Publications by authors named "Kerry J Welsh"

37 Publications

Thrombocytopenia including immune thrombocytopenia after receipt of mRNA COVID-19 vaccines reported to the Vaccine Adverse Event Reporting System (VAERS).

Vaccine 2021 06 30;39(25):3329-3332. Epub 2021 Apr 30.

Division of Epidemiology, Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, United States. Electronic address:

Background: The objective of this study is to assess cases of thrombocytopenia, including immune thrombocytopenia (ITP), reported to the Vaccine Adverse Event Reporting System (VAERS) following vaccination with mRNA COVID-19 vaccines.

Methods: This case-series study analyzed VAERS reports of thrombocytopenia after vaccination with Pfizer-BioNTech COVID-19 Vaccine or Moderna COVID-19 Vaccine.

Results: Fifteen cases of thrombocytopenia were identified among 18,841,309 doses of Pfizer-BioNTech COVID-19 Vaccine and 13 cases among 16,260,102 doses of Moderna COVID-19 Vaccine. The reporting rate of thrombocytopenia was 0.80 per million doses for both vaccines. Based on an annual incidence rate of 3.3 ITP cases per 100,000 adults, the observed number of all thrombocytopenia cases, which includes ITP, following administration of mRNA COVID-19 vaccines is not greater than the number of ITP cases expected.

Conclusions: The number of thrombocytopenia cases reported to VAERS does not suggest a safety concern attributable to mRNA COVID-19 vaccines at this time.
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http://dx.doi.org/10.1016/j.vaccine.2021.04.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086806PMC
June 2021

Myopericarditis after vaccination, Vaccine Adverse Event Reporting System (VAERS), 1990-2018.

Vaccine 2021 01 6;39(5):839-845. Epub 2021 Jan 6.

Immunization Safety Office, Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States.

Background: Myopericarditis after vaccination has been sporadically reported in the medical literature. Here, we present a thorough descriptive analysis of reports to a national passive vaccine safety surveillance system (VAERS) of myopericarditis after vaccines licensed for use in the United States.

Methods: We identified U.S. reports of myopericarditis received by VAERS during 1990-2018 that met a published case definition for myopericarditis or were physician-diagnosed. We stratified analysis by age group (<19, 19-49, ≥50 years), describing reports by serious/non-serious status, sex, time to symptom onset after vaccination, vaccine(s) administered, and exposure to other known causes of myopericarditis. We used Empirical Bayesian data mining to detect disproportionate reporting of myopericarditis after vaccination.

Results: VAERS received 620,195 reports during 1990-2018: 708 (0.1%) met the case definition or were physician-diagnosed as myopericarditis. Most (79%) myopericarditis reports described males; 69% were serious; 72% had symptom onset ≤ 2 weeks postvaccination. Overall, smallpox (59%) and anthrax (23%) vaccines were most commonly reported. By age, among persons aged < 19 years, Haemophilus influenzae type b (22, 22%) and hepatitis B (18, 18%); among persons aged 19-49 years smallpox (387, 79%); among persons aged ≥ 50 years inactivated influenza (31, 36%) and live attenuated zoster (19, 22%) vaccines were most commonly reported. The vaccines most commonly reported remained unchanged when excluding 138 reports describing other known causes of myopericarditis. Data mining revealed disproportionate reporting of myopericarditis only after smallpox vaccine.

Conclusions: Despite the introduction of new vaccines over the years, myopericarditis remains rarely reported after vaccines licensed for use in the United States. In this analysis, myopericarditis was most commonly reported after smallpox vaccine, and less commonly after other vaccines.
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http://dx.doi.org/10.1016/j.vaccine.2020.12.046DOI Listing
January 2021

Inadequate Reporting of Analytical Characteristics of Biomarkers Used in Clinical Research: A Threat to Interpretation and Replication of Study Findings.

Clin Chem 2019 12 31;65(12):1554-1562. Epub 2019 Oct 31.

Department of Laboratory Medicine, Clinical Center, NIH, Bethesda, MD;

Background: Analytical characteristics of methods to measure biomarkers determine how well the methods measure what they claim to measure. Transparent reporting of analytical characteristics allows readers to assess the validity and generalizability of clinical studies in which biomarkers are used. Our aims were to assess the reporting of analytical characteristics of biomarkers used in clinical research and to evaluate the extent of reported characterization procedures for assay precision.

Methods: We searched 5 medical journals (, , , , and ) over a 10-year period for the term "biomarker" in the full-text field. We included studies in which biomarkers were used for inclusion/exclusion of study participants, for patient classification, or as a study outcome. We tabulated the frequencies of reporting of 11 key analytical characteristics (such as analytical accuracy of test results) in the included studies.

Results: A total of 544 studies and 1299 biomarker uses met the inclusion criteria. No information on analytical characteristics was reported for 67% of the biomarkers. For 65 biomarkers (3%), ≥4 characteristics were reported (range, 4-8). The manufacturer of the measurement procedure could not be determined for 688 (53%) of the 1299 biomarkers. The extent of assessments of assay imprecision, when reported, did not meet expectations for clinical use of biomarkers.

Conclusions: Reporting of the analytical performance of biomarker measurements is variable and often absent from published clinical studies. We suggest that readers need fuller reporting of analytical characteristics to interpret study results, assess generalizability of conclusions, and compare results among clinical studies.
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http://dx.doi.org/10.1373/clinchem.2019.309575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055667PMC
December 2019

Adaptive NK cells in people exposed to correlate with protection from malaria.

J Exp Med 2019 06 12;216(6):1280-1290. Epub 2019 Apr 12.

Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD

How antibodies naturally acquired during infection provide clinical immunity to blood-stage malaria is unclear. We studied the function of natural killer (NK) cells in people living in a malaria-endemic region of Mali. Multi-parameter flow cytometry revealed a high proportion of adaptive NK cells, which are defined by the loss of transcription factor PLZF and Fc receptor γ-chain. Adaptive NK cells dominated antibody-dependent cellular cytotoxicity responses, and their frequency within total NK cells correlated with lower parasitemia and resistance to malaria. -infected RBCs induced NK cell degranulation after addition of plasma from malaria-resistant individuals. Malaria-susceptible subjects with the largest increase in PLZF-negative NK cells during the transmission season had improved odds of resistance during the subsequent season. Thus, antibody-dependent lysis of -infected RBCs by NK cells may be a mechanism of acquired immunity to malaria. Consideration of antibody-dependent NK cell responses to antigens is therefore warranted in the design of malaria vaccines.
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http://dx.doi.org/10.1084/jem.20181681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547858PMC
June 2019

Human Papillomavirus and Its Testing Assays, Cervical Cancer Screening, and Vaccination.

Adv Clin Chem 2017;81:135-192. Epub 2017 Mar 18.

Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.

Human papillomavirus (HPV) was found to be the causative agent for cervical cancer in the 1980s with almost 100% of cervical cancer cases testing positive for HPV. Since then, many studies have been conducted to elucidate the molecular basis of HPV, the mechanisms of carcinogenesis of the virus, and the risk factors for HPV infection. Traditionally, the Papanicolaou test was the primary screening method for cervical cancer. Because of the discovery and evolving understanding of the role of HPV in cervical dysplasia, HPV testing has been recommended as a new method for cervical cancer screening by major professional organizations including the American Cancer Society, American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology. In order to detect HPV infections, many sensitive and specific HPV assays have been developed and used clinically. Different HPV assays with various principles have shown their unique advantages and limitations. In response to a clear causative relationship between high-risk HPV and cervical cancer, HPV vaccines have been developed which utilize virus-like particles to create an antibody response for the prevention of HPV infection. The vaccines have been shown in long-term follow-up studies to be effective for up to 8 years; however, how this may impact screening for vaccinated women remains uncertain. In this chapter, we will review the molecular basis of HPV, its pathogenesis, and the epidemiology of HPV infection and associated cervical cancer, discuss the methods of currently available HPV testing assays as well as recent guidelines for HPV screening, and introduce HPV vaccines as well as their impact on cervical cancer screening and treatments.
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http://dx.doi.org/10.1016/bs.acc.2017.01.004DOI Listing
April 2019

Assessment of thyroid function in intensive care unit patients by liquid chromatography tandem mass spectrometry methods.

Clin Biochem 2017 Apr 25;50(6):318-322. Epub 2016 Nov 25.

Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD 20892, United States; (SJS) Departments of Endocrinology and Metabolism, Georgetown University, Washington, DC, United States. Electronic address:

Objectives: Patients with non-thyroidal illness syndrome have many abnormalities in thyroid hormone tests. Such patients have medical comorbidities associated with low serum proteins and are on multiple medications that interfere with thyroid hormone measurement by immunoassay platforms. It is unknown if these thyroid hormone measurements reflect physiologic conditions or if they are artifacts of testing methodology.

Methods: Fifty patients were selected from the intensive care unit (ICU) from our institution. Total and free thyroid hormones in plasma were measured by gold standard liquid chromatography-tandem mass spectrometry (LC-MSMS). The results were compared to the Roche Cobas 6000. Patient medical comorbidities and binding protein levels were assessed.

Results: Concentrations of total 3,5,5'-triidothyronine (TT3) and total thyroxine (TT4) were significantly more likely to be low by LC-MSMS compared to immunoassay. Free 3,5,5'-triidothyronine (FT3) levels were similar by immunoassay and LC-MSMS. However, FT4 concentrations were mildly elevated for many patients when measured by ultrafiltration LC-MSMS (19/50, 38%) compared to 1/50 (2%) when measured by immunoassay (p=0.0001). Decreased albumin and thyroxine binding globulin were common and patients were on an average of 11.7±5.0 medications, all factors known to interfere with results found on immunoassays.

Conclusions: Marked discrepancies in thyroid hormone measurement were noted between reference LC-MSMS and a common immunoassay platform. It is hypothesized that T4 binding to low affinity albumin is displaced by several drugs, raising concentrations of FT4 by LC-MSMS compared to immunoassay, and that the immunoassay values are falsely decreased due to low binding proteins in our patient population.
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http://dx.doi.org/10.1016/j.clinbiochem.2016.11.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429196PMC
April 2017

DIAGNOSIS OF ENDOCRINE DISEASE: How reliable are free thyroid and total T3 hormone assays?

Eur J Endocrinol 2016 Dec;175(6):R255-R263

Clinical Chemistry DivisionDepartment of Laboratory Medicine, National Institutes of Health, Bethesda, Maryland, USA

Hypothyroidism is a very common disorder worldwide, for which the usual treatment is monotherapy with levothyroxine (L-T). However, a number of patients treated with L-T continue to report symptoms of hypothyroidism despite seemingly normal levels of thyroid-stimulating hormone (TSH), free-T (FT) and free-T (FT) measured by immunoassay. This review summarizes the limitations of the immunoassays commonly used to measure thyroid hormone levels and emphasizes the advantages of the role of liquid chromatography-tandem mass spectrometry (LC-MS/MS). Immunoassays for free thyroid hormone are affected by alterations in serum binding proteins that occur in many physiological and disease states. Multiple studies show falsely normal values for T, FT and FT by immunoassay that are below the reference interval when measured by (ultrafiltration) LC-MS/MS, a reference method. We suggest evaluation of thyroid hormone levels by ultrafiltration LC-MS/MS for patients who continue to experience hypothyroid symptoms on LT-4. This may help identify the approximately 20% subset of patients who would benefit from addition of T to their treatment regimen (combination therapy).
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http://dx.doi.org/10.1530/EJE-16-0193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5113291PMC
December 2016

Algorithmic Approach With Clinical Pathology Consultation Improves Access to Specialty Care for Patients With Systemic Lupus Erythematosus.

Am J Clin Pathol 2016 Sep 10;146(3):312-8. Epub 2016 Aug 10.

From the Department of Pathology and Laboratory Medicine.

Objectives: Harris Health System (HHS) is a safety net system providing health care to the underserved of Harris County, Texas. There was a 6-month waiting period for a rheumatologist consult for patients with suspected systemic lupus erythematosus (SLE). The objective of the intervention was to improve access to specialty care.

Methods: An algorithmic approach to testing for SLE was implemented initially through the HHS referral center. The algorithm was further offered as a "one-click" order for physicians, with automated reflex testing, interpretation, and case triaging by clinical pathology.

Results: Data review revealed that prior to the intervention, 80% of patients did not have complete laboratory workups available at the first rheumatology visit. Implementation of algorithmic testing and triaging of referrals by pathologists resulted in decreasing the waiting time for a rheumatologist by 50%.

Conclusions: Clinical pathology intervention and case triaging can improve access to care in a county health care system.
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http://dx.doi.org/10.1093/ajcp/aqw122DOI Listing
September 2016

Is This Patient Pregnant?

Clin Chem 2016 08;62(8):1163-4

Department of Laboratory Medicine, Clinical Chemistry Service, National Institutes of Health, Bethesda, MD.

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http://dx.doi.org/10.1373/clinchem.2015.253039DOI Listing
August 2016

Role of Glycated Proteins in the Diagnosis and Management of Diabetes: Research Gaps and Future Directions.

Diabetes Care 2016 08;39(8):1299-306

Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD

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http://dx.doi.org/10.2337/dc15-2727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955935PMC
August 2016

Pathology Consultation on Patients With a Large Rh Immune Globulin Dose Requirement.

Am J Clin Pathol 2016 Jun 6;145(6):744-51. Epub 2016 Jun 6.

From the Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston.

Objectives: To review the differential diagnosis and laboratory issues for women with a large calculated dose of Rh immune globulin (RhIG).

Methods: A case-based approach is used to review the differential diagnosis of patients with a large calculated dose of RhIG, RhIG dosing for women with baseline elevations in hemoglobin F, the formulations of RhIG, and issues for the transfusion medicine service with the release of large doses of RhIG.

Results: A large fetomaternal bleed after delivery requiring multiple doses of RhIG is rare. Such patients may require intravenous RhIG to avoid multiple injections. Patients with a large percentage of circulating fetal RBCs should be evaluated for a disorder of hemoglobin synthesis and, if present, should have quantification of the circulating fetal RBCs by flow cytometry.

Conclusions: Accurate laboratory evaluation of women with large fetomaternal bleeds is essential for appropriate RhIG administration.
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http://dx.doi.org/10.1093/ajcp/aqw051DOI Listing
June 2016

Sirt1-Positive Lymphocytes in Acute Cellular Cardiac Allograft Rejection: Contributor to Pathogenesis and a Therapeutic Target.

ASAIO J 2016 May-Jun;62(3):349-53

From the Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston, Houston, Texas.

Cardiac allograft rejection remains a problem, despite advances with immunosuppressants. Understanding the mechanisms behind rejection is essential for developing targeted therapies. The goal of this investigation is to explore Sirtuin 1 (Sirt1) as a therapeutic target for cardiac allograft rejection. Thirteen endomyocardial biopsy specimens with acute cellular rejection (grade 2R or 3R) were selected. CD3, CD4, CD8, CD20, CD68, T-cell intracytoplasmic antigen (TIA-1), and Sirt1 expressions were determined by immunohistochemical stains. Comparison of Sirt1 expression was made with 10 cases of grade 0R and grade 1R. Quantitative image analysis was performed. There were 2 cases of grade 3R and 11 cases of grade 2R acute cellular rejection. Sirtuin 1 expression was present in the majority of mononuclear cells (median percentage, 73.5; interquartile range, 51.2-100%); staining was also observed in cardiomyocytes. Twelve of the 13 cases (92.3%) had an elevated CD8/FoxP3 ratio, coinciding with acute cellular rejection. Sirtuin 1 expression in the nuclei of FoxP3+ cells can lead to deacetylation and inactivation of FoxP3 rendering the T-suppressor cells inactive and promoting acute cellular rejection. The use of a Sirt1 inhibitor may be a therapeutic option in expanding the functionality of the FoxP3+ T-suppressor cells and moderating the severity of such rejection.
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http://dx.doi.org/10.1097/MAT.0000000000000338DOI Listing
October 2017

Bioinformatics Analysis to Determine Prognostic Mutations of 72 de novo Acute Myeloid Leukemia Cases from the Cancer Genome Atlas (TCGA) with 23 Most Common Mutations and no Abnormal Cytogenetics.

Ann Clin Lab Sci 2015 ;45(5):515-21

Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA

Objectives: Up to 40% of acute myeloid leukemia (AML) patients have normal cytogenetics (CN-AML) but they may have gene mutations. An important issue in the treatment of CN-AML is how gene mutation patterns may help with patient management. The Cancer Genome Atlas (TCGA) database has data from 200 cases of de novo AML including cytogenetics, gene mutations, and survival duration (prognosis).

Methods: Cases with the most common mutations and no cytogenetic abnormalities were selected from the TCGA. Unsupervised neural network analysis was performed to group them into clusters according to their pattern of mutations and survival.

Results: 72 cases of CN-AML with the 23 most common mutations were obtained from TCGA. Clustering was found to be based on 6 mutations, with the following prognostic groups: (a) good: NPM1, CEBPA, or TET2, (b) intermediate: NPM1/DNMT3A, or other mutations, (c) poor: RUNX1, FLT3-ITD, FLT3-ITD/NPM1, or FLT3-ITD/CEBPA. Some discrepancy between our results and those from previous studies is most likely due to inclusion of AML cases transformed from myeloproliferative neoplasms or myelodysplastic syndrome in previous studies.

Conclusions: This study provides further molecular characterization and prognostic data most specific for the de novo subgroup of CN-AML patients.
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October 2016

Utility of VerifyNow for Point-of-Care Identification of an Aspirin Effect Prior to Emergency Cardiac Surgery.

Ann Clin Lab Sci 2015 ;45(4):377-81

Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, TX, USA

Background: Patients with cardiovascular disease are frequently on aspirin, which may place them at risk for bleeding during surgical procedures. The utility of the VerifyNow test to rapidly identify an aspirin effect and predict bleeding risk prior to cardiac surgery was explored.

Methods: A retrospective study was performed of patients on a clinical pathology consultation service that provides laboratory and transfusion support for patients undergoing major cardiac surgery. Patients who had VerifyNow testing for aspirin effect were selected.

Results: A total of 88 patients had VerifyNow aspirin testing during the study period. The VerifyNow test correctly identified 52/63 (82.5%) patients with documented aspirin use, and missed 11/63 (17.5%) of aspirin users. Light transmission aggregometry (LTA) showed an aspirin effect in the majority of aspirin users missed by the VerifyNow assay. Moderate correlations were found between LTA and VerifyNow. Low aspirin reaction units were not associated with significant bleeding in these cardiac surgery patients.

Conclusions: We propose the VerifyNow assay for point-of-care identification of aspirin effect prior to emergency surgeries.
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May 2016

Therapeutic plasma exchange as a therapeutic modality for the treatment of IVIG complications.

J Clin Apher 2015 Dec 30;30(6):371-4. Epub 2015 Jun 30.

Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston, Houston, Texas.

Intravenous immunoglobulin (IVIG) is used for the treatment of a number of inflammatory conditions. Hemolysis due to passive transfer of blood group antibodies is a well recognized complication of IVIG therapy. Therapy is largely supportive and consists of blood product support and hemodialysis. We report the use of therapeutic plasma exchange (TPE) as adjunct therapy for three patients with complications attributed to IVIG. Two patients had hemolysis attributed to IVIG; one patient was blood group A and the other blood group O. The third patient was an orthotopic heart transplant recipient with a type A donor heart, and anti-A antibodies detected after infusion of IVIG for suspected antibody mediated rejection. Two patients had anti-A titers available that decreased after initiation of plasma exchange. The blood group O patient with hemolysis had a gradual stabilization of hemoglobin and resolution of the positive DAT. TPE may be useful therapy for patients with severe hemolysis caused by IVIG or at risk for tissue damage by blood group antibodies.
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http://dx.doi.org/10.1002/jca.21386DOI Listing
December 2015

Exploring New Ways to Deliver Value to Healthcare Organizations: Algorithmic Testing, Data Integration, and Diagnostic E-consult Service.

Ann Clin Lab Sci 2015 ;45(3):239-47

Department of Pathology and Laboratory Medicine, University of Texas - Houston Medical School, Houston, TX, USA.

As the USA Health Care System undergoes transformation and transitions to value-based models it is critical for laboratory medicine/clinical pathology physicians to explore opportunities and find new ways to deliver value, become an integral part of the healthcare team. This is also essential for ensuring financial health and stability of the profession when the payment paradigm changes from fee-for-service to fee-for-performance. About 5 years ago we started searching for ways to achieve this goal. Among other approaches, the search included addressing the laboratory work-ups for specialists' referrals in the HarrisHealth System, a major safety net health care organization serving mostly indigent and underserved population of Harris County, TX. We present here our experience in improving the efficiency of laboratory testing for the referral process and in building a prototype of a diagnostic e-consult service using rheumatologic diseases as a starting point. The service incorporates algorithmic testing, integration of clinical, laboratory and imaging data, issuing structured comprehensive consultation reports, incorporating all the relevant information, and maintaining personal contacts and an e-line of communications with the primary providers and referral center personnel. Ongoing survey of providers affords testimony of service value in terms of facilitating their work and increasing productivity. Analysis of the cost effectiveness and of other value indicators is currently underway. We also discuss our pioneering experience in building pathology residents and fellows training in integrated diagnostic consulting service.
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March 2016

An unusual case of heterozygous hemoglobin S/hemoglobin Fannin-Lubbock misidentified by capillary hemoglobin electrophoresis.

Ann Clin Lab Sci 2015 ;45(2):199-201

Department of Pathology and Laboratory Medicine, University of Texas at Houston, Houston, TX, USA

A 58-year-old Hispanic man under treatment for a gangrenous toe was found to have chronic microcytic anemia and a positive sickle cell screen. High-performance liquid chromatography and isoelectric focusing electrophoresis showed that the patient is double heterozygous for hemoglobin S and hemoglobin Fannin-Lubbock. The patient does not have any manifestations of a sickling disorder. Capillary hemoglobin electrophoresis initially misclassified this unusual combination of hemoglobin variants.
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January 2016

Thromboelastography is a suboptimal test for determination of the underlying cause of bleeding associated with cardiopulmonary bypass and may not predict a hypercoagulable state.

Am J Clin Pathol 2014 Oct;142(4):492-7

From the Department of Pathology and Laboratory Medicine, University of Texas at Houston.

Objectives: Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) are at risk of bleeding. The goal of this investigation was to compare thromboelastography (TEG) with standard coagulation tests (prothrombin time [PT], partial thromboplastin time [PTT], fibrinogen, and D-dimer) in patients with active bleeding.

Methods: A retrospective study of patients who underwent cardiac surgery with CPB was performed. A second analysis was performed to determine if a shortened TEG R time is associated with thrombosis.

Results: Paired TEG and standard coagulation tests were available from 21 bleeding patients; of the 15 patients with normal TEG values and three with a shortened R time, all had abnormalities of standard coagulation tests. Eighteen of 67 patients who underwent surgery with CPB had an episode of postoperative bleeding. The TEG R time and coagulation index, PT, and PTT collected after CPB were associated with postoperative bleeding in the univariate analysis, but only PT was independently associated with postoperative bleeding in the multivariate analysis. In the second analysis, three of 38 patients with a normal TEG and four of 43 patients with a shortened R time had a thrombotic event during hospitalization (P = 1.00).

Conclusions: TEG had limited utility in identifying the underlying cause of bleeding and was not predictive of postoperative bleeding associated with cardiac surgery compared with conventional coagulation tests. A shortened TEG R time may not represent a hypercoagulable state.
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http://dx.doi.org/10.1309/AJCPVB73TMIDFNCBDOI Listing
October 2014

Rapid detection of the active cardiac glycoside convallatoxin of lily of the valley using LOCI digoxin assay.

Am J Clin Pathol 2014 Sep;142(3):307-12

From the Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston.

Objectives: To explore the luminescent oxygen channeling technology-based digoxin immunoassay (LOCI digoxin assay) for rapid detection of lily of the valley extract and convallatoxin. The potential in vitro binding of convallatoxin with Digibind was also evaluated.

Methods: Aliquots of a drug-free serum pool and a digoxin serum pool were supplemented with lily of the valley extract or convallatoxin, and then apparent digoxin concentrations were measured using the LOCI digoxin assay. Mice were administered lily of the valley extract or 50 μg of convallatoxin, and digoxin concentrations in serum specimens were measured 1 and 2 hours after gavage. Aliquots of a serum pool supplemented with convallatoxin or lily of the valley extract were further supplemented with various concentrations of Digibind and free apparent digoxin concentrations were measured.

Results: Apparent digoxin concentrations were observed when aliquots of a drug-free serum pool were supplemented with convallatoxin or lily of the valley extract, and also with convallatoxin or herbal extract. Bidirectional interference of convallatoxin and lily of the valley extract with serum digoxin measurement using the LOCI assay was also observed. Digibind was capable of binding convallatoxin in vitro.

Conclusions: LOCI digoxin assay can be used for rapid detection of convallatoxin, and Digibind can bind convallatoxin in vitro.
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http://dx.doi.org/10.1309/AJCPCOXF0O5XXTKDDOI Listing
September 2014

How do we manage cardiopulmonary bypass coagulopathy?

Transfusion 2014 Sep 18;54(9):2158-66. Epub 2014 Jun 18.

Department of Pathology and Laboratory Medicine.

Background: Patients who undergo cardiopulmonary bypass (CPB) are at risk for coagulopathy. Suboptimal turnaround time (TAT) of laboratory coagulation testing results in empiric administration of blood products to treat massive bleeding. We describe our initiative in establishing the coagulation-based hemotherapy (CBH) service, a clinical pathology consultation service that uses rapid TAT coagulation testing and provides comprehensive assessment of bleeding in patients undergoing CPB. A transfusion algorithm that treats the underlying cause of coagulopathy was developed.

Study Design And Methods: The coagulation testing menu includes all aspects of coagulopathy with close proximity of the laboratory to the operating room to allow for rapid test results. The hemotherapy pathologist monitors laboratory results at several stages in surgery and uses a comprehensive algorithm to monitor a patient's hemostasis. The optimal number and type of blood products are selected when the patient is taken off CPB.

Results: The CBH service was consulted for 44 ventricular assist device implants, 30 heart transplants, and 31 other cardiovascular surgeries from May 2012 through November 2013. The TAT for laboratory tests was 15 minutes for complete blood count, antithrombin, and coagulation panel and 30 minutes for VerifyNow and thromboelastography, in comparison to 45 to 60 minutes in normal settings. The transfusion algorithms were used with optimal administration of blood components with preliminary data suggestive of reduced blood product usage and better patient outcomes.

Conclusion: We described the successful introduction of a novel pathology consultation service that uses a rapid TAT coagulation testing menu with transfusion algorithms for improved management of CPB patients.
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http://dx.doi.org/10.1111/trf.12751DOI Listing
September 2014

Trehalose 6,6'-dimycolate--a coat to regulate tuberculosis immunopathogenesis.

Tuberculosis (Edinb) 2013 Dec;93 Suppl:S3-9

Department of Pathology, Medical School, University of Texas-Houston Medical School, Houston, Texas, USA. Electronic address:

Tuberculosis (TB) remains a significant public health burden worldwide. Treatment of this disease requires a minimum of six months and there is no vaccine available for the most common form of the disease. Increasing evidence suggests that the mycobacterial glycolipid trehalose 6,6' dimycolate (TDM; cord factor) plays a key role in the pathogenesis of TB disease. TDM protects the TB bacilli from macrophage-mediated killing, inhibits effective antigen presentation, and reduces the formation of protective T-cell responses. TDM promotes initiation of granuloma formation and likely plays a role in caseation. Furthermore, TDM may contribute to the development of post primary disease. Receptors for TDM were recently described and are expected to contribute to our knowledge of the molecular pathogenesis of TB disease. In this manner, understanding TDM may prove promising towards development of targeted TB therapeutics to limit clinical pathologies.
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http://dx.doi.org/10.1016/S1472-9792(13)70003-9DOI Listing
December 2013

Bidirectional (negative/positive) interference of oleandrin and oleander extract on a relatively new Loci digoxin assay using Vista 1500 analyzer.

J Clin Lab Anal 2014 Jan 27;28(1):16-20. Epub 2013 Dec 27.

Department of Pathology and Laboratory Medicine, The University of Texas Medical School at Houston, Texas.

Background: Oleander interferes with serum digoxin measurements using various immunoassays. The potential interference of oleander and its active ingredient, oleandrin, with a relatively new homogenous sequential chemiluminescent digoxin assay based on luminescent oxygen channeling technology (LOCI digoxin assay, Siemens Diagnostics) has not been previously reported.

Methods: Aliquots of a digoxin-free serum pool were supplemented with increasing concentrations of oleandrin, or with oleander extract, followed by measuring the apparent digoxin concentrations using the LOCI digoxin assay using Vista 1500 analyzer. Mice were fed oleandrin or oleander extract, and their blood digoxin levels at 1 and 2 h were measured with the LOCI digoxin assay. In addition, two digoxin serum pools were prepared by combining sera of patients receiving digoxin; aliquots of both pools were supplemented with oleandrin or oleander extract and digoxin concentrations were again measured. Attempts to overcome this interference were made by measuring free digoxin concentration using a third digoxin pool.

Results: Significant apparent digoxin concentrations were observed after supplementing aliquots of the drug-free serum pool with oleandrin or oleander extract. Mice fed with oleandrin or oleander extract also showed apparent digoxin levels 1 and 2 h after feeding. Digoxin values were also falsely lower or elevated (bidirectional interference) when aliquots of digoxin serum pools were further supplemented with oleandrin or oleander extract depending on concentration; this interference was not eliminated by free digoxin monitoring.

Conclusions: Oleandrin interferes with LOCI digoxin assay.
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http://dx.doi.org/10.1002/jcla.21637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6807570PMC
January 2014

Novel spot tests for detecting the presence of zinc sulfate in urine, a newly introduced urinary adulterant to invalidate drugs of abuse testing.

Am J Clin Pathol 2013 Oct;140(4):572-8

Dept of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, 6431 Fannin, MSB 2.292, Houston, TX 77030; e-mail:

Objectives: To find a suitable method for detecting zinc sulfate in adulterated urine.

Methods: Two rapid spot tests to detect the presence of zinc sulfate in urine were developed.

Results: Addition of 3 to 4 drops of 1N sodium hydroxide solution to approximately 1 mL of urine containing zinc sulfate led to the formation of a white precipitate, which was soluble in excess sodium hydroxide. In the second spot test, addition of 3 to 4 drops of 1% sodium chromate solution to 1 mL of urine containing zinc sulfate followed by the addition of 4 to 5 drops of 1N sodium hydroxide led to formation of a yellow precipitate (zinc chromate). Detection limit of these visual spot tests was 10 mg/mL of zinc sulfate in urine. Twenty drug-free urine specimens and urine containing high amounts of sugar or reducing substances were tested with no false-positive spot test results observed. However, if lead is present in high amounts in urine, it may cause false-positive spot test results. When aliquots of urine controls for drugs of abuse testing were supplemented with different amounts of zinc sulfate, false-negative drug test results were observed except for amphetamine. Zinc sulfate also falsely reduced measured urine alcohol level in urine.

Conclusions: Zinc sulfate can invalidate urine drug and alcohol testing but can be detected using the novel spot tests developed.
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http://dx.doi.org/10.1309/AJCP2FJ9VBPXJYTQDOI Listing
October 2013

Complement factor C7 contributes to lung immunopathology caused by Mycobacterium tuberculosis.

Clin Dev Immunol 2012 30;2012:429675. Epub 2012 Jul 30.

Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, TX 77030, USA.

Mycobacterium tuberculosis (MTB) remains a significant global health burden despite the availability of antimicrobial chemotherapy. Increasing evidence indicates a critical role of the complement system in the development of host protection against the bacillus, but few studies have specifically explored the function of the terminal complement factors. Mice deficient in complement C7 and wild-type C57BL/6 mice were aerosol challenged with MTB Erdman and assessed for bacterial burden, histopathology, and lung cytokine responses at days 30 and 60 post-infection. Macrophages isolated from C7 -/- and wild-type mice were evaluated for MTB proliferation and cytokine production. C7 -/- mice had significantly less liver colony forming units (CFUs) at day 30; no differences were noted in lung CFUs. The C7 deficient mice had markedly reduced lung occlusion with significantly increased total lymphocytes, decreased macrophages, and increased numbers of CD4+ cells 60 days post-infection. Expression of lung IFN-γ and TNF-α was increased at day 60 compared to wild-type mice. There were no differences in MTB-proliferation in macrophages isolated from wild-type and knock-out mice. These results indicate a role for complement C7 in the development of MTB induced immunopathology which warrants further investigation.
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http://dx.doi.org/10.1155/2012/429675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3438787PMC
January 2013

Prevalence of bipolar disorder and schizophrenia in Houston Outreach Medicine, Education, and Social Services (HOMES) Clinic patients: implications for student-managed clinics for underserved populations.

Acad Med 2012 May;87(5):656-61

University of Texas Medical School at Houston, USA.

Purpose: Psychiatric conditions require aggressive management that is challenging to provide in free clinics. The purpose of this study was to determine the prevalence of certain mental illnesses and comorbid conditions among the patients of a student-managed free clinic for the homeless.

Method: The authors conducted a retrospective analysis of the records of patients who visited the student-run Houston Outreach Medicine, Education, and Social Services (HOMES) Clinic from May 2007 through May 2008. They assessed the prevalence of bipolar disorder and schizophrenia among patients. They compared demographics, health insurance status, comorbid medical conditions, and social habit data of patients with these mental illnesses with those of other clinic patients.

Results: Of 286 patients (74.5% male, mean age 45.8 years), 25 (8.7%) had a diagnosis of schizophrenia and 45 (15.7%) had bipolar disorder. Compared with other clinic patients, patients with bipolar disorder or schizophrenia were less likely to be male (P < .0001) and were more likely to have publicly funded insurance (P = .024). They were also more likely to have certain comorbid conditions, including asthma (P = .0004), seizures (P = .0007), kidney disease (P = .01), and heart disease (P = .02).

Conclusions: The high prevalence of these mental illnesses combined with the increased burden of medical comorbidity among HOMES Clinic patients has implications for student-managed free clinics, which often operate on limited budgets. Strategies for providing care for these patients in this setting include integrated care, street medicine, and case management.
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http://dx.doi.org/10.1097/ACM.0b013e31824d4540DOI Listing
May 2012

Influence of oral lactoferrin on Mycobacterium tuberculosis induced immunopathology.

Tuberculosis (Edinb) 2011 Dec 3;91 Suppl 1:S105-13. Epub 2011 Dec 3.

Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, 6431 Fannin, MSB 2.214, Houston, TX 77030, USA.

The ability of lactoferrin to provide protection and decrease immunopathology in infectious diseases was evaluated using an aggressive aerosol model of Mycobacterium tuberculosis (MTB) infection. C57BL/6 mice were challenged with MTB strain Erdman and treated with 0.5% bovine lactoferrin added to the drinking water starting at day 0 or day 7 post-infection. Mice were sacrificed at three weeks post-challenge and evaluated for organ bacterial burden, lung histopathology, and ELISpot analysis of the lung and spleen for immune cell phenotypes. Mice given tap water alone had lung log10 colony forming units (CFUs) of 7.5 ± 0.3 at week 3 post-infection. Lung CFUs were significantly decreased in mice given lactoferrin starting the day of infection (6.4 ± 0.7), as well as in mice started therapeutically on lactoferrin at day 7 after established infection (6.5 ± 0.4). Quantitative immunohistochemistry using multispectral imaging demonstrated that lung inflammation was significantly reduced in both groups of lactoferrin treated mice, with decreased foamy macrophages, increased total lymphocytes, and increased numbers of CD4+ and CD8+ cells. ELISpot analysis showed that lactoferrin treated mice had increased numbers of CD4 + IFN-γ+ and IL-17 producing cells in the lung, cells that have protective functions during MTB infection. Lactoferrin alone did not alter the proliferation of MTB in either broth or macrophage culture, but enhanced IFN-γ mediated MTB killing by macrophages in a nitric oxide dependent manner. These studies indicate that lactoferrin may be a novel therapeutic for the treatment of tuberculosis, and may be useful in infectious diseases to reduced immune-mediated tissue damage.
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http://dx.doi.org/10.1016/j.tube.2011.10.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248969PMC
December 2011

Comparing efficacy of BCG/lactoferrin primary vaccination versus booster regimen.

Tuberculosis (Edinb) 2011 Dec 15;91 Suppl 1:S90-5. Epub 2011 Nov 15.

Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, 6431 Fannin, MSB 2.214, Houston, TX 77030, USA.

Lactoferrin is an iron binding glycoprotein possessing multiple immune modulatory activities, including ability to affect macrophage cytokine production, promote maturation of T- and B-lymphocyte and immature dendritic cells, and enhance the ability of macrophages and dendritic cells to stimulate antigen-specific T-cells. These characteristics of lactoferrin suggested that it could function as an effective adjuvant enhance efficacy of the BCG, the current vaccine for tuberculosis disease. Admix of lactoferrin to the BCG vaccine promoted host protective responses that surpasses activity of the BCG vaccine alone as determined by decreasing pulmonary pathology upon challenge with virulent Mycobacterium tuberculosis (MTB). This study builds on previous reports by examining the effectiveness of the lactoferrin adjuvant comparing primary vaccination versus an immunization schedule with a booster administered at 8 weeks. BCG/lactoferrin vaccinating, given once or twice, demonstrated an improvement in pulmonary disease compared to both the BCG vaccinated and non-immunized groups. The splenic recall profiles showed a difference in cytokine production induced by mycobacterial antigen from splenocytes isolated from mice immunized with BCG/lactoferrin once or twice. Production of IL-17 is increased in the BCG/lactoferrin 2× group compared to the primary vaccinated group. Both BCG/lactoferrin vaccinated group exhibited increase production of IFN-γ compared to the non-immunized group and decreased production of IL-10 compared to the group vaccinated with only BCG. This study illustrates that the adjuvant activity of lactoferrin to enhance BCG efficacy occurs whether the vaccination regimen is a single delivery or combined with a booster, leading to enhanced host protection and decreased disease manifestation.
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http://dx.doi.org/10.1016/j.tube.2011.10.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248975PMC
December 2011

Predictors of relapse of methicillin-resistant Staphylococcus aureus bacteremia after treatment with vancomycin.

J Clin Microbiol 2011 Oct 24;49(10):3669-72. Epub 2011 Aug 24.

Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston, 6431 Fannin, MSB 2.210, Houston, TX 77030, USA.

The risk factors for relapse of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia after vancomycin treatment are unknown. Diversilab typing was used to classify recurrent bacteremia as relapse or reinfection. Bacteremia for >7 days and staphylococcal cassette chromosome mec element (SCCmec) type II were independently associated with relapse of MRSA bacteremia after vancomycin treatment.
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http://dx.doi.org/10.1128/JCM.05287-11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3187311PMC
October 2011

Determination of vancomycin and daptomycin MICs by different testing methods for methicillin-resistant Staphylococcus aureus.

J Clin Microbiol 2011 Jun 30;49(6):2272-3. Epub 2011 Mar 30.

Department of Pathology, University of Texas Medical School, Houston, Texas 77030, USA.

Vancomycin and daptomycin MICs from 161 isolates of methicillin-resistant Staphylococcus aureus (MRSA) were compared using commercial and in-house broth microdilution, Etest, and common automated methods. Vancomycin Etest MICs were higher than those of other methods, whereas the MICs for daptomycin testing were comparable. Vancomycin MICs vary depending on the testing methodology.
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http://dx.doi.org/10.1128/JCM.02215-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122735PMC
June 2011

IL-6 mediates 11βHSD type 2 to effect progression of the mycobacterial cord factor trehalose 6,6'-dimycolate-induced granulomatous response.

Neuroimmunomodulation 2011 8;18(4):212-25. Epub 2011 Mar 8.

Department of Laboratory Medicine, University of Washington, Seattle, WA, USA.

Granulomatous structures are highly dynamic during active mycobacterial infection, with accompanying responsive inflammation contributing to modulation of pathology throughout the course of disease. The heightened inflammatory response coinciding with initiation and maintenance of newly developing granulomatous structures must be limited to avoid excessive damage to bystander tissue. Modulating the cellular bioavailability of glucocorticoids by local regulation of 11βHSD enzymes within responding tissue and parenchyma would allow controlled inflammatory response during infection. Mycobacterial glycolipid trehalose 6,6'-dimycolate was used to induce strong pulmonary granulomatous inflammation immunopathology. Pulmonary corticosterone was significantly increased at days 3 and 5 after administration. An inverse relationship of 11βHSD1 and 11βHSD2 message correlated with pathology development. Immunohistochemical analysis also demonstrated that 11βHSD2 is expressed in proximity to granulomatous lesions. A role for pro-inflammatory IL-6 cytokine in regulation of converting enzymes to control the granulomatous response was confirmed using gene-disrupted IL-6-/- mice. A model is proposed linking IL-6 to endocrine-derived factors which allows modification of active corticosterone into inert 11-dehydrocorticosterone at the site of granuloma formation to limit excessive parenchymal damage.
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http://dx.doi.org/10.1159/000323776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068753PMC
October 2011