Research

The Impact of Hemolysis on Cell-Free microRNA Biomarkers

Kirschner MB, Edelman JJ, Kao SC, Vallely MP, van Zandwijk N, Reid G

Front Genet 2013;4:94

PMID: 23745127

Abstract

Cell-free microRNAs in plasma and serum have become a promising source of biomarkers for various diseases. Despite rapid progress in this field, there remains a lack of consensus regarding optimal quantification methods, reference genes, and quality control of samples. Recent studies have shown that hemolysis occurring during blood collection has substantial impact on the microRNA content in plasma/serum. To date, the impact of hemolysis has only been investigated for a limited number of microRNAs, mainly the red blood cell (RBC)-enriched miRs-16 and -451. In contrast, the effect of hemolysis on other microRNAs – in particular those proposed as biomarkers – has not been addressed. In this study we profiled the microRNA content of hemolyzed and non-hemolyzed plasma as well as RBCs to obtain a profile of microRNAs in the circulation affected or unaffected by hemolysis. Profiling by TaqMan Array Microfluidic Cards was used to compare three pairs of hemolyzed and non-hemolyzed plasma (with varying degrees of hemolysis) and one RBC sample. A total of 136 microRNAs were detectable in at least two of the samples, and of those 15 were at least twofold elevated in all three hemolyzed samples. This number increased to 88 microRNAs for the sample with the highest level of hemolysis, with all of these also detected in the RBC profile. Thus these microRNAs represent a large proportion of detectable microRNAs and those most likely to be affected by hemolysis. Several of the hemolysis-susceptible microRNAs (e.g., miRs-21, -106a, -92a, -17, -16) have also been previously proposed as plasma/serum biomarkers of disease, highlighting the importance of rigorous quality control of plasma/serum samples used for measurement of circulating microRNAs. As low-level hemolysis is a frequent occurrence during plasma/serum collection it is critical that this is taken into account in the measurement of any candidate circulating microRNA.

Drug-eluting stents versus coronary artery bypass graft surgery in left main coronary artery disease: a meta-analysis of early outcomes from randomized and nonrandomized studies

Cao C, Manganas C, Bannon P, Vallely M, Yan TD

J. Thorac. Cardiovasc. Surg. 2013 Mar;145(3):738-47

PMID: 22405674

Abstract

OBJECTIVE: The present meta-analysis aimed to compare the short-term safety and efficacy of drug-eluting stents and coronary artery bypass graft surgery for patients with left main coronary artery disease.

METHODS: Fourteen relevant studies were identified from 5 electronic databases. End points included mortality, stroke, myocardial infarction, repeat revascularization, and major adverse cardiac and cerebrovascular events.

RESULTS: Results indicate that all-cause mortality was similar between drug-eluting stents and coronary artery bypass grafting at 30 days and at follow-up beyond 1 year. Likewise, the incidence of myocardial infarction was similar between drug-eluting stents and coronary artery bypass grafting at 12 months and at follow-up beyond 1 year. However, drug-eluting stents were associated with a lower incidence of all-cause mortality at 12 months and a higher incidence of myocardial infarction at 30 days compared with coronary artery bypass grafting. Drug-eluting stents were consistently associated with a higher incidence of repeat revascularization, whereas coronary artery bypass grafting had a higher incidence of stroke. The incidence of major adverse cardiac and cerebrovascular events was similar between the 2 groups at 30 days but higher for drug-eluting stents at 12 months and beyond.

CONCLUSIONS: Patients treated by drug-eluting stents in randomized controlled trials and observational studies in the current literature are often a preselected subgroup with less complex lesions compared with the overall target population. Results drawn from these studies should be viewed with caution. Coronary artery bypass grafting is associated with a lower incidence of major adverse cardiac and cerebrovascular events at 1 year and beyond, and thus should be regarded as the standard of treatment. However, drug-eluting stents may have a role for selected patients with percutaneously amenable left main disease who are poor surgical candidates.

Off-pump coronary artery bypass surgery induces prolonged alterations to host neutrophil physiology

Edelman JJ, Fung YL, Pennings GJ, Reddel CJ, Bannon PG, Bayfield MS, Kritharides L, Fraser JF, Vallely MP

Shock 2013 Feb;39(2):149-54

PMID: 23324884

Abstract

Persistent alteration to host polymorphonuclear cell (PMN) physiology has been demonstrated after cardiac surgery performed with cardiopulmonary bypass (CPB). However, to date, PMN physiology and function beyond the first 24 h have not been investigated after cardiac surgery performed without CPB (off-pump coronary artery bypass grafting [OPCAB]). Blood samples of 15 patients were collected preoperatively and on days 1, 3, and 5 after OPCAB. Expression of CD11b, CD18, CBRM1/5, and CD62L were assessed by flow cytometry under resting conditions and after stimulation with formyl methionyl-leucyl-phenylalanine (fMLF), and respiratory burst activity was also measured. Under resting conditions, PMN CD11b, CBRM1/5, and CD62L expressions were minimally altered by surgery. Compared with the response of preoperative PMNs, PMNs assayed on days 3 and 5 after OPCAB demonstrated a significantly blunted increase in the expression of CD11b and CBRM1/5 after fMLF, significantly diminished shedding of CD62L in response to platelet-activating factor and fMLF, and diminished superoxide production after stimulation on day 3. The alteration of PMN function after OPCAB implies that cardiac surgical trauma without CPB directly modulates host PMN physiology.

Cardiac surgery versus stenting: what is better for the patient?

Edelman JJ, Wilson MK, Bannon PG, Vallely MP

ANZ J Surg 2012 Nov;82(11):792-8

PMID: 22989330

Abstract

Patterns of myocardial revascularization have changed significantly over the past decade. There has been a relative decrease of coronary artery bypass grafting (CABG) compared with percutaneous coronary intervention (PCI) and some patients are undergoing PCI for coronary lesions traditionally reserved for CABG. The mid- to long-term results of several trials comparing PCI with CABG have recently been published. For three-vessel disease, CABG is superior to PCI, with lower rates of major adverse cardiac events. PCI may be equivalent to CABG for three-vessel disease in the lowest disease complexity tercile (SYNTAX score <22; ∼20% of patients). This review focuses on the most recent evidence for myocardial revascularization in patients with multi-vessel and left main coronary artery disease.

Serum biomarkers of neurologic injury in cardiac operations

Seco M, Edelman JJ, Wilson MK, Bannon PG, Vallely MP

Ann. Thorac. Surg. 2012 Sep;94(3):1026-33

PMID: 22857981

Abstract

Assessment of subtle neurocognitive decline after surgical procedures has been hampered by heterogeneous testing techniques and a lack of reproducibility. This review summarizes the sensitivity and specificity of biomarkers of neurologic injury to determine whether they can be applied in the postoperative period to accurately predict neurocognitive decline. Creatine kinase-brain type, neuron-specific enolase, and S100B can be released into serum during operations by extracranial sources. Glial fibrillary acidic protein is a sensitive marker, and there are extracranial sources that are antigenically different from the brain-derived form. Serum levels of tau protein after acute neurologic injury do not reliability correlate with incidence.

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