Pub Date : 2025-12-30DOI: 10.1093/clinchem/hvaf159
Pauline H Herroelen, Koen Swaerts, Patrick Descheemaeker, Piet Claerhout, Adriaan Vanderstichele, Elke Boone, Inge De Cuyper, Frederik Van Hoecke, Geert A Martens, Dieter De Smet
Background: Congenital cytomegalovirus (cCMV) infection is a leading cause of sensorineural hearing loss in children. Recent evidence that high-dose valacyclovir reduces vertical transmission following primary maternal infection has renewed the urgency for screening. We investigated the utility of quantifying cell-free CMV DNA from noninvasive prenatal screening (NIPS) data to identify pregnancies at risk for primary CMV infection and cCMV.
Methods: In this retrospective study, we analyzed NIPS data from 22 333 unselected pregnancies at 12 weeks gestation. CMV-aligned reads were quantified from low-pass whole-genome sequencing data and validated against quantitative PCR (qPCR) for viral load, maternal serology for infection status and systematic newborn screening for cCMV.
Results: CMV read counts demonstrated good correlation with qPCR-measured viral loads (rs = 0.76; 95%CI: 0.68-0.81). Presence of ≥1 CMV read count (2.1% of pregnancies) was highly predictive of cCMV [likelihood ratio (LR) = 21.1; 95% confidence interval (CI): 14.9-30.1]. CMV read counts showed good diagnostic accuracy for primary infection [area under the receiver operator characteristic curve (AUROC) = 0.77; 95% CI: 0.72-0.82] and for cCMV (AUROC = 0.82; 95% CI: 0.76-0.86). A threshold of ≥4 read counts identified a subgroup with significantly elevated risk for primary infection (LR = 7.8; 95% CI: 4.3-14.2) and cCMV (LR = 6.0; 95% CI: 3.3-10.8), achieving positive predictive value for cCMV of 51.7%.
Conclusion: Quantification of CMV DNA during NIPS is an accurate and sensitive method for CMV viral load. This approach effectively stratifies risk for both primary maternal infection and cCMV, enabling identification of pregnancies that may benefit from antiviral therapy.
{"title":"Universal Screening of Cytomegalovirus Viral Load by Low-Pass Whole-Genome Sequencing in First-Trimester Pregnancy: Clinical Validation.","authors":"Pauline H Herroelen, Koen Swaerts, Patrick Descheemaeker, Piet Claerhout, Adriaan Vanderstichele, Elke Boone, Inge De Cuyper, Frederik Van Hoecke, Geert A Martens, Dieter De Smet","doi":"10.1093/clinchem/hvaf159","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf159","url":null,"abstract":"<p><strong>Background: </strong>Congenital cytomegalovirus (cCMV) infection is a leading cause of sensorineural hearing loss in children. Recent evidence that high-dose valacyclovir reduces vertical transmission following primary maternal infection has renewed the urgency for screening. We investigated the utility of quantifying cell-free CMV DNA from noninvasive prenatal screening (NIPS) data to identify pregnancies at risk for primary CMV infection and cCMV.</p><p><strong>Methods: </strong>In this retrospective study, we analyzed NIPS data from 22 333 unselected pregnancies at 12 weeks gestation. CMV-aligned reads were quantified from low-pass whole-genome sequencing data and validated against quantitative PCR (qPCR) for viral load, maternal serology for infection status and systematic newborn screening for cCMV.</p><p><strong>Results: </strong>CMV read counts demonstrated good correlation with qPCR-measured viral loads (rs = 0.76; 95%CI: 0.68-0.81). Presence of ≥1 CMV read count (2.1% of pregnancies) was highly predictive of cCMV [likelihood ratio (LR) = 21.1; 95% confidence interval (CI): 14.9-30.1]. CMV read counts showed good diagnostic accuracy for primary infection [area under the receiver operator characteristic curve (AUROC) = 0.77; 95% CI: 0.72-0.82] and for cCMV (AUROC = 0.82; 95% CI: 0.76-0.86). A threshold of ≥4 read counts identified a subgroup with significantly elevated risk for primary infection (LR = 7.8; 95% CI: 4.3-14.2) and cCMV (LR = 6.0; 95% CI: 3.3-10.8), achieving positive predictive value for cCMV of 51.7%.</p><p><strong>Conclusion: </strong>Quantification of CMV DNA during NIPS is an accurate and sensitive method for CMV viral load. This approach effectively stratifies risk for both primary maternal infection and cCMV, enabling identification of pregnancies that may benefit from antiviral therapy.</p>","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"72 1","pages":"173-182"},"PeriodicalIF":6.3,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145861383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-30DOI: 10.1093/clinchem/hvaf125
Qiliang Ding, Kyle T Salsbery, Noemi Vidal-Folch, Devin Oglesbee, Linda Hasadsri
{"title":"Prenatal Testing of a Complex Pathogenic Variant following Positive Carrier Screening for Gaucher Disease.","authors":"Qiliang Ding, Kyle T Salsbery, Noemi Vidal-Folch, Devin Oglesbee, Linda Hasadsri","doi":"10.1093/clinchem/hvaf125","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf125","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"72 1","pages":"11-15"},"PeriodicalIF":6.3,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145862490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Creatinine Measurement in Pediatrics: Is There Still a Role for the Compensated Jaffe Method?","authors":"Kobe Truijens,Edith Vermeulen,Wim Lemahieu,Benjamin Possemiers,Inge Geerts","doi":"10.1093/clinchem/hvaf171","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf171","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"13 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145801296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-19DOI: 10.1093/clinchem/hvaf156
Grace Drew,Colleen S Kraft,Nirja Mehta
BACKGROUNDThe safety and efficacy of fecal microbiota transplantation for prevention of recurrent Clostridioides difficile infection relies on complex interactions between the donor and recipient microbiome.CONTENTScreening of donor stool has largely aimed to ensure safety; however, metagenomic and metabolic features of the stool, which may affect efficacy of the fecal microbiota transplantation (FMT), have been largely overlooked.SUMMARYIn this review, we discuss the nascent field of metagenomic and metabolic donor and recipient characteristics that may affect efficacy of FMT and future directions for this field to allow for more precise and personalized therapies.
{"title":"Fecal Microbiota Therapy: Clinical Laboratory Testing and Metabolomic Approaches for Donor Screening, Product Assessment, and Patient Monitoring.","authors":"Grace Drew,Colleen S Kraft,Nirja Mehta","doi":"10.1093/clinchem/hvaf156","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf156","url":null,"abstract":"BACKGROUNDThe safety and efficacy of fecal microbiota transplantation for prevention of recurrent Clostridioides difficile infection relies on complex interactions between the donor and recipient microbiome.CONTENTScreening of donor stool has largely aimed to ensure safety; however, metagenomic and metabolic features of the stool, which may affect efficacy of the fecal microbiota transplantation (FMT), have been largely overlooked.SUMMARYIn this review, we discuss the nascent field of metagenomic and metabolic donor and recipient characteristics that may affect efficacy of FMT and future directions for this field to allow for more precise and personalized therapies.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"4 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-16DOI: 10.1093/clinchem/hvaf170
Jack W Goodall,Thomas G Nadin,Bethan S Lloyd Jones,Otto C Willan,Adam C Lomas,Athina Tampaki,Thomas C Darton,Rachel S Tattersall
{"title":"Improving Recognition of Secondary Hemophagocytic Lymphohistiocytosis (HLH) through a Ferritin-Based Automated Alert: An Interrupted Time Series Analysis.","authors":"Jack W Goodall,Thomas G Nadin,Bethan S Lloyd Jones,Otto C Willan,Adam C Lomas,Athina Tampaki,Thomas C Darton,Rachel S Tattersall","doi":"10.1093/clinchem/hvaf170","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf170","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"31 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145759868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-16DOI: 10.1093/clinchem/hvaf166
Clara Daschner,Marcus E Kleber,Anders H Berg,Faeq Husain-Syed,Jürgen E Scherberich,Bernhard K Krämer,Winfried März,Babak Yazdani
BACKGROUNDSerum uromodulin (SUmod) and carbamylated albumin (C-Alb) are emerging biomarkers for chronic kidney disease (CKD) progression and mortality. SUmod reflects tubular health, while C-Alb is associated with excretory kidney function, CKD progression, and cardiovascular (CV) mortality. We hypothesized that the combined use of these markers would improve mortality risk assessments.METHODSWe analyzed the associations of C-Alb and SUmod levels with the estimated glomerular filtration rate (eGFR) along with their combined predictive value for assessing mortality in 3316 participants of the Ludwigshafen Risk and Cardiovascular Health study showing mid to high CV risk.RESULTSSUmod correlated moderately with eGFR (ρ = 0.39, P < 0.001) and weakly and inversely with C-Alb (ρ = -0.19, P < 0.001); C-Alb negatively correlated with eGFR (ρ = -0.38, P < 0.001). Patients in the C-Alb high/SUmod low group had the highest mortality risk [hazard ratio (HR)= 3.30; 95% CI, 2.73-3.99], which remained significant after adjustment for confounders, including eGFR (HR = 1.89; 95% CI, 1.24-1.89). In risk-prediction models for all-cause mortality, adding SUmod increased the area under the curve (AUC) from 0.728 to 0.746 (P < 0.001), C-Alb to 0.738 (P = 0.026), and both combined to 0.751 (P < 0.001). For CV mortality, AUC rose from 0.698 to 0.721 with SUmod (P < 0.001), to 0.711 with C-Alb (P = 0.018), and to 0.727 (P = 0.004) in the combined model.CONCLUSIONSSUmod and C-Alb levels yield complementary insights into kidney function, biology, and mortality risk beyond eGFR. Low SUmod/high C-Alb revealed the highest mortality risk, even after multivariate adjustment.GERMAN CLINICAL TRIALS REGISTER NUMBERDRKS00032641.
{"title":"Association of Serum Uromodulin and Carbamylated Albumin with All-Cause and Cardiovascular Mortality in Patients with No or Mild Chronic Kidney Disease.","authors":"Clara Daschner,Marcus E Kleber,Anders H Berg,Faeq Husain-Syed,Jürgen E Scherberich,Bernhard K Krämer,Winfried März,Babak Yazdani","doi":"10.1093/clinchem/hvaf166","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf166","url":null,"abstract":"BACKGROUNDSerum uromodulin (SUmod) and carbamylated albumin (C-Alb) are emerging biomarkers for chronic kidney disease (CKD) progression and mortality. SUmod reflects tubular health, while C-Alb is associated with excretory kidney function, CKD progression, and cardiovascular (CV) mortality. We hypothesized that the combined use of these markers would improve mortality risk assessments.METHODSWe analyzed the associations of C-Alb and SUmod levels with the estimated glomerular filtration rate (eGFR) along with their combined predictive value for assessing mortality in 3316 participants of the Ludwigshafen Risk and Cardiovascular Health study showing mid to high CV risk.RESULTSSUmod correlated moderately with eGFR (ρ = 0.39, P < 0.001) and weakly and inversely with C-Alb (ρ = -0.19, P < 0.001); C-Alb negatively correlated with eGFR (ρ = -0.38, P < 0.001). Patients in the C-Alb high/SUmod low group had the highest mortality risk [hazard ratio (HR)= 3.30; 95% CI, 2.73-3.99], which remained significant after adjustment for confounders, including eGFR (HR = 1.89; 95% CI, 1.24-1.89). In risk-prediction models for all-cause mortality, adding SUmod increased the area under the curve (AUC) from 0.728 to 0.746 (P < 0.001), C-Alb to 0.738 (P = 0.026), and both combined to 0.751 (P < 0.001). For CV mortality, AUC rose from 0.698 to 0.721 with SUmod (P < 0.001), to 0.711 with C-Alb (P = 0.018), and to 0.727 (P = 0.004) in the combined model.CONCLUSIONSSUmod and C-Alb levels yield complementary insights into kidney function, biology, and mortality risk beyond eGFR. Low SUmod/high C-Alb revealed the highest mortality risk, even after multivariate adjustment.GERMAN CLINICAL TRIALS REGISTER NUMBERDRKS00032641.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"20 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145759870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-12DOI: 10.1093/clinchem/hvaf175
Marlies Oostendorp,Eline A Van der Hagen,Stanley Lo,Vincent Delatour,Denis Grote-Koska,Antje Staaden,Marieke A Frasa,Jenny E Kootstra-Ros,Lauren Westenberg,Libor Vítek,Aleš Dvořák,David Křepelka,Cas Weykamp,Christian V Hulzebos,Miranda Van Berkel
{"title":"The Analytical Performance of Neonatal Total Bilirubin Assays Does Not Meet the Clinical Need.","authors":"Marlies Oostendorp,Eline A Van der Hagen,Stanley Lo,Vincent Delatour,Denis Grote-Koska,Antje Staaden,Marieke A Frasa,Jenny E Kootstra-Ros,Lauren Westenberg,Libor Vítek,Aleš Dvořák,David Křepelka,Cas Weykamp,Christian V Hulzebos,Miranda Van Berkel","doi":"10.1093/clinchem/hvaf175","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf175","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"125 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145732752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-03DOI: 10.1093/clinchem/hvaf155
Yusheng Zhu,Jarrett Sell
BACKGROUNDHuman immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) encompasses the use of antiviral medications to prevent HIV acquisition in individuals without HIV who are at risk. Currently available HIV PrEP medications are nucleoside reverse transcriptase inhibitors and integrase inhibitors. HIV testing is required to confirm that patients do not have an HIV infection before PrEP, when restarting PrEP after a long pause, and during ongoing maintenance of PrEP.CONTENTThis article reviews current practices and recent developments in PrEP. Daily oral HIV PrEP is a common approach for HIV PrEP. The challenge with oral HIV PrEP is medication adherence. Recently, long-acting injectable medications for HIV PrEP have become available, which may improve adherence. HIV testing plays a critical role in PrEP programs. Methods for HIV testing for PrEP programs include laboratory-based antigen/antibody immunoassays, rapid testing with reflex confirmation, and RNA testing. The World Health Organization encourages the use of rapid HIV assays for self-testing because provider-administered testing may be a barrier to PrEP uptake. Currently available HIV self-testing (HIVST) methods are primarily antibody-based rapid assays. To improve the effectiveness of HIV PrEP, a greater range of medications, including novel long-acting antiretroviral agents, broadly neutralizing antibodies, and other drugs, are needed. Additionally, more accessible PrEP service delivery and high-sensitivity HIV tests, especially nucleic acid-based HIVST methods, are warranted.SUMMARYHIV PrEP and related monitoring are essential parts of HIV prevention. More effective medications will improve the effectiveness of HIV PrEP, and more accessible PrEP service delivery and high-sensitivity HIV tests, especially HIVST methods, can improve HIV prevention with PrEP.
{"title":"Pre-Exposure Prophylaxis (PrEP)-Associated HIV Monitoring and Self-Testing.","authors":"Yusheng Zhu,Jarrett Sell","doi":"10.1093/clinchem/hvaf155","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf155","url":null,"abstract":"BACKGROUNDHuman immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) encompasses the use of antiviral medications to prevent HIV acquisition in individuals without HIV who are at risk. Currently available HIV PrEP medications are nucleoside reverse transcriptase inhibitors and integrase inhibitors. HIV testing is required to confirm that patients do not have an HIV infection before PrEP, when restarting PrEP after a long pause, and during ongoing maintenance of PrEP.CONTENTThis article reviews current practices and recent developments in PrEP. Daily oral HIV PrEP is a common approach for HIV PrEP. The challenge with oral HIV PrEP is medication adherence. Recently, long-acting injectable medications for HIV PrEP have become available, which may improve adherence. HIV testing plays a critical role in PrEP programs. Methods for HIV testing for PrEP programs include laboratory-based antigen/antibody immunoassays, rapid testing with reflex confirmation, and RNA testing. The World Health Organization encourages the use of rapid HIV assays for self-testing because provider-administered testing may be a barrier to PrEP uptake. Currently available HIV self-testing (HIVST) methods are primarily antibody-based rapid assays. To improve the effectiveness of HIV PrEP, a greater range of medications, including novel long-acting antiretroviral agents, broadly neutralizing antibodies, and other drugs, are needed. Additionally, more accessible PrEP service delivery and high-sensitivity HIV tests, especially nucleic acid-based HIVST methods, are warranted.SUMMARYHIV PrEP and related monitoring are essential parts of HIV prevention. More effective medications will improve the effectiveness of HIV PrEP, and more accessible PrEP service delivery and high-sensitivity HIV tests, especially HIVST methods, can improve HIV prevention with PrEP.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"198200 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-03DOI: 10.1093/clinchem/hvaf161
Mari L DeMarco
{"title":"Phosphorylated Tau in Developing and Degenerating Brains: A 30-Year-Old Puzzle Revisited.","authors":"Mari L DeMarco","doi":"10.1093/clinchem/hvaf161","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf161","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"198200 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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