Hemodynamic Determinants of the Biologic Variation of N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Stable Systolic Chronic Heart Failure.

BACKGROUND CONTEXT: Biologic variation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in chronic heart failure (CHF) may affect blood levels and risk stratification. The sources of NT-proBNP variation are unknown. METHODS AND RESULTS: We performed NT-proBNP measurements and clinical and hemodynamic assessments in 50 patients with heart failure with reduced ejection fraction (HFrEF) who met criteria for clinical stability over 2 time intervals. Hemodynamic variables were measured with the use of inert gas rebreathing and impedance cardiography. Heart rhythm was monitored with the use of external electrocardiographic event recorders throughout the study. Determinants of NT-proBNP-levels and both absolute (ΔNT-proBNPabs) and relative (ΔNT-proBNP%) changes at 1-week and 2-week intervals were identified with the use of univariable and multivariable linear mixed-effects models and linear regression analyses, respectively. Clinical and hemodynamic variables did not significantly change between study visits. The individual variation of NT-proBNP at 2 weeks was 9.2% (range 3.9%-18.6%). Weight and glomerular filtration rate were independently associated with baseline NT-proBNP concentrations (P = .01 and P = .005, respectively). There was no relationship between absolute and relative changes of NT-proBNP at 1-week intervals and changes in clinical and hemodynamic variables. Absolute change of NT-proBNP at 2-week intervals was associated with absolute change in left cardiac work index (P = .008), and relative change in NT-proBNP at 2-week intervals was determined by relative change of thoracic fluid content index (P = .008) and diastolic blood pressure (P = .01). The coefficients of determination (R2) for the multivariable models with Δ1wkNT-proBNPabs, Δ2-weeksNT-proBNPabs, Δ1wkNT-proBNP%, and Δ2wksNT-proBNP% as dependent variables were 0.21, 0.19, 0.10, and 0.32, respectively. CONCLUSIONS: In patients with stable HFrEF, changes in clinical and hemodynamic variables only marginally contribute to the variation of NT-proBNP.

PD-1 and PD-L1 expression in bone and soft tissue sarcomas.

PD-1 and its ligands have been shown to play a significant role in evasion of malignant tumour cells from the immune system. Last year, the Unites States Food and Drug Administration (FDA) approved anti-PD-1 inhibitors for treatment of non-small cell lung carcinoma and recently expanded the use of immunotherapy for metastatic urothelial cell carcinoma and Hodgkin lymphoma. However, studies on expression of PD-1 and its ligand in malignant bone and soft tissue sarcoma are sparse. In this study, we evaluated PD-1 and PD-L1 expression on variants of liposarcomas and rhabdomyosarcomas, osteosarcomas and chondrosarcomas. Tissue microarrays (TMAs) for liposarcomas (well differentiated, myxoid/round cell, and pleomorphic), rhabdomyosarcomas (alveolar, embryonal, pleomorphic, and spindle cell), conventional osteosarcomas and chondrosarcomas were stained for PD-1 and PD-L1 antibodies. Adipose tissue, skeletal muscle, bone, osteochondroma and lipoma were used as control and benign counterparts. Western blot was performed to evaluate expression of PD-1 and PD-L1 in four sarcoma cell lines. Osteosarcomas, chondrosarcomas, and all variants of liposarcomas and rhabdomyosarcomas over-expressed PD-1 relative to normal tissue. Expression of PD-1 in rhabdomyosarcomas was associated with higher tumour stage. Only one case of pleomorphic liposarcoma, one case of pleomorphic rhabdomyosarcoma and two cases of alveolar rhabdomyosarcomas were positive for PD-L1. Normal adipose tissue, skeletal muscle, and bone were negative for both PD-1 and PD-L1 and lipomas and osteochondroma weakly expressed PD-1 but not PD-L1. Western blot confirmed the presence of PD-1 protein in all four sarcoma cell lines. Overall, our results showed cytoplasmic expression of PD-1 in the bone and soft tissue sarcomas, while PD-L1 was negative. Whether these data are an indication for effectiveness of immunotherapy in the management of malignant bone and soft tissue sarcomas remains to be elucidated.

Enhanced expression of Programmed cell death 1 (PD-1) protein in benign vascular anomalies.

Programmed cell death 1 (PD-1) and its ligands have been shown to play a significant role in evasion of malignant tumour cells from the immune system. Last year, the United States Food and Drug Administration (FDA) approved anti-PD-1 inhibitors for treatment of non-small cell lung carcinoma and recently has approved anti-PD-L1 blocker for treatment of metastatic urothelial cell carcinoma. However, the role that the immune system might have on benign tumours including vascular anomalies has received less attention. In this study, we evaluated PD-1 and PD-L1 expression on two benign vascular anomalies: infantile haemangiomas and venous malformations. Tissue microarrays (TMAs) from these two entities were stained for PD-1 and PD-L1 antibodies. Blood vessels from normal tissue were used as control. The endothelial cells in both infantile haemangioma and venous malformation showed high expression of PD-1 but were negative for PD-L1. Endothelial cells within the blood vessels in normal tissues were negative for both PD-1 and PD-L1. Our results showed over-expression of PD-1 in subsets of vascular anomalies, while PD-L1 was negative. This would raise the possibility of immunotherapy in benign vascular tumour when other options are exhausted.

Healthcare Cost of Over-Diagnosis of Low-Grade Dysplasia in Barrett's Esophagus.

INTRODUCTION: Published reports have demonstrated that many Barrett's esophagus patients are over-diagnosed as low-grade dysplasia (BE-LGD). We performed an analysis of the surveillance and treatment costs associated with the over-diagnosis of BE-LGD. METHODS: As the principal cost variables, we used endoscopic and histologic procedures performed during the recommended surveillance intervals for patients with BE-LGD, the national average Medicare reimbursement for the Current Procedural Terminology codes of the procedures performed, and a spreadsheet-based tool we created to determine the overall healthcare cost associated with the over-diagnosis of BE-LGD in the US population. RESULTS: The average excess cost (range) for every patient in the US who is over-diagnosed with BE-LGD is estimated to be $5557 ($3115 to $8072). The principal contributors to the excess cost of over-diagnosis of BE-LGD in these patients are: endoscopy ($2626 to $4639), pathologist biopsy review ($275 to $2185), and esophagogastroduodenoscopy-guided endoscopic ablation ($214 to $1249). CONCLUSIONS: The healthcare cost of over-diagnosis of BE-LGD is significant. To reduce the overall healthcare cost impact of over-diagnosis of BE-LGD, strict adherence to the recommendations of the American Gastroenterological Association, American College of Gastroenterology, and American Society for Gastrointestinal Endoscopy that pathology review of all BE biopsy specimens be performed by a gastrointestinal pathologist is warranted.

α-Glutathione S-Transferase: A New Biomarker for Liver Injury?

BACKGROUND: Serum alanine and aspartate aminotransferases (ALT/AST) have been the gold standard for detection and quantification of liver injury for over 6 decades, but have relatively long half-lives (T½) (literature estimates approximately 17 and 47 h, respectively) and thus do not reflect immediate changes in liver injury or recovery. A new point-of-care immunoassay for α-glutathione S-transferase (α-GST) measures this cytosolic liver enzyme with a predicted T½ of 60-90 min based on preliminary studies and might enable earlier detection of improving or worsening liver injury than conventional enzyme testing. METHODS: Serial serum samples collected daily from 31 patients enrolled in the Acute Liver Failure Study Group, with acetaminophen (APAP) toxicity, drug-induced liver injury, ischemic hepatopathy (IH), or autoimmune hepatitis were analyzed to determine α-GST using the Qualigen FastPack® α-GST Assay (Carlsbad), a chemiluminescent immunoassay using a paramagnetic particle matrix with an upper limit of normal of 11 ng/mL. AST and ALT values were obtained from the medical record and have an upper limit of normal of 40 IU/L. The T½ values for α-GST, AST, and ALT were calculated from the peak value for APAP and IH etiologies considered as single time point injuries, using an exponential trendline equation of the serial values. RESULTS: Median α-GST for all etiologies were increased on day 1, returning to normal by day 3, whereas median AST and ALT values did not return to normal, even at day 7. The median T½ for α-GST, AST, and ALT were 6.4, 22.2, and 33.9 h, respectively. CONCLUSIONS: α-GST is a more responsive marker of liver injury/recovery, allowing for more rapid real-time assessment of improvement or worsening of liver disease.

Biological variation, reference change value (RCV) and minimal important difference (MID) of inspiratory muscle strength (PImax) in patients with stable chronic heart failure.

BACKGROUND: Despite the widespread application of measurements of respiratory muscle force (PImax) in clinical trials there is no data on biological variation, reference change value (RCV), or the minimal important difference (MID) for PImax irrespective of the target cohort. We addressed this issue for patients with chronic stable heart failure. METHODS AND RESULTS: From the outpatients' clinic of the University of Heidelberg we retrospectively selected three groups of patients with stable systolic chronic heart failure (CHF). Each group had two measurements of PImax: 90 days apart in Group A (n = 25), 180 days apart in Group B (n = 93), and 365 days apart in Group C (n = 184). Stability was defined as (a) no change in NYHA class between visits and (b) absence of cardiac decompensation 3 months prior, during, and 3 months after measurements. For each group, we determined within-subject (CVI), between-subject (CVG), and total (CVT) coefficient of variation (CV), the index of individuality (II), RCV, reliability coefficient, and MID of PImax. CVT was 8.7, 7.5, and 6.9 % for groups A, B, and C, respectively. The II and RCV were 0.21, 0.20, 0.16 and 13.6, 11.6, 10.8 %, respectively. The reliability coefficient and MID were 0.83, 0.87, 0.88 and 1.44, 1.06, 1.12 kPa, respectively. Results were similar between age, gender, and aetiology subgroups. CONCLUSION: In patients with stable CHF, measurements of PImax are highly stable for intervals up to 1 year. The low values for II suggest that evaluation of change in PImax should be performed on an individual (per patient) basis. Individually significant change can be assumed beyond 14 % (RCV) or 1.12 kPa (MID).

Biological variation of the cardiac index in patients with stable chronic heart failure: inert gas rebreathing compared with impedance cardiography.

AIMS: In chronic heart failure (CHF), changes in cardiac function define the course of the disease. The cardiac index (CI) is the most adequate indicator of cardiac function. Interpretation of serial CI measurements, however, requires knowledge of the biological variation of CI. Because measurements of CI can be confounded by the clinical situation or the method applied, biological variation might be subject to the same confounders. METHODS AND RESULTS: We prospectively included 50 CHF patients who met rigid criteria for clinical stability. CI was measured by both inert gas rebreathing (IGR) and impedance cardiography (ICG) in weekly intervals over 3 weeks-each measurement performed at rest (IGRrest/ICGrest) and during low-exercise 10 Watt pedalling (IGR10W/ICG10W). Intra-class correlation coefficients (ICCs), reference change values, and minimal important differences of CI were determined for IGRrest, ICGrest, IGR10W, and ICG10W. Impedance cardiography and IGR showed moderate agreement at rest (20% (6-36)) and good agreement at 10 Watt (-4% (-23-16)). Depending on time interval, measurement modality for CI, and mode, ICC ranged between 0.42 and 0.78, ICC values for IGR were lower than those for ICG. Reference change value ranged between 3 and 15%, and minimal important difference ranged between 0.2 and 0.5 L/min/m2. Values for IGR were lower at rest and higher at 10 Watt than those for ICG. CONCLUSION: Non-invasive measurements of CI are stable over time. Measurement modalities for CI, however, are not interchangeable. Biological variation is less pronounced when obtained by ICG. The influence of low-level exercise on stability of CI depends on the measurement modality.

Minimal important difference for 6-minute walk test distances among patients with chronic heart failure.

BACKGROUND: The 6-minute walk test (6 WT) is an established tool in the assessment of endurance and prognosis in patients with chronic heart failure (CHF). For these patients there is very limited data on biological variation of 6 WT distances. We determined the minimal important difference (MID) for the 6 WT in patients with stable systolic CHF. METHODS: Two cohorts of patients with stable systolic CHF were included from the outpatients' clinic of the University of Heidelberg. In these cohorts, two 6 WT measurements were performed - in cohort 1 (n=461) 180 days and in cohort 2 (n=512) 365 days apart. Stability was defined as the absence of clinical events (3 months before the first test, between both tests, and 6 months after the second test) and stability of symptoms (NYHA) between tests. Using a standard error of measurement (SEM)-based approach, we determined the MID for both cohorts. RESULTS: The intraclass correlation coefficient was 0.89 at 180 days and 0.88 at 365 days. The results were consistent for groups stratified for age, gender, etiology of CHF, and individual NYHA class. The MID for the 6 WT in stable CHF patients was 35 m and 37 m between presentation and 180 and 365 days, respectively. CONCLUSION: Submaximal exercise capacity as represented by the 6 WT varies little in stable CHF patients for up to 1-year intervals. The MID for changes in 6 WT values in patients with stable CHF over a period of 6 to 12 months is ~ 36 m.

Identification of designer drug 2C-E (4-ethyl-2, 5-dimethoxy-phenethylamine) in urine following a drug overdose.

In recent years, access to information regarding acquisition and synthesis of newer designer drugs has been at an all-time high due largely to the Internet. As these drugs have become more prevalent, laboratory techniques have been developed and refined to identify and screen for this burgeoning population of drugs. This provides a unique opportunity for learning about many of these methods. Laboratory testing techniques and instrumentation are obscure to many health care professionals, yet their results are crucial. Here, we present a case of an overdose of an uncommon designer drug (2C-E) and discuss the basics of liquid chromatography and mass spectrometry, two important techniques used in isolating and identifying the drug. Although often overlooked and taken for granted, these techniques can play a pivotal role in the diagnosis and subsequent management of select patients.

Biological variation and reference change value of high-sensitivity troponin T in healthy individuals during short and intermediate follow-up periods.

BACKGROUND: Acute myocardial infarction is defined by a troponin concentration >99th percentile with an acute increase and/or decrease, the magnitude of which has not yet been well defined. To aid the interpretation of changes in cardiac troponin concentration, we sought to establish biological variation and reference change values (RCVs) by applying both the normal and lognormal approaches for cardiac troponin T (cTnT) sampled at hourly and weekly intervals in healthy individuals and measured on the Roche E 170 and Elecsys® 2010 automated platforms. METHODS: High-sensitivity cTnT (hsTnT) was measured at baseline, and after 1, 2, 3, and 4 h and after 1, 2, 3, and 4 weeks in 20 and 17 healthy individuals, respectively. A healthy status was established by physical examination, MRI analysis at rest and during dobutamine stress, lung function testing, and blood sample testing. RESULTS: Hourly total and within-individual CVs were 18% and 15%, respectively, for the E 170 assay, and 24% and 21%, respectively, for the Elecsys 2010 assay. Weekly total and within-individual CVs for these assays were 32% and 31%, respectively, for the E 170 assay, and 32% and 30%, respectively, for the Elecsys 2010 assay. The RCVs for the E 170 and Elecsys 2010 assays were ±46% and ±62% (hourly), respectively, and ±87% and ±86% (weekly), respectively. The corresponding lognormal values were +64%/-39% and +90%/-47% (hourly), and +138%/-58% and +135%/-58% (weekly). CONCLUSIONS: RCVs appear attractive for interpreting hsTnT results. The short-term biological variation of hsTnT is low but becomes somewhat more important at intermediate sampling intervals. Knowledge of this variation is important for interpreting results from patients in whom cTnT values increase from low concentrations.

Performance evaluation of the new ADVIA Centaur system cyclosporine assay (single-step extraction).

BACKGROUND: Cyclosporine (CsA) monitoring is essential for transplant success. We report a performance study of the recently released, fully automated Siemens ADVIA Centaur CsA assay. METHODS: Whole blood samples from 248 transplant patients were prepared using a new 1-step extraction method. Performance evaluations vs. HPLC-tandem MS (LC-MS/MS), Abbott TDx and AxSYM assays were conducted according to CLSI EP5-A2 and EP9-A2 guidelines. RESULTS: The correlation coefficient for LC-MS/MS and ADVIA Centaur was > or = 0.97 at each site, and for each transplant type. Regression analysis yielded y=0.94x+19 for all sites: 95% CI=0.91-0.96 (slope) and 10-28 (intercept). Absolute and relative bias was minimal for C0 and C2 sampling. Centaur vs. Abbott TDx and AxSYM assays: y = 0.72x+6, r = 0.98, 95% CI = 0.70-0.73 (slope), 3-9 (intercept); and y = 0.69x+18, r = 0.97, 95% CI = 0.67-0.71 (slope), 8-27(intercept). Within run CVs were 4.5%-7.1%, total CVs were 5.3%-7.7%. CONCLUSIONS: The ADVIA Centaur assay compared favorably with LC-MS/MS and Abbott assays, displaying good correlation for all transplant types and methods.

Longitudinal studies of cardiac troponin-I concentrations in serum from male Sprague Dawley rats: baseline reference ranges and effects of handling and placebo dosing on biological variability.

Serum cardiac troponin-I has been validated as a biomarker for cardiotoxicity in numerous animal models; however, baseline reference ranges for cTnI concentration in a healthy population of laboratory rats, as well as an investigation of biological cTnI variability in rats with respect to time, handling, and placebo dosing methods, have not been reported. In this study, we used an ultrasensitive cTnI immunoassay to quantify hourly concentrations of cTnI in live rats handled under standard laboratory conditions using 15 microL of serum per determination. The baseline reference range (mean 4.94 pg/mL, range 1-15 pg/mL, 99% confidence interval [CI]) of cTnI concentration in rats was consistent with previously reported reference ranges for cTnI in humans (1-12 pg/mL) and with preliminary studies in dogs (1-4 pg/mL) and monkeys (4-5 pg/mL) using the same cTnI assay method. In addition, cTnI concentrations in individual rat serum samples show minimal biological variability over a twenty-four-hour interval when compared to a meaningful reference change value of 193% to 206%. Furthermore, measurements of cTnI concentration were consistent within the reference limits in individual rats over long periods and under three different standard laboratory handling conditions. Thus, using this new method, rats can be followed longitudinally at hourly intervals, and a doubling of cTnI concentration would be significant above biological variability. This is a new paradigm for preclinical testing, which allows transient changes in cTnI concentration to be accurately quantified. This understanding of baseline and biological variability in rats will be fundamental for designing and analyzing future studies that assess potential cardiotoxicity in drug development.

Rapid cortisol assays improve the success rate of adrenal vein sampling for primary aldosteronism.

OBJECTIVE: We hypothesized that an adrenal vein sampling (AVS) algorithm incorporating rapid cortisol assays, which enables resampling of the adrenal veins, would improve the success rate by a team of radiologists. SUMMARY BACKGROUND DATA: AVS is the most accurate means to localize aldosterone production in primary aldosteronism (PA). However, cannulation of the right adrenal vein (RAV) is difficult, and success is assumed from venography without the support of steroid assays. Furthermore, few institutions can assign all studies to 1 dedicated and experienced AVS interventional radiologist. METHODS: Retrospective chart review of patients with PA at our university hospitals who underwent AVS. We compared results for 30 AVS studies incorporating rapid cortisol assays with 30 conventional AVS studies. RESULTS: The success rate for the control period was 73% (22/30 studies). For the first 30 studies after incorporating rapid cortisol assay, the success rate increased to 97% (29/30 studies). Resampling the RAV was required for 2 studies, and prolonged sheath insertion did not cause any complications. CONCLUSIONS: High AVS success rates may be achieved by a team of interventional radiologists at 1 center using defined AVS protocols. Rapid cortisol assay allows for resampling of the RAV and improves AVS success rates.

False positive acetaminophen concentrations in patients with liver injury.

BACKGROUND: Acetaminophen toxicity is the most common form of acute liver failure in the U.S. After acetaminophen overdoses, quantitation of plasma acetaminophen can aid in predicting severity of injury. However, recent case reports have suggested that acetaminophen concentrations may be falsely increased in the presence of hyperbilirubinemia. METHODS: We tested sera obtained from 43 patients with acute liver failure, mostly unrelated to acetaminophen, utilizing 6 different acetaminophen quantitation systems to determine the significance of this effect. In 36 of the 43 samples with bilirubin concentrations ranging from 1.0-61.5 mg/dl no acetaminophen was detectable by gas chromatography-mass spectroscopy. These 36 samples were then utilized to test the performance characteristics of 2 immunoassay and 4 enzymatic-colorimetric methods. RESULTS: Three of four colorimetric methods demonstrated 'detectable' values for acetaminophen in from 4 to 27 of the 36 negative samples, low concentration positive values being observed when serum bilirubin concentrations exceeded 10 mg/dl. By contrast, the 2 immunoassay methods (EMIT, FPIA) were virtually unaffected. The false positive values obtained were, in general, proportional to the quantity of bilirubin in the sample. However, prepared samples of normal human serum with added bilirubin showed a dose-response curve for only one of the 4 colorimetric assays. CONCLUSIONS: False positive acetaminophen tests may result when enzymatic-colorimetric assays are used, most commonly with bilirubin concentrations >10 mg/dl, leading to potential clinical errors in this setting. Bilirubin (or possibly other substances in acute liver failure sera) appears to affect the reliable measurement of acetaminophen, particularly with enzymatic-colorimetric assays.

Measurement of 18-hydroxycorticosterone during adrenal vein sampling for primary aldosteronism.

CONTEXT: In primary aldosteronism, elevated serum 18-hydroxycorticosterone (18OHB) suggests aldosterone-producing adenoma (APA) rather than bilateral, idiopathic hyperaldosteronism (IHA), but little is known about the relative production of 18OHB and aldosterone (A) in APAs compared with IHA. OBJECTIVES: We measured 18OHB, A, and cortisol (F) in blood from adrenal vein sampling (AVS) studies. We compared the discriminatory power of gradients in 18OHB/A and 18OHB/F ratios with A/F ratio gradients for distinguishing APA from IHA. DESIGN, SETTING, AND SUBJECTS: We measured 18OHB and A in excess serum from 23 AVS studies performed at our university hospitals. MAIN OUTCOME MEASURES: We calculated the ratios 18OHB/A, 18OHB/F, and A/F for all specimens, and determined the adrenal vein gradients for these ratios. RESULTS: The 18OHB/A ratios were much lower in blood draining APAs (2.17 +/- 0.62) than in blood draining the contralateral adrenals (12.96 +/- 12.76; P < 0.001) but similar to blood draining IHA adrenals (4.69 +/- 4.32; P = 0.02). In contrast, the 18OHB/F ratios were elevated in specimens from APAs (26.03 +/- 11.51) compared with IHA adrenals (9.22 +/- 5.18; P < 0.001) or the contralateral adrenals (6.23 +/- 2.97; P < 0.001). Using 18OHB/F gradient greater than two or 18OHB/A gradient less than 0.5 as criteria for lateralization, interpretations agreed with lateralizations based on A/F gradients in 21 of 23 cases. CONCLUSIONS: High serum 18OHB in APA reflects augmented production of both 18OHB and A, not disproportionate 18OHB secretion relative to A. The 18OHB/A and 18OHB/F gradients are useful adjuncts but not as reliable as A/F gradients for A lateralization during AVS.

Spurious prostate-specific antigen (PSA) recurrence after radical prostatectomy: interference by human antimouse heterophile antibodies.

Human antimouse heterophile antibodies (HAMA) are naturally occurring antibodies that can interfere with modern serum assays. We report a case of HAMA interference with a commonly used prostate-specific antigen (PSA) assay, leading to false elevation (2.17-2.46 ng/mL) after radical prostatectomy. Pre-operative PSA was 4.4 ng/mL, and final pathology was Gleason 3 + 3, pT2cNXMX. This markedly elevated postoperative PSA led to unnecessary imaging for metastasis and psychological distress to the patient. Direct measurement of HAMA in the patient's serum yielded a value of 440 ng/mL (<74 ng/mL). An alternate PSA assay using goat detection antibody eliminated interference, with all values 0.05 ng/mL. When a patient's PSA is inconsistent with the clinical scenario, one should consider immunological interference by HAMA in PSA assays.

The variability of results between point-of-care testing glucose meters and the central laboratory analyzer.

CONTEXT: Point-of-care testing glucose meters are strongly recommended in the management of diabetes and are increasingly being used for making therapeutically important decisions. Thus, it is essential that their results correlate well with those of laboratory analyzers. OBJECTIVES: To test the reliability of point-of-care testing glucose meters. DESIGN: Two studies were performed: (1), an in-house study comparing accuracy of point-of-care testing glucose meters with a reference analyzer using fresh whole blood specimens (2), a real-time comparison of (a) 2 successive glucose meter readings and (b) glucose meter reading to central laboratory analyzer reading. SETTING: (1), Seven glucose meters from 4 manufacturers were compared with the Yellow Springs YSI 2300 blood glucose analyzer using whole blood without preservative. (2), (a) Whole blood samples were read within 5 minutes of each other using Accu-Chek meters and (b) between a glucose meter and a Hitachi laboratory analyzer. RESULTS: (1) Within the Accu-Chek group of glucose meters, fresh, preservative-free whole blood samples showed the lowest bias. (2) At the hypoglycemic level, successive glucose meter readings agreed well, but there was considerable disagreement between glucose meter and central laboratory values. Because laboratory analyzers are of proven accuracy, they are used as the reference. In the glucose meter-central laboratory analyzer correlation, for both hypoglycemic and hyperglycemic values, readings in which the differences were greater than 10% occurred more than 61% of the time. In the hypoglycemic range, differences greater than 20% occurred 57% of the time. CONCLUSIONS: One should scrutinize point-of-care testing glucose meter readings at the hypoglycemic and hyperglycemic levels and whenever possible to corroborate these clinical results with central laboratory analyzers.