American Association for Clinical Chemistry
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April 2011 Clinical Laboratory News: Diagnostic Profiles

Diagnostic Profiles

POCT Cardiac Panel Improves ED Treatment Outcomes

A team of British investigators found that patients with suspected myocardial infarction (MI) who were tested using a panel of point-of-care (POCT) cardiac markers had shorter median, but not mean, lengths of stay in the emergency department (ED) and were discharged more frequently without inpatient admission (Heart 2011;97:190–196). The purpose of the study, called the Randomized Assessment of Treatment using Panel Assay of Cardiac Markers (RATPAC), was to assess whether the panel of markers would change ED patient management or reduce hospital admissions.

RATPAC involved 2,243 patients who presented at six U.K. hospitals with suspected MI. Patients were randomized to receive either standard ED care without the POCT cardiac panel or a diagnostic work-up that included the POCT cardiac panel. The panel, which consisted of creatine kinase-MB, myoglobin, and cardiac troponin I (cTn), was measured at presentation and 90 minutes later. Diagnostics for patients in the control arm varied depending on the existing guidance at each facility, for example, different cTn assays with different detection limits measured at different intervals. The primary outcome was the proportion of patients successfully discharged home after being assessed in the ED, without experiencing adverse events such as death or MI during the following 3 months. The researchers set a discharge criterion of within 4 hours of arrival to meet with a national target for that parameter.

The investigators found that patients who had testing with the POCT cardiac panel were nearly four times more likely to have a successful discharge than those who received regular care. They also noted that the median but not the mean length of stay was markedly shorter in the POCT panel group, primarily because patients in the POCT arm who were admitted to the hospital tended to accrue more hospital days. The investigators concluded that use of the POCT panel changed ED disposition and could reduce inpatient bed turnover, but not inpatient bed occupancy.

Guideline-Recommended Role of PSA Velocity Questioned

An analysis by Memorial Sloan-Kettering Cancer Center researchers indicates that prostate-specific antigen (PSA) velocity adds little to the predictive value of high PSA levels or positive digital rectal examination (DRE) (J Natl Cancer Inst 2011;103:1–8). The researchers suggest their findings call into question recommendations by prostate cancer treatment guidelines that men with high PSA velocity >0.35 ng/mL per year should consider biopsy even if the absolute level of PSA is low.

To assess the role of PSA velocity, the researchers analyzed data from 5,519 participants in the placebo arm of the Prostate Cancer Prevention Trial (PCPT), a randomized controlled trial that assessed whether the drug finasteride prevented prostate cancer in men at least 55 years old. PCPT participants had baseline PSA levels ≤3.9 ng/mL and normal DRE, and underwent yearly PSA tests during 7 years of follow-up. They received a biopsy when PSA levels were >4.0 ng/mL and underwent an end-of-study biopsy.

The researchers analyzed the PCPT data in a logistic regression model with standard predictors for prostate cancer on biopsy, and compared the area under the curve (AUC) for this model against one that included the standard predictors plus PSA velocity. They also repeated the analyses with different methods for calculating PSA velocity.

The investigators found that incorporating PSA velocity slightly increased AUC from 0.702 to 0.709. However, they also determined that applying guideline recommendations to this group would have identified 115 additional cancers but required 433 unnecessary biopsies. They concluded that a PSA threshold of 2.5 ng/mL has the same specificity as the PSA velocity threshold of 0.35 ng/mL per year but a higher sensitivity for any cancer, high-grade tumors, and clinically significant disease. 

Pulmonary Arterial Hypertension, Blood Progenitor Cells Linked

New research indicates that levels of blood progenitor cells are increased in the bone marrow, blood, and lungs of patients with pulmonary arterial hypertension (PAH), and that PAH patients also have elevated hypoxia-inducing factors in their blood (Blood 2011;DOI 10.1182/blood-2010-09-306357). The findings point to an interdependent hematopoietic and angiogenic pathology in PAH, and suggest that drugs targeting the bone marrow myeleoproliferative process may be effective in treating the proliferative angiogenic processes in PAH, according to the authors.

The study, conducted by Cleveland Clinic researchers, involved patients with familial, idiopathic, and associated PAH, their non-affected family members, and healthy controls. In addition, the investigators harvested and cultured pulmonary artery endothelial cells from PAH subjects undergoing lung transplants and from donor lungs not used in transplantation. Subjects provided blood samples and underwent bone marrow biopsy and aspirate. The researchers analyzed a variety of different blood and bone marrow components, including: CD34+CD133+ progenitor cells; hypoxia-inducing factors such as erythropoietin (Epo), hepatocyte growth factor, and vascular endothelial growth factor; and Epo receptor expression.

The authors found not only that PAH patients had higher levels of circulating CD34+CD133+ cells than controls but also that proliferation of these cells was significantly higher in PAH patients. They also found that levels of different analytes varied across different types of PAH. For example, familial PAH patients had the highest level of circulating progenitor cells, and familial and associated PAH patients had nearly double the erythroid progenitors of those with idiopathic PAH. They also found that all non-affected family members had levels of circulating CD34+CD133+ cells similar to their PAH-afflicted relatives. 

Cytomegalovirus PCR of Dried Blood Spots Comparable to Reference Method

A study comparing the performance of two polymerase chain reaction assays for detecting congenital cytomegalovirus (CMV) from dried blood spots indicates that both had high sensitivity, specificity, and positive- and negative- predictive value in comparison to the reference technique of urine-based CMV PCR assay (Clin Infect Dis 2011; 52:575–81). The authors propose that this data should be considered in the ongoing debate about neonatal screening for CMV generally, as well as the appropriateness of CMV PCR assays of dried blood spots. CMV PCR assays of dried blood spots were developed initially for retrospective diagnosis of children with hearing loss or other congenital CMV-related symptoms not diagnosed at birth, and they have been proposed, but not adopted, in neonatal screening.

This prospective study involved 271 neonates born either with symptoms compatible with congenital CMV or to mothers with a history of primary CMV infection in pregnancy. The researchers used two different CMV PCR assays of dried blood spots and one CMV PCR of urine samples taken during the babies’ first week of life. The authors caution that their high positive predictive values should not be transposed to a general population of neonates in which CMV prevalence is much lower.