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Clinical Chemistry     Full-text available via subscription   (Followers: 61, SJR: 2.281, CiteScore: 3)
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Clinical Chemistry
Journal Prestige (SJR): 2.281
Citation Impact (citeScore): 3
Number of Followers: 61  
 
  Full-text available via subscription Subscription journal
ISSN (Print) 0009-9147 - ISSN (Online) 1530-8561
Published by AACC Homepage  [1 journal]
  • Targeting DNA Methylation as an Epigenetic Leukocyte Counting Tool

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      Authors: Pittella-Silva F.
      Pages: 613 - 615
      Abstract: The methylation of CpG islands in gene promoters is a well-stablished epigenetic mechanism essential to mammalian development. During development, a dynamic process involving both de novo DNA methylation and demethylation in the genome affects the pattern of DNA methylation. This process results in differentiated cells with distinctive and stable DNA methylation signatures that regulate tissue-specific transcriptional programming of genes (1). Specific patterns of DNA methylation can therefore be explored as valuable biomarkers to stratify cell lineage and cell subsets in complex samples such as whole blood. DNA methylation markers that can be used to distinguish and quantify T cells, B cells, monocytes, eosinophils, basophils, neutrophils, and natural killer cells may have a broad clinical application. Leukocyte counts are usually determined based on morphological analysis, flow cytometric measurements, and immunophenotypic classification of lymphocyte subsets. New techniques based on DNA methylation signature may complement and help to overcome several limitations from conventional methods.
      PubDate: Sat, 12 Mar 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvac035
      Issue No: Vol. 68, No. 5 (2022)
       
  • A Novel Approach to Improve Accuracy of CYP2D6 Enzyme Activity and Drug
           Response Predictions

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      Authors: Moyer A; Langman L, Black J, III.
      Pages: 616 - 618
      Abstract: Cytochrome P450 2D6 (CYP2D6) is a highly polymorphic enzyme that metabolizes at least ¼ of commonly prescribed medications. As such, it is frequently the subject of pharmacogenomic testing. Additionally, CYP2D6 is a challenging gene to test due to homology with pseudogenes, copy number variation, and structural rearrangements that result in hybrid alleles. In recent years, major efforts to standardize clinical CYP2D6 pharmacogenomic testing have been undertaken. The Pharmacogene Variation Consortium (PharmVar) catalogs the genetic variant(s) that define each individual haplotype, which is also known as a star (*)-allele. The Association for Molecular Pathology, in conjunction with the College of American Pathologists, and the Pharmacogenetics Working Group of the Royal Dutch Association of Pharmacists (DPWG) have established recommendations for which specific genetic variants and alleles should be included in testing, which at present is typically performed by targeted genotyping of predefined variants (1). The Clinical Pharmacogenetics Implementation Consortium (CPIC) and DPWG established consensus recommendations for translation from CYP2D6 genotype to phenotype by adding together categorical activity score (AS) assignments for each allele identified. The categorical scores for each allele are currently 0 for nonfunctional alleles, 0.5 for those with partial function (except *10, which is assigned 0.25), 1.0 for alleles with normal function, and 2.0 for alleles with increased activity (2).
      PubDate: Tue, 11 Jan 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvab269
      Issue No: Vol. 68, No. 5 (2022)
       
  • A Paradigm Shift: Engagement of Clinical Chemistry and Laboratory Medicine
           Trainees by Innovative Teaching Methods

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      Authors: Wiencek J; Chambliss A, Bertholf R, et al.
      Pages: 619 - 626
      Abstract: clinical chemistryeducationlab medicinepathologypedagogy
      PubDate: Tue, 15 Mar 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvac036
      Issue No: Vol. 68, No. 5 (2022)
       
  • Multiple Copy Number Variants Detected by Noninvasive Prenatal Testing

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      Authors: Paolucci S; Ma K, Paulson V, et al.
      Pages: 627 - 632
      Abstract: geneticspregnancybreast cancer
      PubDate: Wed, 18 May 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvac040
      Issue No: Vol. 68, No. 5 (2022)
       
  • Multiple Copy Number Variants Detected by Noninvasive Prenatal Testing

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      Authors: Paolucci S; Ma K, Paulson V, et al.
      Pages: 627 - 632
      Abstract: geneticspregnancybreast cancer
      PubDate: Wed, 18 May 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvac040
      Issue No: Vol. 68, No. 5 (2022)
       
  • Commentary on Multiple Copy Number Variants Detected by Noninvasive
           Prenatal Screening

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      Authors: Almontashiri N.
      Pages: 633 - 633
      Abstract: The current noninvasive prenatal testing (NIPT) assays, whether targeted to common aneuploidies or whole genome (WG)-based, cannot separate fetal from maternal cell-free DNA (cfDNA). Therefore, incidental findings (IFs) of chromosomal abnormalities not relevant to the fetus are inevitable. The identification of the cfDNA source and clinical significance of IFs can be determined through the adopted interpretation pipeline, follow-up confirmatory testing, clinical evaluation, and correlation. There are established maternal and non-maternal factors that influence the results and interpretation of NIPT, such as maternal weight, confined placental mosiacism, and occult maternal malignancies (1).
      PubDate: Mon, 11 Apr 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvac041
      Issue No: Vol. 68, No. 5 (2022)
       
  • Commentary on Multiple Copy Number Variants Detected by Noninvasive
           Prenatal Screening

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      Authors: Almontashiri N.
      Pages: 633 - 633
      Abstract: The current noninvasive prenatal testing (NIPT) assays, whether targeted to common aneuploidies or whole genome (WG)-based, cannot separate fetal from maternal cell-free DNA (cfDNA). Therefore, incidental findings (IFs) of chromosomal abnormalities not relevant to the fetus are inevitable. The identification of the cfDNA source and clinical significance of IFs can be determined through the adopted interpretation pipeline, follow-up confirmatory testing, clinical evaluation, and correlation. There are established maternal and non-maternal factors that influence the results and interpretation of NIPT, such as maternal weight, confined placental mosiacism, and occult maternal malignancies (1).
      PubDate: Mon, 11 Apr 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvac041
      Issue No: Vol. 68, No. 5 (2022)
       
  • Commentary on Multiple Copy Number Variants Detected by Noninvasive
           Prenatal Testing

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      Authors: Vermeesch J; Lenaerts L.
      Pages: 634 - 634
      Abstract: This case report by Ma et al. describes yet another example of how an aberrant noninvasive prenatal screening (NIPS) result led to the detection of an incipient cancer during pregnancy. NIPS, designed to detect aneuploidies present in fetal cell-free DNA in maternal circulation, also detected the presence of tumor-derived aneuploidies. In this case, NIPS indicated a breast cancer. The laboratory faced the difficult choice whether or not to report this result. The lab and clinicians have to weigh the duty to disclose information for the benefit of patients against the need to avoid unnecessary follow-up examination and distress, during this most precious period of a woman’s life.
      PubDate: Mon, 11 Apr 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvac042
      Issue No: Vol. 68, No. 5 (2022)
       
  • Commentary on Multiple Copy Number Variants Detected by Noninvasive
           Prenatal Testing

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      Authors: Vermeesch J; Lenaerts L.
      Pages: 634 - 634
      Abstract: This case report by Ma et al. describes yet another example of how an aberrant noninvasive prenatal screening (NIPS) result led to the detection of an incipient cancer during pregnancy. NIPS, designed to detect aneuploidies present in fetal cell-free DNA in maternal circulation, also detected the presence of tumor-derived aneuploidies. In this case, NIPS indicated a breast cancer. The laboratory faced the difficult choice whether or not to report this result. The lab and clinicians have to weigh the duty to disclose information for the benefit of patients against the need to avoid unnecessary follow-up examination and distress, during this most precious period of a woman’s life.
      PubDate: Mon, 11 Apr 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvac042
      Issue No: Vol. 68, No. 5 (2022)
       
  • Biomarkers and Clinical Laboratory Detection of Acute and Chronic Ethanol
           Use

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      Authors: Tawiah K; Riley S, Budelier M.
      Pages: 635 - 645
      Abstract: AbstractBackgroundEthanol use can lead to many health and socio-economic problems. Early identification of risky drinking behaviors helps provide timely clinical and social interventions. Laboratory testing of biomarkers of ethanol use supports the timely identification of individuals with risky drinking behaviors. This review provides an overview of the utility and limitations of ethanol biomarkers in the clinical laboratory.ContentDirect assessment of ethanol in tissues and body fluids has limited utility due to the pharmacokinetics of ethanol. Therefore, the evaluation of ethanol use relies on nonvolatile metabolites of ethanol (direct biomarkers) and measurement of the physiological response to the toxic metabolites of ethanol (indirect biomarkers). Ethanol biomarkers help monitor both chronic and acute ethanol use. The points discussed here include the clinical utility of ethanol biomarkers, testing modalities used for laboratory assessment, the specimens of choice, limitations, and clinical interpretation of results. Finally, we discuss the ethical principles that should guide physicians and laboratorians when using these tests to evaluate alcohol use.SummaryIndirect biomarkers such as carbohydrate-deficient transferrin, mean corpuscular volume, and liver enzymes activities may suggest heavy ethanol use. They lack sensitivity and specificity for timely detection of risky drinking behavior and have limited utility for acute ethanol use. Direct biomarkers such as ethyl glucuronide, ethyl sulfate, and phosphatidylethanol are considered sensitive and specific for detecting acute and chronic ethanol use. However, laboratory assessment and result interpretation lack standardization, limiting clinical utility. Ethical principles including respect for persons, beneficence, and justice should guide testing.
      PubDate: Tue, 22 Mar 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvac004
      Issue No: Vol. 68, No. 5 (2022)
       
  • Toward Clinical Application of Leukocyte Counts Based on Targeted DNA
           Methylation Analysis

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      Authors: Sontag S; Bocova L, Hubens W, et al.
      Pages: 646 - 656
      Abstract: AbstractBackgroundDifferential leukocyte counts are usually measured based on cellular morphology or surface marker expression. It has recently been shown that leukocyte counts can also be determined by cell-type–specific DNA methylation (DNAm). Such epigenetic leukocyte counting is applicable to small blood volumes and even frozen material, but for clinical translation, the method needs to be further refined and validated.MethodsWe further optimized and validated targeted DNAm assays for leukocyte deconvolution using 332 venous and 122 capillary blood samples from healthy donors. In addition, we tested 36 samples from ring trials and venous blood from 266 patients diagnosed with different hematological diseases. Deconvolution of cell types was determined with various models using DNAm values obtained by pyrosequencing or digital droplet PCR (ddPCR).ResultsRelative leukocyte quantification correlated with conventional blood counts for granulocytes, lymphocytes, B cells, T cells (CD4 or CD8), natural killer cells, and monocytes with pyrosequencing (r = 0.84; r = 0.82; r = 0.58; r = 0.50; r = 0.70; r = 0.61; and r = 0.59, respectively) and ddPCR measurements (r = 0.65; r = 0.79; r = 0.56; r = 0.57; r = 0.75; r = 0.49; and r = 0.46, respectively). In some patients, particularly with hematopoietic malignancies, we observed outliers in epigenetic leukocyte counts, which could be discerned if relative proportions of leukocyte subsets did not sum up to 100%. Furthermore, absolute quantification was obtained by spiking blood samples with a reference plasmid of known copy number.ConclusionsTargeted DNAm analysis by pyrosequencing or ddPCR is a valid alternative to quantify leukocyte subsets, but some assays require further optimization.
      PubDate: Mon, 14 Feb 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvac006
      Issue No: Vol. 68, No. 5 (2022)
       
  • Error Characterization and Statistical Modeling Improves Circulating Tumor
           DNA Detection by Droplet Digital PCR

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      Authors: Henriksen T; Drue S, Frydendahl A, et al.
      Pages: 657 - 667
      Abstract: AbstractBackgroundDroplet digital PCR (ddPCR) is a widely used and sensitive application for circulating tumor DNA (ctDNA) detection. As ctDNA is often found in low abundance, methods to separate low-signal readouts from noise are necessary. We aimed to characterize the ddPCR-generated noise and, informed by this, create a sensitive and specific ctDNA caller.MethodsWe built 2 novel complimentary ctDNA calling methods: dynamic limit of blank and concentration and assay-specific tumor load estimator (CASTLE). Both methods are informed by empirically established assay-specific noise profiles. Here, we characterized noise for 70 mutation-detecting ddPCR assays by applying each assay to 95 nonmutated samples. Using these profiles, the performance of the 2 new methods was assessed in a total of 9447 negative/positive reference samples and in 1311 real-life plasma samples from colorectal cancer patients. Lastly, performances were compared to 7 literature-established calling methods.ResultsFor many assays, noise increased proportionally with the DNA input amount. Assays targeting transition base changes were more error-prone than transversion-targeting assays. Both our calling methods successfully accounted for the additional noise in transition assays and showed consistently high performance regardless of DNA input amount. Calling methods that were not noise-informed performed less well than noise-informed methods. CASTLE was the only calling method providing a statistical estimate of the noise-corrected mutation level and call certainty.ConclusionsAccurate error modeling is necessary for sensitive and specific ctDNA detection by ddPCR. Accounting for DNA input amounts ensures specific detection regardless of the sample-specific DNA concentration. Our results demonstrate CASTLE as a powerful tool for ctDNA calling using ddPCR.
      PubDate: Fri, 14 Jan 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvab274
      Issue No: Vol. 68, No. 5 (2022)
       
  • ALK-Fusion Transcripts Can Be Detected in Extracellular Vesicles (EVs)
           from Nonsmall Cell Lung Cancer Cell Lines and Patient Plasma: Toward
           EV-Based Noninvasive Testing

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      Authors: Sánchez-Herrero E; Campos-Silva C, Cáceres-Martell Y, et al.
      Pages: 668 - 679
      Abstract: AbstractBackgroundALK rearrangements are present in 5% of nonsmall cell lung cancer (NSCLC) tumors and identify patients who can benefit from ALK inhibitors. ALK fusions testing using liquid biopsies, although challenging, can expand the therapeutic options for ALK-positive NSCLC patients considerably. RNA inside extracellular vesicles (EVs) is protected from RNases and other environmental factors, constituting a promising source for noninvasive fusion transcript detection.MethodsEVs from H3122 and H2228 cell lines, harboring EML4-ALK variant 1 (E13; A20) and variant 3 (E6a/b; A20), respectively, were successfully isolated by sequential centrifugation of cell culture supernatants. EVs were also isolated from plasma samples of 16 ALK-positive NSCLC patients collected before treatment initiation.ResultsPurified EVs from cell cultures were characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and flow cytometry. Western blot and confocal microscopy confirmed the expression of EV-specific markers as well as the expression of EML4-ALK-fusion proteins in EV fractions from H3122 and H2228 cell lines. In addition, RNA from EV fractions derived from cell culture was analyzed by digital PCR (dPCR) and ALK-fusion transcripts were clearly detected. Similarly, plasma-derived EVs were characterized by NTA, flow cytometry, and the ExoView platform, the last showing that EV-specific markers captured EV populations containing ALK-fusion protein. Finally, ALK fusions were identified in 50% (8/16) of plasma EV-enriched fractions by dPCR, confirming the presence of fusion transcripts in EV fractions.ConclusionsALK-fusion transcripts can be detected in EV-enriched fractions. These results set the stage for the development of EV-based noninvasive ALK testing.
      PubDate: Mon, 28 Mar 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvac021
      Issue No: Vol. 68, No. 5 (2022)
       
  • A Multicancer Malignant Pleural Effusion Diagnostic Test Using Hexokinase
           2 and Single-Cell Sequencing

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      Authors: Chen J; Yang Y, Wang Z, et al.
      Pages: 680 - 690
      Abstract: AbstractBackgroundMalignant pleural effusion (MPE) represents advanced malignant disease with poor prognosis. To date, pleural effusion cytology remains the best test to diagnose MPE but suffers from limited diagnostic sensitivity and high variation. We report a hexokinase 2-based method (HK2-seq) as a novel diagnostic method for multicancer MPE diagnosis.MethodsHK2-seq employed HK2 as a new metabolic function-associated marker to detect disseminated tumor cells engaging increased glycolysis in pleural effusion from many cancer types. Single-cell sequencing was used to confirm the malignancy of HK2-derived high glycolytic tumor cells (hgTCs) at the single-cell level via surveying genome-wide copy number alterations (CNAs), leading to establishment of definitive MPE diagnosis.ResultsIn a prospective cohort study including 111 patients with pleural effusion, the HK2 test showed diagnostic sensitivity, diagnostic specificity, positive predictive value, and negative predictive value of 91% (95% CI: 80%–97%), 84% (95% CI: 68%–93%), 90% (95% CI: 79%–96%), and 86% (95% CI: 70%–95%), respectively, in MPE diagnosis across 12 different cancer types. In contrast, pleural effusion cytology exhibits an overall diagnostic sensitivity of 45%. In addition to confirming the tumor origin of hgTCs, single-cell sequencing allowed identification of prognostic or targetable CNAs in hgTCs, especially CNAs found in liquid biopsies but absent in solid biopsies.ConclusionsHK2-seq establishes definitive MPE diagnosis across many cancer types with high diagnostic performance. It has the potential to be used for multicancer detection of circulating tumor cells in blood and other types of body fluids, as well as liquid biopsy-based genomic characterization for informative diagnosis.
      PubDate: Thu, 10 Feb 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvac003
      Issue No: Vol. 68, No. 5 (2022)
       
  • Single-Cell Phenotypic and Molecular Characterization of Circulating Tumor
           Cells Isolated from Cryopreserved Peripheral Blood Mononuclear Cells of
           Patients with Lung Cancer and Sarcoma

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      Authors: Vismara M; Reduzzi C, Silvestri M, et al.
      Pages: 691 - 701
      Abstract: AbstractBackgroundThe isolation of circulating tumor cells (CTCs) requires rapid processing of the collected blood due to their inherent fragility. The ability to recover CTCs from peripheral blood mononuclear cells (PBMCs) preserved from cancer patients could allow for retrospective analyses or multicenter CTC studies.MethodsWe compared the efficacy of CTC recovery and characterization using cryopreserved PMBCs vs fresh whole blood from patients with non-small cell lung cancer (NSCLC; n = 8) and sarcoma (n = 6). Two epithelial cellular adhesion molecule (EpCAM)-independent strategies for CTC enrichment, based on Parsortix® technology or immunomagnetic depletion of blood cells (AutoMACS®) were tested, followed by DEPArray™ single-cell isolation. Phenotype and genotype, assessed by copy number alterations analysis, were evaluated at a single-cell level. Detection of target mutations in CTC-enriched samples from frozen NSCLC PBMCs was also evaluated by digital PCR (dPCR).ResultsThe use of cryopreserved PBMCs from cancer patients allowed for the retrospective enumeration of CTCs and their molecular characterization, using both EpCAM-independent strategies that performed equally in capturing CTC. Cells isolated from frozen PBMCs were representative of whole blood-derived CTCs in terms of number, phenotype, and copy number aberration profile/target mutations. Long-term storage (≥3 years) did not affect the efficacy of CTC recovery. Detection of target mutations was also feasible by dPCR in CTC-enriched samples derived from stored PBMCs.ConclusionsIsolating CTCs from longitudinally collected PBMCs using an unbiased selection strategy can offer a wider range of retrospective genomic/phenotypic analyses to guide patients’ personalized therapy, paving the way for sample sharing in multicenter studies.
      PubDate: Sat, 19 Mar 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvac019
      Issue No: Vol. 68, No. 5 (2022)
       
  • Evaluation of Neutralizing Antibodies against SARS-CoV-2 Variants after
           Infection and Vaccination Using a Multiplexed Surrogate Virus
           Neutralization Test

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      Authors: Lynch K; Zhou S, Kaul R, et al.
      Pages: 702 - 712
      Abstract: AbstractBackgroundThe SARS-CoV-2 virus has mutated and evolved since the inception of the COVID-19 pandemic bringing into question the future effectiveness of current vaccines and antibody therapeutics. With evolution of the virus updated methods for the evaluation of the immune response in infected and vaccinated individuals are required to determine the durability of the immune response to SARS-CoV-2 variants.MethodsWe developed a multiplexed surrogate virus neutralization test (plex-sVNT) that simultaneously measures the ability of antibodies in serum to inhibit binding between angiotensin converting enzyme-2 (ACE2) and 7 SARS-CoV-2 trimeric spike protein variants, including wild type, B.1.1.7(α), B.1.351(β), P.1(γ), B.1.617.2(δ), B.1.617.1(κ), and B.1.429(ε). The assay was validated against a plaque reduction neutralization test (PRNT).We evaluated 170 samples from 97 COVID-19 patients and 281 samples from 188 individuals that received the Pfizer-BioNTech or Moderna mRNA vaccines.ResultsThe plex-sVNT demonstrated >96% concordance with PRNT. Antibody neutralization activity was significantly reduced for all SARS-CoV-2 variants compared to wild type in both the infected and vaccinated cohorts. There was a decline in overall antibody neutralization activity, within both cohorts, out to 5 months post infection or vaccination, with the rate of decline being more significant for the vaccinated.ConclusionsThe plex-sVNT provides a correlative measure to PRNT and a convenient approach for evaluating antibody neutralization against SARS-CoV-2 variants. Neutralization of SARS-CoV-2 variants is reduced compared to wild type and declines over the ensuing months after exposure or vaccination within each cohort, however it is still unknown what degree of neutralizing capacity is protective.
      PubDate: Sun, 09 Jan 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvab283
      Issue No: Vol. 68, No. 5 (2022)
       
  • Circulating Concentrations of C-Type Natriuretic Peptides Increase with
           Sacubitril/Valsartan Treatment in Healthy Young Men

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      Authors: Thonsgaard S; Prickett T, Hansen L, et al.
      Pages: 713 - 720
      Abstract: AbstractBackgroundC-type natriuretic peptide (CNP) is a cardioprotective peptide with high affinity for the ectoenzyme neutral endopeptidase (neprilysin). We aimed to determine whether angiotensin receptor-neprilysin inhibitor treatment acutely affects circulating concentrations of bioactive CNP and its molecular amino-terminal precursor (NT-proCNP).MethodsWe included 9 and 10 healthy young men in 2 randomized crossover trials with sacubitril/valsartan vs control (Trial 1) and sacubitril/valsartan and sitagliptin vs sitagliptin (Trial 2). The participants were randomized to a single dose of sacubitril/valsartan (194/206 mg) or control at the first visit 30 min prior to a standardized meal intake. We obtained blood samples at 12 time points over 5 h and measured plasma concentrations of NT-proCNP in both trials and CNP in Trial 2.ResultsNT-proCNP concentrations increased 3.5 h after sacubitril/valsartan treatment, and at 4.5 h concentrations were 42% and 65% higher compared with control in Trial 1 and Trial 2, respectively. The total area under the curve (tAUC)15–270 min was 22% higher (P = 0.007) in Trial 1 and 17% higher with treatment (P = 0.017) in Trial 2. Concentrations of bioactive CNP followed a similar temporal pattern with an increase of 93% at 4.5 h and a 31% higher tAUC15–270 min compared with control (P = 0.001) in Trial 2.ConclusionsSacubitril/valsartan augments circulating concentrations of both bioactive CNP and NT-proCNP in healthy young men. The increase in bioactive CNP is most likely caused by de novo synthesis and secretion rather than diminished breakdown through neprilysin inhibition.ClinicalTrials.gov registration number NCT03717688
      PubDate: Thu, 17 Feb 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvac005
      Issue No: Vol. 68, No. 5 (2022)
       
  • Imprecision and Delta Criteria for a New ESC 0/2-Hour Algorithm

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      Authors: Kavsak P; Hulett M, Worster A.
      Pages: 721 - 722
      Abstract: high-sensitivity cardiac troponinESC 0/2-hour algorithmimprecision
      PubDate: Tue, 08 Mar 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvac026
      Issue No: Vol. 68, No. 5 (2022)
       
  • Laboratory Community Should Be More Proactive in Highlighting the Negative
           Impact of Analytical Non-Selectivity of Some Creatinine Assays

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      Authors: Panteghini M.
      Pages: 723 - 723
      PubDate: Mon, 07 Mar 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvac031
      Issue No: Vol. 68, No. 5 (2022)
       
  • Diet Is a Small Contributor to Interindividual Variation of Urinary Free
           Catecholamines and Related Metabolites Determined by LC-MS/MS for the
           Screening of Catecholamine-Secreting Tumors

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      Authors: Violin A; Stoerkler A, Renaud C, et al.
      Pages: 724 - 726
      Abstract: metanephrinescatecholaminespheochromocytomaneuroblastomaLC-MS/MSinterference
      PubDate: Tue, 05 Apr 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvac025
      Issue No: Vol. 68, No. 5 (2022)
       
  • LC-MS/MS Peptide Assay Validation: A Plea for Robust Stability Studies

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      Authors: Grouzmann E; Eugster P.
      Pages: 727 - 728
      Abstract: mass spectrometryLC/MSpeptide hormones
      PubDate: Wed, 16 Mar 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvac037
      Issue No: Vol. 68, No. 5 (2022)
       
  • In Reply to LC–MS/MS Peptide Assay Validation: A Plea for Robust
           Stability Studies

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      Authors: Yu S; Ma X, Zou Y, et al.
      Pages: 729 - 731
      Abstract: peptide hormonesLC–MS/MSstability
      PubDate: Wed, 16 Mar 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvac038
      Issue No: Vol. 68, No. 5 (2022)
       
  • Targeting the Diagnosis in an Adolescent with Epilepsy and Intellectual
           Disability through Next-Generation Metabolic Screening

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      Authors: Tseng L; Engelke U, Huigen M, et al.
      Pages: 732 - 735
      Abstract: inherited metabolic disordersuntargeted metabolomicsbiomarkerspyridoxine dependent epilepsy
      PubDate: Mon, 11 Apr 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvab276
      Issue No: Vol. 68, No. 5 (2022)
       
  • Sweet Sphere of Influence

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      Authors: Marin M; Schwietert M, Winter W, et al.
      Pages: 736 - 737
      PubDate: Mon, 11 Apr 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvab224
      Issue No: Vol. 68, No. 5 (2022)
       
  • Lifting the Limit: Updated ISSCR Guidance for Lab-Grown Human Embryos

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      Authors: Shetty S; Noguez J.
      Pages: 738 - 738
      Abstract: The International Society for Stem Cell Research (ISSCR) is a global, multidisciplinary, science-based organization dedicated to promoting basic and translational human embryonic stem cell research. Lab-grown human embryos represent a scientific feat for mankind but on the flipside present both ethical and legal dilemmas. With recent scientific advances and the potential to pave the way for new therapies; the ISSCR has recognized the need to set global standards for harnessing these emerging technologies and their impact on human health. The first set of ISSCR guidelines, published in 2006, focused on providing technical guidance such as how to generate, preserve, and bank stem cells from human embryos. Updates were published in 2016 and recently in 2021 to set standards for advances such as gene editing and more. The 2021 guidelines (1) also relaxed the 14-day limit for growing human embryos in the laboratory following fertilization, a rule firmly established in the research community. Day 14 is roughly 1 week after the embryo implants in the womb and around the time that stem cells start to differentiate into the cell types they are meant to be. Although only a few laboratories around the world have perfected the techniques for growing human embryos up to day 14, this rule change has opened the door for a public conversation about the ethical boundaries. Up until now, researchers have created a variety of nonhuman embryo models to provide a glimpse into the developmental stages beyond day 14, but with the relaxed rule these surrogate models may be unnecessary.
      PubDate: Mon, 11 Apr 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvac008
      Issue No: Vol. 68, No. 5 (2022)
       
  • From the Manhattan Project to COVID-19

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      Authors: Annesley T.
      Pages: 739 - 741
      Abstract: In March of 2015, Microsoft founder Bill Gates walked onto a TED Conference stage pulling a huge army-green nuclear war survival barrel filled with cans of food and water (1). He used this barrel to contrast the threat the world faced when he was a child and the threat the world now faced. The modern threat was not missiles but microbes. For Bill Gates, the world was not prepared for handling a pandemic resulting from a highly infectious virus. Technology could help contain the spread of the virus. To tackle a pandemic head on, governments needed to learn from how nations prepared for war. News agencies wrote stories of his talk and his prediction of a worldwide pandemic. Of course, Bill Gates was correct and is now considered one of the leading voices on the dangers of new diseases.
      PubDate: Mon, 11 Apr 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvac039
      Issue No: Vol. 68, No. 5 (2022)
       
  • Pandemic Reflections

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      Authors: El-Khoury J.
      Pages: 742 - 743
      Abstract: lakereflectionpandemic
      PubDate: Wed, 18 May 2022 00:00:00 GMT
      DOI: 10.1093/clinchem/hvab209
      Issue No: Vol. 68, No. 5 (2022)
       
 
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