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Papers by Darci Block

Research paper thumbnail of Biological Variability of Small Dense LDL, HDL3, and Triglyceride-Rich Lipoprotein Cholesterol

American Journal of Clinical Pathology, 2021

The guideline-recommended lipid panel for cardiovascular disease (CVD) risk assessment measures t... more The guideline-recommended lipid panel for cardiovascular disease (CVD) risk assessment measures total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and calculated low-density lipoprotein (LDL) cholesterol. Measured cholesterol in subfractions of HDL and LDL purportedly improve CVD risk prediction. Homogenous enzymatic methods are now available for measurement of the cholesterol within small dense LDL (sLDL), small dense HDL (HDL3), and triglyceride-rich lipoproteins (TRL). For meaningful interpretation of these measurements, an understanding of the potential sources and extent of result variability is needed. The smallest difference between serial measurements within a patient that likely reflects a change in clinical status is called the reference change value (RCV). Biological variability and reference change values (RCV) are well-characterized for basic lipids but there is limited information for sLDL, HDL3 or TRL. The objective of this study was to dete...

Research paper thumbnail of 45 Human Chorionic Gonadotropin (hCG) Heterophile Interference Investigations: Experience from a Referral Laboratory

American Journal of Clinical Pathology, 2018

Research paper thumbnail of Biological variability of lipoprotein-associated phospholipase A2 activity in healthy individuals

Clinical biochemistry, Jan 25, 2016

Measuring lipoprotein-associated phospholipase A2 (Lp-PLA2) activity can aid in identifying indiv... more Measuring lipoprotein-associated phospholipase A2 (Lp-PLA2) activity can aid in identifying individuals at higher risk of coronary heart disease. However, the biological variation of Lp-PLA2 activity and corresponding reference change value (RCV) is unknown which limits interpretation of results. In this study we aim to define the intra- and inter-individual variability of Lp-PLA2 activity in a healthy reference population. A total of 24 healthy individuals (22-47years of age) were prospectively collected at several time points: daily for five days (after overnight fast), daily for three days (while non-fasting), weekly for four weeks (after overnight fast), and monthly for 6months (after overnight fast). Intra-individual and inter-individual variability was determined. The index of individuality (IoI) and reference change value (RCV) were calculated for each time period. Variability in Lp-PLA2 activity was not different in fasting versus non-fasting states and also did not change i...

Research paper thumbnail of Implementation of Clinical Decision Support Rules to Reduce Repeat Measurement of Serum Ionized Calcium, Serum Magnesium, and N-Terminal Pro-B-Type Natriuretic Peptide in Intensive Care Unit Inpatients

Clinical chemistry, 2016

We assessed the impact of clinical decision support (CDS) rules within the electronic health reco... more We assessed the impact of clinical decision support (CDS) rules within the electronic health record for ionized calcium (iCa), serum magnesium (Mg), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in intensive care unit (ICU) inpatients at a large academic center. A repeat order for measurement of iCa or Mg placed within 24 (iCa) or 48 (Mg) h of a previously nonactionable result, or additional orders for NT-proBNP beyond 1 within a single hospitalization, triggered a CDS pop-up alert showing the prior result and offering the opportunity to cancel the order or to place the order after entering an indication for repeat testing. The number of tests performed for each of these analytes and incidence of adverse clinical outcomes potentially associated with hypocalcemia or hypomagnesemia were compared between the 90-day period before CDS implementation and two 90-day periods immediately following. iCa test volumes decreased by 48%, Mg by 39%, and NT-proBNP by 28% in the 90-day p...

Research paper thumbnail of Lymphocyte Subset Quantitation by Flow Cytometry: Analytical Insights for the Clinical Laboratory

American Journal of Clinical Pathology

Research paper thumbnail of Utility of Immature Granulocytes for the Prediction of Septic Shock

American Journal of Clinical Pathology

Research paper thumbnail of Body fluid analysis: Clinical utility and applicability of published studies to guide interpretation of today’s laboratory testing in serous fluids

Critical Reviews in Clinical Laboratory Sciences, 2013

Requests for testing various analytes in serous fluids (e.g., pleural, peritoneal, pericardial ef... more Requests for testing various analytes in serous fluids (e.g., pleural, peritoneal, pericardial effusions) are submitted daily to clinical laboratories. Testing of these fluids deviates from assay manufacturers' specifications, as most laboratory assays are optimized for testing blood or urine specimens. These requests add a burden to clinical laboratories, which need to validate assay performance characteristics in these fluids to exclude matrix interferences (given the different composition of body fluids) while maintaining regulatory compliance. Body fluid testing for a number of analytes has been reported in the literature; however, understanding the clinical utility of these analytes is critical because laboratories must address the analytic and clinical validation requirements, while educating clinicians on proper test utilization. In this article, we review the published data to evaluate the clinical utility of testing for numerous analytes in body fluid specimens. We also highlight the pre-analytic and analytic variables that need to be considered when reviewing published studies in body fluid testing. Finally, we provide guidance on how published studies might (or might not) guide interpretation of test results in today's clinical laboratories.

Research paper thumbnail of A Case of Floating Gel

Clinical Chemistry, 2012

Two unrelated patients underwent coronary angiography and a percutaneous intervention. At the end... more Two unrelated patients underwent coronary angiography and a percutaneous intervention. At the end of the procedures, blood was collected (Vacutainer® SST™; BD) for troponin, creatine kinase (CK), and CK-MB isoenzyme analysis. After centrifugation with the Roche Modular Pre-Analytics system (Roche Diagnostics), pipetting error alerts were triggered on the aliquoting module of the Pre-Analytics system. Investigation revealed that the separator gel had migrated above the serum (Fig. 1A), preventing separation of the serum from the cells (Fig. 1B). A second collection obtained from each patient 2 h later manifested proper gel separation, and error-free measurements were accomplished.

Research paper thumbnail of Clinical Laboratory Informatics and Analytics: Challenges and Opportunities

Research paper thumbnail of The Biological Variability of Plasma Ceramides in Healthy Subjects

The Journal of Applied Laboratory Medicine, 2022

BackgroundCeramides are bioactive lipid species that mediate numerous cell-signaling events. Elev... more BackgroundCeramides are bioactive lipid species that mediate numerous cell-signaling events. Elevated plasma ceramides concentration constitutes a risk factor for several pathologies. Multiple studies have affirmed the plasma concentrations of 4 specific ceramides (Cer16:0, Cer18:0, Cer24:0, and Cer24:1) can predict cardiovascular disease risk. Furthermore, these ceramides can be altered by many lipid-lowering therapies. Understanding the biological variability within an individual, and within a population, will further inform the clinical use of plasma ceramides as a biomarker. In this study, we aimed to define the intra- and interbiological variability of ceramides in a healthy reference population in a weekly and monthly manner.MethodsFasting plasma from 24 healthy adults was collected daily (5 days), weekly (4 weeks), and monthly (7 months). Ceramide concentrations were measured with liquid chromatography–mass spectrometry (LC–MS). For analysis, we used random-effects regression...

Research paper thumbnail of Investigation of the correlation between immature reticulocyte fraction and reticulocyte hemoglobin content with common tests for iron deficiency anemia

American Journal of Clinical Pathology, 2021

Reticulocyte hemoglobin content (Ret-He, the hemoglobin within reticulocytes or immature red bloo... more Reticulocyte hemoglobin content (Ret-He, the hemoglobin within reticulocytes or immature red blood cells) and immature reticulocyte fraction (IRF, the immature fraction of the absolute-reticulocyte-count) are tests that provide insight into erythropoiesis and iron status earlier than conventional iron studies offering the added benefit of not being acute-phase-reactants. Studies have shown that Ret-He is a diagnostic marker for iron-deficiency-anemia (IDA), but fewer studies have investigated IRF. Our laboratory is currently planning to report these parameters when reticulocyte is ordered. Since these are new parameters, we wanted to investigate their overall correlation with complete blood count (CBC) and other iron studies to gain a better appreciation of their utility in our patient population. The aim of this study was to compare the overall correlation of Ret-He and IRF with seven tests used in the evaluation of IDA. To our knowledge these parameters have not all been directly ...

Research paper thumbnail of Diagnostic body fluid testing

Body fluid testing is often requested by clinicians to help evaluate abnormal fluid collections a... more Body fluid testing is often requested by clinicians to help evaluate abnormal fluid collections and to establish or narrow suspected clinical diagnoses. This chapter aims to provide background around the regulations regarding body fluid testing and guidance for laboratories performing analytical validation of body fluid assays. Common body fluids are then discussed, including an introduction to the anatomy and pathophysiology for those body fluids frequently encountered in the clinical chemistry laboratories. Clinical presentation, symptomatology, differential diagnosis, and diagnostic approach through analysis of each body fluid are also reviewed.

Research paper thumbnail of Synovial fluid α defensin has comparable accuracy to synovial fluid white blood cell count and polymorphonuclear percentage for periprosthetic joint infection diagnosis

The Bone & Joint Journal, 2021

Aims The aim of this study was to determine the diagnostic accuracy of α defensin (AD) lateral fl... more Aims The aim of this study was to determine the diagnostic accuracy of α defensin (AD) lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) tests for periprosthetic joint infection (PJI) in comparison to conventional synovial white blood cell (WBC) count and polymorphonuclear neutrophil percentage (PMN%) analysis. Methods Patients undergoing joint aspiration for evaluation of pain after total knee arthroplasty (TKA) or total hip arthroplasty (THA) were considered for inclusion. Synovial fluids from 99 patients (25 THA and 74 TKA) were analyzed by WBC count and PMN% analysis, AD LFA, and AD ELISA. WBC and PMN% cutoffs of ≥ 1,700 cells/mm3 and ≥ 65% for TKA and ≥ 3,000 cells/mm3 and ≥ 80% for THA were used, respectively. A panel of three physicians, all with expertise in orthopaedic infections and who were blinded to the results of AD tests, independently reviewed patient data to diagnose subjects as with or without PJI. Consensus PJI classification was used as the r...

Research paper thumbnail of COVID-19 Mortality Prediction From Deep Learning in a Large Multistate Electronic Health Record and Laboratory Information System Data Set: Algorithm Development and Validation

Journal of Medical Internet Research, 2021

Background COVID-19 is caused by the SARS-CoV-2 virus and has strikingly heterogeneous clinical m... more Background COVID-19 is caused by the SARS-CoV-2 virus and has strikingly heterogeneous clinical manifestations, with most individuals contracting mild disease but a substantial minority experiencing fulminant cardiopulmonary symptoms or death. The clinical covariates and the laboratory tests performed on a patient provide robust statistics to guide clinical treatment. Deep learning approaches on a data set of this nature enable patient stratification and provide methods to guide clinical treatment. Objective Here, we report on the development and prospective validation of a state-of-the-art machine learning model to provide mortality prediction shortly after confirmation of SARS-CoV-2 infection in the Mayo Clinic patient population. Methods We retrospectively constructed one of the largest reported and most geographically diverse laboratory information system and electronic health record of COVID-19 data sets in the published literature, which included 11,807 patients residing in 41...

Research paper thumbnail of Comparative analysis of 23 synovial fluid biomarkers for hip and knee periprosthetic joint infection detection

Journal of Orthopaedic Research, 2020

There is interest in novel synovial fluid biomarkers for detection of periprosthetic joint infect... more There is interest in novel synovial fluid biomarkers for detection of periprosthetic joint infection (PJI). Here, we assessed the diagnostic accuracy of 23 simple or sophisticated synovial fluid biomarkers for prosthetic hip or knee infection detection. 107 subjects were studied, 57 of whom had aseptic failure (AF) and 50 PJI. The following synovial fluid biomarkers were tested using spectrophotometric assays, immunoassays, lateral flow tests, or test strips: Leukocyte count, monocyte percentage, lymphocyte

Research paper thumbnail of Managing Spectral Interferences Using Optical Coagulation Methods

American Journal of Clinical Pathology, 2018

Research paper thumbnail of Clinical Validation of Fecal Electrolytes for Chronic Diarrhea

American Journal of Clinical Pathology, 2018

Introduction: Fecal electrolytes are measured to help narrow the differential diagnosis for chron... more Introduction: Fecal electrolytes are measured to help narrow the differential diagnosis for chronic diarrhea, defined as symptoms lasting more than 4 weeks. Our laboratory offers a comprehensive panel that includes measurement of chloride, magnesium, osmolality, phosphorous, sodium, and calculated osmotic gap (OG) using published interpretive information for identifying osmotic (OG >50 mmol/L), secretory (OG <50 mmol/L), and magnesium-induced (Mg >110 mg/dL) diarrhea. The objective of this study was to determine the diagnostic accuracy of calculated osmotic gap and magnesium in our patient population to optimize the testing algorithm. Methods: Fecal electrolyte results between August 7, 2013, and December 22, 2017, were extracted from the electronic medical record for 435 unique patients (male = 153, female = 282, mean age = 57) at Mayo Clinic Rochester, MN. Random liquid fecal specimens submitted for testing were centrifuged for 1 hour at 14,000 rpm, transferred to a new tube, stored refrigerated, and tested in daily batches. Electrolytes were measured using Roche Cobas c501 (Roche Diagnostics, Indianapolis, IN). Osmotic gap was calculated as 290 mOsm/kg-(2[Na] + 2[K]). Chart review was conducted to document the cause of diarrhea and medications containing magnesium and other laxatives. Receiver operator curve (ROC) analysis with area under the curve (AUC) was calculated using AnalyzeIT (Microsoft Excel). This study was conducted with Mayo Clinic IRB approval. Results: Chronic diarrhea was classified as osmotic (n = 27), secretory (n = 107), inflammatory (n = 85), steatorrhea (n = 14), and of unknown etiology (n = 202). The prevalence of magnesium-induced diarrhea in our population was only 1.4%. OG differentiates osmotic from nonosmotic causes of diarrhea with an AUC of 0.866, having an optimal decision limit for OG >82 mOsm/kg, sensitivity = 83%, and specificity = 83%. OG differentiates secretory from nonsecretory causes of diarrhea with an AUC of 0.545. A decision limit with sensitivity = 50% is <22 mOsm/kg and has specificity = 37%, while the OG having sensitivity = 95% is <-30mOsm/kg and specificity = 11%. Mean (±SD) results of magnesium were significantly higher in osmotic = 70 (±64) mg/dL than in secretory = 35 (±35) mg/dL, inflammatory = 26 (±25) mg/ dL, and steatorrhea = 25 (±28) mg/dL causes (P ≤ .001, ≤.0001, ≤.05, respectively). The AUC for elevated magnesium in patients reporting Mg-containing medication use was 0.579. The optimal decision limit is Mg >106 mg/dL, having sensitivity = 15% and specificity = 97%. Mg was >106 mg/dL in 3.3% of those tested, resulting in a negative predictive value (NPV) = 98.8%. With one exception,

Research paper thumbnail of Proposed Plasma Ammonia Reference Intervals in a Reference Group of Hospitalized Term and Preterm Neonates

The Journal of Applied Laboratory Medicine, 2020

BackgroundPlasma ammonia is commonly measured in the diagnostic evaluation of hospitalized newbor... more BackgroundPlasma ammonia is commonly measured in the diagnostic evaluation of hospitalized newborns, but reference values are not well defined.MethodsWe prospectively enrolled newborns admitted to the level III/IV neonatal intensive care unit and level II intermediate special care nursery from January 2017 to January 2018. Infants with inborn errors of metabolism or liver disease were excluded. Plasma ammonia concentrations were measured once within the first week of life and evaluated by sex, gestational age, timing of the draw, blood collection method, and type of nutrition. Reference intervals were calculated.Results127 neonates were included; one third (34%) were term infants born at ≥37 weeks gestation, and two thirds (66%) were born preterm at <37 weeks gestation. Median plasma ammonia concentrations were 32 μmol/L (range <10 to 86 μmol/L). Median ammonia concentrations were higher among preterm compared to term infants (35 vs. 28 μmol/L, p = 0.0119), and term female com...

Research paper thumbnail of Laboratory Utilization and Analytical Validation of Fecal Electrolyte Tests

The Journal of Applied Laboratory Medicine, 2017

Background Chronic diarrhea can be categorized as fatty, watery, or inflammatory. Watery diarrhea... more Background Chronic diarrhea can be categorized as fatty, watery, or inflammatory. Watery diarrhea is further divided into secretory or osmotic types and can be differentiated by measuring fecal electrolytes and osmotic gap. However, with widespread use of endoscopy, it is unclear if these measurements are being used clinically. Furthermore, because stool is not a validated specimen type for Food and Drug Administration–approved electrolyte assays, utilization is a practical concern for laboratories before analytical validation. Here, we determined the clinical utility and validated the performance characteristics of stool electrolytes on the Beckman Coulter AU680. Methods Historical results and literature review were used to determine the clinically relevant ranges for stool electrolytes (Na+, Cl−, K+, phosphate, and Mg2+). Additionally, medical chart review was performed (n = 44 patients) on results to evaluate their clinical utility in chronic diarrhea work-up. Linearity, precisio...

Research paper thumbnail of Analytical Evaluation of BioRad D-100 HPLC Analyzer and Workflow Comparison to BioRad TurboLink Variant II HPLC With Reflex to Boronate Affinity

American Journal of Clinical Pathology, 2019

Introduction Measurement of hemoglobin A1c (HbA1C) is used for the diagnosis and management of pa... more Introduction Measurement of hemoglobin A1c (HbA1C) is used for the diagnosis and management of patients with diabetes. Methods for measuring HbA1C are classified on the basis of charge differences (cation exchange chromatography) or structural differences (boronate affinity chromatography). Some cation exchange high-performance liquid chromatography (HPLC) analyzers may be prone to interferences from hemoglobin variants. Historically, our lab used two methods to report HbA1C results: cation exchange HPLC (VariantII) with reflex to boronate affinity HPLC (Ultra2) methods. A new analyzer (BioRad D-100) with improved interference detection and thresholds for interference was evaluated. The objectives of this study were (1) assess the comparability of HbA1c results between D-100, VariantII, and Ultra2; (2) evaluate the need for maintaining a reflex method; and (3) calculate cancellation rates before and after implementing D-100. Methods HbA1c was measured by cation exchange methods usin...

Research paper thumbnail of Biological Variability of Small Dense LDL, HDL3, and Triglyceride-Rich Lipoprotein Cholesterol

American Journal of Clinical Pathology, 2021

The guideline-recommended lipid panel for cardiovascular disease (CVD) risk assessment measures t... more The guideline-recommended lipid panel for cardiovascular disease (CVD) risk assessment measures total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and calculated low-density lipoprotein (LDL) cholesterol. Measured cholesterol in subfractions of HDL and LDL purportedly improve CVD risk prediction. Homogenous enzymatic methods are now available for measurement of the cholesterol within small dense LDL (sLDL), small dense HDL (HDL3), and triglyceride-rich lipoproteins (TRL). For meaningful interpretation of these measurements, an understanding of the potential sources and extent of result variability is needed. The smallest difference between serial measurements within a patient that likely reflects a change in clinical status is called the reference change value (RCV). Biological variability and reference change values (RCV) are well-characterized for basic lipids but there is limited information for sLDL, HDL3 or TRL. The objective of this study was to dete...

Research paper thumbnail of 45 Human Chorionic Gonadotropin (hCG) Heterophile Interference Investigations: Experience from a Referral Laboratory

American Journal of Clinical Pathology, 2018

Research paper thumbnail of Biological variability of lipoprotein-associated phospholipase A2 activity in healthy individuals

Clinical biochemistry, Jan 25, 2016

Measuring lipoprotein-associated phospholipase A2 (Lp-PLA2) activity can aid in identifying indiv... more Measuring lipoprotein-associated phospholipase A2 (Lp-PLA2) activity can aid in identifying individuals at higher risk of coronary heart disease. However, the biological variation of Lp-PLA2 activity and corresponding reference change value (RCV) is unknown which limits interpretation of results. In this study we aim to define the intra- and inter-individual variability of Lp-PLA2 activity in a healthy reference population. A total of 24 healthy individuals (22-47years of age) were prospectively collected at several time points: daily for five days (after overnight fast), daily for three days (while non-fasting), weekly for four weeks (after overnight fast), and monthly for 6months (after overnight fast). Intra-individual and inter-individual variability was determined. The index of individuality (IoI) and reference change value (RCV) were calculated for each time period. Variability in Lp-PLA2 activity was not different in fasting versus non-fasting states and also did not change i...

Research paper thumbnail of Implementation of Clinical Decision Support Rules to Reduce Repeat Measurement of Serum Ionized Calcium, Serum Magnesium, and N-Terminal Pro-B-Type Natriuretic Peptide in Intensive Care Unit Inpatients

Clinical chemistry, 2016

We assessed the impact of clinical decision support (CDS) rules within the electronic health reco... more We assessed the impact of clinical decision support (CDS) rules within the electronic health record for ionized calcium (iCa), serum magnesium (Mg), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in intensive care unit (ICU) inpatients at a large academic center. A repeat order for measurement of iCa or Mg placed within 24 (iCa) or 48 (Mg) h of a previously nonactionable result, or additional orders for NT-proBNP beyond 1 within a single hospitalization, triggered a CDS pop-up alert showing the prior result and offering the opportunity to cancel the order or to place the order after entering an indication for repeat testing. The number of tests performed for each of these analytes and incidence of adverse clinical outcomes potentially associated with hypocalcemia or hypomagnesemia were compared between the 90-day period before CDS implementation and two 90-day periods immediately following. iCa test volumes decreased by 48%, Mg by 39%, and NT-proBNP by 28% in the 90-day p...

Research paper thumbnail of Lymphocyte Subset Quantitation by Flow Cytometry: Analytical Insights for the Clinical Laboratory

American Journal of Clinical Pathology

Research paper thumbnail of Utility of Immature Granulocytes for the Prediction of Septic Shock

American Journal of Clinical Pathology

Research paper thumbnail of Body fluid analysis: Clinical utility and applicability of published studies to guide interpretation of today’s laboratory testing in serous fluids

Critical Reviews in Clinical Laboratory Sciences, 2013

Requests for testing various analytes in serous fluids (e.g., pleural, peritoneal, pericardial ef... more Requests for testing various analytes in serous fluids (e.g., pleural, peritoneal, pericardial effusions) are submitted daily to clinical laboratories. Testing of these fluids deviates from assay manufacturers&amp;amp;amp;amp;amp;amp;#39; specifications, as most laboratory assays are optimized for testing blood or urine specimens. These requests add a burden to clinical laboratories, which need to validate assay performance characteristics in these fluids to exclude matrix interferences (given the different composition of body fluids) while maintaining regulatory compliance. Body fluid testing for a number of analytes has been reported in the literature; however, understanding the clinical utility of these analytes is critical because laboratories must address the analytic and clinical validation requirements, while educating clinicians on proper test utilization. In this article, we review the published data to evaluate the clinical utility of testing for numerous analytes in body fluid specimens. We also highlight the pre-analytic and analytic variables that need to be considered when reviewing published studies in body fluid testing. Finally, we provide guidance on how published studies might (or might not) guide interpretation of test results in today&amp;amp;amp;amp;amp;amp;#39;s clinical laboratories.

Research paper thumbnail of A Case of Floating Gel

Clinical Chemistry, 2012

Two unrelated patients underwent coronary angiography and a percutaneous intervention. At the end... more Two unrelated patients underwent coronary angiography and a percutaneous intervention. At the end of the procedures, blood was collected (Vacutainer® SST™; BD) for troponin, creatine kinase (CK), and CK-MB isoenzyme analysis. After centrifugation with the Roche Modular Pre-Analytics system (Roche Diagnostics), pipetting error alerts were triggered on the aliquoting module of the Pre-Analytics system. Investigation revealed that the separator gel had migrated above the serum (Fig. 1A), preventing separation of the serum from the cells (Fig. 1B). A second collection obtained from each patient 2 h later manifested proper gel separation, and error-free measurements were accomplished.

Research paper thumbnail of Clinical Laboratory Informatics and Analytics: Challenges and Opportunities

Research paper thumbnail of The Biological Variability of Plasma Ceramides in Healthy Subjects

The Journal of Applied Laboratory Medicine, 2022

BackgroundCeramides are bioactive lipid species that mediate numerous cell-signaling events. Elev... more BackgroundCeramides are bioactive lipid species that mediate numerous cell-signaling events. Elevated plasma ceramides concentration constitutes a risk factor for several pathologies. Multiple studies have affirmed the plasma concentrations of 4 specific ceramides (Cer16:0, Cer18:0, Cer24:0, and Cer24:1) can predict cardiovascular disease risk. Furthermore, these ceramides can be altered by many lipid-lowering therapies. Understanding the biological variability within an individual, and within a population, will further inform the clinical use of plasma ceramides as a biomarker. In this study, we aimed to define the intra- and interbiological variability of ceramides in a healthy reference population in a weekly and monthly manner.MethodsFasting plasma from 24 healthy adults was collected daily (5 days), weekly (4 weeks), and monthly (7 months). Ceramide concentrations were measured with liquid chromatography–mass spectrometry (LC–MS). For analysis, we used random-effects regression...

Research paper thumbnail of Investigation of the correlation between immature reticulocyte fraction and reticulocyte hemoglobin content with common tests for iron deficiency anemia

American Journal of Clinical Pathology, 2021

Reticulocyte hemoglobin content (Ret-He, the hemoglobin within reticulocytes or immature red bloo... more Reticulocyte hemoglobin content (Ret-He, the hemoglobin within reticulocytes or immature red blood cells) and immature reticulocyte fraction (IRF, the immature fraction of the absolute-reticulocyte-count) are tests that provide insight into erythropoiesis and iron status earlier than conventional iron studies offering the added benefit of not being acute-phase-reactants. Studies have shown that Ret-He is a diagnostic marker for iron-deficiency-anemia (IDA), but fewer studies have investigated IRF. Our laboratory is currently planning to report these parameters when reticulocyte is ordered. Since these are new parameters, we wanted to investigate their overall correlation with complete blood count (CBC) and other iron studies to gain a better appreciation of their utility in our patient population. The aim of this study was to compare the overall correlation of Ret-He and IRF with seven tests used in the evaluation of IDA. To our knowledge these parameters have not all been directly ...

Research paper thumbnail of Diagnostic body fluid testing

Body fluid testing is often requested by clinicians to help evaluate abnormal fluid collections a... more Body fluid testing is often requested by clinicians to help evaluate abnormal fluid collections and to establish or narrow suspected clinical diagnoses. This chapter aims to provide background around the regulations regarding body fluid testing and guidance for laboratories performing analytical validation of body fluid assays. Common body fluids are then discussed, including an introduction to the anatomy and pathophysiology for those body fluids frequently encountered in the clinical chemistry laboratories. Clinical presentation, symptomatology, differential diagnosis, and diagnostic approach through analysis of each body fluid are also reviewed.

Research paper thumbnail of Synovial fluid α defensin has comparable accuracy to synovial fluid white blood cell count and polymorphonuclear percentage for periprosthetic joint infection diagnosis

The Bone & Joint Journal, 2021

Aims The aim of this study was to determine the diagnostic accuracy of α defensin (AD) lateral fl... more Aims The aim of this study was to determine the diagnostic accuracy of α defensin (AD) lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) tests for periprosthetic joint infection (PJI) in comparison to conventional synovial white blood cell (WBC) count and polymorphonuclear neutrophil percentage (PMN%) analysis. Methods Patients undergoing joint aspiration for evaluation of pain after total knee arthroplasty (TKA) or total hip arthroplasty (THA) were considered for inclusion. Synovial fluids from 99 patients (25 THA and 74 TKA) were analyzed by WBC count and PMN% analysis, AD LFA, and AD ELISA. WBC and PMN% cutoffs of ≥ 1,700 cells/mm3 and ≥ 65% for TKA and ≥ 3,000 cells/mm3 and ≥ 80% for THA were used, respectively. A panel of three physicians, all with expertise in orthopaedic infections and who were blinded to the results of AD tests, independently reviewed patient data to diagnose subjects as with or without PJI. Consensus PJI classification was used as the r...

Research paper thumbnail of COVID-19 Mortality Prediction From Deep Learning in a Large Multistate Electronic Health Record and Laboratory Information System Data Set: Algorithm Development and Validation

Journal of Medical Internet Research, 2021

Background COVID-19 is caused by the SARS-CoV-2 virus and has strikingly heterogeneous clinical m... more Background COVID-19 is caused by the SARS-CoV-2 virus and has strikingly heterogeneous clinical manifestations, with most individuals contracting mild disease but a substantial minority experiencing fulminant cardiopulmonary symptoms or death. The clinical covariates and the laboratory tests performed on a patient provide robust statistics to guide clinical treatment. Deep learning approaches on a data set of this nature enable patient stratification and provide methods to guide clinical treatment. Objective Here, we report on the development and prospective validation of a state-of-the-art machine learning model to provide mortality prediction shortly after confirmation of SARS-CoV-2 infection in the Mayo Clinic patient population. Methods We retrospectively constructed one of the largest reported and most geographically diverse laboratory information system and electronic health record of COVID-19 data sets in the published literature, which included 11,807 patients residing in 41...

Research paper thumbnail of Comparative analysis of 23 synovial fluid biomarkers for hip and knee periprosthetic joint infection detection

Journal of Orthopaedic Research, 2020

There is interest in novel synovial fluid biomarkers for detection of periprosthetic joint infect... more There is interest in novel synovial fluid biomarkers for detection of periprosthetic joint infection (PJI). Here, we assessed the diagnostic accuracy of 23 simple or sophisticated synovial fluid biomarkers for prosthetic hip or knee infection detection. 107 subjects were studied, 57 of whom had aseptic failure (AF) and 50 PJI. The following synovial fluid biomarkers were tested using spectrophotometric assays, immunoassays, lateral flow tests, or test strips: Leukocyte count, monocyte percentage, lymphocyte

Research paper thumbnail of Managing Spectral Interferences Using Optical Coagulation Methods

American Journal of Clinical Pathology, 2018

Research paper thumbnail of Clinical Validation of Fecal Electrolytes for Chronic Diarrhea

American Journal of Clinical Pathology, 2018

Introduction: Fecal electrolytes are measured to help narrow the differential diagnosis for chron... more Introduction: Fecal electrolytes are measured to help narrow the differential diagnosis for chronic diarrhea, defined as symptoms lasting more than 4 weeks. Our laboratory offers a comprehensive panel that includes measurement of chloride, magnesium, osmolality, phosphorous, sodium, and calculated osmotic gap (OG) using published interpretive information for identifying osmotic (OG >50 mmol/L), secretory (OG <50 mmol/L), and magnesium-induced (Mg >110 mg/dL) diarrhea. The objective of this study was to determine the diagnostic accuracy of calculated osmotic gap and magnesium in our patient population to optimize the testing algorithm. Methods: Fecal electrolyte results between August 7, 2013, and December 22, 2017, were extracted from the electronic medical record for 435 unique patients (male = 153, female = 282, mean age = 57) at Mayo Clinic Rochester, MN. Random liquid fecal specimens submitted for testing were centrifuged for 1 hour at 14,000 rpm, transferred to a new tube, stored refrigerated, and tested in daily batches. Electrolytes were measured using Roche Cobas c501 (Roche Diagnostics, Indianapolis, IN). Osmotic gap was calculated as 290 mOsm/kg-(2[Na] + 2[K]). Chart review was conducted to document the cause of diarrhea and medications containing magnesium and other laxatives. Receiver operator curve (ROC) analysis with area under the curve (AUC) was calculated using AnalyzeIT (Microsoft Excel). This study was conducted with Mayo Clinic IRB approval. Results: Chronic diarrhea was classified as osmotic (n = 27), secretory (n = 107), inflammatory (n = 85), steatorrhea (n = 14), and of unknown etiology (n = 202). The prevalence of magnesium-induced diarrhea in our population was only 1.4%. OG differentiates osmotic from nonosmotic causes of diarrhea with an AUC of 0.866, having an optimal decision limit for OG >82 mOsm/kg, sensitivity = 83%, and specificity = 83%. OG differentiates secretory from nonsecretory causes of diarrhea with an AUC of 0.545. A decision limit with sensitivity = 50% is <22 mOsm/kg and has specificity = 37%, while the OG having sensitivity = 95% is <-30mOsm/kg and specificity = 11%. Mean (±SD) results of magnesium were significantly higher in osmotic = 70 (±64) mg/dL than in secretory = 35 (±35) mg/dL, inflammatory = 26 (±25) mg/ dL, and steatorrhea = 25 (±28) mg/dL causes (P ≤ .001, ≤.0001, ≤.05, respectively). The AUC for elevated magnesium in patients reporting Mg-containing medication use was 0.579. The optimal decision limit is Mg >106 mg/dL, having sensitivity = 15% and specificity = 97%. Mg was >106 mg/dL in 3.3% of those tested, resulting in a negative predictive value (NPV) = 98.8%. With one exception,

Research paper thumbnail of Proposed Plasma Ammonia Reference Intervals in a Reference Group of Hospitalized Term and Preterm Neonates

The Journal of Applied Laboratory Medicine, 2020

BackgroundPlasma ammonia is commonly measured in the diagnostic evaluation of hospitalized newbor... more BackgroundPlasma ammonia is commonly measured in the diagnostic evaluation of hospitalized newborns, but reference values are not well defined.MethodsWe prospectively enrolled newborns admitted to the level III/IV neonatal intensive care unit and level II intermediate special care nursery from January 2017 to January 2018. Infants with inborn errors of metabolism or liver disease were excluded. Plasma ammonia concentrations were measured once within the first week of life and evaluated by sex, gestational age, timing of the draw, blood collection method, and type of nutrition. Reference intervals were calculated.Results127 neonates were included; one third (34%) were term infants born at ≥37 weeks gestation, and two thirds (66%) were born preterm at <37 weeks gestation. Median plasma ammonia concentrations were 32 μmol/L (range <10 to 86 μmol/L). Median ammonia concentrations were higher among preterm compared to term infants (35 vs. 28 μmol/L, p = 0.0119), and term female com...

Research paper thumbnail of Laboratory Utilization and Analytical Validation of Fecal Electrolyte Tests

The Journal of Applied Laboratory Medicine, 2017

Background Chronic diarrhea can be categorized as fatty, watery, or inflammatory. Watery diarrhea... more Background Chronic diarrhea can be categorized as fatty, watery, or inflammatory. Watery diarrhea is further divided into secretory or osmotic types and can be differentiated by measuring fecal electrolytes and osmotic gap. However, with widespread use of endoscopy, it is unclear if these measurements are being used clinically. Furthermore, because stool is not a validated specimen type for Food and Drug Administration–approved electrolyte assays, utilization is a practical concern for laboratories before analytical validation. Here, we determined the clinical utility and validated the performance characteristics of stool electrolytes on the Beckman Coulter AU680. Methods Historical results and literature review were used to determine the clinically relevant ranges for stool electrolytes (Na+, Cl−, K+, phosphate, and Mg2+). Additionally, medical chart review was performed (n = 44 patients) on results to evaluate their clinical utility in chronic diarrhea work-up. Linearity, precisio...

Research paper thumbnail of Analytical Evaluation of BioRad D-100 HPLC Analyzer and Workflow Comparison to BioRad TurboLink Variant II HPLC With Reflex to Boronate Affinity

American Journal of Clinical Pathology, 2019

Introduction Measurement of hemoglobin A1c (HbA1C) is used for the diagnosis and management of pa... more Introduction Measurement of hemoglobin A1c (HbA1C) is used for the diagnosis and management of patients with diabetes. Methods for measuring HbA1C are classified on the basis of charge differences (cation exchange chromatography) or structural differences (boronate affinity chromatography). Some cation exchange high-performance liquid chromatography (HPLC) analyzers may be prone to interferences from hemoglobin variants. Historically, our lab used two methods to report HbA1C results: cation exchange HPLC (VariantII) with reflex to boronate affinity HPLC (Ultra2) methods. A new analyzer (BioRad D-100) with improved interference detection and thresholds for interference was evaluated. The objectives of this study were (1) assess the comparability of HbA1c results between D-100, VariantII, and Ultra2; (2) evaluate the need for maintaining a reflex method; and (3) calculate cancellation rates before and after implementing D-100. Methods HbA1c was measured by cation exchange methods usin...