OBJECTIVE:False-reactive results of the fourth-generation HIV-1/2 antigen/antibody (Ag/Ab) Combo assay trigger additional testing, increased costs, and patient anxiety. Large-scale analyses of false-reactive results spanning the COVID-19 pandemic in high-prevalence communities are lacking. This study aims to investigate the frequency of false-reactive HIV-1/2 Ag/Ab Combo screening results before, during, and after the COVID-19 pandemic and to identify associated patient factors. DESIGN:We conducted a retrospective study of HIV-1/2 Ag/Ab Combo assays performed from 2019 to 2024 at a tertiary care medical center in Baltimore, MD. False-reactive proportions were compared across pre-pandemic (January - December 2019; n = 12,347), pandemic (January 2020 - June 2023, n = 33,546), and post-pandemic (July 2023 - December 2024; n = 12,238). Associations between false-reactive results and selected patient factors were assessed. RESULTS:Among 58,131 screens, 1236 (2.1%) were reactive; 185 were false-reactive, yielding a false-reactive proportion of 15.0% among reactive results. The false-reactive proportion increased from 5% pre-pandemic to 17.9% at the onset of the COVID-19 pandemic and remained near 20% during the pandemic, declining to approximately 14% by 2024 post-pandemic. In multivariable analysis, age > 65 or < 21, White race, and American Indian/Alaska Native race were associated with higher odds of false-reactive results, whereas coinfection of syphilis was associated with lower odds. Most false-reactive results clustered at low signal-to-cutoff ratio (S/CO) values. CONCLUSIONS:False-reactive HIV Ag/Ab screening results increased during the pandemic and remained elevated afterward. Associated factors analysis and S/CO distributions may help interpretation of questionable reactive screens. Our findings reinforce the importance of reflex HIV nucleic acid testing (NAT) for discordant results.

BACKGROUND:Residual major adverse cardiovascular event (MACE) risk persists despite successful prevention of cardiovascular disease (CVD) with statin therapy among people with HIV (PWH). Identifying key biomarkers related to residual cardiovascular risk is critical for PWH. OBJECTIVES:The objective of the current analysis was to assess the association of immune, inflammatory, cardiac, and lipid-related biomarkers among contemporary antiretroviral therapy-treated PWH in the REPRIEVE global primary cardiovascular prevention trial in residual risk analyses. METHODS:We assessed relationships of baseline inflammatory, cardiac, and lipid-related biomarkers to incident MACE using Cox models adjusted for randomized statin treatment and atherosclerotic CVD risk. Population attributable fractions (PAFs) were assessed for biomarkers. RESULTS:Of the 7769 REPRIEVE participants, 7,005 (90%) had biomarker data available at baseline, with the median follow-up of 5.6 years. Relatively high percentages of participants had elevated inflammatory (high-sensitivity C-reactive protein >3 mg/L [49%], interleukin [IL]-6 ≥3.3 pg/mL [33%]) and cardiac markers (high-sensitivity troponin ≥6 ng/L [35%], N-terminal pro-B-type natriuretic peptide ≥50 pg/mL [33%]). Inflammatory biomarkers showed minimal correlation with cardiac or lipid biomarkers (apolipoprotein B-100, oxidized low-density lipoprotein, and lipoprotein(a)). Individual biomarkers were related to MACE in analyses adjusted for PCE and statin randomization, with the largest HRs for IL-6 (HR: 2.2; 95% CI: 1.3-3.9) and high-sensitivity troponin (HR: 2.2; 95% CI: 1.2-4.1) comparing those with highest vs lowest biomarker levels. PAFs were highest for IL-6, 18.6% (95% CI: 7.4%-30.5%) and high-sensitivity C-reactive protein 17.2% (95% CI: 1.6%-32.9%). CONCLUSIONS:Among PWH with low-moderate predicted CVD risk and well-controlled HIV, persistent inflammation, innate immune activation, and subclinical cardiac dysfunction are common, and strongly relate to residual MACE risk, accounting for a large PAF. (Evaluating the Use of Pitavastatin to Reduce the Risk of Cardiovascular Disease in HIV-Infected Adults [REPRIEVE]; NCT02344290.

BACKGROUND:Ruling out myocardial infarction (MI) in patients with an initial indeterminate (detectable to mildly elevated) troponin measure is challenging. Myocardial-Ischaemic-Injury Index (MI3) is a machine-learning algorithm designed to diagnose MI, but its utility in patients with indeterminate troponins is unclear. This study seeks to evaluate its diagnostic performance in patients with an initial indeterminate troponin. METHODS:We conducted a secondary analysis of a cohort (Cardiovascular Magnetic Resonance-Invasive-based Strategies in Patients with Chest Pain and Detectable to Mildly Elevated Serum Troponin) of adult patients with symptoms suggestive of acute coronary syndrome and an initial clinical contemporary troponin of 0.006-1.0 ng/mL across four US hospitals. Patients with initial and 3-hour high-sensitivity cardiac troponin I (Abbott Laboratories) measures were classified by MI3 into low-risk, intermediate-risk and high-risk groups. The primary outcome was adjudicated MI at 30 days. The sensitivity, specificity and negative likelihood ratio (-LR) of MI3 for MI at 30 days were calculated and reported with 95% CIs. A receiver operator characteristics curve for MI at 30 days was created and area under the curve (AUC) for MI3 was calculated. RESULTS:Among 207 patients, 34.3% (71/207) were female with a mean age of 61±11 years. MI at 30 days occurred in 43.5% (90/207). The AUC for MI3 for the detection of MI at 30 days was 0.882 (95% CI 0.833 to 0.932). MI3 classified 34.8% (72/207) of patients as low-risk, of which 8.3% (6/72) had MI at 30 days, yielding a sensitivity of 93.3% (95% CI 86.1 to 97.5%) and -LR of 0.12 (95% CI 0.05 to 0.26). Among the 47.3% (98/207) classified as intermediate-risk, MI at 30 days occurred in 48.0% (47/98). MI3 classified 17.9% (37/207) as high-risk, among which 100% (37/37) had MI at 30 days, yielding a specificity of 100% (95% CI 96.9% to 100%). CONCLUSIONS:Among emergency department patients with an initial indeterminate troponin measure, the MI3 machine-learning algorithm had high AUC and specificity for 30-day MI.

A challenge in the implementation of rapid risk-stratification algorithms for patients with suspected acute coronary syndrome is the turnaround time for cardiac troponin (cTn) from blood sampling to reporting of results. Measurement of cTn in whole blood using point of care (POC) offers a solution. There is lack of consensus on how these instruments should be assessed and deployed when implemented into routine practice. A pragmatic strategy is needed to balance the requirement for appropriate evaluation, validation and local verification of POC high sensitivity (hs) cTn assays whilst avoiding unnecessary duplication of previously conducted work using central laboratory assays. The International Federation of Clinical Chemistry and Laboratory Medicine Committee on Clinical Application of Cardiac Bio-Markers (IFCC C-CB) has developed an educational document to provide practical suggestions as to how hs-cTn POC assays may be implemented in acute health care settings and networks. The objective of this document is to provide a pragmatic framework for implementation of such systems. The article describes the validation and verification procedures and outlines what should be the responsibility of the manufacturers and provides recommendations on how a local verification may be undertaken before instruments are implemented into routine clinical practice.

Transdermal biosensors may provide an alternative to conventional blood-based biomarker measurement. Our purpose was to determine the binary correlation between transdermal (Infrasensor™; RCE, Inc, Carlsbad, CA) and conventional blood-based measurements. This was a secondary analysis from a previously published observational cardiac troponin I (cTnI) study performed to establish the upper reference level of cTnI, at 10 US hospitals. After obtaining informed consent, 2 cohorts of patients were enrolled: 1) those who completed a health assessment questionnaire and appeared healthy, and 2) those with a known elevated cTnI per the local hospital standard assay. All blood lab analyses were performed at the University of Maryland Medical Center, Baltimore, MD. Normal was defined as cTnI <53.48 ng/L (male) or 34.11 ng/L (female) using the Siemens Atellica IM assay (Siemens Medical Solutions, Mountain View, CA), NT-proBNP <450 pg/mL (>75 years) or <124 pg/mL (<75 years), creatinine >1.17 mg/dL (male) or >0.95 mg/dL (female), and HbA1c <6.4%. The Infrasensor was placed on the patient’s wrist for measurement and blood drawn for analysis at approximately the same time. Of 840 enrolled patients, the median (IQR) age was 46 (30,57), 416 (49.5%) were female, 10.36% Hispanic, 6.7% Asian, 12.9% African American, and 69.1% White. Elevated lab tests were 102 hscTnI’s, 156 NTproBNP’s, 37 HbA1C’s, and 163 creatinine’s. Significant binary correlations were found between all transdermal signals and the corresponding lab blood levels Infrasensor transcutaneous measurement demonstrates similar results as that obtained from blood testing in the central laboratory. The Infrasensor (RCE, Inc, Carlsbad, CA, USA) is rapid point of care transcutaneous biomarker measurement device. This study evaluated its ability to provide qualitative results for troponin I, NTproBNP, creatinine, and HbA1c levels in 840 patients. Significant correlations were found between all transdermal signals and the corresponding binary lab blood levels.

BACKGROUND:Critical illness in coronavirus disease 2019 may require extracorporeal membrane oxygenation support. We quantified immunothrombotic markers in patients with COVID-19 receiving ECMO and evaluated their predictive capacity for death. METHODS:We performed a retrospective analysis of 74 consecutive patients with COVID-19 on ECMO at a single academic medical center between March 2020 and February 2021. Severe acute respiratory syndrome coronavirus-2 nucleocapsid RNA and 16 immunothrombotic biomarkers were longitudinally quantified and their trajectories were used to predict death and decannulation across multiple models. RESULTS:Male sex, smoking, serum bilirubin levels, and low partial arterial oxygen pressure-fraction of inspired oxygen ratio were associated with increased risk of death. Plasma levels of 10 immunothrombotic markers were significantly elevated in fatal cases and some were associated with an increased hazard of death (eg, interleukin 8, von Willebrand factor) or decreased hazard for decannulation (eg, angiopoietin 2, interleukin 1β) when adjusting for sex, smoking status, and time to cannulation. Predictive models incorporating biomarkers were superior to demographics alone and equivalent to models including clinical information. CONCLUSIONS:We found that male sex, smoking, and select clinical variables and immunothrombotic markers were risk factors for death in patients with COVID-19 on ECMO informing pathogenesis and prognostication of severe COVID-19.

High-sensitivity cardiac troponin (hs-cTn) assays are the gold standard for the early diagnosis and risk stratification of acute myocardial infarction (AMI). PERFORM-TSIX (clinicaltrials.gov identifier: NCT06734117) is a prospective, international, observational, longitudinal cohort study to evaluate the clinical performance of the next-generation Elecsys® Troponin T hs Gen 6 assay; the study design is presented here. The primary objective is to determine the sensitivity of the Troponin T hs Gen 6 assay for the detection of centrally adjudicated AMI diagnosis at 3 h post-emergency department (ED) presentation. Secondary objectives include evaluation of clinical performance at 0, 1-, 5-, and 6-h post-ED presentation and validation of thresholds for a 0/1-h algorithm to rule out AMI. Exploratory objectives include validation of thresholds for a 0/1-h algorithm to rule in AMI and a 0/2-h algorithm to rule in/out AMI and evaluation of prognostic performance at 30 and 180 days. PERFORM–TSIX enrolled 5631 participants across 50 sites from the USA, Europe, China, and Japan. Patients aged ≥ 20 years presenting to the ED with symptoms/signs of acute coronary syndrome were enrolled. All patients were required to have cTn measured as part of their routine care; AMI diagnosis was adjudicated by an independent clinical events committee in accordance with the Fourth Universal Definition of MI, blinded to the results of the Troponin T hs Gen 6 assay. PERFORM-TSIX will determine the clinical performance of the Troponin T hs Gen 6 assay for the diagnosis of AMI in a large, diverse global population.

BACKGROUND:High-sensitivity cardiac troponin (hs-cTn) assays are recommended for the diagnosis of acute myocardial infarction. Here, we characterize the analytical performance of a next-generation hs-cTn assay, Elecsys® Troponin T hs Gen 6 (Roche Diagnostics International). METHODS:Surplus lithium-heparin plasma or serum samples from patients or healthy volunteers were run on Cobas® e 801, e 402, and Pro analyzers. Limits of blank (LoB), limits of detection (LoD), and limits of quantitation (LoQ) were determined according to CLSI EP17-A2, with target values of 1.0 and 1.5 ng/L for LoB/LoD and 3.0 ng/L (10% CV) and 1.5 ng/L (20% CV) for LoQ, respectively. Precision was measured, per CLSI EP17-A2, using 3 QC samples (approximately 4, 30, and 220 ng/L), 12 native samples, and 3 reagent lots. Linearity, per CLSI EP06-Ed2, was determined by diluting samples with cardiac troponin T (cTnT) concentration above the measuring range with a low/blank sample. Interference (per Glick) with endogenous and assay components at 5 cTnT concentrations was assessed. RESULTS:Measured values for LoB, LoD, and LoQ at 10% and 20% CV were 0.1 to 0.7 ng/L, 0.3 to 1.4 ng/L, 1.0 to 2.9 ng/L, and 0.4 to 1.2 ng/L, respectively. Repeatability CVs were 1.0 to 5.8% for mean cTnT concentrations of 2.6 to 9230 ng/L in lithium-heparin plasma. High precision was shown across lots, and linearity was observed across the measuring range (1.5 to 9500 ng/L, all Pearson's r = 1.00). No interferences were observed, specified up to ≤1000 mg/dL hemoglobin, ≤50 mg/dL [≤855 µmol/L] icterus/bilirubin, and ≤1200 ng/mL biotin. CONCLUSIONS:The analytical performance characterization of the assay demonstrated high sensitivity, high precision at the low end and across the measuring range, and resistance to interference.

Complement activation is a major barrier to xenotransplantation. We report detailed complement monitoring in a 58-year-old man who received a 10 gene-edited porcine heart expressing human complement regulators CD46 and CD55. Despite these transgenes and prophylactic systemic complement inhibition with C1 esterase inhibitor (C1INH), early surveillance biopsy on post-operative day (POD) 13 showed significant histologic evidence of complement deposition with C3d and C4d within capillaries and endothelial activation. In light of these findings, treatment was escalated to terminal complement inhibition using eculizumab. Post-operative complement activity was assessed via immunohistochemistry and dynamic ex vivo serum assays, including a novel bioluminescent modified Ham (bmHam) assay. Following eculizumab initiation, serum sC5b-9 dropped to undetectable levels, and bmHam cytotoxicity decreased significantly, confirming terminal pathway inhibition. Dilutional bmHam assays further demonstrated stronger complement blockade with eculizumab than with C1INH. However, repeat transplant biopsy on POD 30 biopsy showed persistence of anti-C4d+ and anti-C3c+ staining, and increased C5b-9 compared to POD13. This breakthrough was identified by the dilutional bmHam but was not detected by changes in CH50 or sC5b-9. These findings highlight the potential need for early terminal complement inhibition and integrated functional monitoring as critical components of xenotransplant management.

BACKGROUND:Serial Highly Sensitive Cardiac Troponin I (hscTnI) measures are commonly performed in patients presenting to the ED to exclude suspected Acute Myocardial Infarction (AMI). The previously published FAST-TRAC study prospectively enrolled patients presenting to the ED within 6 h of onset of symptoms consistent with suspected AMI. Our purpose was to evaluate the performance of a single hscTnI measurement, termed "one-and-done" using this cohort. METHODS:In emergency department suspected acute coronary syndrome patients, serial blood samples were prospectively obtained for blinded hscTnI measurement (Access TnI, Beckman Coulter, Brea, CA) at 1, 2, 3-4, and 6-12 h after presentation. Patients were followed for 30-day Major Adverse Cardiac Events (MACE) determined by adjudicators blinded to hsTnI results. RESULTS:Of 1520 patients enrolled, 113 (7.4%) were adjudicated as AMI, with 59% male, median (IQR: Interquartile Rank) age of 57 years (48-67), 66% White, 28% African American, and 3% Asian American. The overall median (IQR) time to first hscTnI draw after symptom onset was 3.67 (2.50-5.09) hours. Serial hscTnI and one-and-done strategies had comparable C-statistics for AMI; 0.95 (0.93-0.98) vs 0.93 (0.91-0.96), respectively. In no circumstance did the 99th percentile cutpoint meet an adequate rule-out AMI sensitivity of 99%. Serial measures using either the 10% or 20% Coefficient of Variation (CV) Level of Quantification (LOQ) cutpoint had the same sensitivity of 99.1%, but the 10% CV LOQ had higher specificity, 61.7%, (95% CI = 59.1-64.2). For a "one-and-done" strategy, only the 20% CV LOQ, with a sensitivity of 99.1 (95.2-99.8), met the 99% sensitivity goal. Using the 20% CV LOQ, a "one-and-done" strategy would have immediately ruled out 39% (n = 550) of patients for AMI, with only 61% (n = 857) requiring additional serial hscTnI testing. CONCLUSIONS:A "one-and-done" strategy using a hscTnI <20% CV LOQ provides the most efficient AMI rule-out performance. REGISTRATION:NCT00880802.

BACKGROUND:N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement has class 1, level of evidence A recommendations in heart failure (HF) guidelines for diagnosis and prognosis. Analytical characterization of a novel automated NT-proBNP assay is necessary to examine its fitness for validation in pivotal clinical trials. METHODS:The Access NT-proBNP assay is an immunoenzymatic assay using monoclonal capture and detection reagents on the DxI 9000 Immunoassay Analyzer. Clinical and Laboratory Standards Institute guidelines directed limit of blank (LoB), limit of detection (LoD), limit of quantitation (LoQ), linearity, imprecision, interference, and method comparison studies. Age-specific 97.5th percentile upper reference limits (URLs) were established with 675 healthy US adults that are 54.7% female, 79% White, 15% Black, and 8% Latinx. RESULTS:LoB = 1.1 ng/L; LoD = 4.8 ng/L; LoQ = 4.8 ng/L, linearity = 25 000 ng/L; and no interfering/cross-reacting substances were identified. Repeatability and reproducibility CVs were 1.5% to 3.5% and 2.7% to 7.9%, respectively, at NT-proBNP concentrations from 38 ng/L to 23 848 ng/L. The Passing-Bablock regression equation for method comparison is Beckman Access = 0.92 * Elecsys-1.20 ng/L, r = 0.99. Age-specific 97.5th percentile URLs for the Access NT-proBNP assay are <50 years, 162 ng/L; 50 to 75 years, 311 ng/L; and >75 years, 457 ng/L. CONCLUSIONS:A method comparison showed good harmony with an established assay, and analytic parameters demonstrated satisfactory overall performance. Imprecision across the measurement range is <8%. The Access NT-proBNP assay yielded age-specific 97.5th percentile URLs in harmony with the Elecsys reference method. The Access NT-proBNP assay demonstrated robust analytical performance that is fit for the purpose of supporting an NT-proBNP clinical trial for HF diagnosis and prognosis.

Following our previous experience with cardiac xenotransplantation of a genetically modified porcine heart into a live human, we sought to achieve improved results by selecting a healthier recipient and through more sensitive donor screening for potential zoonotic pathogens. Here we transplanted a 10-gene-edited pig heart into a 58-year-old man with progressive, debilitating inotrope-dependent heart failure due to ischemic cardiomyopathy who was not a candidate for standard advanced heart failure therapies. He was maintained on a costimulation (anti-CD40L, Tegoprubart) blockade-based immunomodulatory regimen. The xenograft initially functioned well, with excellent systolic and diastolic function during the first several weeks posttransplantation. Subsequently, the xenograft developed rapidly progressing diastolic heart failure, biventricular wall thickening and, ultimately, near-complete loss of systolic function necessitating initiation of extracorporeal membranous oxygenation on day 31. Given these setbacks, the patient chose to transition to comfort care after 40 days. As with our first patient, histology did not reveal substantial immune cell infiltration but suggested capillary endothelial injury with interstitial edema and early fibrosis. No evidence of porcine cytomegalovirus replication in the xenograft was observed. Strategies to overcome the obstacle of antibody-mediated rejection are needed to advance the field of xenotransplantation. In the second case in which a genetically modified pig heart was transplanted into a living person, the xenografted heart functioned well initially, but antibody-mediated rejection occurred thereafter, pointing to the need for improved strategies to avoid this complication.

BACKGROUND: The High-STEACS (High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome) pathway risk stratifies emergency department patients with possible acute coronary syndrome. This study aims to determine if the High-STEACS hs-cTnT (high-sensitivity cardiac troponin T) pathway can achieve the ≥99% negative predictive value (NPV) safety threshold for 30-day cardiac death or myocardial infarction (CDMI) in a multisite US cohort of patients with and without known coronary artery disease (CAD). METHODS: A secondary analysis of the STOP-CP (High-Sensitivity Cardiac Troponin T [Gen 5 STAT Assay] to Optimize Chest Pain Risk Stratification) cohort, which enrolled adult emergency department patients with possible acute coronary syndrome at 8 US sites (January 25, 2017–September 6, 2018). Participants were classified into outpatient and admission dispositions using the High-STEACS hs-cTnT pathway. Known CAD was defined as prior MI, coronary revascularization, or ≥70% coronary stenosis. Outcomes included 30-day CDMI and efficacy, defined as the proportion identified for outpatient disposition. NPVs and negative likelihood ratios for 30-day CDMI were calculated. NPVs were compared between CAD subgroups using a Fisher exact test. RESULTS: Among 1351 patients, 53.2% (719/1351) were male, 31.4% (424/1351) had known CAD, and the mean age was 57.4±12.8 years. At 30 days, CDMI occurred in 13.8% (187/1351). High-STEACS classified 63.4% (857/1351) to outpatient disposition, of which 2.0% (17/857) had 30-day CDMI, corresponding to an NPV of 98.0% (95% CI, 96.8–98.8) and negative likelihood ratio of 0.13 (95% CI, 0.08–0.20). In patients with CAD, 46.9% (199/424) were classified to outpatient disposition, of which 4.0% (8/199) had 30-day CDMI. Among patients without CAD, 71.0% (658/927) were classified to outpatient disposition with 1.4% (9/658) having 30-day CDMI. The NPV for 30-day CDMI was 96.0% (95% CI, 92.2–98.2) in patients with CAD versus 98.6% (95% CI, 97.4–99.4) among patients without CAD ( P =0.04). The negative likelihood ratio for 30-day CDMI among patients with CAD was 0.16 (95% CI, 0.08–0.31) and 0.12 (95% CI, 0.06–0.22) among patients without CAD. CONCLUSIONS: The High-STEACS hs-cTnT pathway had high efficacy but was unable to achieve the ≥99% NPV safety threshold for 30-day CDMI. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02984436.

Abstract Background The fully automated 4th gen HIV Ag/Ab combo assay by Beckman Coulter, Inc. on the DxI 9000 Access Immunoassay analyzer allows for separate reporting of HIV-1 p24 Ag and HIV-1/HIV-2 Ab results, with a time to first result of ̴30 minutes and a sample volume of 60µL. To evaluate its performance, a U.S. multisite study was conducted to compare the Access HIV Ag/Ab combo assay with the ARCHITECT HIV Ag/Ab Combo assay. False positive rates were assessed in low and high risk U.S. populations with unknown HIV status by comparing the new Access HIV Ag/Ab combo assay with the ARCHITECT HIV Ag/Ab Combo assay.1 Footnotes Methods The evaluation tested 6,981 low risk and 799 high risk samples (adult, pregnant, pediatric) at 3 clinical trial sites. Following the CDC recommended algorithm, samples that initially tested reactive were subjected to duplicate testing, if repeatedly reactive, were further confirmed using the HIV 1/2 differentiation assay (Geenius HIV-1/2 Supplemental Assay, Bio-Rad), and the HIV-1 RNA PCR Assay (Aptima HIV-1 Quantitative Dx Assay, Hologic, Inc).2 Results The Access HIV Ag/Ab combo assay showed a lower incidence of false positive results (n=25) in the low risk group with a specificity of 99.6% (n=6981; 95% CI: 99.5-99.8%) compared to the ARCHITECT HIV Ag/Ab Combo assay (n=87) with a specificity of 98.8% (n=6981; 95% CI: 98.5-99.0%). Similarly, in the high risk group, the Access HIV Ag/Ab combo assay yielded fewer false positive results (n=1) with a specificity of 99.9% (n=799; 95% CI: 99.3-100.0%) than the ARCHITECT HIV Ag/Ab Combo assay (n=11) with a specificity of 98.6% (n=799; 95% CI: 97.6-99.2%). Conclusion Falsely reactive HIV test results can have significant consequences for patients and healthcare providers. Selecting an appropriate HIV assay with high sensitivity and specificity is essential. This study provides evidence that the Access HIV Ag/Ab combo assay is an attractive alternative to the ARCHITECT HIV Ag/Ab Combo assay with fewer false positive results, suggesting improved accuracy in identifying HIV infections in both low and high risk U.S. populations. Disclosures Fred S. Apple, PhD, Mindray: Advisor/Consultant|Werfen: Advisor/Consultant Robert H. Christenson, PhD, DABCC, FADLM, FACC, Beckman Coulter: Advisor/Consultant|Beckman Coulter: Grant/Research Support|Beckman Coulter: Honoraria|Becton Dickinson: Advisor/Consultant|Becton Dickinson: Grant/Research Support|Becton Dickinson: Honoraria|QuidelOrtho: Advisor/Consultant|QuidelOrtho: Grant/Research Support|QuidelOrtho: Honoraria|Roche Diagnostics: Advisor/Consultant|Roche Diagnostics: Board Member|Roche Diagnostics: Grant/Research Support|Roche Diagnostics: Honoraria|Siemens Healthineers: Advisor/Consultant|Siemens Healthineers: Board Member|Siemens Healthineers: Grant/Research Support|Siemens Healthineers: Honoraria

Beckman Coulter, Inc. has developed a fully automated Access Syphilis assay* for use on the DxI 9000 and Access 2 Immunoassay Analyzers. This assay can report results in =40 minutes using a serum or plasma sample volume of just 50 µL or less with no duplicate retesting. This study aims to evaluate the analytical and clinical performance of this assay. Imprecision and reproducibility studies were conducted in accordance with CLSI EP05-A3 on both DxI 9000 and Access 2 analyzers. Imprecision was evaluated in a 20-day, 2 runs/day, 2 replicates/run study on serum and plasma samples with three reagent lots. Reproducibility was evaluated at 3 US clinical laboratories with serum and quality control samples (n=360 reps per sample) on three reagent lots. Cross-reactivity was evaluated using 337 specimens from 35 potential cross-reactant categories from individuals with conditions unrelated to syphilis infection (e.g., infections, auto-immunity, rheumatoid factor). The clinical performance on the DxI 9000 and Access 2 analyzers was evaluated at three U.S clinical laboratories. The performance of the Access Syphilis assay was compared to a final comparator result obtained using a composite algorithm of results from commercially available syphilis assays: the Abbott Architect Syphilis TP assay, a non-treponemal assay (Becton Dickenson Macro-Vue Rapid Plasma Reagin [RPR] Card), and a second treponemal assay (Fujirebio Inc. Serodia Treponema pallidum Particle Agglutination [TP-PA]). For positive samples, imprecision of < 9% and <8% and reproducibility of <6% and <9% on Access 2 and DxI 9000, respectively, were observed. For negative samples, imprecision of <0.041 and <0.075 SD and reproducibility of <0.035 and <0.052 SD on Access 2 and DxI 9000, respectively, were observed. No cross-reactivity was observed on either platform for any sample/condition. The clinical study results demonstrated a positive percent agreement (PPA) of 100% for the Access Syphilis assay (n=184; 95% CI: 98-100%) and a negative percent agreement (NPA) of 96.7% (n=920; 95% CI: 95.4-97.7%) in the intended use population on both platforms. The newly developed Access Syphilis assay for the DxI 9000 and Access 2 Immunoassay Analyzers has shown excellent analytical and clinical performance consistent with currently marketed syphilis assays. *FDA cleared in the US, not yet available for in vitro diagnostic use in all countries IVD: In Vitro Diagnostic Products. These products are labeled "For In Vitro Diagnostic Use."

BACKGROUND:Thirty-day performance of the high-sensitivity troponin T (hs-cTnT) European Society of Cardiology 0/1-hour (ESC 0/1-h) and "one-and-done" (hs-cTnT<limit of quantification) strategies are established. However, 90-day performance is unclear. Our objective was to evaluate the 90-day performance of these hs-cTnT strategies in a US cohort. METHODS:A preplanned secondary analysis of a prospective multisite US cohort was conducted. Adults with chest pain were enrolled from 8 emergency departments (January 2017-September 2018). hs-cTnT measures (0- and 1-h) were used to classify patients by the ESC 0/1-h algorithm into rule-out, observation, and rule-in zones. Patients with 0-h measures <limit of quantification were considered ruled out by the one-and-done strategy. The primary outcome was adjudicated 90-day cardiac death or myocardial infarction (MI). Negative predictive value (NPV) for the primary endpoint and efficacy (proportion ruled out) were calculated for each strategy alone and in combination with the History, ECG, Age, Risk factor, and Troponin (HEART) score. RESULTS:Among 1462 patients with a mean age of 57.6 ± 12.9 years, 46.4% (678/1462) were female, and 14.0% (205/1462) had cardiac death or MI at 90 days. One-and-done strategy efficacy was 32.8% (479/1462), and NPV was 99.0% [95% confidence interval (CI), 97.6-99.7]. Adding the HEART score decreased efficacy to 20.1% (293/1462) and increased NPV to 99.7% (95% CI, 98.1-100). ESC 0/1-h efficacy was 57.8% (826/1430) and NPV was 98.3% (95% CI, 97.2-99.1). Combined with a HEART score, NPV increased to 99.3% (95% CI, 98.0-99.9), but efficacy decreased to 30.8% (95% CI, 28.3-33.2). CONCLUSIONS:The one-and-done strategy and ESC 0/1-hour algorithm had modest rates of missed 90-day cardiac death or MI. Adding a HEART score improved safety but decreased efficacy.

People with human immunodeficiency virus (HIV; PWH) smoke cigarettes at triple the rate of the general population in the United States. Efforts to increase quit rates in this group have met with limited success. The nicotine metabolite ratio (NMR) has shown promise as a phenotypic marker that may be useful in selecting the most appropriate cessation treatments for people who smoke cigarettes. We completed a randomized controlled trial of individual intensive counseling and/or varenicline treatment for PWH in the Baltimore area who smoke cigarettes, and we measured serum 3 ' hydroxycotinine and cotinine at baseline and calculated the ratio of these two values, i.e., the NMR, for each participant. Herein, we present summary statistics and measures of association, or lack thereof, of NMR values with a variety of behavioral parameters and clinical outcomes related to tobacco use and tobacco treatment. The NMR was calculated for 155 PWH who were currently using tobacco cigarettes. The mean age was 52.9 years, 62.3% male, 91.0% Black, and they smoked a mean of 10.6 cigarettes/day. The mean NMR was 0.43, similar to that reported from other PWH cohorts. We did not find any significant correlation between NMR and cigarettes/day, nicotine dependence, temptation to smoke, or nicotine withdrawal symptoms. We did not find that lower NMR was predictive of successful cessation, nor was it associated with varenicline intolerance in those who received varenicline.Prevention Relevance: People with HIV suffer disproportionately from lung, head and neck, and other tobacco-related cancers as a consequence of high smoking rates. There is an urgent need to mitigate this harm, and the use of the NMR to personalize tobacco treatment is an area of active interest.