Regulatory T Cell Biomarkers Identify Patients at Risk of Developing Acute Cellular Rejection in the First Year Following Heart Transplantation.

Background: Acute cellular rejection (ACR), an alloimmune response involving CD4+ and CD8+ T cells, occurs in up to 20% of patients within the first year following heart transplantation. The balance between a conventional versus regulatory CD4+ T cell alloimmune response is believed to contribute to developing ACR. Therefore, tracking these cells may elucidate whether changes in these cell populations could signal ACR risk.

The impact of IgG subclass deficiency on the risk of mortality in hospitalized patients with COPD.

Background: Immunoglobulin G (IgG) deficiency increases the risk of acute exacerbations and mortality in chronic obstructive pulmonary disease (COPD). However, the impact of IgG subclass deficiency on mortality in COPD is unknown. Here, we determined which IgG subclass, if any, is associated with increased risk of mortality in COPD.

Automated medical chart review for breast cancer outcomes research: a novel natural language processing extraction system.

Background: Manually extracted data points from health records are collated on an institutional, provincial, and national level to facilitate clinical research. However, the labour-intensive clinical chart review process puts an increasing burden on healthcare system budgets. Therefore, an automated information extraction system is needed to ensure the timeliness and scalability of research data.

Nonsurgical maxillary orthopedic protraction treatment for an adult patient with hyperdivergent facial morphology, Class III malocclusion, and bilateral crossbite.

Optimal treatment for an adult patient with hyperdivergent facial morphology, Class III malocclusion, bilateral posterior crossbite, and skeletal disharmony usually requires comprehensive orthodontics combined with extractions, orthognathic surgery, or both. However, treatment becomes more challenging when the patient rejects surgery because of fear or cost. This case report presents the orthodontic treatment of a 24-year-old woman with a Class III malocclusion and bilateral posterior crossbite without surgery using orthopedic and comprehensive orthodontic approaches.

Epigenetic marker of telomeric age is associated with exacerbations and hospitalizations in chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is an age-related condition that has been associated with early telomere attrition; the clinical implications of telomere shortening in COPD are not well known. In this study we aimed to determine the relationship of the epigenetic regulation of telomeric length in peripheral blood with the risk of exacerbations and hospitalization in patients with COPD.

Methods: Blood DNA methylation profiles were obtained from 292 patients with COPD enrolled in the placebo arm of the Macrolide Azithromycin to Prevent Rapid Worsening of Symptoms Associated with Chronic Obstructive Pulmonary Disease (MACRO) Study and who were followed for 1-year.

Aortic Dimensions, Biophysical Properties, and Plasma Biomarkers in Children and Adults with Marfan or Loeys-Dietz Syndrome.

Background: Aortic dilation, stiffening, and dissection are common and potentially lethal complications of Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS), which involve abnormal transforming growth factor beta (TGF-β) signalling. The relation of aortic dimensions, stiffness, and biomarker levels is unknown. The objective of this study was to measure aortic dimensions, stiffness, TGF-β and matrix metalloproteinase (MMP) levels, and endothelial function in patients with MFS, and to compare TGF-β levels in patients with MFS receiving different therapeutic regimens.

Analytical Validation of HEARTBiT: A Blood-Based Multiplex Gene Expression Profiling Assay for Exclusionary Diagnosis of Acute Cellular Rejection in Heart Transplant Patients.

Background: HEARTBiT is a whole blood-based gene profiling assay using the nucleic acid counting NanoString technology for the exclusionary diagnosis of acute cellular rejection in heart transplant patients. The HEARTBiT score measures the risk of acute cellular rejection in the first year following heart transplant, distinguishing patients with stable grafts from those at risk for acute cellular rejection. Here, we provide the analytical performance characteristics of the HEARTBiT assay and the results on pilot clinical validation.

HEARTBiT: A Transcriptomic Signature for Excluding Acute Cellular Rejection in Adult Heart Allograft Patients.

Background: Nine mRNA transcripts associated with acute cellular rejection (ACR) in previous microarray studies were ported to the clinically amenable NanoString nCounter platform. Here we report the diagnostic performance of the resulting blood test to exclude ACR in heart allograft recipients: HEARTBiT.

Methods: Blood samples for transcriptomic profiling were collected during routine post-transplantation monitoring in 8 Canadian transplant centres participating in the Biomarkers in Transplantation initiative, a large (n = 1622) prospective observational study conducted between 2009 and 2014.

Effect of short-term oral prednisone therapy on blood gene expression: a randomised controlled clinical trial.

Background: Effects of systemic corticosteroids on blood gene expression are largely unknown. This study determined gene expression signature associated with short-term oral prednisone therapy in patients with chronic obstructive pulmonary disease (COPD) and its relationship to 1-year mortality following an acute exacerbation of COPD (AECOPD).

Methods: Gene expression in whole blood was profiled using the Affymetrix Human Gene 1.

Blood biomarkers to predict short-term pulmonary exacerbation risk in children and adolescents with CF: A pilot study.

In CF, pulmonary exacerbations (PEx) can lead to permanent loss in lung function and thus should be prevented. Previously, we identified a blood protein biosignature consisting of 6 proteins capable of predicting short-term PEx events in CF adults. In this study, we utilized blood samples from the placebo arm of a randomized controlled trial to assess whether this candidate protein biosignature was also capable of predicting short-term PEx events in CF children and adolescents.

Ensembling Electrical and Proteogenomics Biomarkers for Improved Prediction of Cardiac-Related 3-Month Hospitalizations: A Pilot Study.

Background: Many risk models for predicting mortality, hospitalizations, or both in patients with heart failure have been developed but do not have sufficient discriminatory ability. The purpose of this study was to identify predictive biomarkers of hospitalizations in heart failure patients using omics-based technologies applied to blood and electrical monitoring of the heart.

Methods: Blood samples were collected from 58 heart failure patients during enrollment into this study.

Phenotyping and outcomes of hospitalized COPD patients using rapid molecular diagnostics on sputum samples.

Background: Etiologies of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are heterogeneous. We phenotyped severe AECOPD based on molecular pathogen detection of sputum samples collected at hospitalization of COPD patients and determined their outcomes.

Methods: We phenotyped 72 sputum samples of COPD patients who were hospitalized with a primary diagnosis of AECOPD using a molecular array that detected common bacterial and viral respiratory pathogens.

Development and Validation of Apolipoprotein AI-Associated Lipoprotein Proteome Panel for the Prediction of Cholesterol Efflux Capacity and Coronary Artery Disease.

Background: Cholesterol efflux capacity (CEC) is a measure of HDL function that, in cell-based studies, has demonstrated an inverse association with cardiovascular disease. The cell-based measure of CEC is complex and low-throughput. We hypothesized that assessment of the lipoprotein proteome would allow for precise, high-throughput CEC prediction.

Sputum Microbiome Is Associated with 1-Year Mortality after Chronic Obstructive Pulmonary Disease Hospitalizations.

Lung dysbiosis promotes airway inflammation and decreased local immunity, potentially playing a role in the pathogenesis of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). We sought to determine the relationship between sputum microbiome at the time of AECOPD hospitalization and 1-year mortality in a COPD cohort. We used sputum samples from 102 patients hospitalized because of AECOPD.

Phenotyping COPD exacerbations using imaging and blood-based biomarkers.

Rationale: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are caused by a variety of different etiologic agents. Our aim was to phenotype COPD exacerbations using imaging (chest X-ray [CXR] and computed tomography [CT]) and to determine the possible role of the blood tests (C-reactive protein [CRP], the N-terminal prohormone brain natriuretic peptide [NT-proBNP]) as diagnostic biomarkers.

Materials And Methods: Subjects who were hospitalized with a primary diagnosis of AECOPD and who had had CXRs, CT scans, and blood collection for CRP and NT-proBNP were assessed in this study.

Thrombospondin-1 and disease progression in dysferlinopathy.

The purpose of this study was to determine whether thrombospondin (TSP)-1 promotes macrophage activity and disease progression in dysferlinopathy. First, we found that levels of TSP-1 are elevated in blood of non-ambulant dysferlinopathy patients compared with ambulant patients and healthy controls, supporting the idea that TSP-1 levels are correlated with disease progression. We then crossed dysferlinopathic BlaJ mice with TSP-1 knockout mice and assessed disease progression longitudinally with magnetic resonance imaging (MRI).

Multiple reaction monitoring mass spectrometry to identify novel plasma protein biomarkers of treatment response in cystic fibrosis pulmonary exacerbations.

Background: Systemic inflammation decreases with IV antibiotics during the treatment of CF pulmonary exacerbations (PEx). We used multiple reaction monitoring mass spectrometry and immunoassays to monitor blood proteins during PEx treatment to determine if early changes could be used to predict PEx outcomes following treatment.

Methods: Blood samples from 25 PEx (22 unique adults) were collected within 24h of admission, day 5, day 10, and at IV antibiotic completion.

Differentiating heart failure phenotypes using sex-specific transcriptomic and proteomic biomarker panels.

Aims: Heart failure with preserved ejection fraction (HFpEF) accounts for 30-50% of patients with heart failure (HF). A major obstacle in HF management is the difficulty in differentiating between HFpEF and heart failure with reduced ejection fraction (HFrEF) using conventional clinical and laboratory investigations. The aim of this study is to develop robust transcriptomic and proteomic biomarker signatures that can differentiate HFpEF from HFrEF.

PGCA: An algorithm to link protein groups created from MS/MS data.

The quantitation of proteins using shotgun proteomics has gained popularity in the last decades, simplifying sample handling procedures, removing extensive protein separation steps and achieving a relatively high throughput readout. The process starts with the digestion of the protein mixture into peptides, which are then separated by liquid chromatography and sequenced by tandem mass spectrometry (MS/MS). At the end of the workflow, recovering the identity of the proteins originally present in the sample is often a difficult and ambiguous process, because more than one protein identifier may match a set of peptides identified from the MS/MS spectra.

Integrative Genomics of Emphysema-Associated Genes Reveals Potential Disease Biomarkers.

Chronic obstructive pulmonary disease is the third leading cause of death worldwide. Gene expression profiling across multiple regions of the same lung identified genes significantly related to emphysema. We sought to determine whether the lung and epithelial expression of 127 emphysema-related genes was also related to lung function in independent cohorts, and whether any of these genes could be used as biomarkers in the peripheral blood of patients with chronic obstructive pulmonary disease.

C-reactive protein and N-terminal prohormone brain natriuretic peptide as biomarkers in acute exacerbations of COPD leading to hospitalizations.

There are currently no accepted and validated blood tests available for diagnosing acute exacerbations of chronic obstructive pulmonary disease (AECOPD). In this study, we sought to determine the discriminatory power of blood C-reactive protein (CRP) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) in the diagnosis of AECOPD requiring hospitalizations. The study cohort consisted of 468 patients recruited in the COPD Rapid Transition Program who were hospitalized with a primary diagnosis of AECOPD, and 110 stable COPD patients who served as controls.

Clinical utility of C-reactive protein to predict treatment response during cystic fibrosis pulmonary exacerbations.

Rationale: C-reactive protein (CRP) is a systemic marker of inflammation that correlates with disease status in cystic fibrosis (CF). The clinical utility of CRP measurement to guide pulmonary exacerbation (PEx) treatment decisions remains uncertain.

Objectives: To determine whether monitoring CRP during PEx treatment can be used to predict treatment response.