BACKGROUND:Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening adverse drug reaction with numerous diagnostic challenges. Diagnosis of HIT begins with 4T score clinical assessment, followed by laboratory testing for those not deemed low risk. Laboratory testing for HIT includes screening [enzyme-linked immunosorbent assay (ELISA)] and confirmatory [serotonin release assay (SRA)] assays, wherein SRA testing can be pursued following a positive ELISA result. These tests aid diagnosis of HIT, but also introduce interpretive challenges, additional costs, and delays in clinical intervention. METHODS:A retrospective review of 1011 HIT ELISA and 169 SRA tests performed over 5 years was conducted. ELISA percent inhibition and ELISA low-heparin optical density (OD) were evaluated for positive predictive value (PPV). Based on these findings, HIT ELISA reporting and management algorithm changes were implemented and metrics compared for 5 months pre- and post-intervention to assess intervention success. RESULTS:Equivocal and positive HIT ELISA interpretation showed poor PPV based on percent inhibition (0.20 and 0.32, respectively). However, rising low-heparin OD correlated with increasing PPV (PPV of 0.00 for OD values 0.40-1.00, 0.29 for values 1.00-1.99, and 0.91 for values >2.00). Data-driven intervention decreased ELISA positivity rates (13% to 5%), decreased rates of SRA confirmatory testing overall (13% to 9%), decreased SRA testing rates for patients with non-negative ELISAs (78% to 43%), and increased heparin resumption (20% to 57%). Hematology consults remained relatively stable (78% and 86%). CONCLUSIONS:Low-heparin OD-based HIT ELISA interpretation yielded enhanced PPV compared with percent inhibition-based interpretation. Implementation of data-driven changes improved testing stewardship and clinical management for patients with non-negative ELISAs.

Journal Article Beyond the Screen: Navigating Remote Work within Medicine Get access Anna E Merrill, Anna E Merrill Clinical Associate Professor, Associate Director of Clinical Chemistry, Department of Pathology, University of Iowa Health Care, Iowa City, IA, United States Address correspondence to this author at: University of Iowa Health Care, Department of Pathology, 200 Hawkins Dr., Iowa City, IA 52242, United States. Tel (319) 678-8400; e-mail anna-merrill@uiowa.edu. https://orcid.org/0000-0002-5945-5937 Search for other works by this author on: Oxford Academic Google Scholar Sarah A Hackenmueller, Sarah A Hackenmueller Technical Director, Rapid Response Laboratories, Providence Health & Services Oregon, Portland, OR, United States Search for other works by this author on: Oxford Academic Google Scholar Colin Derdeyn, Colin Derdeyn Professor and Chair, Department of Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, VA, United States https://orcid.org/0000-0002-5932-2683 Search for other works by this author on: Oxford Academic Google Scholar Jonathan Genzen, Jonathan Genzen Chief Medical Officer and Senior Director of Governmental Affairs, ARUP Laboratories, Salt Lake City, UT, United StatesProfessor, Department of Pathology, University of Utah, Salt Lake City, UT, United States https://orcid.org/0000-0002-7219-0259 Search for other works by this author on: Oxford Academic Google Scholar Damien Gruson, Damien Gruson Professor and Head, Department of Laboratory Medicine, Cliniques Universitaires Saint Luc, Brussels, Belgium Search for other works by this author on: Oxford Academic Google Scholar Melissa Ludgate, Melissa Ludgate Clinical Assistant Professor, Departments of Internal Medicine and Psychiatry, University of Iowa Health Care, Iowa City, IA, United StatesPsychiatry Clerkship Co-Director, University of Iowa Carver College of Medicine, Iowa City, IA, United States https://orcid.org/0000-0003-0166-9630 Search for other works by this author on: Oxford Academic Google Scholar Surabhi Mulchandani, Surabhi Mulchandani Associate Vice President and Vice Chair of Administration, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, United States Search for other works by this author on: Oxford Academic Google Scholar M Laura Parnas, M Laura Parnas Disease Area Network Lead, Cardiometabolism and Neurology, Medical and Scientific Affairs, Roche Diagnostics Corporation, Indianapolis, IN, United States Search for other works by this author on: Oxford Academic Google Scholar Erik Ranheim Erik Ranheim Professor and Chair, Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, hvae078, https://doi.org/10.1093/clinchem/hvae078 Published: 14 June 2024 Article history Received: 08 May 2024 Accepted: 20 May 2024 Published: 14 June 2024

Journal Article Ready, Set, Screen: The Role of the Clinical Laboratory in Eliminating Chronic Hepatitis B Infection Get access Jane E Persons, Jane E Persons Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, United States https://orcid.org/0000-0002-2393-6886 Search for other works by this author on: Oxford Academic Google Scholar Anna E Merrill Anna E Merrill Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, United States Address correspondence to this author at: Department of Pathology, University of Iowa Hospitals and Clinics, 200 Hawkins Dr., Iowa City, IA 52242, United States. E-mail anna-merrill@uiowa.edu. https://orcid.org/0000-0002-5945-5937 Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 70, Issue 3, March 2024, Pages 567–568, https://doi.org/10.1093/clinchem/hvad208 Published: 02 March 2024 Article history Received: 06 October 2023 Accepted: 02 November 2023 Published: 02 March 2024

Journal Article Data Analytics in Clinical Laboratories: Advancing Diagnostic Medicine in the Digital Age Get access Anna E Merrill, Anna E Merrill Clinical Associate Professor of Pathology, University of Iowa College of Medicine; Associate Director of Clinical Chemistry, University of Iowa Hospitals and Clinics, Iowa City, IA, United States Address correspondence to this author at: University of Iowa Hospitals and Clinics, Department of Pathology, 200 Hawkins Drive, RCP 6234, Iowa City, IA, 52242, United States. E-mail anna-merrill@uiowa.edu. https://orcid.org/0000-0002-5945-5937 Search for other works by this author on: Oxford Academic Google Scholar Thomas J S Durant, Thomas J S Durant Assistant Professor of Laboratory Medicine, Biomedical Informatics and Data Science, Yale School of Medicine; Medical Director of Chemical Pathology and Laboratory Informatics, Associate Director of ACGME Chemical Pathology Fellowship, Yale-New Haven Hospital, New Haven, CT, United States Search for other works by this author on: Oxford Academic Google Scholar Jason Baron, Jason Baron Clinical Data Scientist, Roche Diagnostics Corporation, Indianapolis, IN, United States Search for other works by this author on: Oxford Academic Google Scholar J Stacey Klutts, J Stacey Klutts Deputy Director, National Pathology and Laboratory Medicine Service, Veterans Health Administration, Washington, DC, United StatesClinical Associate Professor of Pathology, University of Iowa College of Medicine, Iowa City, IA, United States Search for other works by this author on: Oxford Academic Google Scholar Amrom E Obstfeld, Amrom E Obstfeld Associate Chair of Pathology Informatics, Children's Hospital of Philadelphia; Associate Professor of Clinical Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States Search for other works by this author on: Oxford Academic Google Scholar David Peaper, David Peaper Associate Professor of Laboratory Medicine, Yale School of Medicine; Medical Director of Clinical Microbiology Laboratory, Yale-New Haven Hospital, New Haven, CT, United States https://orcid.org/0000-0002-9952-5012 Search for other works by this author on: Oxford Academic Google Scholar Michelle Stoffel, Michelle Stoffel Associate Chief Medical Information Officer for Laboratory Medicine & Pathology, Medical Director of Laboratory Medicine & Pathology Informatics, M Health Fairview; Assistant Professor of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, MN, United States https://orcid.org/0000-0002-4041-748X Search for other works by this author on: Oxford Academic Google Scholar Sarah Wheeler, Sarah Wheeler Associate Professor of Pathology, University of Pittsburgh Medical Center; Associate Medical Director of Clinical Immunopathology, Medical Director of Automated Laboratory UPMC Mercy and Clinical Chemistry UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States https://orcid.org/0000-0002-7851-9836 Search for other works by this author on: Oxford Academic Google Scholar Mark A Zaydman Mark A Zaydman Assistant Professor of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 69, Issue 12, December 2023, Pages 1333–1341, https://doi.org/10.1093/clinchem/hvad183 Published: 14 November 2023 Article history Received: 06 October 2023 Accepted: 17 October 2023 Published: 14 November 2023

PURPOSE:The activated partial thromboplastin time (aPTT) is a coagulation assay commonly utilized for monitoring therapeutic heparin anticoagulation. aPTT methods based on optical detection are vulnerable to spectral interference from hemolysis, icterus, lipemia, and other substances. Intravenous lipid emulsions of primarily 20% have been shown to interfere with multiple clinical laboratory assays, including those measuring aPTT by optical methods, but there is limited data on propofol's effect. The primary objective of this study was to determine the rate of interference of propofol with aPTT measurements in patients receiving both propofol and intravenous heparin.METHODS:A retrospective observational cohort study of intensive care unit patients who received concomitant propofol and heparin infusions (N = 38 patients) and whose heparin therapy was monitored by aPTT (N = 531 aPTTs) was conducted. Review of the electronic medical record was completed to obtain relevant clinical and laboratory data, while the laboratory information system was queried for analytical interference with the aPTT assay.RESULTS:A total of 109 aPTTs (21%) spanning 21 patients (55%) had documented aPTT interference. All 21 patients had at least one aPTT requiring ultracentrifugation prior to reporting, and 12 aPTTs from 4 patients were unreportable due to interference. Patients with and without aPTT interference received similar doses of propofol. None of the cases of aPTT interference were caused by hemolysis or hyperbilirubinemia.CONCLUSION:A potential medication-assay interaction was observed in approximately half of patients who received concomitant propofol and heparin infusions and had aPTT measured for anticoagulation management. Sample ultracentrifugation removes the optical interference in most cases but significantly prolongs aPTT reporting and delays appropriate adjustments to heparin dosing.

Testing for antiphospholipid antibodies (aPLs) is recommended and widely practiced for patients with recurrent pregnancy loss (RPL) based, in part, on a reported prevalence of antiphospholipid syndrome ranging from 8%–42% in patients experiencing multiple miscarriages (1The Practice Committee of the American Society for Reproductive Medicine. Evaluation and treatment of recurrent pregnancy loss: a committee opinion.Fertil Steril. 2012; 98: 1103-1111Abstract Full Text Full Text PDF PubMed Scopus (746) Google Scholar). However, this prevalence may be inflated because these studies were performed before the implementation of new standardized guidelines for aPLs testing. Our primary objective was to evaluate the rate of confirmed aPL positivity in patients with RPL as currently defined by the American Society for Reproductive Medicine practice guidelines and according to the international recommendations for proper laboratory testing. Secondary objectives were to determine the costs associated with aPL testing and the clinical factors associated with aPL positivity among patients with RPL. The University of Iowa Institutional Review Board reviewed and approved the methods for this study (IRB# 202112378). We conducted a cohort study of 506 consecutive patients seen at the University of Iowa Hospitals and Clinics and tested for aPLs during evaluation for RPL between August 2, 2014 and December 31, 2021. RPL was defined as 2 or more failed clinical pregnancies before 20 weeks of gestational age as documented by ultrasonography or histopathological examination (1The Practice Committee of the American Society for Reproductive Medicine. Evaluation and treatment of recurrent pregnancy loss: a committee opinion.Fertil Steril. 2012; 98: 1103-1111Abstract Full Text Full Text PDF PubMed Scopus (746) Google Scholar). Among those tested for aPLs for pregnancy losses, 114 did not meet the American Society for Reproductive Medicine definition of RPL as they had <2 clinical miscarriages combined with 1 or more biochemical pregnancies. Of note, none were positive for aPLs. These patients were not included in the 506-woman RPL study population. For comparison, we reviewed the results of aPL testing of 199 female patients with ICD-10-CM diagnosis codes of systemic lupus erythematosus (SLE) ordered by the University of Iowa Hospitals and Clinics rheumatologists over the same time. All patients were tested for lupus anticoagulant, and IgG and IgM isotypes of anticardiolipin antibodies, as well as anti-β2-glycoprotein-I antibodies. Per international guidelines, a high titer of aPL (for our laboratory, >20 IU/mL) should be detected again with confirmatory testing at least 12 weeks after the initial testing (2Devreese K.M.J. Ortel T.L. Pengo V. de Laat B. Laboratory criteria for antiphospholipid syndrome: communication from the SSC of the ISTH.J Thromb Haemost. 2018; 16: 809-813Abstract Full Text Full Text PDF PubMed Scopus (159) Google Scholar). A chart review was performed to collect variables of interest for the RPL study group. The laboratory charges were provided by our center's patient billing services. Total accrued laboratory charges were calculated by summing the total number of tests performed and multiplying by the laboratory charge for the respective test. Details of all the patients with RPLs are found in Table 1, and details about those with RPL and persistently positive aPLs are found in Table 2. Further details about antibody testing and statistical analysis are available in Supplemental Methods (available online).Table 1Characteristics of the RPL population (N = 506).VariableMean ± SDRangeAge (y)32.3 ± 5.518–47BMI (kg/m2)30.5 ± 7.817.0– 60.8Gravidity4.6 ± 2.52–8Parity1.1 ± 1.20–6# of first trimester miscarriages2.7 ± 1.70–16# of second-trimester miscarriages0.3 ± 0.60–5# of clinical miscarriages3.1 ± 1.72–16# of biochemical pregnancies0.2 ± 0.60–5N%Mullerian or uterine anomalies142.8%fibroids5611.1%Asherman's or uterine cavity scarring30.6%Diabetes mellitus275.3%Type 181.6%Type 2193.8%Autoimmune disorder224.4%Hypothyroidism7013.8%Primary5811.5%Subclinical112.2%Gestational10.2%History of thromboses163.2%# of karyotypes performed∗includes maternal and/or paternal karyotyping20340.1%Parental chromosomal abnormalities42.0%percent of chromosomal abnormalities per test performed# of women with a prior live birth30159.5%RaceWhite40379.6%Black and African American499.7%Hispanic and Latino295.7%Asian224.4%Unknown30.6%BMI = body mass index; RPL = recurrent pregnancy loss.∗ includes maternal and/or paternal karyotyping∗∗ percent of chromosomal abnormalities per test performed Open table in a new tab Table 2Patients with RPL and confirmed positive aPLs.Pregnancy lossesAge (y)BMI (kg/m2)ParityFirst trimesterSecond trimesterFirst aPLs resultSecond aPLs resultHistory of clotting event or preeclampsia?3560.8040LACLACPulmonary embolism4230.5130LACLACNone3236.8111LACLACNone3538.2120LACLACNone3035.0011LACLACNone2939.8020LAC aCL– IgG 110 IU/mLLAC aCL – IgG 104 IU/mLStroke3744.1640anti-β2GPI – IgM 112 IU/mLanti-β2GPI – IgM 78 IU/mLNone3230021anti-β2GPI – IgG 29 IU/mLanti-β2GPI – IgG 39 IU/mLNone2747.3311LAC anti-β2GPI –IgM 28 IU/mLanti-β2GPI – IgM 24 IU/mLPreeclampsia3628.8030aCL – IgM 50 IU/mLanti-β2GPI – IgM 48 IU/mLaCL – IgM 51 IU/mLanti-β2GPI – IgM 59 IU/mLNone3527.1111aCL – IgM 48 IU/mLanti-β2GPI – IgM 44 IU/mLaCL – IgM 53 IU/mLanti-β2GPI – IgM 49 IU/mLNone3523.9520aCL – IgG 28 IU/mLanti-β2GPI – IgG 26 IU/mLaCL – IgG 26 IU/mLanti-β2GPI – IgG 23 IU/mLPreeclampsia3321.9111aCL– IgG 113 IU/mL– IgM 23 IU/mL anti-β2GPI – IgG 113 IU/mL– IgM 25 IU/mLaCL – IgG 29 IU/mLanti-β2GPI – IgG 20 IU/mLNoneaCL = anticardiolipin antibodies; anti-β2GPI = anti-β2-glycoprotein-I antibodies; aPLs = antiphospholipid antibodies; LAC = lupus anticoagulant; RPL = recurrent pregnancy loss. Open table in a new tab BMI = body mass index; RPL = recurrent pregnancy loss. aCL = anticardiolipin antibodies; anti-β2GPI = anti-β2-glycoprotein-I antibodies; aPLs = antiphospholipid antibodies; LAC = lupus anticoagulant; RPL = recurrent pregnancy loss. Forty-eight (9.5%) of 506 patients with RPL had initial positive results for aPLs, but only 13 (2.6%) of 506 had persistent aPLs at or after 12 weeks. By comparison, 40 (20.1%) of 199 female patients with an SLE diagnostic code had an initial positive result, and 19 (9.6%) of 199 women had persistently high aPLs (2.6% vs. 9.6%, P<.001, Supplemental Table 1, available online). The mean antibody titers among patients with RPLs with at least 1 positive result were lower than those in patients with SLE (range of 38.6–48.8 IU/mL vs. range of 69.4–78.9 IU/mL, respectively), reaching statistical significance for the IgM isotypes anticardiolipin antibodies and anti-β2-glycoprotein-I antibodies (Supplemental Table 2, available online). The number needed to test to find 1 confirmed positive result was 39 in the RPL population vs. 11 in the SLE population. There was a total of $947,507 and $352,519 in aPL laboratory charges in the populations with RPL and SLE, respectively (Supplemental Table 3, available online). The cost for finding 1 patient with RPL with persistently positive aPLs was $72,885, which was 4 times the cost ($18,554) in the SLE group. A history of thrombotic events was more common in patients with RPLs with positive aPLs than in those with negative aPLs (15.4% vs. 2.8%, P=.06). Having at least 1 second-trimester pregnancy loss was significantly more common in patients with positive aPLs (46.2% vs. 19.1%, P=.04). We found confirmed positive aPLs in 6 of 100 women with at least 1 second-trimester loss vs. 7 of 406 with only first trimester losses (6% vs. 1.7%, P=.027). Among patients with RPL, there was no significant difference in age, parity, or body mass index between those with positive vs. negative aPL tests. The prevalence of positive aPLs in a healthy general population has been reported between 1% and 5%, the same prevalence we and others are now finding in large populations with RPL (3Petri M. Epidemiology of the antiphospholipid antibody syndrome.J Autoimmun. 2000; 15: 145-151Crossref PubMed Scopus (404) Google Scholar, 4Bowman Z.S. Wünsche V. Porter T.F. Silver R.M. Branch D.W. Prevalence of antiphospholipid antibodies and risk of subsequent adverse obstetric outcomes in women with prior pregnancy loss.J Reprod Immunol. 2015; 107: 59-63Crossref PubMed Google Scholar, 5Shehata H. Ali A. Silva-Edge M. Haroon S. Elfituri A. Viswanatha R. et al.Thrombophilia screening in women with recurrent first trimester miscarriage: is it time to stop testing? - a cohort study and systematic review of the literature.BMJ Open. 2022; 12e059519Crossref PubMed Scopus (8) Google Scholar). The 14th International Congress on Antiphospholipid Antibodies Task Force concluded that the association between positive aPLs and RPLs remains inconclusive. Combined with weak evidence for the effectiveness of treating aPLs to prevent miscarriage, this leads us to question routine testing of aPLs in all patients with RPLs. Our findings suggest that a more cost-effective approach may be to test only those patients who have RPL with a history of a thrombotic event or second-trimester pregnancy loss.

INTRODUCTION:Screening for hepatitis C virus (HCV) is performed by testing for anti-HCV antibodies, which may yield false-positive results leading to additional testing and other downstream consequences for the patient. We report our experience in a low prevalence population (<0.05%) using a two-assay algorithm aimed at testing specimens with borderline or weak positive anti-HCV reactivity in the screening assay by a second anti-HCV assay prior to confirming positive anti-HCV results with RT-PCR.MATERIALS AND METHODS:Retrospective analysis of 58,908 plasma samples was obtained over a 5-year period. Samples were initially tested using the Elecsys Anti-HCV II assay (Roche Diagnostics), with borderline or weakly positive results (defined in our algorithm as a Roche cutoff index of 0.9-19.99) reflexively analyzed using the Architect Anti-HCV assay (Abbott Diagnostics). The Abbott anti-HCV results dictated the final anti-HCV interpretation for reflexed samples.RESULTS:Our testing algorithm resulted in 180 samples requiring second-line testing, with final anti-HCV results interpreted as 9% positive, 87% negative, and 4% indeterminate. The positive predictive value (PPV) of a weakly positive Roche result was 12%, which was significantly lower than the PPV using our two-assay approach (65%).CONCLUSIONS:The incorporation of a two-assay serological testing algorithm in a low prevalence population provides a cost-effective method of improving the PPV of HCV screening in specimens with borderline or weakly positive anti-HCV results.

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is arranged as a trimer on the virus surface, composed of three S1 and three S2 subunits. Infected and vaccinated individuals generate antibodies against spike, which can neutralize the virus. Most antibodies target the receptor-binding domain (RBD) and N-terminal domain (NTD) of S1; however, antibodies against other regions of spike have also been isolated. The interhost variability in domain specificity and relative neutralization efficacy of the antibodies is still poorly characterized. To this end, we tested serum and plasma samples collected from 85 coronavirus disease 2019 (COVID-19) convalescent subjects. Samples were analyzed using seven immunoassays that employ different domains, subunits, and oligomeric forms of spike to capture the antibodies. Samples were also tested for their neutralization of pseudovirus containing SARS-CoV-2 spike and of replication-competent SARS-CoV-2. While the total amount of anti-spike antibodies produced varied among convalescent subjects, we observed an unexpectedly fixed ratio of RBD- to NTD-targeting antibodies. The relative potency of the response (defined as the measured neutralization efficacy relative to the total level of spike-targeting antibodies) also exhibited limited variation between subjects and was not associated with the overall amount of antispike antibodies produced. These studies suggest that host-to-host variation in the polyclonal response elicited against SARS-CoV-2 spike in early pandemic subjects is primarily limited to the quantity of antibodies generated rather than their domain specificity or relative neutralization potency. IMPORTANCE Infection by SARS-CoV-2 elicits antibodies against various domains of the spike protein, including the RBD and NTD of subunit S1 and against subunit S2. The antibody responses of different infected individuals exhibit different efficacies to inactivate (neutralize) the virus. Here, we show that the observed variation in the neutralizing activity of the antibody responses in COVID-19 convalescent subjects is caused by differences in the amounts of antibodies rather than their recognition properties or the potency of their antiviral activity. These findings suggest that COVID-19 vaccine strategies that focus on enhancing the overall level of the antibodies will likely elicit a more uniformly efficacious protective response.

Objective: To determine if ABO blood group, age, body mass index (BMI), or symptomatic COVID-19 infection are associated with COVID-19 antibody response in unvaccinated COVID-19 antibody positive pregnant women at time of delivery. Methods: At the time of delivery, 2,499 consecutive pregnant women were tested for ABO blood group and antibodies to both the spike protein and nucleocapsid protein of the COVID-19 virus. The DiaSorin assay was used for antibody to spike protein analysis and the Roche assay for antibody to nucleocapsid protein. Gamma regression models with a log link were used to compare antibody signals, with blood group, age, and BMI as the predictors. Results: 260 (10.4%) of 2,499 women who had not been vaccinated for COVID-19, were positive for both spike and nucleocapsid protein antibodies to COVID-19. The mean signal for COVID-19 nucleocapsid antibody was significantly lower for blood group AB (p=0.028) compared with blood group O. A relationship between blood group and presence of symptomatic COVID-19 was detected (p = 0.028), with asymptomatic individuals having blood group B at a higher rate than the symptomatic individuals do. No other significant pairwise differences between blood groups were detected. There was no significant difference in signal level of antibodies to COVID-19 spike protein between any of the blood groups. Mean signals for antibodies to spike and nucleocapsid proteins were significantly higher in older women (p=0.001 for spike protein antibody and p=0.002 for nucleocapsid antibody). Significantly higher signal levels of antibody to spike and nucleocapsid proteins were found in women with class 2/3 obesity (p=0.022 and p=0.003, respectively). Conclusions: Pregnant women of AB blood group had lower antibody signal to nucleocapsid protein compared to the O blood group, and women of older age and greater BMI had higher antibody signal to COVID-19 spike and nucleocapsid proteins. There was a significant association between women with blood group B and asymptomatic infections.

BACKGROUND:The measurement of plasma concentrations of retinol binding protein is a component of nutritional assessment in neonatal intensive care. However, serial testing in newborns is hampered by the limited amount of blood that can be sampled. Limitations are most severe with preterm infants, for whom close monitoring may be most important.METHODS:We developed an assay to quantify retinol binding protein using trypsin digestion and liquid chromatography-tandem mass spectrometry, which requires a serum or plasma volume of 5 µl. Additionally, we validated the method according to current recommendations and performed comparison with a standard nephelometry platform in clinical use.RESULTS:The assay demonstrated linearity from below 1 mg/dL (0.48 µM) to more than 20 mg/dL (9.7 µM), and an imprecision of 11.8% at 0.43 mg/dL (0.21 µM). The distribution of results observed with the new method was different when compared with nephelometry.CONCLUSION:Liquid chromatography-tandem mass spectrometry facilitated testing a smaller sample volume, thereby increasing the ability to monitor key nutritional markers in premature infants. The differences in results compared with a commercially-available nephelometric assay revealed questionable results for lower concentrations by immunoassay.

Purpose. Oral factor Xa inhibitors (FXaIs) are increasingly utilized for outpatient anticoagulation therapy; however, laboratory monitoring is not routinely used to assess the safety and efficacy of these agents. We aimed to evaluate the role of chromogenic anti-factor Xa (anti-Xa) assays in the emergency department (ED) in the setting of patients with an acute bleed or requiring emergent procedures. Methods. A retrospective review of anti-Xa levels obtained in the ED between June 1, 2019, and April 30, 2020, was completed. Data were collected to describe the clinical setting of anti-Xa level collection, oral FXaIs used before admission, administration of reversal agents, and patient disposition to further characterize the role of anti-Xa levels in the management of rivaroxaban and apixaban reversal. Results. Thirty anti-Xa levels were included in the final analysis. The median time from sample collection to anti-Xa assay result was 45.9 minutes (interquartile range, 35.3-54.7 minutes). Eleven patients (37%) received anticoagulation reversal after their anti-Xa levels were determined. Anticoagulation reversal agents included either activated prothrombin complex concentrates (aPCCs) or prothrombin complex concentrates (PCCs). Anti-Xa levels were collected in 2 patients who had received PCCs before arrival at our ED. Of the patients with anti-Xa levels below 30 ng/mL, none received aPCCs or PCCs after their anti-Xa levels were determined. Anti-Xa assays were used to rule out the presence of FXaIs in 3 patients. Conclusion. This study illustrates the novel role of anti-Xa levels in managing patients with an emergent need for reversal in the ED. The assay may be used to rule out the presence of oral FXaIs and avoid unnecessary administrations of anticoagulation reversal agents.

INTRODUCTION:Maternal obesity has been linked to adverse outcomes for mothers and their offspring, including, but not limited to gestational hypertension (gHTN), gestational diabetes (GDM), pre-eclampsia, fetal macrosomia, and emergency cesarean section. Recent investigations have also shown that obesity, as defined by a body mass index (BMI) ≥ 30, especially severe obesity (BMI ≥ 40), is a risk factor for both hospitalization and death from COVID-19.OBJECTIVES:The objective of this study is to determine the prevalence and association of maternal obesity at delivery with adverse antenatal, intrapartum, and neonatal outcomes in a cohort of consecutive delivering patients at a tertiary care center in Iowa from May to September 2020. A secondary objective is to determine if maternal obesity has any relationship to past or current COVID-19 infection status at the time of delivery. This is a secondary analysis of a prospective cohort study to analyze obstetric outcomes among COVID-19 infected and uninfected patients.METHODS:We conducted a prospective cohort study using demographic and clinical data obtained from the electronic medical record. Excess plasma was collected from routine blood samples obtained at delivery admission to determine the seroprevalence of COVID-19 antibody using the DiaSorin and Roche antibody assays. Frequency variables were each calculated separately, and a comparison of maternal and neonatal outcomes was conducted using the generalized linear mixed modeling (GLMM) framework to account for varying distributions (normal and binary).RESULTS:1001 women delivered during the study period and 89.7% met criteria for being overweight or obese; 17.9% met criteria for severe obesity. Women with obesity had 49.8% lower odds of possessing private insurance, and women with severe obesity were less than half as likely to plan to breastfeed at the time of discharge. Women with obesity of any kind had a significantly increased odds of GDM and gHTN, and an increased risk of an infant with macrosomia, hypoglycemia, and NICU admission. No significant association was found between BMI and COVID-19 infection or disease severity.CONCLUSION:This study provides insight into obstetric complications facing women with obesity, especially those with severe obesity. This report serves to highlight potential challenges, such as insurance status and labor complications, that impact women of high BMI to a greater degree when compared to their normal-weight counterparts.

Pain, in the appropriate context, is an essential component of life. It alerts us to danger, promotes healing, and plays a critical psychological role in normal growth and development. Chronic pain, in contrast, is physically and emotionally debilitating, and lies at the heart of some of the greatest challenges to our modern society. According to the Centers for Disease Control and Prevention, approximately 1 in 5 Americans suffer from chronic pain, costing an estimated $560 billion annually due to lost productivity, direct healthcare expenditures, and disability. Furthermore, well-intentioned efforts to combat chronic pain have contributed to an opioid crisis that has claimed an estimated 500 000 lives and continues to ravage vulnerable communities. Here we highlight recent studies seeking to better understand the physiologic underpinning of pain by examining the close relationship between the peripheral nervous system and cells of the immune system. In a recent review, Kavelaars and Heinjen explore the interface between neurons and cells of the innate and adaptive immune systems, providing compelling evidence that the two are tightly intertwined within the context of pain (1). The language through which neurons and immune cells communicate, namely cytokines and chemokines, is fundamental to the understanding of this so-called “neuroimmune pain circuit.” If one broadly divides these chemical signals, and the cells producing them, into pro- and anti-inflammatory groups, it is becoming increasingly evident that pro-inflammatory cytokines facilitate the transmission of and sensitization to pain, whereas anti-inflammatory signals mediate pain tolerance and promote its resolution. Several lines of evidence now support this notion and indeed, these observations fit nicely into the larger conceptual framework in immunology that seeks to classify subpopulations of cells by their pro- or anti-inflammatory phenotype.

Molecular techniques, especially reverse transcriptase polymerase chain reaction (RT-PCR), have been the gold standard for the diagnosis of acute severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Serological tests for SARS-CoV-2 have been widely used for serosurveys, epidemiology, and identification of potential convalescent plasma donors. However, the clinical role of serologic testing is still limited and evolving. In this report, we describe the experience of selecting, validating, and implementing SARS-CoV-2 serologic testing for clinical purposes at an academic medical center in a rural state. Successful implementation involved close collaboration between pathology, infectious diseases, and outpatient clinics. The most common clinician concerns were appropriateness/utility of testing, patient charges/insurance coverage, and assay specificity. In analyzing test utilization, serologic testing in the first month after go-live was almost entirely outpatient and appeared to be strongly driven by patient interest (including health care workers and others in high-risk occupations for exposure to SARS-CoV-2), with little evidence that the results impacted clinical decision-making. Test volumes for serology declined steadily through October 31, 2020, with inpatient ordering assuming a steadily higher percentage of the total. In a 5-month period, SARS-CoV-2 serology test volumes amounted to only 1.3% of that of reverse transcriptase polymerase chain reaction. Unlike reverse transcriptase polymerase chain reaction, supply chain challenges and reagent availability were not major issues for serology testing. We also discuss the most recent challenge of requirements for SARS-CoV-2 testing in international travel protocols. Overall, our experience at an academic medical center shows that SARS-CoV-2 serology testing assumed a limited clinical role.

Objectives: The aims of this study were to identify the causes of severe icterus in an academic medical center patient population and to assess the impact of icterus on clinical chemistry testing using assay package insert thresholds. Design: and Methods: In this retrospective study at an academic medical center core clinical laboratory, icteric, hemolysis, and lipemia indices were available for all serum and plasma chemistry specimens analyzed on Roche Diagnostics cobas 8000 analyzers over a 12-month period, encompassing 414,502 specimens from 94,081 unique patients (51,851 females; 42,230 males) including children, inpatient, outpatient, and emergency department patients. Extensive chart review was done for all 57 patients (4 pediatric, 53 adult; 534 total specimens) who had one or more samples with an icteric index of 40 or higher (defined as severe icterus). Results: Specimen icteric index exceeded package insert icteric index thresholds in 0.14% of clinical chemistry assays, with the highest number of instances for creatinine (1358 samples, 0.6% of total tests), total protein (1194 samples, 2.2%), and ammonia (161 samples, 3.9%). The 57 patients with an icteric index of 40 or higher accounted for 49.7% of all instances where the icteric index exceeded the specific assay package insert limit. The most common etiologies of this group of 57 patients were alcohol-related liver disease (34 patients), biliary tract disease (7 patients), and neoplasms (6 patients). Conclusions: Approximately half of all instances where specimen icteric index exceeded assay package insert thresholds occurred in a small cohort of patients with severe liver/biliary tract disease.