Sandra C Bryant

Mayo Clinic - Rochester, Рочестер, Minnesota, United States

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Publications (98)448.34 Total impact

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    ABSTRACT: Free cortisol (FC) is potentially superior to total cortisol (TC) measurements in selected clinical settings; however, the advantages of uniform use of FC in outpatient settings are unclear. The objectives of this study were to describe the dynamic response of FC during cosyntropin stimulation Testing (CST) compared to TC, and to determine the rates of discordance. This is a cross-sectional study of two hundred ninety-five stable patients who underwent CST in an outpatient Endocrine Testing Center. The main outcome measures were TC and FC measurements during CST. Two hundred ninety-five subjects participated in the study (mean age 49.1 [16.9] years). Of 218 women, 43 were taking estrogen-containing therapy (ET) at the time of testing. Adrenal insufficiency (AI) was diagnosed in 41/295 (14%) patients. The FC concentrations were associated with TC concentrations at baseline (R(2)=0.77, P <.001), 30 minutes (R(2)=0.87, P<.001), and at 60 minutes (R(2)=0.90, P<.001). FC cutoff for AI was 873 ng/dL at 30 minutes, and 1170 ng/dL at 60 minutes. The FC had a more pronounced fold change from baseline to peak than TC (median 3.2 versus 1.7, P<.001). Both TC and FC at baseline were higher in women on ET when compared to women not on ET and to men; however peak TC and FC values were similar. In 3/43 women on ET, FC and TC results were discordant (P=.003). We report 99% concordance of TC and FC measurements in a large outpatient cohort. The discordant rates were high in women treated with ET (7%). The FC measurements during CST in women on ET may provide a more rapid and accurate diagnosis of AI.
    No preview · Article · Sep 2015 · Endocrine Practice
  • Brad S Karon · Jeffrey W Meeusen · Sandra C Bryant
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    ABSTRACT: We retrospectively studied the impact of glucose meter error on the efficacy of glycemic control after cardiovascular surgery. Adult patients undergoing intravenous insulin glycemic control therapy after cardiovascular surgery, with 12-24 consecutive glucose meter measurements used to make insulin dosing decisions, had glucose values analyzed to determine glycemic variability by both standard deviation (SD) and continuous overall net glycemic action (CONGA), and percentage glucose values in target glucose range (110-150 mg/dL). Information was recorded for 70 patients during each of 2 periods, with different glucose meters used to measure glucose and dose insulin during each period but no other changes to the glycemic control protocol. Accuracy and precision of each meter were also compared using whole blood specimens from ICU patients. Glucose meter 1 (GM1) had median bias of 11 mg/dL compared to a laboratory reference method, while glucose meter 2 (GM2) had a median bias of 1 mg/dL. GM1 and GM2 differed little in precision (CV = 2.0% and 2.7%, respectively). Compared to the period when GM1 was used to make insulin dosing decisions, patients whose insulin dose was managed by GM2 demonstrated reduced glycemic variability as measured by both SD (13.7 vs 21.6 mg/dL, P < .0001) and CONGA (13.5 vs 19.4 mg/dL, P < .0001) and increased percentage glucose values in target range (74.5 vs 66.7%, P = .002). Decreasing glucose meter error (bias) was associated with decreased glycemic variability and increased percentage of values in target glucose range for patients placed on intravenous insulin therapy following cardiovascular surgery. © 2015 Diabetes Technology Society.
    No preview · Article · Aug 2015 · Journal of diabetes science and technology
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    ABSTRACT: Recent reports have suggested an association between variation in the serotonin transporter and primary pulmonary hypertension and myocardial infarction. We set out to determine whether these associations were present in a population of patients who underwent SLC6A4 genotyping and to explore whether genetic variation in the serotonin transporter might be also associated with other cardiovascular functional and structural abnormalities. Included were 3473 patients who were genotyped for the SLC6A4 5HTTLPR polymorphism and a subset for rs25531 (n=816) and STin2 (n=819). An association was observed between 5HTTLPR and primary pulmonary hypertension (p=0.0130), anomalies of the cerebrovascular system (p<0.0001), and other anomalies of great veins (p=0.0359). The combined 5HTTLPR and rs25531 genotype was associated with tachycardia (p=0.0123). There was an association of the STin2 genotype with abnormal electrocardiogram (ECG) (p=0.0366) and abnormal cardiac study (0.0311). Overall, these results represent a step toward the understanding of the impact of SLC6A4 variation on cardiovascular pathology.
    No preview · Article · Feb 2015 · Genetic Testing and Molecular Biomarkers
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    ABSTRACT: Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare clinical syndrome associated with significant mortality. Although the use of plasma exchange (PE) in TA-TMA continues to be explored, evidence for its efficacy is debated. We performed a single institution, retrospective study to evaluate the efficacy of PE in treating TA-TMA patients. Special attention was given to efficacy in relation to the timing of presentation with TA-TMA since transplant. Thirty-three patients diagnosed with TA-TMA and treated with PE between January 1999 and December 2010 were included in the study. Clinical improvement was seen in eight patients (24%); four patients achieved complete resolution while the remaining four achieved partial resolution. All-cause day-30 and day-100 mortality was 33 and 55%, respectively. There was a trend toward a better outcome (complete/partial) for those presenting ≥ 100 days after transplantation (42%) vs. < 100 days after transplantation (14%; P-value = 0.15). Similarly, those presenting at ≥ 100 days had better, but not significantly, 30-day and 100-day all-cause mortality rates (17 and 33%, respectively) than those presenting at < 100 days (43 and 67%, respectively) (P-value = 0.25 and 0.08, for 30- and 100-day all-cause mortality, respectively). This is the first study looking at the efficacy of PE while considering the time of presentation since transplantation and is one of the largest single institution series of TA-TMA. The overall efficacy of PE is poor; however, patients who present with TA-TMA ≥100 days after transplant may have better outcome and lower mortality. J. Clin. Apheresis, 2014. © 2014 Wiley Periodicals, Inc.
    No preview · Article · Sep 2014 · Journal of Clinical Apheresis
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    ABSTRACT: Context.- Systems-based practice (SBP) is 1 of 6 core competencies required in all resident training programs accredited by the Accreditation Council for Graduate Medical Education. Reliable methods of assessing resident competency in SBP have not been described in the medical literature. Objective.- To develop and validate an analytic grading rubric to assess pathology residents' analyses of SBP problems in clinical chemistry. Design.- Residents were assigned an SBP project based upon unmet clinical needs in the clinical chemistry laboratories. Using an iterative method, we created an analytic grading rubric based on critical thinking principles. Four faculty raters used the SBP project evaluation rubric to independently grade 11 residents' projects during their clinical chemistry rotations. Interrater reliability and Cronbach α were calculated to determine the reliability and validity of the rubric. Project mean scores and range were also assessed to determine whether the rubric differentiated resident critical thinking skills related to the SBP projects. Results.- Overall project scores ranged from 6.56 to 16.50 out of a possible 20 points. Cronbach α ranged from 0.91 to 0.96, indicating that the 4 rubric categories were internally consistent without significant overlap. Intraclass correlation coefficients ranged from 0.63 to 0.81, indicating moderate to strong interrater reliability. Conclusions.- We report development and statistical analysis of a novel SBP project evaluation rubric. The results indicate the rubric can be used to reliably assess pathology residents' critical thinking skills in SBP.
    Full-text · Article · Jun 2014 · Archives of pathology & laboratory medicine
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    ABSTRACT: Background The cold agglutinin (CAGG) titer is offered at our institution to aid in diagnosing cold agglutinin disease (CAD). Our goal was to create a seasonally adjusted reference range using prospective samples and compare it to a reference range generated retrospectively.Study Design and Methods Prospective CAGG titer testing was performed on healthy blood donors. Retrospective electronic analysis was performed on patients in two groups defined by current and historical testing methods. Blood donor testing was performed in January and July to determine if seasonal variation existed. Retrospective patients with conditions associated with CAD were excluded from analysis. Additional prospective CAGG testing using reference range program volunteers was performed to verify blood donor and patient result differences.ResultsTiters from the blood donor and patient cohorts had no age association (p > 0.44). Titers from those same cohorts did not show winter/summer variation (p > 0.11). No sex association was found with titer reference ranges in the blood donor and historical patient cohort. A sex association was found with titers in the current method patient cohort (male 64 to 512 and female ≤64; p < 0.0001). Blood donor CAGG titer lower 95% reference range was not more than 4 while historical and current patient cohorts ranges were not more than 32 and not more than 64, respectively. Reference range volunteers confirmed the narrow reference range in healthy individuals when compared to patients and blood donors.Conclusion Prospective blood donor CAGG titers were lower than retrospective patient cohorts. This may be due to blood donors representing a healthier population than the patient cohorts.
    No preview · Article · May 2014 · Transfusion
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    ABSTRACT: The use of hematopoietic progenitor cell (HPC) transplant has risen over the past two decades. A variety of adverse events (AEs) of varying severity have been noted during HPC infusions. These AEs have been associated with several factors such as the amount of dimethyl sulfoxide and white blood cells in the HPC product. We performed a single-institution retrospective analysis to determine the effect of two different HPC infusion techniques, manual push with syringes versus infusion from bags with the aid of gravity, on the occurrence of infusion-related AEs. Infusions between December 2008 and November 2010 involving peripheral blood HPCs were reviewed. Pertinent clinical and HPC product-related information was recorded. Data were analyzed to determine the incidence of infusion-related AEs and its association with patient and product-related variables. We found 461 AEs in 645 patients during the study period. A total of 325 (50%) experienced at least one AE. Flushing was the most common type of AE followed by nausea and hypertension. The use of syringe infusion was more commonly associated with AEs (odds ratio, 1.82 [95% confidence interval, 1.32-2.50]; p = 0.002). Other independent risk factors were cryopreserved products and the amount of polymorphonuclear leukocytes in the product. To our knowledge, this is the first study examining the effect of two different infusion techniques on infusion-related AEs. Our findings suggest that the use of bags for infusion protected the patients from AEs.
    No preview · Article · Feb 2014 · Transfusion
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    ABSTRACT: Our facility changed antibody screening methods from a gel microcolumn-based test (ID-Micro Typing System Gel TEst; Ortho Clinical Diagnostics, Inc., Raritan, NJ) to an automated solid-phase test (Galileo/Capture-R Ready Screen [I and II], Immucor, Inc., Norcross, GA). To determine whether detection rates for commonly encountered clinically significant red blood cell antibodies differed as a consequence of this change, preimplementation and postimplementation antibody identification records were retrospectively reviewed. A statistically significant difference in the percentage of positive screening tests during the gel microcolumn testing period (73,903 total screens, 1.56% confirmed positive) versus the solid0-phase screening period (80,242 total screens, 1.81% confirmed positive; p< 0.0002) was observed . The number of antibodies to K identified was significantly lower with solid phase that with gel (27% decrease; p=0.004). It is unknown whether there is a statistical difference in delayed or hemolytic transfusion reaction rates as this was not evaluated.
    No preview · Article · Dec 2013 · Immunohematology / American Red Cross

  • No preview · Article · Nov 2013 · Mitochondrion
  • Z Amini · S Bryant · C Smith · R Singh · Seema Kumar
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    ABSTRACT: Background/aims: Serum 25 hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) levels correlate inversely. The 25(OH)D level at which PTH is maximally suppressed and below which PTH begins to rise (inflection point) has been used to define optimum 25(OH)D levels. While serum 25(OH)D levels are lower in obese individuals, likely due to sequestration of vitamin D in the adipose tissue, it is not known if the lower 25(OH)D levels in obese children are associated with a PTH increase in the same manner as it is in normal weight children. Methods: A retrospective record review of children between 2 and 18 years of age (n = 269) undergoing simultaneous measurement of serum 25(OH)D and PTH levels was performed. Results: The level of serum 25(OH)D below which PTH begins to rise was significantly lower (p < 0.001) in overweight/obese children compared to normal weight children [12.4 (95% CI 9.8-15.0) vs. 17.0 ng/ml (95% CI 11.4-22.6)]. Conclusions: In overweight and obese children, the PTH axis is activated at much lower 25(OH)D levels than in normal weight children. These findings are a consequence of similar ionized calcium levels in these groups despite lower serum 25(OH)D levels in obese children.
    No preview · Article · Sep 2013 · Hormone Research in Paediatrics
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    Full-text · Dataset · Aug 2013
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    Full-text · Dataset · Aug 2013
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    ABSTRACT: Background: Maintaining consistency of results over time is a challenge in laboratory medicine. Lot-to-lot reagent changes are a major threat to consistency of results. Methods: For the period October 2007 through July 2012, we reviewed lot validation data for each new lot of insulin-like growth factor 1 (IGF-1) reagents (Siemens Healthcare Diagnostics) at Mayo Clinic, Rochester, MN, and the University of Virginia, Charlottesville, VA. Analyses of discarded patient samples were used for comparison of lots. For the same period, we determined the distributions of reported patient results for each lot of reagents at the 2 institutions. Results: Lot-to-lot validation studies identified no reagent lot as significantly different from the preceding lot. By contrast, significant lot-to-lot changes were seen in the means and medians of 105 668 reported patient IGF-I results during the period. The frequency of increased results increased nearly 2-fold to a high of 17%, without detectable changes in the underlying patient demographics. Retrospective statistical analysis indicated that lot-to-lot comparison protocols were underpowered and that validation studies for this assay required testing >100 samples to achieve 90% power to detect reagent lots that would significantly alter the distributions of patient results. Conclusions: The number of test samples required for adequate lot-to-lot validation protocols is high and may be prohibitively large, especially for low-volume or complex assays. Monitoring of the distributions of patient results has the potential to detect lot-to-lot inconsistencies relatively quickly. We recommend that manufacturers implement remote monitoring of patient results from analyzers in multiple institutions to allow rapid identification of between-lot result inconsistency.
    Full-text · Article · Apr 2013 · Clinical Chemistry
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    ABSTRACT: Background: The cause of pulmonary necrotizing granulomas is often unclear, even after histologic examination. Our aim was to determine the clinical significance of histologically unexplained necrotizing granulomas. Methods: Pulmonary necrotizing granulomas surgically resected at the Mayo Clinic (1994-2004) were retrieved and reviewed retrospectively. Cases in which a cause was evident at the time of initial histologic examination were excluded. The analysis cohort comprised 131 completely resected histologically unexplained pulmonary necrotizing granulomas. Clinical and laboratory information was abstracted from medical records, chest CT scans were reviewed, histologic slides were reexamined, and additional ancillary studies were performed in selected cases. Results: A cause was determined on review in more than one-half of the histologically unexplained necrotizing granulomas (79 of 131, 60%) by reexamining histologic slides (47), incorporating the results of cultures (26), fungal serologies (14), and other laboratory studies (eight), and correlating histologic findings with clinical and radiologic information (13). Infections accounted for the majority (64 of 79), the most common being histoplasmosis (37) and nontuberculous mycobacterial infections (18). Noninfectious diagnoses (15 of 79) were rheumatoid nodule (five), granulomatosis with polyangiitis (Wegener) (five), sarcoidosis (four), and chronic granulomatous disease (one). Many cases remained unexplained even after extensive review (52 of 131, 40%). Most of these patients received no medical therapy and did not progress clinically or develop new nodules (median follow-up, 84 months). Conclusions: A cause, the most common being infection, can be established in many surgically resected pulmonary necrotizing granulomas that appear unexplained at the time of initial histologic diagnosis. Patients whose granulomas remain unexplained after a rigorous review have a favorable outcome. Most do not develop new nodules or progress clinically, even without medical therapy.
    No preview · Article · Apr 2013 · Chest
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    ABSTRACT: Background: Variability of response to statins has been related to polymorphisms in genes involved in cholesterol homeostasis and statin metabolism, such as CYP3A4 and CYP3A5. We investigated the effects of atorvastatin on CYP3A4 and CYP3A5 mRNA expression in mononuclear cells and on CYP3A activity and their interactions with common variants. Methods: Unrelated individuals (n=121) with hypercholesterolemia (HC) were treated with atorvastatin (10 mg/day/4 weeks). Ninety-two normolipidemic (NL) subjects were selected as a control group. Genotype analysis of CYP3A4*1B (rs2740574), CYP3A4*22 (rs35599367), CYP3A5*3C (rs776746), and CYP3A5*1D (rs15524) and mRNA levels in peripheral blood mononuclear cells (PBMCs) were estimated. CYP3A activity was phenotyped by the urinary cortisol to 6-beta-hydroxy-cortisol ratio. Results: LDL cholesterol reduction in response to atorvastatin was positively correlated with change in CYP3A4 (R(2)=0.039, p=0.037) and CYP3A5 (R(2)=0.047, p=0.019) mRNA levels and negatively correlated with CYP3A activity (R(2)=0.071, p=0.022). CYP3A5*3C (AGT haplotype) was associated to lower basal CYP3A5 mRNA expression in HC (p<0.045), however none of the haplotype groups impacted treatment. Conclusion: It is likely that cholesterolemia status changes promoted by atorvastatin play a role in regulating CYP3A4 and CYP3A5 mRNA expression in PBMCs, as well as CYP3A activity. CYP3A5*3C (AGT haplotype) also contributes for the variability of CYP3A5 mRNA levels in PBMCs.
    Full-text · Article · Mar 2013 · Clinica chimica acta; international journal of clinical chemistry
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    Preview · Article · Feb 2013 · Biology of Blood and Marrow Transplantation
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    ABSTRACT: BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) protein is a promising biomarker to detect acute kidney injury (AKI). Earlier detection of AKI could facilitate evaluation of novel therapeutic strategies.METHODS: Random and 24-h urine samples were prospectively obtained from 125 normal volunteers for analytic validation of a urinary enzyme-linked immunosorbent assay for NGAL. For clinical validation of the test, urine from 363 emergency department patients admitted to the hospital was obtained for NGAL enzyme-linked immunosorbent assay and urinalysis and AKI was determined by the use of Acute Kidney Injury Network (AKIN) criteria.RESULTS: NGAL was stable in urine for 7 days when ambient, 4°C or frozen (-20 or -70°C). The assay was linear between 0.24 and10 000 ng/mL with a limit of quantitation of 0.24 ng/mL. Intra- and inter-assay precision were excellent (coefficient of variation <5%); however, urinary white blood cells were associated with increased NGAL levels. The 95th percentile reference value for NGAL in females is ≤65.0 and ≤23.4 ng/mL in males. Urinary NGAL levels increased with AKI stage but had only fair sensitivity (65%) and specificity (65%) to differentiate no AKI versus Stages 1, 2 or 3 (area under the curve 0.70). Urinalysis with microscopy was very specific (91%) but not very sensitive (22%) with an area under the curve of 0.57.CONCLUSIONS: NGAL can be reliably measured in clinical urine samples, although pyuria is an important potential confounder. In our cohort, increased urinary NGAL was associated with AKI by the AKIN criteria; however, the sensitivity and specificity were only fair, in part because patients with pre-renal causes are not excluded by AKIN criteria. Conversely, findings on microscopic urinalysis are very specific for AKI.
    Preview · Article · Apr 2012 · Nephrology Dialysis Transplantation
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    ABSTRACT: Late-night salivary cortisol (LNSC) measurements have been increasingly used by physicians as an initial diagnostic test for evaluation of patients with clinical suspicion of Cushing's syndrome (CS). Published studies include various numbers of cases, controls and importantly, various assay methods (vast majority various immunoassays), as well as various methods to generate cut-points. The retrospective study evaluated the diagnostic utility of LNSC measurements in 249 patients evaluated for possibility of CS because of various clinical conditions using liquid chromatography/tandem mass spectrometry method (LC-MS/MS). CS was confirmed in 47 patients (18·9%) and excluded in 202 (81·1%) patients at the time of analysis. Late-night salivary cortisol was abnormal or >2·8 nmol/l in 35 of 47 patients with CS; sensitivity of 74·5% and elevated in 20 of 202 patients who were found not to have CS; specificity 90·1%. Using receiver-operator characteristic statistics for calculation of the most optimal sensitivity and specificity, the cut-off based on this data was LNSC > 2·1 nmol/l with sensitivity of 83·0% and specificity of 84·2%. Analysis of data at one referral institution showed somewhat limited sensitivity of LNSC for diagnosis of CS using current reference ranges.
    No preview · Article · Sep 2011 · Clinical Endocrinology

  • No preview · Article · Sep 2011 · Transfusion
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    ABSTRACT: To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort. Cumulative percentiles of amino acids and acylcarnitines in dried blood spots of approximately 25–30 million normal newborns and 10,742 deidentified true positive cases are compared to assign clinical significance, which is achieved when the median of a disorder range is, and usually markedly outside, either the 99th or the 1st percentile of the normal population. The cutoff target ranges of analytes and ratios are then defined as the interval between selected percentiles of the two populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity taking all available factors into consideration. As of December 1, 2010, 130 sites in 45 countries have uploaded a total of 25,114 percentile data points, 565,232 analyte results of true positive cases with 64 conditions, and 5,341 cutoff values. The average rate of submission of true positive cases between December 1, 2008, and December 1, 2010, was 5.1 cases/day. This cumulative evidence generated 91 high and 23 low cutoff target ranges. The overall proportion of cutoff values within the respective target range was 42% (2,269/5,341). An unprecedented level of cooperation and collaboration has allowed the objective definition of cutoff target ranges for 114 markers to be applied to newborn screening of rare metabolic disorders.
    Full-text · Article · Feb 2011 · Genetics in medicine: official journal of the American College of Medical Genetics

Publication Stats

3k Citations
448.34 Total Impact Points


  • 1992-2015
    • Mayo Clinic - Rochester
      • • Department of Hematology
      • • Department of Laboratory Medicine & Pathology
      • • Department of Gastroenterology and Hepatology
      • • Department of Health Science Research
      • • Department of Endocrinology, Diabetes, Metabolism and Nutrition
      • • Department of Urology
      Рочестер, Minnesota, United States
  • 2010
    • The University of Chicago Medical Center
      Chicago, Illinois, United States
  • 2007
    • McMaster University
      Hamilton, Ontario, Canada
  • 2001
    • CUNY Graduate Center
      New York, New York, United States