Causes of Elevated Cardiac Troponins in the Emergency Department and Their Associated Mortality.

OBJECTIVE: Cardiac troponins (cTn) are structural components of myocardial cells and are expressed almost exclusively in the heart. Elevated cTn levels indicate myocardial cell damage/death but not reflect the underlying etiology. The third universal definition of myocardial infarction (MI) differentiates MI into various types. Type 1 (T1MI) is due to plaque rupture with thrombus, while type 2 (T2MI) is a result of a supply:demand mismatch. Non-MI cTn elevations are also common. We determined the causes of elevated cTn in a tertiary care emergency department (ED) and the associated in-hospital mortality. METHODS: We performed a structured, retrospective review of all consecutive adult ED patients with elevated troponin I (defined as > 99th percentile of the normal population, as run on the ADVIA Centaur platform; Siemens USA) during 1 year. Causes of elevated cTn were classified based on the third universal definitions. Comparisons between groups were performed using chi-square and Mann-Whitney U-tests. RESULTS: Of 96,612 ED patients presenting from May 2012 to April 2013, a total of 13,502 (14%) had cTn measured, of which 1,310 (9.7%) were elevated. Of these, 340 (26.5%, 95% confidence interval [CI], 24.2% to 29.0%) were T1MI, 452 (35.2%, 95% CI = 32.7% to 37.9%) T2MI, 458 (35.7%, 95% CI = 33.1% to 38.4%) multifactorial, and 33 (2.5%, 95% CI = 1.8% to 3.5%) due to nonischemic injury. Non-T1MI patients were slightly older, more likely female, and had higher blood urea nitrogen and creatinine. Comorbidities were more common in non-T1MI while cardiac risk factors were more common in T1MI. Non-T1MI patients were less likely to have diagnostic ECGs and had lower initial and subsequent cTn levels. In-hospital mortality rates were similarly high for T1MI and non-T1MI (11% [95% CI = 8% to 15%] vs. 10% [95% CI = 8% to 12%], p = 0.48). CONCLUSIONS: Of all ED patients with elevated cTn, ~75% have a non-T1MI. The mortality of patients with non-T1MI is similar to the mortality in patients with T1MI.

Biomarkers of folate status in NHANES: a roundtable summary.

A roundtable to discuss the measurement of folate status biomarkers in NHANES took place in July 2010. NHANES has measured serum folate since 1974 and red blood cell (RBC) folate since 1978 with the use of several different measurement procedures. Data on serum 5-methyltetrahydrofolate (5MTHF) and folic acid (FA) concentrations in persons aged ≥60 y are available in NHANES 1999-2002. The roundtable reviewed data that showed that folate concentrations from the Bio-Rad Quantaphase II procedure (Bio-Rad Laboratories, Hercules, CA; used in NHANES 1991-1994 and NHANES 1999-2006) were, on average, 29% lower for serum and 45% lower for RBC than were those from the microbiological assay (MA), which was used in NHANES 2007-2010. Roundtable experts agreed that these differences required a data adjustment for time-trend analyses. The roundtable reviewed the possible use of an isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) measurement procedure for future NHANES and agreed that the close agreement between the MA and LC-MS/MS results for serum folate supported conversion to the LC-MS/MS procedure. However, for RBC folate, the MA gave 25% higher concentrations than did the LC-MS/MS procedure. The roundtable agreed that the use of the LC-MS/MS procedure to measure RBC folate is premature at this time. The roundtable reviewed the reference materials available or under development at the National Institute of Standards and Technology and recognized the challenges related to, and the scientific need for, these materials. They noted the need for a commutability study for the available reference materials for serum 5MTHF and FA.

Biomarkers of vitamin B-12 status in NHANES: a roundtable summary.

A roundtable to discuss the measurement of vitamin B-12 (cobalamin) status biomarkers in NHANES took place in July 2010. NHANES stopped measuring vitamin B-12-related biomarkers after 2006. The roundtable reviewed 3 biomarkers of vitamin B-12 status used in past NHANES--serum vitamin B-12, methylmalonic acid (MMA), and total homocysteine (tHcy)--and discussed the potential utility of measuring holotranscobalamin (holoTC) for future NHANES. The roundtable focused on public health considerations and the quality of the measurement procedures and reference methods and materials that past NHANES used or that are available for future NHANES. Roundtable members supported reinstating vitamin B-12 status measures in NHANES. They noted evolving concerns and uncertainties regarding whether subclinical (mild, asymptomatic) vitamin B-12 deficiency is a public health concern. They identified the need for evidence from clinical trials to address causal relations between subclinical vitamin B-12 deficiency and adverse health outcomes as well as appropriate cutoffs for interpreting vitamin B-12-related biomarkers. They agreed that problems with sensitivity and specificity of individual biomarkers underscore the need for including at least one biomarker of circulating vitamin B-12 (serum vitamin B-12 or holoTC) and one functional biomarker (MMA or tHcy) in NHANES. The inclusion of both serum vitamin B-12 and plasma MMA, which have been associated with cognitive dysfunction and anemia in NHANES and in other population-based studies, was preferable to provide continuity with past NHANES. Reliable measurement procedures are available, and National Institute of Standards and Technology reference materials are available or in development for serum vitamin B-12 and MMA.

Advances in standardization of laboratory measurement procedures: implications for measuring biomarkers of folate and vitamin B-12 status in NHANES.

Population studies such as NHANES analyze large numbers of laboratory measurements and are often performed in different laboratories using different measurement procedures and over an extended period of time. Correct clinical and epidemiologic interpretations of the results depend on the accuracy of those measurements. Unfortunately, considerable variability has been observed among assays for folate, vitamin B-12, and related biomarkers. In the past few decades, the science of metrology has advanced considerably, with the development of improved primary reference measurement procedures and high-level reference materials, which can serve as the basis for accurate measurement. A rigorous approach has been established for making field methods traceable to the highest-level reference measurement procedures and reference materials. This article reviews some basic principles of metrology and describes their recent application to measurements of folate and vitamin B-12.

Educating medical students in laboratory medicine: a proposed curriculum.

As the 100th anniversary of the Flexner report nears, medical student education is being reviewed at many levels. One area of concern, expressed in recent reports from some national health care organizations, is the adequacy of training in the discipline of laboratory medicine (also termed clinical pathology). The Academy of Clinical Laboratory Physicians and Scientists appointed an ad hoc committee to review this topic and to develop a suggested curriculum, which was subsequently forwarded to the entire membership for review. The proposed medical student laboratory medicine curriculum defines goals and objectives for training, provides guidelines for instructional methods, and gives examples of how outcomes can be assessed. This curriculum is presented as a potentially helpful outline for use by medical school faculty and curriculum committees.

Comparison of emergency department patient classification by point-of-care and central laboratory methods for cardiac troponin I.

For patients admitted to the emergency department (ED) with suspected acute coronary syndrome, we compared results of a rapid, point-of-care whole blood assay for cardiac troponin I (Abbott i-STAT, Abbott Point-of-Care, East Windsor, NJ) (Tn-P) with an automated central laboratory plasma assay (Siemens TnI-Ultra, Siemens Medical Solutions Diagnostics, Tarrytown, NY) (Tn-U). Clinical data were obtained during a 6-month period during which ED patients were screened by Tn-P, with retesting of elevated results by Tn-U. Of 5,909 Tn-P results, 573 (9.7%) were elevated; these and a random selection of 137 negative specimens were retested by Tn-U. Of the specimens with elevated results, 4.5% retested negative by Tn-U, even though Tn-U typically gave about 50% higher results and had a lower manufacturer-specified 99th percentile cutoff. Of the negatives, 5.8% retested as elevated by Tn-U, but with levels no higher than 0.1 ng/mL (0.1 microg/L). Rapid whole blood testing for cardiac troponin I gave generally reliable patient classifications compared with plasma testing in the central laboratory, but besides missing small elevations, produced some apparent false-positives.

Introduction of a stat laboratory reduces emergency department length of stay.

OBJECTIVES: Emergency department (ED) length of stay (LOS) impacts patient satisfaction and overcrowding. Laboratory turnaround time (TAT) is a major determinant of ED LOS. The authors determined the impact of a Stat laboratory (Stat lab) on ED LOS. The authors hypothesized that a Stat lab would reduce ED LOS for admitted patients by 1 hour. METHODS: This was a before-and-after study conducted at an academic suburban ED with 75,000 annual patient visits. All patients presenting to the ED during the months of August and October 2006 were considered. A Stat lab located within the central laboratory was introduced in September 2006 to reduce laboratory TAT. The test TATs and ED LOS before (August 2006) and after (October 2006) implementing the Stat lab for all ED patients were the data of interest. ED LOS before and after the Stat lab was introduced was compared with the Mann-Whitney U-test. A sample size of 5,000 patients in each group had 99% power to detect a 1-hour difference in ED LOS. RESULTS: There were 5,631 ED visits before and 5,635 visits after implementing the Stat lab. Groups were similar in age (34 years vs. 36 years) and gender (51% males in both). The percentages of patients with laboratory tests before and after Stat lab implementation were 68.7 and 71.3%, respectively. Test TATs for admitted patients were significantly improved after the Stat lab introduction. Implementation of the Stat lab was associated with a significant reduction in the median ED LOS from 466 (interquartile range [IQR] = minutes before to 402 (IQR = 296-553) minutes after implementing the Stat lab. The effects of the Stat lab on ED LOS were less marked for discharged patients. CONCLUSIONS: Introduction of a Stat lab dedicated to the ED within the central laboratory was associated with shorter laboratory TATs and shorter ED LOS for admitted patients, by approximately 1 hour.

Comparison of fresh frozen serum to traditional proficiency testing material in a College of American Pathologists survey for ferritin, folate, and vitamin B12.

CONTEXT: Comparison of different analytical methods in proficiency surveys may be affected by the artificial nature of the survey material. OBJECTIVE: To compare intermethod differences in proficiency survey results between 2 types of survey material, conventional proficiency testing material (PTM) and fresh frozen human serum (FFS), for 3 markers of anemia: ferritin, folate, and vitamin B12. DESIGN: Data were gathered from a 2003 survey event in the College of American Pathologists Ligand ("K") Series, in which the specimens to be tested by each participating laboratory included 1 vial of FFS and 2 vials of PTM with different analyte concentrations. The more than 1600 laboratories subscribing to the survey were not advised as to the nature of the specimens. MAIN OUTCOME MEASURES: The bias of each method relative to the median of method means for each analyte and each type of survey material, and the interlaboratory coefficient of variation for each method. RESULTS: For each of the 3 analytes, moderate to large method biases were observed. For ferritin, method biases correlated strongly between comparable PTM and FFS specimens (Spearman r = 0.863, P < .001), whereas virtually no correlation was found for folate (r = -0.224, P = .48), and a marginally significant correlation existed for B12 (r = 0.55, P = .049). CONCLUSIONS: With ferritin, proficiency survey performance of PTM is similar to that of FFS, implying that method biases relate mainly to calibration. With folate and to a lesser extent with B12, PTM and FFS exhibit different method biases, implying that the biases reflect analyte heterogeneity and/or matrix effects.

How sensitive is a prostate-specific antigen measurement? How sensitive does it need to be?

Assays are now available that can measure very low concentrations of prostate-specific antigen (PSA), but their analytic performance and clinical utility are not well defined. This brief article highlights some of the clinical issues related to the limited prognostic significance of small changes in PSA concentrations in men with prostate cancer who have been treated with prostate ablation therapy. College of American Pathologists proficiency survey data are presented, illustrating the performance of commercial PSA assays with low PSA concentration survey samples tested between 1998 and 2002. The performance of the assays appears to be improving, but many of the currently used assays have intralaboratory coefficients of variation greater than 20% for PSA concentrations less than 0.4 ng/mL. Also, there are major differences in the level of PSA reported by various assays in these low concentration samples. These level differences (if they are also seen in clinical samples) may cause clinical problems when fixed serum PSA thresholds (eg, 0.2 ng/mL) are used to make clinical decisions related to prostate tumor recurrence.

Prediction of respiratory distress syndrome using the Abbott FLM-II amniotic fluid assay.

BACKGROUND: Most laboratories using the Abbott FLM-II assay for assessing fetal lung maturity follow the manufacturer's recommendations for interpreting the surfactant to albumin ratio (S/A). Thus, values >55 mg/g are considered mature and values <40 mg/g, immature-leaving a wide range of indeterminate values. Little data is available to assist the clinician in interpreting values between 40 and 55 mg/g. The goal of this study was to determine decision levels that would more clearly identify risk for RDS based on S/A results. METHODS: Respiratory distress syndrome was identified based on medical record review in 46 infants (born at six hospitals), who had S/A measurements on amniotic fluid within 72 h of delivery. An additional 257 women, who had had the S/A test requested but had non-RDS infants, were also identified for this study. The probability of RDS was calculated based on S/A values and on gestational age. Odds ratios were computed for different S/A ratios and different gestational ages. RESULTS: Probability of RDS increased with decreasing S/A and decreasing gestational age. At gestational age >36 weeks, the probability of developing RDS ranged from 1% at S/A>44 mg/g to 39% at S/A44 mg/g to 92% at S/A

Test strategies for the detection of myocardial damage.

In the space of half a century, cardiac marker testing has advanced incrementally from enzymes present in nearly all tissues to proteins having remarkable specificity for myocardium. Markers with other desirable properties, such as earlier release, have also been introduced and others may be anticipated, although a single perfect marker is not on the horizon. Optimum application of these new markers still requires improved robustness and harmonization of commercial assays, and continuing insights in the pathophysiology of acute coronary syndromes. As these advances occur, future testing will likely focus more on therapeutic decisions than on arbitrary diagnostic classifications.