MMP2 in addition to inhibiting a number of MMPs.

Tissue inhibitor of metalloproteinases (TIMPs) in heart failure.

Remodeling of the myocardium and the extracellular matrix (ECM) occurs in heart failure irrespective of its initial cause. The ECM serves as a scaffold to provide structural support as well as housing a number of cytokines and growth factors. Hence, disruption of the ECM will result in structural instability as well as activation of a number of signaling pathways that could lead to fibrosis, hypertrophy, and apoptosis.

Loss of PI3Kγ enhances cAMP-dependent MMP remodeling of the myocardial N-cadherin adhesion complexes and extracellular matrix in response to early biomechanical stress.

Rationale: Mechanotransduction and the response to biomechanical stress is a fundamental response in heart disease. Loss of phosphoinositide 3-kinase (PI3K)γ, the isoform linked to G protein-coupled receptor signaling, results in increased myocardial contractility, but the response to pressure overload is controversial.

Objective: To characterize molecular and cellular responses of the PI3Kγ knockout (KO) mice to biomechanical stress.

Early activation of matrix metalloproteinases underlies the exacerbated systolic and diastolic dysfunction in mice lacking TIMP3 following myocardial infarction.

Extracellular matrix (ECM) remodeling is a critical aspect of cardiac remodeling following myocardial infarction. Tissue inhibitors of metalloproteinases (TIMPs) are physiological inhibitors of matrix metalloproteinases (MMPs) that degrade the ECM proteins. TIMP3 is highly expressed in the heart, and is markedly downregulated in patients with ischemic cardiomyopathy.

TIMP2 deficiency accelerates adverse post-myocardial infarction remodeling because of enhanced MT1-MMP activity despite lack of MMP2 activation.

Rationale: Myocardial infarction (MI) results in remodeling of the myocardium and the extracellular matrix (ECM). Tissue inhibitors of metalloproteinases (TIMPs) are critical regulators of ECM integrity via inhibiting matrix metalloproteinases (MMPs). TIMP2 is highly expressed in the heart and is the only TIMP that, in addition to inhibiting MMPs, is required for cell surface activation of pro-MMP2.

Tumor necrosis factor induces matrix metalloproteinases in cardiomyocytes and cardiofibroblasts differentially via superoxide production in a PI3Kgamma-dependent manner.

Tumor necrosis factor (TNF) is an inflammatory cytokine that is upregulated in a number of cardiomyopathies. Adverse cardiac remodeling and dilation result from degradation of the extracellular matrix by matrix metalloproteinases (MMPs). We investigated whether TNF can directly trigger expression and activation of MMPs in cardiac cells.

Loss of TIMP3 enhances interstitial nephritis and fibrosis.

The balance of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) determines the integrity of the extracellular matrix. TIMP3 is the most highly expressed tissue inhibitor of metalloproteinase (TIMP) in the kidney, but its function in renal disease is incompletely understood. In this study, TIMP3-/- mice demonstrated an age-dependent chronic tubulointerstitial fibrosis.