Bio


Dr. Raffick Bowen is Clinical Professor of Pathology and Co-Director of Clinical Chemistry and Immunology Laboratory at Stanford University Medical Center. Dr. Bowen received his certification in Medical Laboratory Technology (MLT similar to MT in the United States) from the Canadian Society for Medical Laboratory Science (CSMLS) and has a license as a Clinical Chemist Specialist from the State of California. He completed his BSc in Medical Laboratory Science (MLS) and Ph.D. focusing on omega-6 and omega-3 fatty acids on brain neuronal and glial cells membrane structure and function with implications to the manufacturing of infant formula's fatty acid composition from the University of Alberta. Dr. Bowen completed a post-doctoral diploma in Clinical Chemistry (DClChem) from the University of Toronto and he became a Fellow of the Canadian Academy of Clinical Biochemistry (FCACB). Dr. Bowen has also spent a few years at the National Institutes of Health in Bethesda, Maryland as a Fogarty Post-Doctoral Fellow at the NIH Clinical Center. Dr. Bowen is a Diplomate of the American Board of Clinical Chemistry (DABCC). Also, Dr. Bowen is a Fellow of the American Academy of Clinical Biochemistry (FAACC). Dr. Bowen has also completed his Master in Health Administration (MHA) degree from the University of British Columbia. In summary, he is a Medical Technologist, Clinical Biochemist/Scientist with advanced business concepts as they relate to the healthcare system.

I believe that philosophy dictates practice and by engaging in this self-reflection process will result in an increased understanding of our beliefs about the nature of our professional work and life.

As a leader, I believe in teamwork, collaboration, and collective decision-making. W. Edwards Deming is the main influence of my management philosophy: It is not enough to do your best; you must know what to do, and then do your best. I also believe that financial accountability, transparency, and continuous improvement are essential for the success of a diagnostic laboratory. " In God we trust; all others must bring data." - Dr. Deming

My vision of Laboratory Medicine is to provide a continuous quality of service that is beyond the expectations of our clients.

"Never regard study as a duty, but as the enviable opportunity to learn to know the liberating influence of beauty in the realm of the spirit for your own personal joy and to the profit of the community to which your later work belongs"

Author: Albert Einstein

Clinical Focus


  • Clinical Biochemistry
  • Clinical Pathology

Academic Appointments


  • Clinical Professor, Pathology

Administrative Appointments


  • Co-Director of Clinical Chemistry and Immunology Laboratory, Stanford Healthcare (2013 - Present)
  • Associate Director of Clinical Chemistry and Immunology Laboratory, STANFORD HEALTHCARE (2006 - 2013)

Honors & Awards


  • Resident Teaching Award,, Faculty of Pathology (2017)
  • Value-Based Research Award, Department of Pathology (2017)
  • Best Poster Award, European Conference on Preanalytical Phase (EFLM) (2015)
  • Clinical Chemist Recognition Award, American Association of Clinical Chemistry (2015)
  • Outstanding Speaker Award, American Association of Clinical Chemistry (2013)
  • Clinical Chemist Recognition Award, American Association of Clinical Chemistry (2012)
  • Fellow, National Academy of Clinical Biochemistry (2012)
  • Resident Teaching Award, Faculty of Pathology (2011)
  • Outstanding Speaker Award, American Association of Clinical Chemistry (2010)
  • Distinguished Abstract, National Academy of Clinical Biochemistry (2009)
  • Diplomate, American Board of Clinical Chemistry (2007)
  • Distinguished Abstract, National Academy of Clinical Biochemistry (2006)
  • Fellow, Canadian Academy of Clinical Chemistry (2005)
  • Forgarty Fellowship, National Institutes of Health (2003-2006)
  • Clinical Chemistry Trainee Award, Dade Behring (2003)
  • Fellowship in Clinical Chemistry, Ontario Ministry of Health (2001-2003)

Boards, Advisory Committees, Professional Organizations


  • Member, Roche Advisory Group (2017 - Present)
  • Member, National Academy of Clinical Biochemistry (2012 - Present)
  • Member, American Association of Clinical Chemistry (2003 - Present)
  • Member, Canadian Society of Clinical Chemistry (2003 - Present)

Patents


  • Richard Zare, Samuel Kim, Raffick Bowen. "United States Patent 033,844 Methods for modifying a hydrophobic surface hydrophobic polymer surface and devices thereof-pending", Leland Stanford Junior University

Current Research and Scholarly Interests


Blood collection tubes are much more complex devices than is commonly appreciated by clinical laboratorians. Commercial tubes have multiple components that contribute to the optimal formation of serum or plasma for laboratory analysis.

My research has shown that the silicone surfactant, Silwet L-720, used in blood collection tubes from a major manufacturer interferes with some immunoassays. This surfactant causes desorption of capture antibodies from the solid-phase in some immunoassay reagents. In addition, these tube additives can interfere with other analytical techniques like mass spectrometry.

Since the quality of patient care depends on the quality of all the information that a physician uses in making treatment decisions, blood collection tubes should be manufactured to an extremely high standard like other medical devices. These tube-related interferences unlike patient specimens are not detected by routine quality control or proficiency testing since laboratorians typically do not pour these materials into the tube types used by their lab. Thus, any tube-related interferences will be missed by the clinical lab, which can lead to increased costs due to recollection and retesting, misdiagnosis, erroneous test results, increased turnaround times of test results, delays in patient care, decreased patient satisfaction, and diminished reputation of a healthcare institution.

I am currently testing different types of surfactants and tube wall surface modification on immunoassays. This work will hopefully lead to blood collection tubes with minimum or no assay interferences and a better understanding of the effects of blood collection tube surfactant and additives on clinical assays, particularly, immunoassays.

2021-22 Courses


All Publications


  • Impact of recentrifugation of blood collection tubes on chemistry and immunochemistry analytes after 24 and 72 hours of refrigerated storage on the Roche Cobas 8000 platform. Clinica chimica acta; international journal of clinical chemistry Bowen, R. A., Esguerra, V., Walker, M., Cheng, P., Nguyen, T. 2022

    Abstract

    BACKGROUND: We discovered that blood collection tubes (BCTs) were inadvertently recentrifuged due to improper placement on our automated preanalytical system. This study was undertaken to determine the impact of recentrifugation of blood specimens collected in serum separator (SSTs) and plasma separator (PSTs) tubes after refrigerated storage for 24 and 72 h on the concentrations of chemistry and immunochemistry analytes.METHODS: Blood was collected from 20 volunteers in SSTs and PSTs, centrifuged, and 36 chemistry and 14 immunochemistry analytes were measured at baseline in single-centrifuged tubes on a Roche Cobas 8000 chemistry platform. After baseline testing, the BCTs were refrigerated for 24 or 72 h, recentrifuged and retested. The results were compared to the single-centrifuged tubes for statistical significance.RESULTS: Recentrifugation of BCTs after 24 or 72 h of refrigerated storage showed statistically significant increases in lactate dehydrogenase activity and potassium concentration and statistically significant decreases in glucose (except in SSTs after 24 h of refrigerated storage) and CO2 concentration, but no significant differences in immunochemistry analyte concentrations.CONCLUSION: It may be safe to report most routine chemistry and immunochemistry analyte concentrations from recentrifuged SSTs and PSTs on the Roche Cobas 8000, which may save time and costs associated with recollection and retesting.

    View details for DOI 10.1016/j.cca.2022.04.1002

    View details for PubMedID 35513039

  • Unexpectedly low tacrolimus concentrations attributed to inappropriately labeled water container from the instrument manufacturer. Clinical chemistry and laboratory medicine Ames, E., Bowen, R. A. 2022

    View details for DOI 10.1515/cclm-2022-0204

    View details for PubMedID 35405044

  • Preanalytical error: Improper gel barrier formation in a serum separator tube despite appropriate centrifugation condition. Clinica chimica acta; international journal of clinical chemistry Allard, L., Bowen, R. A. 2021

    Abstract

    The clinical laboratory is a significant component of patient care, as laboratory data inform 60-70% of critical decisions related to admission, discharge, and medication administration. However, missteps occurring in specimen collection, transport and storage (preanalytical phase); testing (analytical phase); and reporting (post-analytical phase) may produce errors that affect patient safety and unnecessarily burden hospital budgets. Preanalytical errors may result from the devices used for blood collection. These devices have complex interactions with blood and can alter the composition of the serum and plasma fractions in ways that are not always fully appreciated by health care professionals. In some cases, such alterations can adversely affect laboratory test results. For instance, components of blood collection tubes (BCTs), including stoppers, stopper lubricants, tube walls, surfactants, clot activators, tube additives, and separator gels, may cause inaccuracies in test results by changing the chemical composition of the blood sample. Examples in the literature include BCTs leaching constituents into blood, adsorbing elements, or interacting with protein and cellular components. Additives and chemicals associated with BCT manufacturing can also significantly alter analyte stability in blood specimens. Here, we describe the case of a 14-month-old female with infectious mediastinitis and mild anemia who underwent a CT scan with contrast medium before blood collection. She has an increased INR and receives periodic boluses of diluted papaverine. After blood collection and subsequent tube centrifugation, abnormal gel migration was observed in one serum separator tube (SST), with gel trapped at the bottom of the tube below the clot. A review of the preanalytical system software confirmed that the SSTs from this patient were placed on the preanalytical line and centrifuged at 1300g for 10 min. We performed several tests to determine the cause of the displaced gel at the bottom of the SSTs after centrifugation. Although not recommended by the tube manufacturer, recentrifugation (1300g for 10 min) of the problematic SSTs resulted in proper gel separation. Thus, we hypothesized that the gel in the SSTs was defective and required additional centrifugation to move the gel upward in the tube to be positioned between the serum and cellular constituents. Abnormal gel movement to the top of the serum or plasma layer in SSTs or plasma separator tubes during centrifugation has been reported. This phenomenon has been attributed to an increased specific gravity of the serum or plasma, which in turn may be caused by hyperproteinemia or the presence of contrast medium used in diagnostic imaging. However, to our knowledge, ours is the first reported case of centrifuged gel remaining at the bottom of the SST. The finding of the gel at the bottom of an SST after centrifugation is important to laboratorians. Many clinical laboratories use preanalytical lines to centrifuge and transport tubes directly to chemistry instruments for analysis. These tubes are typically not visually inspected before the specimen is tested, hence improper gel separation in bottom of the tube. Partial or complete obstruction of the sample probes with cellular constituents may produce erroneous test results and increase turnaround time and costs, ultimately impacting patient care. Thus, this case may serve to remind clinical laboratorians that BCT failures are a source of preanalytical errors, and investigation of the integrity of BCTs is an essential part of trouble-shooting erroneous test results.

    View details for DOI 10.1016/j.cca.2021.01.016

    View details for PubMedID 33515538

  • Does the number of plasma separator tube inversions alter clinical chemistry and immunoassay test results on a Roche Cobas 8000 clinical chemistry platform? Clinica chimica acta; international journal of clinical chemistry Bowen, R. A., Esguerra, V., Walker, M. 2020

    View details for DOI 10.1016/j.cca.2020.12.033

    View details for PubMedID 33388305

  • Ethical and organizational considerations for mandatory COVID-19 vaccination of health care workers: A clinical laboratorian's perspective CLINICA CHIMICA ACTA Bowen, R. R. 2020; 510: 421–22
  • Ethical and organizational considerations for mandatory COVID-19 vaccination of health care workers: a clinical laboratorian's perspective. Clinica chimica acta; international journal of clinical chemistry Bowen, R. A. 2020

    View details for DOI 10.1016/j.cca.2020.08.003

    View details for PubMedID 32771485

  • Utility of High-Sensitivity and Conventional Troponin in Patients Undergoing Transcatheter Aortic Valve Replacement: Incremental Prognostic Value to B-type Natriuretic Peptide. Scientific reports Kobayashi, Y., Kim, J. B., Moneghetti, K. J., Fischbein, M., Lee, A., Watkins, C. A., Yeung, A. C., Liang, D., Ozen, M. O., Demirci, U., Bowen, R., Fearon, W. F., Haddad, F. 2019; 9 (1): 14936

    Abstract

    High-sensitivity Troponin (hs-Tn) has emerged as a useful marker for patients with myocardial injury or heart failure. However, few studies have compared intermediate and hs-Tn in patients undergoing transcatheter aortic valve replacement (TAVR). Moreover, there remains uncertainty of which thresholds are the most useful for discriminating ventricular dysfunction or outcome. In this study we prospectively enrolled 105 patients with severe aortic stenosis (AS) who underwent TAVR as well as blood sampling for high-sensitivity (hs-TnI) and conventional troponin I (EXL-LOCI and RXL) assessment. Patients underwent comprehensive pre-procedure echocardiography. Ventricular dysfunction was defined using left ventricular mass index (LVMI), LV global longitudinal strain (LVGLS) and LV end-diastolic pressure. The mean age was 84.0±8.7 years old and 60% were male sex with mean transaortic pressure gradient of 50.1±16.0mmHg and AVA of 0.63±0.19cm2. When using a threshold of 6ng/L, 77% had positive hs-TnI while 27% had positive hs-TnI using recommended thresholds (16ng/L for female and 34ng/L for male). Troponin levels were higher in the presence of abnormal LV phenotypes. The strongest correlate of troponin was LVMI. During median follow-up of 375 days, 21 patients (20%) died. Lower threshold of hs-TnI and EXL-TnI was more discriminatory for overall mortality (Log-rank P=0.03 for both), while higher threshold of hs-TnI (p=0.75) and RXL-TnI were not (p=0.30). Combining hs-TnI and BNP improved to predict long-term outcome (p=0.004). In conclusion, hs-TnI levels correlated with the degree of LV dysfunction phenotypes. Furthermore, applying a lower threshold for hs-TnI performed better for outcome prediction than a recommended threshold in patients undergoing TAVR. Combining hs-TnI with BNP helped better risk stratification.

    View details for DOI 10.1038/s41598-019-51371-x

    View details for PubMedID 31624275

  • Detection of Circulating Tumor DNA in Patients With Uterine Leiomyomas JCO PRECISION ONCOLOGY Przybyl, J., Spans, L., Lum, D. A., Zhu, S., Vennam, S., Forgo, E., Varma, S., Ganjoo, K., Hastie, T., Bowen, R., Debiec-Rychter, M., van de Rijn, M. 2019; 3
  • Detection of Circulating Tumor DNA in Patients With Uterine Leiomyomas. JCO precision oncology Przybyl, J., Spans, L., Lum, D. A., Zhu, S., Vennam, S., Forgó, E., Varma, S., Ganjoo, K., Hastie, T., Bowen, R., Debiec-Rychter, M., van de Rijn, M. 2019; 3

    Abstract

    The preoperative distinction between uterine leiomyoma (LM) and leiomyosarcoma (LMS) is difficult, which may result in dissemination of an unexpected malignancy during surgery for a presumed benign lesion. An assay based on circulating tumor DNA (ctDNA) could help in the preoperative distinction between LM and LMS. This study addresses the feasibility of applying the two most frequently used approaches for detection of ctDNA: profiling of copy number alterations (CNAs) and point mutations in the plasma of patients with LM.By shallow whole-genome sequencing, we prospectively examined whether LM-derived ctDNA could be detected in plasma specimens of 12 patients. Plasma levels of lactate dehydrogenase, a marker suggested for the distinction between LM and LMS by prior studies, were also determined. We also profiled 36 LM tumor specimens by exome sequencing to develop a panel for targeted detection of point mutations in ctDNA of patients with LM.We identified tumor-derived CNAs in the plasma DNA of 50% (six of 12) of patients with LM. The lactate dehydrogenase levels did not allow for an accurate distinction between patients with LM and patients with LMS. We identified only two recurrently mutated genes in LM tumors (MED12 and ACLY).Our results show that LMs do shed DNA into the circulation, which provides an opportunity for the development of ctDNA-based testing to distinguish LM from LMS. Although we could not design an LM-specific panel for ctDNA profiling, we propose that the detection of CNAs or point mutations in selected tumor suppressor genes in ctDNA may favor a diagnosis of LMS, since these genes are not affected in LM.

    View details for DOI 10.1200/po.18.00409

    View details for PubMedID 32232185

    View details for PubMedCentralID PMC7105159

  • Best practices in mitigating the risk of biotin interference with laboratory testing. Clinical biochemistry Bowen, R., Benavides, R., Colon-Franco, J. M., Katzman, B. M., Muthukumar, A., Sadrzadeh, H., Straseski, J., Klause, U., Tran, N. 2019

    Abstract

    Dietary biotin intake does not typically result in blood biotin concentrations that exceed interference thresholds for in vitro diagnostic tests. However, recent trends of high-dose biotin supplements and clinical trials of very high biotin doses for patients with multiple sclerosis have increased concerns about biotin interference with immunoassays. Estimates of the prevalence of high biotin intake vary, and patients may be unaware that they are taking biotin. Since 2016, 92 cases of suspected biotin interference have been reported to the US Food and Drug Administration. Immunoassays at greatest risk from biotin interference include thyroid and reproductive hormones, cardiac, and immunosuppressive drug tests. Several case studies have highlighted the challenge of biotin interference with thyroid hormone assays and the potential misdiagnosis of Graves' disease. Biotin interference should be suspected when immunoassay test results are inconsistent with clinical information; a clinically relevant biotin interference happens when the blood biotin concentration is high and the assay is sensitive to biotin. We propose a best practice workflow for laboratory scientists to evaluate discrepant immunoassay results, comprising: (1) serial dilution; (2) retesting after biotin clearance and/or repeat testing on an alternate platform; and (3) confirmation of the presence of biotin using depletion protocols or direct measurement of biotin concentrations. Efforts to increase awareness and avoid patient misdiagnosis should focus on improving guidance from manufacturers and educating patients, healthcare professionals, and laboratory staff. Best practice guidance for laboratory staff and healthcare professionals would also provide much-needed information on the prevention, detection, and management of biotin interference.

    View details for DOI 10.1016/j.clinbiochem.2019.08.012

    View details for PubMedID 31473202

  • Falsely high sirolimus concentrations due to everolimus cross-reactivity in the Siemens sirolimus immunoassay: Corrective actions implemented CLINICA CHIMICA ACTA Bowen, R., Rieta, R., Joshi, R., Lee, R. C. 2019; 489: 162–63
  • Impact of underfilling heparinized collection tubes on ionized calcium measurements. Clinica chimica acta; international journal of clinical chemistry Tung, J. K., Bowen, R. A. 2019

    View details for DOI 10.1016/j.cca.2019.11.017

    View details for PubMedID 31782994

  • Quality Control Practices for Chemistry and Immunochemistry in a Cohort of 21 Large Academic Medical Centers AMERICAN JOURNAL OF CLINICAL PATHOLOGY Rosenbaum, M. W., Flood, J. G., Melanson, S. F., Baumann, N. A., Marzinke, M. A., Rai, A. J., Hayden, J., Wu, A. B., Ladror, M., Lifshitz, M. S., Scott, M. G., Peck-Palmer, O. M., Bowen, R., Babic, N., Sobhani, K., Giacherio, D., Bocsi, G. T., Herman, D. S., Wang, P., Toffaletti, J., Handel, E., Kelly, K. A., Albeiroti, S., Wang, S., Zimmer, M., Driver, B., Yi, X., Wilburn, C., Lewandrowski, K. B. 2018; 150 (2): 96–104

    Abstract

    In the United States, minimum standards for quality control (QC) are specified in federal law under the Clinical Laboratory Improvement Amendment and its revisions. Beyond meeting this required standard, laboratories have flexibility to determine their overall QC program.We surveyed chemistry and immunochemistry QC procedures at 21 clinical laboratories within leading academic medical centers to assess if standardized QC practices exist for chemistry and immunochemistry testing.We observed significant variation and unexpected similarities in practice across laboratories, including QC frequency, cutoffs, number of levels analyzed, and other features.This variation in practice indicates an opportunity exists to establish an evidence-based approach to QC that can be generalized across institutions.

    View details for DOI 10.1093/AJCP/AQY033

    View details for Web of Science ID 000439051600002

    View details for PubMedID 29850771

  • Surface characterization and free thyroid hormones response of chemically modified poly(ethylene terephthalate) blood collection tubes APPLIED SURFACE SCIENCE Dil, E., Kim, S. C., Saffar, A., Ajji, A., Zare, R. N., Sattayapiwat, A., Esguerra, V., Bowen, R. R. 2018; 442: 602–12
  • Falsely high sirolimus concentrations due to everolimus cross-reactivity in the Siemens sirolimus immunoassay: Corrective actions implemented. Clinica chimica acta; international journal of clinical chemistry Bowen, R. n., Rieta, R. n., Joshi, R. n., Lee, R. C. 2017

    View details for PubMedID 29080689

  • Blood collection tubes as medical devices: The potential to affect assays and proposed verification and validation processes for the clinical laboratory. Clinical biochemistry Bowen, R. A., Adcock, D. 2016

    Abstract

    Blood collection tubes (BCTs) are an often under-recognized variable in the preanalytical phase of clinical laboratory testing. Unfortunately, even the best-designed and manufactured BCTs may not work well in all clinical settings. Clinical laboratories, in collaboration with healthcare providers, should carefully evaluate BCTs prior to putting them into clinical use to determine their limitations and ensure that patients are not placed at risk because of inaccuracies due to poor tube performance. Selection of the best BCTs can be achieved through comparing advertising materials, reviewing the literature, observing the device at a scientific meeting, receiving a demonstration, evaluating the device under simulated conditions, or testing the device with patient samples. Although many publications have discussed method validations, few detail how to perform experiments for tube verification and validation. This article highlights the most common and impactful variables related to BCTs and discusses the validation studies that a typical clinical laboratory should perform when selecting BCTs. We also present a brief review of how in vitro diagnostic devices, particularly BCTs, are regulated in the United States, the European Union, and Canada. The verification and validation of BCTs will help to avoid the economic and human costs associated with incorrect test results, including poor patient care, unnecessary testing, and delays in test results. We urge laboratorians, tube manufacturers, diagnostic companies, and other researchers to take all the necessary steps to protect against the adverse effects of BCT components and their additives on clinical assays.

    View details for DOI 10.1016/j.clinbiochem.2016.10.004

    View details for PubMedID 27765677

  • Falsely low plasma human chorionic gonadotropin (hCG) concentrations: Corrective actions implemented CLINICA CHIMICA ACTA Zemek, A., Rieta, R., Bowen, R. R. 2016; 460: 126–27

    View details for PubMedID 27374300

  • Performance of chemically modified plastic blood collection tubes. Clinical biochemistry Bowen, R. A., Kim, S. C., Sattayapiwat, A., Austria-Esguerra, V., Zare, R. N. 2016; 49 (1): 90-99

    Abstract

    The objective of this study was to compare newly-modified and aged chemoPET tubes, which contain no problematic surfactants, with commercially available serum blood collection tubes (BCTs) for use in analysis of cortisol, total triiodothyronine (TT3), total thyroxine (TT4), and routine clinical chemistry analytes in serum from apparently healthy volunteers and pooled quality control (QC) specimens.Blood specimens collected from 60 apparently healthy volunteers (18 males, 42 females) and pooled QC specimens poured into seven different BCTs were analyzed by a trained phlebotomist. Cortisol, TT3, and TT4 levels were measured on an Immulite 1000 instrument and routine chemistry tests were analyzed on a Siemens RxL instrument. The significance of differences between chemoPET and other BCT types compared to glass tubes were assessed by Student's paired t-test or repeated measures ANOVA or their non-parametric equivalents. The BCT-related biases (deviation from glass tubes) in analyte concentrations were compared with the current desirable allowable bias, derived from biological variation. Serum analyte concentrations in the different BCTs that exceeded their respective significant change limits were considered clinically significant.No statistically and/or clinically significant differences were noted in the analyte concentrations from serum specimens and pooled QC material when our newly modified and aged chemoPET tubes were compared to glass and other BCTs.The chemoPET tubes described here may be a suitable alternative to serum BCTs that contain problematic surfactants known to interfere with some clinical assays on the Immulite 1000 and RxL instruments.

    View details for DOI 10.1016/j.clinbiochem.2015.09.003

    View details for PubMedID 26375014

  • Re-engineering laboratory diagnostics for preventing preanalytical errors. Clinical biochemistry Lippi, G. n., Bowen, R. n., Adcock, D. M. 2016; 49 (18): 1313–14

    View details for PubMedID 27771343

  • Performance of chemically modified plastic blood collection tubes CLINICAL BIOCHEMISTRY Bowen, R. A., Kim, S. C., Sattayapiwat, A., Austria-Esguerra, V., Zare, R. N. 2016; 49 (1-2): 90-99

    Abstract

    The objective of this study was to compare newly-modified and aged chemoPET tubes, which contain no problematic surfactants, with commercially available serum blood collection tubes (BCTs) for use in analysis of cortisol, total triiodothyronine (TT3), total thyroxine (TT4), and routine clinical chemistry analytes in serum from apparently healthy volunteers and pooled quality control (QC) specimens.Blood specimens collected from 60 apparently healthy volunteers (18 males, 42 females) and pooled QC specimens poured into seven different BCTs were analyzed by a trained phlebotomist. Cortisol, TT3, and TT4 levels were measured on an Immulite 1000 instrument and routine chemistry tests were analyzed on a Siemens RxL instrument. The significance of differences between chemoPET and other BCT types compared to glass tubes were assessed by Student's paired t-test or repeated measures ANOVA or their non-parametric equivalents. The BCT-related biases (deviation from glass tubes) in analyte concentrations were compared with the current desirable allowable bias, derived from biological variation. Serum analyte concentrations in the different BCTs that exceeded their respective significant change limits were considered clinically significant.No statistically and/or clinically significant differences were noted in the analyte concentrations from serum specimens and pooled QC material when our newly modified and aged chemoPET tubes were compared to glass and other BCTs.The chemoPET tubes described here may be a suitable alternative to serum BCTs that contain problematic surfactants known to interfere with some clinical assays on the Immulite 1000 and RxL instruments.

    View details for DOI 10.1016/j.clinbiochem.2015.09.003

    View details for Web of Science ID 000368752700017

  • Cyst Fluid Glucose is Rapidly Feasible and Accurate in Diagnosing Mucinous Pancreatic Cysts. American journal of gastroenterology Zikos, T., Pham, K., Bowen, R., Chen, A. M., Banerjee, S., Friedland, S., Dua, M. M., Norton, J. A., Poultsides, G. A., Visser, B. C., Park, W. G. 2015; 110 (6): 909-914

    Abstract

    Better diagnostic tools are needed to differentiate pancreatic cyst subtypes. A previous metabolomic study showed cyst fluid glucose as a potential marker to differentiate mucinous from non-mucinous pancreatic cysts. This study seeks to validate these earlier findings using a standard laboratory glucose assay, a glucometer, and a glucose reagent strip.Using an IRB-approved prospectively collected bio-repository, 65 pancreatic cyst fluid samples (42 mucinous and 23 non-mucinous) with histological correlation were analyzed.Median laboratory glucose, glucometer glucose, and percent reagent strip positive were lower in mucinous vs. non-mucinous cysts (P<0.0001 for all comparisons). Laboratory glucose<50 mg/dl had a sensitivity of 95% and a specificity of 57% (LR+ 2.19, LR- 0.08). Glucometer glucose<50 mg/dl had a sensitivity of 88% and a specificity of 78% (LR+ 4.05, LR- 0.15). Reagent strip glucose had a sensitivity of 81% and a specificity of 74% (LR+ 3.10, LR- 0.26). CEA had a sensitivity of 77% and a specificity of 83% (LR+ 4.67, LR- 0.27). The combination of having either a glucometer glucose<50 mg/dl or a CEA level>192 had a sensitivity of 100% but a low specificity of 33% (LR+ 1.50, LR- 0.00).Glucose, whether measured by a laboratory assay, a glucometer, or a reagent strip, is significantly lower in mucinous cysts compared with non-mucinous pancreatic cysts.

    View details for DOI 10.1038/ajg.2015.148

    View details for PubMedID 25986360

  • Transforming plastic surfaces with electrophilic backbones from hydrophobic to hydrophilic. ACS applied materials & interfaces Kim, S., Bowen, R. A., Zare, R. N. 2015; 7 (3): 1925-1931

    Abstract

    We demonstrate a simple nonaqueous reaction scheme for transforming the surface of plastics from hydrophobic to hydrophilic. The chemical modification is achieved by base-catalyzed trans-esterification with polyols. It is permanent, does not release contaminants, and causes no optical or mechanical distortion of the plastic. We present contact angle measurements to show successful modification of several types of plastics including poly(ethylene terephthalate) (PET) and polycarbonate (PC). Its applicability to blood analysis is explored using chemically modified PET blood collection tubes and found to be quite satisfactory. We expect this approach will reduce the cost of manufacturing plastic devices with optimized wettability and can be generalized to other types of plastic materials having an electrophilic linkage as its backbone.

    View details for DOI 10.1021/am507606r

    View details for PubMedID 25565370

  • Commutability of the Epstein-Barr virus WHO international standard across two quantitative PCR methods. Journal of clinical microbiology Abeynayake, J., Johnson, R., Libiran, P., Sahoo, M. K., Cao, H., Bowen, R., Chan, K. C., Le, Q., Pinsky, B. A. 2014; 52 (10): 3802-3804

    Abstract

    The commutability of international reference standards is critical for ensuring quantitative agreement across different viral load assays. Here, we demonstrate the commutability of the Epstein-Barr virus (EBV) WHO international standard for the BamHI-W and artus EBV assays.

    View details for DOI 10.1128/JCM.01676-14

    View details for PubMedID 25078918

    View details for PubMedCentralID PMC4187779

  • Maternal proteinuria in twin compared with singleton pregnancies. Obstetrics and gynecology Osmundson, S. S., Lafayette, R. A., Bowen, R. A., Roque, V. C., Garabedian, M. J., Aziz, N. 2014; 124 (2): 332-337

    Abstract

    To compare 24-hour urinary protein excretion in twin and singleton pregnancies not complicated by hypertension.We prospectively evaluated mean 24-hour urinary protein excretion in twin and singleton pregnancies between 24 0/7 weeks and 36 0/7 weeks of gestation. Women with urinary tract infections, chronic hypertension, pregestational diabetes, and renal or autoimmune diseases were excluded. Collection adequacy was assessed by urinary creatinine excretion adjusted for maternal weight.Adequate samples were obtained from 50 twin and 49 singleton pregnancies at a mean gestational age of 30 weeks. At collection, the two groups were similar with regard to maternal age, gestational age, body mass index, and blood pressure. Mean urinary protein excretion was higher in twin compared with singleton pregnancies (269.3±124.1 mg compared with 204.3±92.5 mg, P=.004). Proteinuria (300 mg/day protein or greater) occurred in 38.0% (n=19) of twin and 8.2% (n=4) of singleton pregnancies (P<.001). After adjusting for confounding variables, the difference in mean total protein excretion remained significant (P=.004) and twins were more likely to have proteinuria compared with singleton pregnancies (adjusted odds ratio 9.1, 95% confidence interval 2.1-38.5). Nineteen participants developed a hypertensive disorder at a mean of 7.7 weeks after the urine collection (range 2.6-14.5 weeks). After excluding these women, proteinuria was present in 43% of twin and 7% of singleton pregnancies (P<.001).Mean 24-hour urinary protein excretion in twin pregnancies is greater than in singletons. These data suggest a reevaluation of the diagnostic criteria for preeclampsia in twin pregnancies.: II.

    View details for DOI 10.1097/AOG.0000000000000383

    View details for PubMedID 25004349

  • Interferences from blood collection tube components on clinical chemistry assays. Biochemia medica Bowen, R. A., Remaley, A. T. 2014; 24 (1): 31-44

    Abstract

    Improper design or use of blood collection devices can adversely affect the accuracy of laboratory test results. Vascular access devices, such as catheters and needles, exert shear forces during blood flow, which creates a predisposition to cell lysis. Components from blood collection tubes, such as stoppers, lubricants, surfactants, and separator gels, can leach into specimens and/or adsorb analytes from a specimen; special tube additives may also alter analyte stability. Because of these interactions with blood specimens, blood collection devices are a potential source of pre-analytical error in laboratory testing. Accurate laboratory testing requires an understanding of the complex interactions between collection devices and blood specimens. Manufacturers, vendors, and clinical laboratorians must consider the pre-analytical challenges in laboratory testing. Although other authors have described the effects of endogenous substances on clinical assay results, the effects/impact of blood collection tube additives and components have not been well systematically described or explained. This review aims to identify and describe blood collection tube additives and their components and the strategies used to minimize their effects on clinical chemistry assays.

    View details for DOI 10.11613/BM.2014.006

    View details for PubMedID 24627713

    View details for PubMedCentralID PMC3936985

  • Blood collection tube-related alterations in analyte concentrations in quality control material and serum specimens. Clinical biochemistry Bowen, R. A., Sattayapiwat, A., Gounden, V., Remaley, A. T. 2014; 47 (3): 150-157

    Abstract

    Several previous studies have described the effects of interfering substances on clinical assay results; however, the effects of exogenous substances, particularly additives from blood collection tubes on quality control (QC) specimens and serum specimens have not been well examined. This study examines the effects of blood-collection tube additives on total triiodothyronine (TT3), and thyroxine (TT4), cortisol, and routine clinical chemistry tests in QC and serum specimens from apparently healthy volunteers.QC and serum specimens were poured or collected into different blood collection tubes. TT3 and TT4, cortisol, and routine chemistry tests were analyzed from the different blood-collection tube types.The findings of this study demonstrate statistically and/or clinically significant blood collection tube-related alterations in the TT3, TT4, and cortisol concentrations of QC specimens and TT4 concentrations from serum specimens.These findings have important implications for clinical laboratories, demonstrating that QC specimens should ideally, like patients' specimens, be poured into blood collection tubes. This strategy would reveal any adverse effects caused by blood collection tubes, which otherwise would not likely be detected by most routine QC practices. The results of this study also show the importance of producing blood collection tubes that contain additives that are truly inert and do not adversely affect clinical laboratory testing.

    View details for DOI 10.1016/j.clinbiochem.2013.11.003

    View details for PubMedID 24240064

    View details for PubMedCentralID PMC3944914

  • Interferences from blood collection tube components on clinical chemistry assays BIOCHEMIA MEDICA Bowen, R. A., Remaley, A. T. 2014; 24 (1): 31-44

    Abstract

    Improper design or use of blood collection devices can adversely affect the accuracy of laboratory test results. Vascular access devices, such as catheters and needles, exert shear forces during blood flow, which creates a predisposition to cell lysis. Components from blood collection tubes, such as stoppers, lubricants, surfactants, and separator gels, can leach into specimens and/or adsorb analytes from a specimen; special tube additives may also alter analyte stability. Because of these interactions with blood specimens, blood collection devices are a potential source of pre-analytical error in laboratory testing. Accurate laboratory testing requires an understanding of the complex interactions between collection devices and blood specimens. Manufacturers, vendors, and clinical laboratorians must consider the pre-analytical challenges in laboratory testing. Although other authors have described the effects of endogenous substances on clinical assay results, the effects/impact of blood collection tube additives and components have not been well systematically described or explained. This review aims to identify and describe blood collection tube additives and their components and the strategies used to minimize their effects on clinical chemistry assays.

    View details for Web of Science ID 000331269800007

    View details for PubMedCentralID PMC3936985

  • Metabolomic-derived novel cyst fluid biomarkers for pancreatic cysts: glucose and kynurenine GASTROINTESTINAL ENDOSCOPY Park, W. G., Wu, M., Bowen, R., Zheng, M., Fitch, W. L., Pai, R. K., Wodziak, D., Visser, B. C., Poultsides, G. A., Norton, J. A., Banerjee, S., Chen, A. M., Friedland, S., Scott, B. A., Pasricha, P. J., Lowe, A. W., Peltz, G. 2013; 78 (2): 295-?

    Abstract

    BACKGROUND: Better pancreatic cyst fluid biomarkers are needed. OBJECTIVE: To determine whether metabolomic profiling of pancreatic cyst fluid would yield clinically useful cyst fluid biomarkers. DESIGN: Retrospective study. SETTING: Tertiary-care referral center. PATIENTS: Two independent cohorts of patients (n = 26 and n = 19) with histologically defined pancreatic cysts. INTERVENTION: Exploratory analysis for differentially expressed metabolites between (1) nonmucinous and mucinous cysts and (2) malignant and premalignant cysts was performed in the first cohort. With the second cohort, a validation analysis of promising identified metabolites was performed. MAIN OUTCOME MEASUREMENTS: Identification of differentially expressed metabolites between clinically relevant cyst categories and their diagnostic performance (receiver operating characteristic [ROC] curve). RESULTS: Two metabolites had diagnostic significance-glucose and kynurenine. Metabolomic abundances for both were significantly lower in mucinous cysts compared with nonmucinous cysts in both cohorts (glucose first cohort P = .002, validation P = .006; and kynurenine first cohort P = .002, validation P = .002). The ROC curve for glucose was 0.92 (95% confidence interval [CI], 0.81-1.00) and 0.88 (95% CI, 0.72-1.00) in the first and validation cohorts, respectively. The ROC for kynurenine was 0.94 (95% CI, 0.81-1.00) and 0.92 (95% CI, 0.76-1.00) in the first and validation cohorts, respectively. Neither could differentiate premalignant from malignant cysts. Glucose and kynurenine levels were significantly elevated for serous cystadenomas in both cohorts. LIMITATIONS: Small sample sizes. CONCLUSION: Metabolomic profiling identified glucose and kynurenine to have potential clinical utility for differentiating mucinous from nonmucinous pancreatic cysts. These markers also may diagnose serous cystadenomas.

    View details for DOI 10.1016/j.gie.2013.02.037

    View details for Web of Science ID 000321825200015

    View details for PubMedID 23566642

  • Preanalytical quality improvement: in quality we trust CLINICAL CHEMISTRY AND LABORATORY MEDICINE Lippi, G., Becan-McBride, K., Behulova, D., Bowen, R. A., Church, S., Delanghe, J., Grankvist, K., Kitchen, S., Nybo, M., Nauck, M., Nikolac, N., Palicka, V., Plebani, M., Sandberg, S., Simundic, A. 2013; 51 (1): 229-241

    Abstract

    Total quality in laboratory medicine should be defined as the guarantee that each activity throughout the total testing process is correctly performed, providing valuable medical decision-making and effective patient care. In the past decades, a 10-fold reduction in the analytical error rate has been achieved thanks to improvements in both reliability and standardization of analytical techniques, reagents, and instrumentation. Notable advances in information technology, quality control and quality assurance methods have also assured a valuable contribution for reducing diagnostic errors. Nevertheless, several lines of evidence still suggest that most errors in laboratory diagnostics fall outside the analytical phase, and the pre- and postanalytical steps have been found to be much more vulnerable. This collective paper, which is the logical continuum of the former already published in this journal 2 years ago, provides additional contribution to risk management in the preanalytical phase and is a synopsis of the lectures of the 2nd European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)-Becton Dickinson (BD) European Conference on Preanalytical Phase meeting entitled "Preanalytical quality improvement: in quality we trust" (Zagreb, Croatia, 1-2 March 2013). The leading topics that will be discussed include quality indicators for preanalytical phase, phlebotomy practices for collection of blood gas analysis and pediatric samples, lipemia and blood collection tube interferences, preanalytical requirements of urinalysis, molecular biology hemostasis and platelet testing, as well as indications on best practices for safe blood collection. Auditing of the preanalytical phase by ISO assessors and external quality assessment for preanalytical phase are also discussed.

    View details for DOI 10.1515/cclm-2012-0597

    View details for Web of Science ID 000312497600023

    View details for PubMedID 23072858

  • Serum testosterone quantitation by liquid chromatography-tandem mass spectrometry: Interference from blood collection tubes CLINICAL BIOCHEMISTRY Shi, R. Z., van Rossum, H. H., Bowen, R. A. 2012; 45 (18): 1706-1709

    Abstract

    During the development of a testosterone assay by LC-MS/MS, we encountered significant assay interference introduced by blood collection tubes. We examined a number of commonly used blood collection tubes for the presence of interference and its impact on testosterone quantitation.A number of commonly used blood collection tubes were examined by incubation of zero, low and high testosterone concentration samples with them over time, followed by sample preparation using liquid-liquid extraction and analysis by LC-MS/MS. Source of interference was identified by separately incubating blood collection tube coating, stopper and separator gel in clean glass tubes containing zero calibrator.Significant interference was found in some blood collection tubes, with the separator gel identified as the main source. The magnitude of the interference increases over time and mainly affected one of the two testosterone mass transitions used in the quantitation, making it readily detected by the discrepant results obtained by each of the two testosterone mass transitions. We were unable to eliminate the interference by adjustment of the sample preparation procedure, and by changing LC or MS parameters. Accurate quantitation of testosterone is possible when the problematic tubes are avoided, and blood collection tubes free of interference are used instead.Significant LC-MS/MS testosterone assay interference that originated from certain type of blood collection tubes hampered testosterone analysis. Examination of blood collection tube and any other laboratory test tubes for interference should therefore be an integral part of the development and validation of any LC-MS/MS assay used in a clinical diagnostic laboratory.

    View details for DOI 10.1016/j.clinbiochem.2012.08.008

    View details for Web of Science ID 000312048900035

    View details for PubMedID 22971570

  • Tubes and additives for venous and capillary blood collection tubes; approved standard H1-A6 CLSI standard Dubrowny N, A. B. 2010
  • Impact of blood collection devices on clinical chemistry assays CLINICAL BIOCHEMISTRY Bowen, R. A., Hortin, G. L., Csako, G., Otanez, O. H., Remaley, A. T. 2010; 43 (1-2): 4-25

    Abstract

    Blood collection devices interact with blood to alter blood composition, serum, or plasma fractions and in some cases adversely affect laboratory tests. Vascular access devices may release coating substances and exert shear forces that lyse cells. Blood-dissolving tube additives can affect blood constituent stability and analytical systems. Blood tube stoppers, stopper lubricants, tube walls, surfactants, clot activators, and separator gels may add materials, adsorb blood components, or interact with protein and cellular components. Thus, collection devices can be a major source of preanalytical error in laboratory testing. Device manufacturers, laboratory test vendors, and clinical laboratory personnel must understand these interactions as potential sources of error during preanalytical laboratory testing. Although the effects of endogenous blood substances have received attention, the effects of exogenous substances on assay results have not been well described. This review will identify sources of exogenous substances in blood specimens and propose methods to minimize their impact on clinical chemistry assays.

    View details for DOI 10.1016/j.clinbiochem.2009.10.001

    View details for Web of Science ID 000273514400002

    View details for PubMedID 19822139

  • Validation and Verification of Tubes for venous and capillary blood specimen collection; GP34-A CLSI guideline Dubrowny N, A. B. 2010
  • Rapid blood separation is superior to fluoride for preventing in vitro reductions in measured blood glucose concentration JOURNAL OF CLINICAL PATHOLOGY Shi, R. Z., Seeley, E. S., Bowen, R., Faix, J. D. 2009; 62 (8): 752-753

    Abstract

    To determine whether tubes containing sodium fluoride negatively bias blood glucose concentration by directly comparing glucose concentrations in paired blood samples collected in tubes containing lithium heparin (Li-Heparin) and tubes containing sodium fluoride/potassium oxalate (NaF-KOx).Paired blood samples from a group of patients (n = 1040) were collected in tubes containing Li-Heparin and tubes containing NaF-KOx at the same time. All Li-Heparin samples were centrifuged soon after collection and were kept cool in transport along with NaF-KOx samples, which were centrifuged at the receiving location after an average transport time of 4 h, but immediately before analysis. Glucose concentrations in the paired samples were determined simultaneously by an automated oxidase method.The mean glucose concentrations for NaF-KOx samples and Li-Heparin samples were 5.7 mmol/l and 6.1 mmol/l, respectively, with a mean difference of 0.39 mmol/l.Rapid separation of heparinised blood is superior to fluoride alone for abrogating glycolytic effects on blood glucose measurements in the clinical laboratory.

    View details for DOI 10.1136/jcp.2008.062547

    View details for Web of Science ID 000268399100017

    View details for PubMedID 19638548

  • Identification and resolution of exogenous immunoassay interferences Clinical Laboratory International Bowen RAR 2008
  • Differential effect of blood collection tubes on total free fatty acids (FFA) and total triiodothyronine (TT3) concentration: A model for studying interference from tube constituents CLINICA CHIMICA ACTA Bowen, R. A., Vu, C., Remaley, A. T., Hortin, G. L., Csako, G. 2007; 378 (1-2): 181-193

    Abstract

    Besides total triiodothyronine (TT3), total free fatty acids (FFA) concentrations were higher with serum separator tube (SST) than Vacuette tubes.The effects of surfactant, rubber stopper, and separator gel from various tubes were investigated on FFA, beta-hydroxybutyrate (beta-HB), and TT3 with 8 different tube types in blood specimens of apparently healthy volunteers.Compared to Vacuette tubes, serum FFA and TT3 concentrations were significantly higher in SST than glass tubes. Reformulated SST eliminated the increase in TT3 but not FFA. No significant difference was observed for beta-HB concentration among tube types. Surfactant and rubber stoppers from the different tube types significantly increased TT3 but not FFA and beta-HB concentrations. Agitation of whole blood but not serum or plasma specimens with separator gel from SST, reformulated SST and plasma preparation tube (PPT) tubes compared to Vacuette tubes gave higher FFA but not beta-HB levels.Unidentified component(s) from the separator gel in SST, reformulated SST and PPT tubes cause falsely high FFA concentration. In contrast to TT3, falsely high FFA results require exposure of whole blood and not serum to tube constituent(s). The approach employed here may serve as a model for assessing interference(s) from tube constituent(s).

    View details for DOI 10.1016/j.cca.2006.11.020

    View details for Web of Science ID 000244997600030

    View details for PubMedID 17234171

  • Immunoassay interference by a commonly used blood collection tube additive, the organosilicone surfactant Silwet L-720 CLINICAL CHEMISTRY Bowen, R. A., Chan, Y., Ruddel, M. E., Hortin, G. L., Csako, G., Demosky, S. J., Remaley, A. T. 2005; 51 (10): 1874-1882

    Abstract

    A small number of immunoassays on several different types of analyzers were recently adversely affected by tube additives in Becton Dickinson (BD) Vacutainer SST, SST II, and Microtainer blood collection tubes. We examined the effect of a commonly used tube surfactant, Silwet L-720, on immunoassays and the mechanism for the interference.Immunoassays were performed on serum supplemented with Silwet L-720 on the IMMULITE 2500 and AxSYM analyzers. Direct effects of the surfactant on the chemiluminescent detection step of immunoassays and on antibody immobilization on the solid phase were examined.Increasing the final surfactant concentration from 0 to 400 mg/L in serum significantly increased (approximately 51%) the apparent total triiodothyronine (TT3) concentrations measured on the IMMULITE 2500 but not the AxSYM analyzer. Several other competitive, but not noncompetitive, assays were also significantly affected by the surfactant on the IMMULITE 2500 analyzer. The effect was independent of serum components, and the surfactant had no direct effect on chemiluminescence reactions. The capture antibody, however, was displaced from the solid phase by incubation with solutions containing surfactant under conditions similar to the IMMULITE TT3 assay.The Silwet L-720 surfactant, which is used to coat the inner surfaces of tubes, appears to account for previously reported immunoassay interference by BD Vacutainer SST blood collection tubes. One of the mechanisms for the interference is the desorption of antibodies from the solid phase by the surfactant. The results identify an important factor in the selection of suitable blood collection tube surfactants and provide an approach for solving similar tube-assay interference problems in the future.

    View details for DOI 10.1373/clinchem.2005.055400

    View details for Web of Science ID 000232198600018

    View details for PubMedID 16099932

  • Effect of blood collection tubes on total triiodothyronine and other laboratory assays CLINICAL CHEMISTRY Bowen, R. A., Chan, Y., Cohen, J., Rehak, N. N., Hortin, G. L., Csako, G., Remaley, A. T. 2005; 51 (2): 424-433

    Abstract

    Increased total triiodothyronine (TT(3)) assay results in apparently euthyroid patients triggered an investigation of the effect of blood collection tubes on serum TT(3) and other laboratory assays.We examined potential assay interference for three types of tubes: plastic Greiner Bio-One Vacuette; glass Becton Dickinson (BD) Vacutainer; and plastic BD Vacutainer SST tubes. Serum samples from apparently healthy volunteers (age range, 30-60 years; 15 males and 34 females) were collected in different tube types and analyzed in 17 immunoassays (n = 49), 30 clinical chemistry tests (n = 20), and 33 immunology assays (n = 15). Tube effects were also examined by adding pooled serum to different tube types.TT(3) values, when measured by the IMMULITE 2000 but not the AxSYM analyzer, were significantly higher (P <0.0001) for SST (2.81 nmol/L) than either glass (2.15 nmol/L) or Vacuette (2.24 nmol/L) tubes. The effect was large enough to substantially shift the distribution of patient values, increasing the percentage of values above the reference interval from 11.3% to 35.8%. The degree of interference from SST tubes on TT(3) differed among various tube lots and could be attributed to a tube additive shared by other plastic tubes. Results from several other tests statistically differed among tube types, but differences were not considered to be clinically significant.Assay interferences from blood collection tubes represent challenges to clinical laboratories because they are not detected by the usual quality-control or proficiency testing programs. Laboratories can, however, address this problem by monitoring distribution of patients' results.

    View details for DOI 10.1373/clinchem.2004.043349

    View details for Web of Science ID 000226717600021

    View details for PubMedID 15576427

  • Potential interferences from blood collection tubes in mass spectrometric analyses of serum polypeptides CLINICAL CHEMISTRY Drake, S. K., Bowen, R. A., Remaley, A. T., Hortin, G. L. 2004; 50 (12): 2398-2401

    View details for DOI 10.1373/clinchem.2004.040303

    View details for Web of Science ID 000225356700030

    View details for PubMedID 15563493

  • Identification and Resolution of Immunoassay Interferences Handbook of Diagnostic Endocrinology Raffick A.R. Bowen, Alan T. Remaley
  • Metabolomic-derived novel cyst fluid biomarkers for pancreatic cysts: glucose and kynurenine. Gastrointestinal endoscopy Park, W. G., Wu, M., Bowen, R., Zheng, M., Fitch, W. L., Pai, R. K., Wodziak, D., Visser, B. C., Poultsides, G. A., Norton, J. A., Banerjee, S., Chen, A. M., Friedland, S., Scott, B. A., Pasricha, P. J., Lowe, A. W., Peltz, G. 2013; 78 (2): 295-302 e2

    Abstract

    BACKGROUND: Better pancreatic cyst fluid biomarkers are needed. OBJECTIVE: To determine whether metabolomic profiling of pancreatic cyst fluid would yield clinically useful cyst fluid biomarkers. DESIGN: Retrospective study. SETTING: Tertiary-care referral center. PATIENTS: Two independent cohorts of patients (n = 26 and n = 19) with histologically defined pancreatic cysts. INTERVENTION: Exploratory analysis for differentially expressed metabolites between (1) nonmucinous and mucinous cysts and (2) malignant and premalignant cysts was performed in the first cohort. With the second cohort, a validation analysis of promising identified metabolites was performed. MAIN OUTCOME MEASUREMENTS: Identification of differentially expressed metabolites between clinically relevant cyst categories and their diagnostic performance (receiver operating characteristic [ROC] curve). RESULTS: Two metabolites had diagnostic significance-glucose and kynurenine. Metabolomic abundances for both were significantly lower in mucinous cysts compared with nonmucinous cysts in both cohorts (glucose first cohort P = .002, validation P = .006; and kynurenine first cohort P = .002, validation P = .002). The ROC curve for glucose was 0.92 (95% confidence interval [CI], 0.81-1.00) and 0.88 (95% CI, 0.72-1.00) in the first and validation cohorts, respectively. The ROC for kynurenine was 0.94 (95% CI, 0.81-1.00) and 0.92 (95% CI, 0.76-1.00) in the first and validation cohorts, respectively. Neither could differentiate premalignant from malignant cysts. Glucose and kynurenine levels were significantly elevated for serous cystadenomas in both cohorts. LIMITATIONS: Small sample sizes. CONCLUSION: Metabolomic profiling identified glucose and kynurenine to have potential clinical utility for differentiating mucinous from nonmucinous pancreatic cysts. These markers also may diagnose serous cystadenomas.

    View details for DOI 10.1016/j.gie.2013.02.037

    View details for PubMedID 23566642

  • Discordant aPTT and anti-Xa values and outcomes in hospitalized patients treated with intravenous unfractionated heparin. Annals of pharmacotherapy Price, E. A., Jin, J., Nguyen, H. M., Krishnan, G., Bowen, R., Zehnder, J. L. 2013; 47 (2): 151-158

    Abstract

    Both the activated partial thromboplastin time (aPTT) and anti-Xa assay can be used to monitor unfractionated heparin (UFH). Following implementation of an anti-Xa method for heparin dosing protocols in our hospital, we became aware of many patients with discordant aPTT and anti-Xa values.To determine the frequency of discordant aPTT and anti-Xa values in a large cohort of hospitalized patients treated with UFH, as well as the demographics, coagulation status, indication for UFH, and clinical outcomes in this population.All aPTT and anti-Xa values from adults hospitalized between February and August 2009 at Stanford Hospital who were treated with UFH were analyzed. All samples were drawn simultaneously. A polynomial fit correlating aPTT and anti-Xa with a 99% confidence limit was designed. Paired aPTT/anti-Xa values were grouped according to whether the paired values fell within or outside of the concordant area. Patients were placed into groups based on concordance status, and clinical outcomes were assessed.A total of 2321 paired values from 539 patients were studied; 42% of data pairs had a high aPTT value relative to the anti-Xa value. Patients with elevated baseline prothrombin time/international normalized ratio or aPTT frequently demonstrated disproportionate relative prolongation of the aPTT. Patients with at least 2 consecutive high aPTT to anti-Xa values had increased 21-day major bleeding (9% vs 3%; p = 0.0316) and 30-day mortality (14% dead vs 5% dead at 30 days; p = 0.0202) compared with patients with consistently concordant values.aPTT and anti-Xa values are frequently discordant when used to measure UFH in hospitalized patients. A disproportionate prolongation of the aPTT relative to the anti-Xa was the most common discordant pattern in our study. Patients with relatively high aPTT to anti-Xa values appear to be at increased risk of adverse outcomes. Monitoring both aPTT and Xa values may have utility in managing such patients.

    View details for DOI 10.1345/aph.1R635

    View details for PubMedID 23386070

  • Elevated vitamin B-12 levels in autoimmune lymphoproliferative syndrome attributable to elevated haptocorrin in lymphocytes CLINICAL BIOCHEMISTRY Bowen, R. A., Dowdell, K. C., Dale, J. K., Drake, S. K., Fleisher, T. A., Hortin, G. L., Remaley, A. T., Nexo, E., Rao, V. K. 2012; 45 (6): 490-492

    Abstract

    Identify the etiology of elevated B(12) in autoimmune lymphoproliferative syndrome (ALPS).Peripheral blood of ALPS patients with elevated B(12) and controls were evaluated.Total and holo-haptocorrin (HC) levels were 26- and 23-fold higher in ALPS patients, respectively. No abnormal B(12)-binding proteins were found. Western blot revealed HC in lymphocyte lysates only from ALPS patients.Elevated concentrations of B(12) found in ALPS patients were due to increased lymphocyte expression of HC.

    View details for DOI 10.1016/j.clinbiochem.2012.01.016

    View details for Web of Science ID 000302111900023

    View details for PubMedID 22306884

    View details for PubMedCentralID PMC3307947

  • False-negative result for cocaine metabolites on a lateral-flow drug test slide corrected by dilution CLINICAL CHEMISTRY Bowen, R. A., George, D. T., Hortin, G. L. 2005; 51 (4): 790-791

    View details for DOI 10.1373/clinchem.2004.046607

    View details for Web of Science ID 000227936600018

    View details for PubMedID 15788788