Abbott (United States)

ABSTRACTHistorically, clonal hematopoiesis (CH) has been recognized as a confounder of cell‐free DNA (cfDNA) testing. Recent evidence now demonstrates the role of CH as a risk factor in health, generating distinct sources of cfDNA that can be leveraged for liquid biopsy diagnostics. Nonetheless, gaps in standardization challenge the advancement of such diagnostics from development to regulatory approval, through clinical trials, and ultimately, to routine implementation. In 2024, the Blood Profiling Atlas in Cancer (BLOODPAC) Consortium, a collaborative infrastructure for developing standards and best practices for liquid biopsy assays, established the CH/clonal hematopoiesis of indeterminate potential (CHIP) Working Group to address the need for accurate identification and removal of CH from liquid biopsy results. As a first step to support the interpretability of CH/CHIP results, the Working Group developed this lexicon to standardize terms and provide a unified vocabulary related to CH and liquid biopsy, DNA sequencing tests, biomarkers, and clinical use cases, facilitating communication within the field. BLOODPAC's CH/CHIP Working Group believes that terminology agreement across these various stakeholders can improve communication in the field and unify future data collection efforts across studies.

Probe-based capture represents a highly sensitive and cost-effective approach for overcoming host background and enriching viruses in metagenomic NGS (mNGS) libraries. Using clinical specimens collected globally from patients with fever or respiratory illness, we generated mNGS libraries by random priming and Nextera XT tagmentation, followed by target enrichment (teNGS) with Comprehensive Viral Research Panel (CVRP) probes. Capture pool sizes and total reads were optimized, and libraries were initially sequenced separately. Using only 3–4% of reads required for standard mNGS, teNGS achieved increased sensitivity, 100–10,000× increases in depth, and >50% genome coverage for pathogens with titers ≥ 1000 cp/mL. Application to >2000 clinical specimens from various matrices and to contrived samples containing viruses absent from the CVRP probe set enabled detection of diverse viral families and established a minimum 65% nucleotide identity for hybridization, respectively. To save time and resources, teNGS and mNGS libraries were then combined into one sequencing run: teamNGS. In addition to streamlining the workflow, teamNGS also improved genome recovery. Coupling methods maintain the sensitivity and coverage for viruses achieved by enrichment alone while also ensuring comprehensive recovery of non-viral microbes. teamNGS has the potential to improve patient management and lower the rates of unnecessary testing and antibiotic use.

Anabolic resistance, consisting of a diminished ability of aging muscle to respond to anabolic stimuli such as exercise and protein intake, is a key contributor to age-related declines in muscle mass. However, diseases and lifestyle factors associated with aging, including insulin resistance states, overweight/obesity, persistent inflammation and specifically—as a focus herein—physical inactivity and inadequate dietary protein-intake habits, might interact with chronological impairments in muscle anabolism. In this context, master athletes, as individuals who have engaged in lifelong structured exercise, including regular training and sports participation, offer a valuable model for studying processes of chronological vs. inactivity-related aging. While these lifelong exercisers may present improved body composition parameters and other potential benefits in terms of muscle mass and function, it remains unclear whether exercise practice throughout life can prevent the development of anabolic resistance associated with aging. Albeit limited, evidence has indicated that even in lifelong-trained older individuals there is a blunted post-exercise muscle anabolic response compared to younger athletes. However, there is a paucity of data to systematically understand the differences in postprandial anabolic response to varying protein doses in older vs. young athletes. In lieu of the above, it seems reasonable that master athletes may benefit from increasing protein intake closer to the upper limit of current recommendations (1.6–2.0 g/kg/day). In addition, supplementing their diet with ingredients that have established anabolic potential, including branched chain amino acids (BCAAs) such as leucine, the leucine metabolite β-hydroxy-β-methylbutyrate (HMB), and n3-polyunsaturated fatty acids (n3-PUFA), may potentiate the anabolic response to protein and exercise.

Bolus thermodilution is the most commonly used invasive assessment for coronary microvascular dysfunction (CMD). However, variability in thermodilution transit time measurements (TTM) affects calculated Coronary Flow Reserve (CFR) and Index of Microvascular Resistance (IMR) values. This study determined variables associated with transit time variability and quantified confidence intervals for the range of measured CFR and IMR values. The CoroFlow Cardiovascular System (Coroventis, Sweden) and PressureWire™ X Guidewire (Abbott) were used to collect 2541 TTM from 259 vessels at 14 US sites included in the FlowLab Study. Correlations with baseline patient and procedural variables were determined by both linear and mixed linear models. Mixed linear models with the physician or vessel as the random effect were computed. Monte Carlo simulations of CFR and IMR were performed to determine 95% confidence intervals for thresholds of 2.5 for CFR and 25 for IMR. Mixed linear analysis with vessel as the random effect provided the best model fit (R2 = 0.948). In this model, RCA vessel location (p < 0.001) and pressure sensor distance < 5 cm (p < 0.005) were significantly associated with transit time. Monte Carlo simulations identified a "gray zone" range of 2.1-3.1 for CFR and 19-31 for IMR. Minimizing variability in invasive CMD assessment is essential for improving diagnostic accuracy and guiding clinical decision-making as testing becomes more widespread. In this study, target vessel choice (RCA) and pressure sensor placement were identified as key modifiable sources of transit time variability. Clinically applicable confidence intervals around CFR and IMR values were defined.

Dengue virus (DENV) infection has not been previously reported from Bayelsa State, Nigeria. We aimed to determine the prevalence of dengue virus (DENV) infection, malaria, and coinfection, and other pathogens among febrile patients in the capital city, Yenagoa.We conducted a cross-sectional study among persons aged ≥1 year who presented with acute febrile illnesses (AFI) at four hospitals in Bayelsa State during 20 May - 15 June 2022. Blood samples from 443 participants were tested for DENV seromarkers (NS1, IgM, IgG), using serology and RT-PCR, and malaria was diagnosed by thick smear microscopy. Sociodemographic and risk factor data were collected using electronic questionnaires administered via smart phones/tablets and analyzed using univariate and multivariate methods. Metagenomic libraries were prepared and enriched by viral target capture and sequenced by NGS. The seroprevalence of acute DENV infection was 14.5% (n = 64) while the prevalence of malaria was 42.4% (n = 188); 6.5% (n = 29) of participants were coinfected with acute DENV infection and malaria. An additional 17.6% (n = 78) of participants had markers for past DENV infection. Rural/suburban residence and age ≥ 31 years were significantly correlated with having any dengue seromarker. Residence in a larger household (≥5 persons), and borehole water-use were predictors for malaria fever. RT-PCR results revealed multiple DENV serotypes, with serotype 3 dominant. Sequencing of unknown AFI cases revealed numerous viral causes such as adenovirus, EBV, and hepatitis A, as well as additional dengue and malarial infections missed by conventional testing. Of interest were Coxsackievirus A5 (hand, foot and mouth disease; HFMD) which has been diversifying locally for years in Nigeria and an mPox clade IIb (lineage A.2.3) strain that emerged in Nigeria during the 2022 global outbreak. The results of this study provide the first documentation of human DENV infection in Bayelsa State, Nigeria and suggests that dengue is an emerging and important cause of febrile illness in this area. Our findings support the need for routine testing to identify DENV among patients who present with acute febrile disease. Metagenomic NGS results highlight the benefits of unbiased surveillance to identify circulating and emerging pathogens.

Abstract Background We evaluated the analytical performance of four newly developed clinical chemistry assays [Creatinine, Uric Acid, Lactate, Lactate Dehydrogenase (LDH)] on the Abbott Alinity c and ARCHITECT c8000 system. These clinical chemistry assays incorporate a multianalyte calibrator, which has extended stability. For the enzyme assay LDH, both the multianalyte calibrator and a factor calibration are offered. Precision, linearity, method comparison and accuracy were assessed per CLSI guidelines. Sigma metrics were determined to examine the assay variability in relation to allowable performance limits. Methods Precision was assessed by measuring two levels of quality control material (Biorad Chemistry UA) and three pooled patient samples in replicates of five, twice per day, for five days. Method comparison was performed by measuring 134 serum/plasma specimens in duplicate on the new and current Alinity c or ARCHITECT methods. Linearity was evaluated using five to six levels of commercially available linearity material, measured in triplicate. Acceptability criteria were based on the Accreditation Canada Diagnostics (ACD) recommendations. Accuracy was determined in replicates of ten using external NIST standards. For assays where an external standard was not available, calibrators were used. The imprecision and bias from the target value were used to calculate the Sigma value. Total allowable error limits were obtained from the Clinical Laboratory Improvement Amendments (CLIA) and ACD guidelines. Results The results from the precision, accuracy, linearity, and method comparison studies are summarized in the table below. All the next generation chemistry assays demonstrated = 6 Sigma performance on the ARCHITECT and Alinity c systems based on CLIA guidelines. The performance of the factor calibration for the LDH assay was equivalent (data not shown). Conclusion The four next generation clinical chemistry assays (Creatinine2, Uric Acid2, Lactate2, Lactate Dehydrogenase2) demonstrated acceptable performance for precision, accuracy, linearity, and Sigma values on the Alinity c and ARCHITECT system. There was good agreement with the on-market Alinity c and ARCHITECT clinical chemistry assays.

Abstract Background Heart failure is a clinical syndrome that results from a structural or functional cardiac abnormality that impairs the ability of the ventricles to fill and eject blood. The Alere NT-proBNP for Alinity i provides accurate, reliable results with rapid turnaround time, aiding clinicians in providing better patient care. Several studies have established NT-proBNP levels for the diagnosis and exclusion of heart failure for patients presenting to emergency department (ED). A multi-center prospective study including 17 collection sites across the United States (US) was conducted to establish the clinical performance of Alere NT-proBNP for Alinity i. Subjects 18 years and older presenting to the ED with signs and symptoms consistent with a clinical suspicion of new onset or acute exacerbation of HF were included in the study. Subjects with renal insufficiency requiring dialysis or known eGFR less than 15.0 mL/min/1.73 m2 and subjects with dyspnea after chest trauma were excluded from the study. Clinical performance of the Alere NT-proBNP for Alinity i using the ICON rule-in and rule-out cutoffs was compared to that of the Roche Elecsys proBNP II using the study population samples. A method comparison regression analysis was also performed using the subjects with results within the analytical measuring intervals of the Alere NT-proBNP for Alinity i and Roche Elecsys proBNP II assay. Methods The Posttest Probability of HF and Posttest Probability of Non-HF and likelihood ratios were determined by comparing the assay result interpretation using the age-dependent positive cutoffs (450 pg/mL for subjects 18 - &amp;lt;50 years of age; 900 pg/mL for subjects 50–75 years of age; 1800 pg/mL for subjects &amp;gt; 75 years of age) and age-independent negative cutoff of 300 pg/mL against the adjudicated diagnosis of Heart failure/non-Heart failure in the study population. Method comparison evaluation was performed by Passing-Bablok regression using assay results from Roche Elecsys proBNP II assay and Alere NT-proBNP for Alinity i assay. Predicted bias around medical decision levels was also calculated. Results The Posttest Probability of HF across all subjects was 75.0% for the Alere NT-proBNP for Alinity i assay and 74.7% for the Roche Elecsys proBNP II assay. The Posttest Probability of non-HF across all subjects was 94.4% for the Alere NT-proBNP for Alinity i assay and 94.3% for the Roche Elecsys proBNP II assay. The method comparison results between the Alere NT-proBNP for Alinity i versus Roche Elecsys proBNP II assays showed a Passing-Bablok regression slope of 1.07 (95% CI 1.06, 1.07), intercept -3.3 pg/mL (95% CI -4.3, -2.0). The correlation coefficient (r) was 0.992 (95% CI 0.991, 0.993) with a sample concentration range from 34.2 to 34320.8 pg/mL for Alere NT-proBNP for Alinity i assay and a range of 36.3 to 32896.0 pg/mL for Roche Elecsys proBNP II assay. The predicted bias at various medical decision points (125.0, 300.0, 450.0, 900.0, 1800.0 pg/mL) ranged from 4.3% to 6.7%. Conclusion The clinical performance and method comparison results support that the performance of Alere NT-proBNP for Alinity i is comparable to the Roche Elecsys proBNP II assay.