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The International Federation of Clinical Chemistry Committee on Clinical Application of Cardiac Bio-Markers provides evidence-based educational documents to facilitate uniform interpretation and utilization of cardiac biomarkers in clinical laboratories and practice. The committee’s goals are to improve the understanding of certain key analytical and clinical aspects of cardiac biomarkers and how these may interplay in clinical practice. Measurement of high-sensitivity cardiac troponin (hs-cTn) assays is a cornerstone in the clinical evaluation of patients with symptoms and/or signs of acute cardiac ischemia. To define myocardial infarction, the Universal Definition of Myocardial Infarction requires patients who manifest with features suggestive of acute myocardial ischemia to have at least one cTn concentration above the sex-specific 99th percentile upper reference limit (URL) for hs-cTn assays and a dynamic pattern of cTn concentrations to fulfill the diagnostic criteria for MI. This special report provides an overview of how hs-cTn 99th percentile URLs should be established, including recommendations about prescreening and the number of individuals required in the reference cohort, how statistical analysis should be conducted, optimal preanalytical and analytical protocols, and analytical/biological interferences or confounds that can affect accurate determination of the 99th percentile URLs. This document also provides guidance and solutions to many of the issues posed.

Background Concerns exist regarding how the 99th percentile upper reference limit (URL) of cardiac troponin (cTn) is determined and whether it should be derived from normal healthy individuals. Content The 99th percentile URL of cTn is an important criterion to standardize the diagnosis of myocardial infarction (MI) for clinical, research, and regulatory purposes. Statistical heterogeneity in its calculation exists but recommendations have been proposed. Some negativity has resulted from the fact that with some high-sensitivity (hs) cTn assays, a greater number of increases above the 99th percentile are observed when transitioning from a contemporary assay. Increases reflect acute or chronic myocardial injury and provide valuable diagnostic and prognostic information. The etiology of increases can sometimes be difficult to determine, making a specific treatment approach challenging. For those reasons, some advocate higher cutoff concentrations. This approach can contribute to missed diagnoses. Contrary to claims, neither clinical or laboratory guidelines have shifted away from the 99th percentile. To support the diagnosis of acute MI, the 99th percentile URL remains the best-established approach given the absence of cTn assay standardization. Importantly, risk stratification algorithms using hs-cTn assays predict the possibility of MI diagnoses established using the 99th percentile. Summary The 99th percentile of cTn remains the best-established criterion for the diagnosis of acute MI. While not perfect, it is analytically and clinically evidence-based. Until there are robust data to suggest some other approach, staying with the 99th percentile, a threshold that has served the field well for the past 20 years, appears prudent.

Tweets. Hashtags. Blogs. Hangouts. Podcasts. Wikis. What do these social media platforms and verbiage have to do with education, and why should you care? Social media is used on a daily and even hourly basis as a modality to rapidly and effectively communicate, educate, and learn. Some medical specialties have quickly adopted and embraced social media, particularly in the fields of emergency medicine, family medicine, and pediatrics. Other fields, including laboratory medicine and pathology, have had a much slower uptake that may directly correlate with the amount of patient–physician interaction. The specialties that have a high rate of use have also catalyzed implementation of social media into medical education and residency program curriculum, and used it as a modality to recruit physicians and staff at all levels. In addition, the free open-access movement (FOAM)9 has altered how medical education resources and content are accessed by physicians and patients, ultimately shifting and removing geographical and income barriers across the globe. Laboratorians and pathologists have a unique opportunity to move outside the 4 walls of the laboratory and engage other physicians, residents, and even patients in a way that has never been done before. Perhaps it is time we communicate beyond the results reported in the electronic medical record, and instead discuss the value and contributions that our laboratories provide every day. Here, 6 experts in the social media field share their thoughts on social media use, challenges, and opportunities. What are the primary forms of social media you use from a professional and educational standpoint, and how long have you been using them? How has your profession and/or colleagues responded (i.e., fast or slow adopters) to using social media? What do you believe are the primary contributing factors to this response? Shannon Haymond: My primary format for this purpose is …

The IFCC Committee on Clinical Applications of Cardiac Bio-Markers (C-CB) has directives and initiatives focused on providing evidence-based educational resources to aid and improve understanding around key analytical and clinical aspects of cardiac biomarkers used in clinical practice and the research setting. As a task force, we have previously published position statements and recommendations focused on use and analytical aspects of high-sensitivity cardiac troponin assays. The current educational document is the first from the C-CB highlighting important biochemical, analytical, and clinical aspects as they relate to the natriuretic peptides (NPs), including B-type natriuretic peptide (BNP) and N-terminal pro–B-type natriuretic peptide (NT-proBNP), with a focus on heart failure.

BACKGROUNDB-type natriuretic peptides (BNPs) are used clinically to diagnose and monitor heart failure and are present in the circulation as multiple proBNP-derived fragments. We investigated the specificity of BNP immunoassays with glycosylated and nonglycosylated BNP, N-terminal proBNP (NT-proBNP), and proBNP peptides to probe the cross-reactivity of each assay.METHODSNine B-type natriuretic peptides were studied,including synthetic and recombinant BNP (Shionogi, Scios, Mayo), human and synthetic glycosylated and nonglycosylated NT-proBNP (HyTest, Roche Diagnostics), and human glycosylated and nonglycosylated proBNP (HyTest, Scios). Five BNP [Abbott, Abbott POC, Alere, Beckman Coulter, Siemens (Centaur)], 9 NT-proBNP [Ortho-Clinical Diagnostics, Roche, Response, bioMerieux, Siemens (Dimension, Immulite, Stratus CS), Mitsubishi] and 3 research-use-only proBNP immunoassays [Biosite (Alere), Bio-Rad, Goetze] were evaluated. Specificity was assessed by calculating the recovery between baseline and peptide-spiked human plasma pools at target concentrations of 100 ng/L BNP, 300 ng/L proBNP, or 450 ng/L NT-proBNP. All assays were performed in duplicate.RESULTSBNP and NT-proBNP assays demonstrated substantial cross-reactivity with proBNP peptides. NT-proBNP assays do not detect glycosylated forms of either NT-proBNP or proBNP. proBNP assays preferentially detect the BNP 1–32 peptide and have minimal cross-reactivity with BNP peptides and glycosylated proBNP.CONCLUSIONSBNP or NT-proBNP results are not transferable among the current existing immunoassays owing to their differences in cross-reactivity and ability to detect various glycosylated forms of proBNP-derived fragments. Opportunities remain to standardize and harmonize BNP and NT-proBNP assays, as well as to develop specific proBNP assays, to widen their clinical scope of use.

BACKGROUND There is growing interest in fructosamine, glycated albumin, and 1,5-anhydroglucitol (1,5-AG) as alternative measures of hyperglycemia, particularly for use in settings where traditional measures (glucose and HbA1c) are problematic or where intermediate (2–4 weeks) glycemic control is of interest. However, reference intervals for these alternative biomarkers are not established. METHODS We measured fructosamine, glycated albumin, and 1,5-AG in a community-based sample of US black and white adults who participated in the Atherosclerosis Risk in Communities (ARIC) Study. We calculated reference intervals, evaluated demographic differences, and derived cutoffs aligned with current diagnostic cutpoints for HbA1c and fasting glucose. RESULTS In a healthy reference population of 1799 individuals (mean age, 55 years; 51% women; 15% black), the 2.5 and 97.5 percentiles, respectively, were 194.8 and 258.0 μmol/L for fructosamine, 10.7% and 15.1% for glycated albumin, and 8.4 and 28.7 μg/mL for 1,5-AG. Distributions differed by race, sex, and body mass index. Equivalent concentrations of fructosamine and glycated albumin corresponding to an HbA1c of 6.5% (96.5 percentile) were 270.2 μmol/L and 15.6%, respectively. Equivalent concentrations of fructosamine and glycated albumin corresponding to a fasting glucose of 126 mg/dL (93.9 percentile) were 261.7 μmol/L and 15.0%, respectively. CONCLUSIONS The reference intervals for these biomarkers should inform their clinical use. Diagnostic cutpoint equivalents for fructosamine and glycated albumin could be useful to identify persons with hyperglycemia in settings where fasting glucose or HbA1c are not available or where the interpretation of these traditional measures is problematic.

BACKGROUND Aggressive LDL cholesterol (LDL-C)-lowering strategies are recommended for primary and secondary prevention of cardiovascular events. A newly derived equation for LDL-C estimation was recently published that addressed limitations in the commonly used Friedewald LDL-C calculation method. The novel method was reported to classify patients with superior concordance to measured LDL-C compared to the Friedewald method, particularly in patients with LDL-C METHODS We evaluated the performance of the novel method within an independent cohort of 23 055 patients with LDL-C measured by the gold standard β-quantification reference method. RESULTS Overall Friedewald underestimated and the novel method overestimated measured LDL-C. Both estimations significantly deviated from the reference method when LDL-C was 70 mg/dL compared to the Friedewald equation. CONCLUSIONS We compared both novel and Friedewald estimated LDL-C against the LDL-C reference method; in contrast, the prior study relied on validation of a subset of samples by β-quantification to allow the use of the vertical autoprofile method for LDL-C measurement. We conclude that the novel method has some benefits but it is unclear whether improvements over the Friedewald calculation are substantive enough to justify making the change in routine clinical practice and to improve patient outcomes.

Cardiac troponin [cardiac troponin I (cTnI) and cTnT] has become globally recognized as the standard biomarker for the diagnosis of acute myocardial infarction (AMI).8 With improvements in the analytical characteristics of cardiac troponin assays, particularly imprecision at low measurable concentrations, high-sensitivity cardiac troponin (hs-cTn) assays are now being implemented worldwide; but not in the US since the Food and Drug Administration has not yet cleared them for clinical use. With the implementation of hs-cTn assays, improvements in clinical care are beginning to be observed in the peer-reviewed literature. These improvements include early rule out (early hospital discharge) and rule in (right bed for appropriate patient) for MI and improved risk stratification for patients presenting with symptoms suggestive of ischemia, with improved short- and long-term outcomes. Further hs-cTn assays have been part of solidifying the definition of myocardial injury, based on an increased cardiac troponin concentration above the 99th percentile upper reference limit. The high-sensitivity assays have improved the clinical understanding that not all cardiac troponin increases are MI and that patients with nonischemic disease also have increases in cardiac troponin that must be managed accordingly. This Q&A provides the opportunity for 3 cardiologists, 2 laboratory medicine scientists, and 1 emergency medicine physician to share their experiences with the evolving role of cardiac troponin testing in their practices. Ideally, the messages they share will assist in better harmonizing the appropriate utilization of high-sensitivity assays worldwide as we transition away from contemporary cardiac troponin assays. Should all medical centers have a uniform serial order set to assist in ruling in/out AMI? Should a single cardiac troponin order be available? What would your ideal serial order set (timing) be? Allan S. Jaffe: Medical centers would benefit from developing consistent, uniform serial orders to rule in/out AMI. These serial orders should be agreed …

Representation and progression among women with advanced degrees in science and medicine have significantly improved over the past 50 years. A recent report from the Association of American Medical Colleges indicates that despite women being in the minority, the number of female division/section chiefs, department chairs, and deans has increased overall by more than 50% in the past 10 years (https://www.aamc.org/members/gwims/statistics/; accessed April 2, 2012). This information and the election of 3 consecutive female AACC presidents and a new female AACC executive vice president caused us to reflect on the increasing global presence of female leaders in clinical chemistry and laboratory medicine. As female laboratory directors, mothers, and members of AACC's Society for Young Clinical Laboratorians group, we have the perception that our profession is a supportive environment and a well-suited career for young women today, but we wondered if it has always been that way. We posed a series of questions to a multigenerational panel of female clinical chemists, who relate their experiences as women in clinical chemistry and laboratory medicine over the past several decades. How do you think the work climate has changed for women since you began your scientific career, and have you experienced any personal struggles because you are a female in clinical chemistry? What advice would you give young women starting out in the field of clinical chemistry? Helen Free: At times I felt like a second-class citizen, not because I was female, but because I didn't have a PhD! I began my career during WWII, and I was needed because all the men were in the armed forces. I'm 89 and didn't realize there were gender discrepancies in clinical chemistry. I would advise those starting out in the field to go into your career with a positive attitude and work toward equality …

Background: High-sensitivity cardiac troponin assays will augment the frequency of increased results, making important the determination of reference change values to distinguish acute from chronic increases. We assessed short- and long-term biological variability of cardiac troponin T (cTnT) in healthy subjects with a novel high-sensitivity (hs) assay.Methods: We collected blood from 20 healthy volunteers at 5 time points for short-term study and biweekly at 4 times from the same volunteers for long-term study. We analyzed serum samples in duplicate with a hscTnT assay on the Roche Modular E170 and computed reference change values (RCVs) for analytical, intraindividual, interindividual, and total change values (CVA, CVI, CVG, and CVT, respectively) and the index of individuality (II). We calculated RCVs by using a log-normal approach, owing to the skewed results of the data.Results: Short- and long-term CVA values were 53.5% and 98%. CVI and CVG were 48.2% and 85.9%, respectively, for short-term studies and 94% and 94% for long-term studies. Mean δ values for the within-day study were 58% and −57.5%, and between-day mean δ values were 103.4% and −87%. Within- and between-day IIs were 0.8 and 0.14, respectively.Conclusions: The biological variation demonstrated with the hscTnT assay is higher than prior data for cardiac troponin I. This may be attributed to differences in biology or assay imprecision at low concentrations. A short-term change (RCV log normal) of 85% and a long-term change of 315% is necessary to define a changing pattern.

Background: Stroke is a devastating condition encompassing a wide range of pathophysiological entities that include thrombosis, hemorrhage, and embolism. Current diagnosis of stroke relies on physician clinical examination and is further supplemented with various neuroimaging techniques. A single set or multiple sets of blood biomarkers that could be used in an acute setting to diagnosis stroke, differentiate between stroke types, or even predict an initial/reoccurring stroke would be extremely valuable.Content: We discuss the current classification, diagnosis, and treatment of stroke, focusing on use of novel biomarkers (either solitary markers or multiple markers within a panel) that have been studied in a variety of clinical settings.Summary: The current diagnosis of stroke remains hampered and delayed due to lack of a suitable mechanism for rapid (ideally point-of-care), accurate, and analytically sensitive biomarker-based testing. There is a clear need for further development and translational research in this area. Potential biomarkers identified need to be transitioned quickly into clinical validation testing for further evaluation in an acute stroke setting; to do so would impact and improve patient outcomes and quality of life.

Background: Natriuretic peptide concentrations in adults require age- and sex-specific reference intervals for optimal interpretation. Females have higher natriuretic peptide concentrations, and hypotheses suggest that estrogen may be responsible. This study sought to determine the influence of hormone modulation on N-terminal probrain natriuretic peptide (NT-proBNP) by using a pediatric cohort. Children/adolescents typically have rapid hormone changes during puberty, making them an ideal group to study. Methods: We selected 759 specimens (303 male, 456 female; ages 2 months to 18 years, mean 13 years) obtained from the Mayo Clinic Pediatric Residual Specimen Bank. We measured NT-proBNP, sex hormone–binding globulin (SHBG), estradiol, and testosterone by immunoassays or LC-MS/MS and calculated free testosterone. We performed univariate and multivariate analyses to investigate the significance of NT-proBNP with each hormone. Results: Reference values demonstrated a sex difference and sequential age differences in females. Univariate modeling of the hormones with NT-proBNP revealed an independent inverse association of NT-proBNP with testosterone, a direct association with SHBG, and no significant association with estradiol. Multivariate modeling confirmed a strong association of testosterone and SHBG with NT-proBNP. Correlation of hormones with NT-proBNP retained greater significance than either age or sex. Conclusions: In pediatric patients, NT-proBNP is independently associated with both testosterone and SHBG hormone concentrations. Measurements of testosterone are inversely associated with NT-proBNP, and estrogens are marginally associated with NT-proBNP in males but not females, suggesting that androgens and not estrogens modulate sex differences notable in natriuretic peptides. Children and adolescents may require an objective assessment of hormones if optimal interpretation of natriuretic peptide concentrations is desired or the concentrations are confounded. .

A 43-year-old African-American man with a history of hypertension, depression, and chronic alcohol abuse presented to the emergency service of an outside hospital complaining of chest pain. Laboratory testing indicated hepatocellular injury with aspartate aminotransferase (AST)1 of 14000 U/L (reference interval 5–41 U/L) and alanine aminotransferase (ALT) of 6400 U/L (reference interval 8–45 U/L). Because laboratory indicators of liver function worsened, the patient was reinterviewed and confessed to having attempted suicide 3 days prior by ingesting about one-half gallon (approximately 4 L) of vodka and one-half bottle of extra-strength acetaminophen. The patient was administered a bolus of N-acetylcysteine (NAC) at the outside hospital and referred to our institution because of concern for progression to fulminant hepatic failure. Laboratory tests were repeated and results were consistent with significant hepatocellular damage secondary to acetaminophen poisoning, including increased AST of 11 000 U/L (reference interval 8–48 U/L), ALT of 6510 U/L (reference interval 7–55 U/L), total bilirubin of 395 μmol/L (23.1 mg/dL) [reference interval 2–17 μmol/L (0.1–1.0 mg/dL)], and direct-bilirubin of 207 μmol/L (12.1 mg/dL) [reference interval

BACKGROUND We assessed the impact of clinical decision support (CDS) rules within the electronic health record for ionized calcium (iCa), serum magnesium (Mg), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in intensive care unit (ICU) inpatients at a large academic center. METHODS A repeat order for measurement of iCa or Mg placed within 24 (iCa) or 48 (Mg) h of a previously nonactionable result, or additional orders for NT-proBNP beyond 1 within a single hospitalization, triggered a CDS pop-up alert showing the prior result and offering the opportunity to cancel the order or to place the order after entering an indication for repeat testing. The number of tests performed for each of these analytes and incidence of adverse clinical outcomes potentially associated with hypocalcemia or hypomagnesemia were compared between the 90-day period before CDS implementation and two 90-day periods immediately following. RESULTS iCa test volumes decreased by 48%, Mg by 39%, and NT-proBNP by 28% in the 90-day period immediately following implementation and remained decreased by 54%, 49%, and 22%, respectively, during the following 90-day period (all P values 0.17). CONCLUSIONS Implementation of CDS dramatically decreased repeat testing of iCa, Mg, and NT-proBNP without adversely impacting clinical outcomes in the ICU. Expansion of the rules from the ICU units to include the entire hospitalized patient population and expansion to additional analytes is expected to lead to further reductions in testing.

In 2011, a report published by the National Heart, Lung, and Blood Institute on pediatric cardiovascular health and risk reduction put forth a recommendation for universal lipid screening in children and adolescents between the ages of 9 and 11 (1). Although the American Academy of Pediatrics, the National Lipid Association, and the American Heart Association have supported this recommendation, there has been substantial debate questioning this approach. Fuel was added to the fire in this debate when in August of this year the US Preventive Services Task Force (USPSTF) issued a report on childhood dyslipidemia, concluding there is insufficient evidence either in support of or against universal lipid screening in children and adolescents (2). A recent article published in Science entitled “Cholesterol screening for kids …

There is clear pathologic evidence that the process of atherosclerotic cardiovascular disease (CVD)2 begins in childhood with the deposition of fatty streaks within the arterial walls and subsequently progresses into fibrous plaques throughout adolescence and early adulthood. This evidence has generated a substantial interest outside of primary and secondary CVD prevention and a focus toward primordial prevention. The recent National Heart, Lung, and Blood Institute (NHLBI) Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents updated recommendations for the identification, management, and treatment of all major cardiovascular risk factors in pediatrics (1). These guidelines, which have also been endorsed by the American Academy of Pediatrics (AAP), address issues related to nutrition, physical activity, tobacco, high blood pressure, lipids, obesity, and the metabolic syndrome. One major challenge of this integrated approach is accounting for the fact that the manifestation of CVD typically occurs later in life and a variety of environmental factors influence the progression or attenuation of risk. One updated NHLBI recommendation that is likely to cause controversy is the recommendation of universal screening for dyslipidemia by the age of 9–11 years and subsequently at an age of 17–21 years. Lipid screening should be performed with either a fasting lipid panel [total cholesterol, HDL cholesterol (HDL-C), triglycerides, non–HDL-C, LDL cholesterol (LDL-C)] or a nonfasting lipid panel (total cholesterol, HDL-C, non–HDL-C). Initiatives and research emerging over the past 2 decades have led to a variety of approaches and attitudes toward screening for pediatric dyslipidemias, which have produced conflicting recommendations and variations in clinical practice. In 1992, the National Cholesterol Education Program first recommended a tiered approach to pediatric lipid screening, in which a fasting lipid profile was recommended if the child had a positive family history of premature CVD or dyslipidemia, had an unknown …

The Society for Young Clinical Laboratorians (SYCL) is a program created by the AACC to serve the needs of its younger members. The goal of SYCL is to provide clinical laboratorians early in their professional lives with career-enhancement opportunities that include programs, resources, and advice to enrich their professional development. A smaller group of SYCL members selected by the AACC president forms the Executive SYCL Committee, which is tasked with representing the larger SYCL membership and leading the development and support of the Society's goals in collaboration with the organization's leadership. The SYCL program is uniquely supportive of young scientists (

Cardiac troponin assays have evolved substantially over 20 years, owing to the efforts of manufacturers to make them more precise and sensitive. These enhancements have led to high-sensitivity cardiac troponin assays, which ideally would give measureable values above the limit of detection (LoD)4 for 100% of healthy individuals and demonstrate an imprecision (CV) of ≤10% at the 99th percentile. Complete integration and proper use of high-sensitivity cardiac troponin assays into clinical practice will be an important step forward for the diagnosis of myocardial infarction and will allow cardiologists to use cardiac troponin as a prognostic indicator for risk-based outcomes assessment. As laboratorians, we wish to comment on the recently published “ACCF 2012 Expert Consensus Document on Practical Clinical Considerations in the Implementation of Troponin Elevations” (1). Our purpose is to address 8 analytical issues that we believe have the potential to cause confusion and that therefore deserve clarification. Input from the field of laboratory medicine is important for emphasizing our role as analytical-content experts in the process of strengthening our collaborative relationships with various clinical societies. Since the initial publications by the National Academy of Clinical Biochemistry (NACB) in 1999 and by the European Society of Cardiology/American College of Cardiology in 2000, when both organizations endorsed cardiac troponin I (cTnI) or cTnT as the preferred biomarker for the detection of myocardial infaction, numerous other organizations have followed suit and promoted the sole use of cardiac troponin in this clinical application. The American College of Cardiology Foundation (ACCF) 2012 Expert Consensus Document (1) summarizes the recently published 2012 Third Universal Definition of Myocardial Infarction by the Global Task Force (2), thus providing some practical recommendations on the use and interpretation of cardiac troponin in clinical practice. The integration and acceptance of cardiac troponin testing over the past 13 years has …

Background: Enzymatic creatinine assays are routinely used in clinical laboratories to provide more accurate estimated glomerular filtration rates and to avoid a perceived lack of analytical specificity associated with picrate (Jaffe) methods. Negative interferences with the enzymatic creatinine assay, which we noted in several patients on dopamine or dobutamine, prompted our further investigation into interference of catecholamines with enzymatic methods. Methods: Spiked solutions of dopamine, dobutamine, epinephrine, and norepinephrine were added to pooled sera at catecholamine concentrations consistent with clinically relevant dosing. Creatinine was measured enzymatically on the Roche P-Modular, Ortho Clinical Diagnostics Vitros 350, and Abbott i-STAT. Jaffe methods were performed on the Roche P-Modular and Siemens Dimension RxL. In 10 patients receiving dopamine and/or dobutamine via a venous or arterial line we evaluated and compared the extent of in vivo creatinine interference in paired serum samples obtained by venipuncture and from indwelling catheters. Results: All catecholamines caused significant negative interference with the Roche enzymatic creatinine assay, most pronounced for dopamine and dobutamine. The Vitros enzymatic assay demonstrated slight negative interferences, and i-STAT enzymatic and Jaffe methods were unaffected by the presence of catecholamines. Significant (P < 0.001) differences in creatinine concentrations by Roche enzymatic vs Jaffe methods were observed in venipuncture specimens compared with arterial or venous catheter specimens, suggesting dopamine and dobutamine reversibly adhere to the catheter lumen. Conclusions: Negative interferences were pronounced for Roche enzymatic results in blood samples obtained from indwelling catheters, a phenomenon not observed in peripheral draws. Physicians and laboratorians should be alert to the possibility of a falsely low creatinine result and reevaluate questionable samples using a method unaffected by catecholamines.

Background: The International Staging System for multiple myeloma has increased the importance of accurate measurement of serum albumin. Two common albumin assays, bromcresol green (BCG) and agarose gel protein electrophoresis (PEL), frequently yield discordant results, creating confusion regarding which assay is superior for use in myeloma. Methods: We measured albumin by BCG on a Roche Modular system, by PEL with a Helena SPIFE SPE Vis agarose gel, and by immunonephelometry performed on a Dade Behring BNII nephelometer. BCG and PEL were used to measure albumin in 5777 patient samples, and all 3 methods were used in an additional 252 samples. The clinical impact was assessed on 698 myeloma patient samples. Results: For sera with zero/low monoclonal immunoglobulin protein (M)-spike (0 to Conclusions: Both BCG and PEL correlate well to nephelometry in sera with zero/low M-spikes. In the presence of larger M-spikes, PEL correlates poorly to nephelometry or BCG, whereas BCG compares well with nephelometry regardless of M-spike. Thus, albumin measurement can be performed reliably in myeloma patient sera by use of inexpensive, automated BCG assays.

To the Editor: Cardiac troponin is the marker of choice for evaluating myocardial injury (1). High-sensitivity assays improve analytical detection limits, thereby allowing concentrations to be measured in the majority of healthy individuals. This capability allows an assessment of biologic variation (BV)1 to determine what constitutes a clinically important change in the cardiac troponin concentration, a critical metric for identifying acute events. Such an event is often a myocardial infarction, but any acute cardiac injury can cause increasing and/or decreasing values (1). Accordingly, we evaluated BV for a recently developed high-sensitivity cardiac troponin I (hs-cTnI) assay (2) from Beckman Coulter. We performed this study with the same cohort used to define BV for the high-sensitivity cardiac troponin T (hs-cTnT) assay (3) and according to a protocol approved by our institutional review board. For assessment of short-term BV, we collected blood into serum separator tubes (Becton Dickinson) at 0, 1, 2, 3, and 4 h, centrifuged the tubes, and stored the serum samples immediately at −70 °C. …

A 40-year-old woman presented to her physician with complaints of intermittent flank pain. A urine sample was submitted for routine urinalysis. The patient's sample (left) was notable for a milky white appearance after centrifugation (Fig. 1; a normal urine sample is shown at right). The patient was born in India but moved to the US 10 years ago. She has a 5-year self-reported history of occasional cloudy urine with passage of small blood clots. …

Featured Article: Hench PS, Kendall EC, Slocumb CH, Polley HF. The effects of the adrenal cortical hormone 17-hydroxy-11-dehydrocorticosterone (Compound E) on the acute phase of rheumatic fever; preliminary report. Mayo Clin Proc 1949;24:277–97.2 A passage in the New Testament describes a paralyzed man miraculously regaining the ability to stand and walk. In a small town in southeast Minnesota on the morning of September 21, 1948, a similar miracle began to unfold. A 29-year-old woman was hospitalized at the Mayo Clinic (Rochester, MN) for severe rheumatoid arthritis that caused debilitating joint immobility. She was injected with a small amount of an experimental new drug, at the time named Compound E, which was discovered and investigated in tandem by Edward C. Kendall and Philip S. Hench. Two days and 2 more injections later the patient could walk and left the hospital to enjoy a 3-hour shopping spree. Just 2 short years later Kendall and Hench shared the Nobel Prize in Physiology or Medicine with Tadeus Reichstein, a Swiss scientist who independently isolated hormones of the adrenal cortex (1). The …