Clinical biochemistry最新文献

{"title":"Characterizing the SARS-CoV-2 antibody response and associations with patient factors: Serological profiling of participants enrolled in the GENCOV study","authors":"Gregory Morgan ,&nbsp;Chun Yiu Jordan Fung ,&nbsp;Anne-Claude Gingras ,&nbsp;Karen Colwill ,&nbsp;Laurent Briollais ,&nbsp;Erika Frangione ,&nbsp;Dawit Wolday ,&nbsp;Freda Qi ,&nbsp;Adrian Pasculescu ,&nbsp;Melanie Delgado-Brand ,&nbsp;Genevieve Mailhot ,&nbsp;Tulunay Tursun ,&nbsp;Saranya Arnoldo ,&nbsp;Erin Bearss ,&nbsp;Alexandra Binnie ,&nbsp;Bjug Borgundvaag ,&nbsp;Selina Casalino ,&nbsp;Sunakshi Chowdhary ,&nbsp;Marc Dagher ,&nbsp;Luke Devine ,&nbsp;Jennifer Taher","doi":"10.1016/j.clinbiochem.2024.110859","DOIUrl":"10.1016/j.clinbiochem.2024.110859","url":null,"abstract":"<div><h3>Introduction</h3><div>The GENCOV study sought to evaluate serological differences between individuals with differing COVID-19 severity and outcomes. We assessed the SARS-CoV-2 antibody response of GENCOV participants cross-sectionally 1-, 6-, and 12-months following COVID-19 diagnosis to identify patient factors associated with more robust and durable humoral immune responses.</div></div><div><h3>Materials and Methods</h3><div>COVID-19 patients and a control cohort of vaccinated infection-naïve participants were recruited at hospital sites across the Greater Toronto Area in Ontario, Canada. Commercially available and laboratory-developed serological assays were used to characterize features of participants’ antibody responses, including both binding and neutralizing antibodies. Regression analyses were performed to identify associations between participant characteristics and features of the SARS-CoV-2 antibody response.</div></div><div><h3>Results</h3><div>Samples were obtained from participants 1- (n = 938), 6- (n = 842), and 12-months (n = 662) post-infection or vaccination. At all time points, vaccinees, and to a greater extent those who were both infected and vaccinated, had significantly elevated anti-spike antibody levels compared to unvaccinated participants. Increasing age and/or illness severity were associated with significantly higher antibody levels among unvaccinated participants. Among vaccines, those who were vaccinated after infection (i.e., hybrid immunity) had consistently higher antibody levels compared to participants who were infection-naïve or vaccinated before their infection (i.e., breakthrough infections). Additionally, receiving more vaccine doses and having a more recent vaccination were strongly associated with higher antibody levels across all time points.</div></div><div><h3>Conclusions</h3><div>Our findings highlight various patient factors, including vaccination, which contribute to robust, durable SARS-CoV-2 antibody responses. Overall, the findings presented here may inform future vaccine development and rollout plans.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"135 ","pages":"Article 110859"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serological proteomic profiling uncovered CDK5RAP2 as a novel marker in benign prostatic hyperplasia","authors":"Huan Xie ,&nbsp;Junli Fan ,&nbsp;Jiajun Wang ,&nbsp;Tao Liu ,&nbsp;Lili Chen ,&nbsp;Yunbao Pan ,&nbsp;Yirong Li ,&nbsp;Xinran Li","doi":"10.1016/j.clinbiochem.2024.110867","DOIUrl":"10.1016/j.clinbiochem.2024.110867","url":null,"abstract":"<div><h3>Background</h3><div>Benign prostatic hyperplasia (BPH) affects approximately half of men over the age of 50. Early detection and timely treatment facilitate disease intervention and achieve a better clinical outcome. However, current clinical methods, such as prostate specific antigen (PSA), lack the sensitivity to accurately distinguish between BPH and prostate cancer (PCa). Thus, optimal serum markers are warranted to complement existing diagnostic tests.</div></div><div><h3>Methods</h3><div>In this study, we recruited 1987 BPH patients and characterized their clinical features. To explore BPH proteomic alterations, a data independent acquisition-based mass spectrometry proteomics approach was adopted for 66 serum samples from healthy males (n = 22), patients with BPH (n = 22) and prostate cancer (n = 22). Bioinformatic evaluations were performed for proteomic profiling and candidate selection. In addition, a promising candidate was further validated with ELISA assay.</div></div><div><h3>Results</h3><div>Our findings revealed that the level of free PSA correlated with prostate volume. 7.95 % of BPH patients had a PSA value greater than 10 ng/mL, with elevated free PSA, prostate volume, PSA density, and decreased free to total PSA ratio. Mass spectrometry-based serum profiling demonstrated distinct differences between BPH and PCa. CDK5RAP2 was weighted most important in BPH patients’ serum and achieved an area under the receiver operating characteristic curve of 0.900 in distinguishing BPH and PCa, which was further validated by publicly-available mRNA microarray analysis and cellular phenotype evaluation.</div></div><div><h3>Conclusion</h3><div>Our comprehensive analysis systematically explored BPH serum characteristics, proteomic profiles, and identified novel serum markers that may contribute to the understanding of BPH and facilitate early diagnosis and intervention.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"135 ","pages":"Article 110867"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Siemens Atellica AMH assay and comparison with Roche, Beckman and Ansh Labs","authors":"Emily Shang ,&nbsp;Hilario Agustin ,&nbsp;Jason K.Y. Lee ,&nbsp;Matt Scheidegger ,&nbsp;JoAnna Jones ,&nbsp;Charbel Abou-Diwan ,&nbsp;Joe M. El-Khoury ,&nbsp;Jieli Li","doi":"10.1016/j.clinbiochem.2024.110863","DOIUrl":"10.1016/j.clinbiochem.2024.110863","url":null,"abstract":"<div><h3>Background</h3><div>Anti-Müllerian hormone (AMH) is an important marker for ovarian reserve and response to fertility treatments. However, interassay variability exists due to the lack of a standardized method. This study evaluates the performance of the new Siemens Healthineers Atellica IM AMH assay against established assays (Beckman DxI 600 Access, Roche cobas Elecsys® e801, and Ansh Labs AMH ELISA).</div></div><div><h3>Methods</h3><div>We measured AMH concentrations in 120 residual serum samples from patients presenting for routine AMH testing using all four assays. Passing-Bablok regression and Bland-Altman method were used for data analysis.</div></div><div><h3>Results</h3><div>The Siemens Healthineers Atellica IM assay demonstrated strong correlation with Beckman DxI (slope: 1.07, R²: 0.9881) but showed a minimal positive bias. Conversely, the Roche cobas Elecsys® e801 assay exhibited a negative bias compared to Beckman DxI (slope: 0.74, R²: 0.9696), while the Ansh Labs assay demonstrated a significant positive bias with increasing variability at higher AMH concentrations.</div></div><div><h3>Conclusion</h3><div>Overall, the Siemens Healthineers Atellica IM assay shows promise as an alternative method for AMH measurement, demonstrating good correlation with established assays. However, differences were observed between all assays, highlighting the importance of assay-specific interpretation for accurate clinical assessment.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"135 ","pages":"Article 110863"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune complexome analysis reveals an autoimmune signature predictive of COVID-19 severity","authors":"Marino Moriishi ,&nbsp;Takahiro Takazono ,&nbsp;Junya Hashizume ,&nbsp;Nozomi Aibara ,&nbsp;Yuki Jimbayashi Kutsuna ,&nbsp;Masaki Okamoto ,&nbsp;Toyomitsu Sawai ,&nbsp;Teppei Hoshino ,&nbsp;Yusuke Mori ,&nbsp;Yuichi Fukuda ,&nbsp;Yukikazu Awaya ,&nbsp;Hirotomo Yamanashi ,&nbsp;Yuichiro Furusato ,&nbsp;Toyoshi Yanagihara ,&nbsp;Hirotaka Miyamoto ,&nbsp;Kayoko Sato ,&nbsp;Yukinobu Kodama ,&nbsp;Shusaku Mizukami ,&nbsp;Noriho Sakamoto ,&nbsp;Kazuko Yamamoto ,&nbsp;Kaname Ohyama","doi":"10.1016/j.clinbiochem.2024.110865","DOIUrl":"10.1016/j.clinbiochem.2024.110865","url":null,"abstract":"<div><h3>Background</h3><div>The factors contributing to the development of severe coronavirus disease 2019 (COVID-19) following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain unclear. Although the presence of immune complexes (ICs), formed between antibodies and their antigens, has been linked to COVID-19 severity, their role requires further investigation, and the antigens within these ICs are yet to be characterized.</div></div><div><h3>Method</h3><div>Here, a C1q enzyme-liked immunosorbent assay and immune complexome analysis were used to determine IC concentrations and characterize IC antigens, respectively, in the sera of 64 unvaccinated COVID-19 patients with PCR-confirmed SARS-CoV-2 infection, enrolled at seven participating centers in 2020. For the analysis, the patients were split into the severe (n = 35) and non-severe (n = 28) groups on the basis of their COVID-19 symptoms.</div></div><div><h3>Results</h3><div>We found that neither serum IC concentration nor IC antigen number was associated with COVID-19 severity. However, we identified six IC antigens, which were significantly enriched in the severe versus non-severe group. These IC antigens were all derived from human proteins, namely haptoglobin, the serum amyloid A-2 protein, the serum amyloid A-1 protein, clusterin, and lipopolysaccharide-binding protein, and complement-factor-H-related protein 3. Meanwhile, we found no association between COVID-19 severity and IC antigens derived from SARS-CoV-2 proteins. Collectively, the six IC antigens predicted COVID-19 severity with a moderate degree of accuracy (area under the receiver operating characteristic curve = 0.90, sensitivity = 94 %, specificity = 79 %).</div></div><div><h3>Conclusions</h3><div>The IC antigen signature identified in this study may have important implications for the diagnosis and treatment of severe COVID-19.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"135 ","pages":"Article 110865"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of a new soluble transferrin receptor assay and comparison to three measurement procedures","authors":"Mary Kathryn Bohn ,&nbsp;Marvin Berman ,&nbsp;Salman Ali ,&nbsp;Pow Lee Cheng ,&nbsp;Xiao Yan Wang ,&nbsp;Randal J. Schneider ,&nbsp;Vathany Kulasingam","doi":"10.1016/j.clinbiochem.2024.110862","DOIUrl":"10.1016/j.clinbiochem.2024.110862","url":null,"abstract":"<div><h3>Background</h3><div>Soluble transferrin receptor (sTfR) is a useful marker in the differentiation of anemia. Clinical utility is limited by lack of standardization between measurement procedures and interpretative recommendations. Our objective was to evaluate the analytical performance of a research sTfR immunoturbidimetric assay (Alinity c, Abbott Diagnostics) and compare it to three established measurement procedures.</div></div><div><h3>Methods</h3><div>Assay imprecision was assessed with 7 panels across the analytical measuring interval. 159 patient samples were measured across four instrument systems (Alinity c [Abbott Diagnostics], Tina-quant c502 [Roche Diagnostics], Quantex Biokit [Werfen], and ACCESS [Beckman Coulter]). Ferritin was also measured to calculate an sTfR/Log Ferritin ratio. Sera from 100 reference individuals were assayed for sTfR and ferritin (Alinity) for reference interval (RI) verification (sTfR) or establishment (sTfR index).</div></div><div><h3>Results</h3><div>Assay imprecision met defined goals. Method comparison between Alinity c and ACCESS sTfR assays showed good agreement (slope: 1.06, intercept: −0.12, r: 0.989). Comparisons across other assays demonstrated significant proportional bias with slopes ranging from 0.44 (Tina-quant c502, mean bias: −2.52 mg/L) to 1.24 (Quantex Biokit, mean bias: 0.60 mg/L). A proportional bias was observed between other instruments. While the sTfR RI was verified on the Alinity assay, agreement in interpretation (within vs outside RI) between Alinity and other platforms ranged from 74.2 to 80.5 %.</div></div><div><h3>Conclusion</h3><div>We report the first characterization of the performance of a research sTfR immunoturbidimetric assay (Alinity c, Abbott Diagnostics). Our findings emphasize the lack of harmonization between measurement procedures and result interpretation for sTfR and sTfR index, necessitating standardization efforts and clinical studies.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"135 ","pages":"Article 110862"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation levels may contribute to severe hypertriglyceridemia in multifactorial chylomicronemia syndrome","authors":"Simon-Pierre Guay ,&nbsp;Martine Paquette ,&nbsp;Amélie Taschereau ,&nbsp;Véronique Desgagné ,&nbsp;Luigi Bouchard ,&nbsp;Sophie Bernard ,&nbsp;Alexis Baass","doi":"10.1016/j.clinbiochem.2025.110873","DOIUrl":"10.1016/j.clinbiochem.2025.110873","url":null,"abstract":"<div><h3>Background and aims</h3><div>Familial chylomicronemia syndrome (FCS) and multifactorial chylomicronemia syndrome (MCS) are the two main causes of severe hypertriglyceridemia (sHTG). FCS is a rare autosomal recessive form of sHTG, whereas MCS is mainly polygenic in nature with both common and rare variants accumulating and leading to sHTG. However, 30 to 50% of MCS patients have no identified genetic cause of sHTG. DNA methylation (DNAm) is a non-traditional heritable factor known to be associated with triglyceride (TG) levels. The aim of this study is to determine if DNAm level at three candidate genes for hypertriglyceridemia (<em>ABCG1</em>, <em>CPT1A</em> and <em>SREBF1</em>) could contribute to sHTG in MCS patients.</div></div><div><h3>Methods</h3><div>A total of 114 MCS and 20 FCS patients were included in this retrospective study. DNAm levels were measured at <em>ABCG1</em> (cg06500161), <em>CPT1A</em> (cg00574958), and <em>SREBF1</em> (cg11024682) gene loci using pyrosequencing of bisulfite-treated DNA.</div></div><div><h3>Results</h3><div>DNAm levels at <em>ABCG1</em>, <em>CPT1A</em> and <em>SREBF1</em> were significantly associated with TG levels or minimal TG levels in MCS patients. Prevalence of patients with at least 2 loci with DNAm levels into the top tertile of DNAm associated with hypertriglyceridemia was significantly higher in MCS patients with genetically undefined sHTG compared to MCS patients with polygenic sHTG and FCS patients (57 % vs. 24 % vs. 0 %, respectively; <em>p</em> &lt; 0.0001).</div></div><div><h3>Conclusion</h3><div>This study suggests for the first time that DNAm could contribute to sHTG in MCS patients. It suggests that further studies of epivariations may contribute to better understand the clinical heterogeneity seen in MCS patients.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"135 ","pages":"Article 110873"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Constructing a predictive model for high intraoperative excessive bleeding in patients undergoing posterior lumbar decompression and fusion internal fixation surgery during outpatient visits","authors":"Zhenmin Sun ,&nbsp;Nan Yang ,&nbsp;Lei Wang ,&nbsp;Jiansuo Zhou ,&nbsp;Hua Zhang ,&nbsp;Jun Wang","doi":"10.1016/j.clinbiochem.2024.110856","DOIUrl":"10.1016/j.clinbiochem.2024.110856","url":null,"abstract":"<div><h3>Objective</h3><div>1. Construct a risk prediction model to predict the factors of high intraoperative bleeding in patients undergoing posterior lumbar decompression and fusion internal fixation surgery during outpatient visits. 2. Implement pre-hospital blood management for surgery patients, to improve clinical outcomes.</div></div><div><h3>Design &amp; Methods</h3><div>We collected patients who underwent two-segment and three-segment posterior lumbar decompression and fusion internal fixation surgery in our hospital from 2016 to 2021. A total of 24 preoperative indicators were analyzed, covering medical history, demographic characteristics, segment, operator and laboratory test results. We used a logistic regression model to optimize the model’s feature selection. The predictive model was constructed using the multivariable logistic regression method with all included methods, and a nomogram was created to display the model. Activated partial thromboplastin time, surgeon volume, American Society of Anesthesiologists classification, body mass index, and the number of fusion and fixation lumbar segments were used to construct the predictive model. The predictive model’s discrimination, calibration, clinical applicability, and rationality were evaluated.</div></div><div><h3>Results</h3><div>The predictive model’s area under the receiver operating characteristic curve is 0.723, with a 95% confidence interval of (0.685–0.760). The training set’s decision curve analysis demonstrates that applying this diagnostic curve will increase the net benefit when the threshold probability is between 5% and 40%.</div></div><div><h3>Conclusion</h3><div>This study developed a novel nomogram with relatively good accuracy to assist clinical doctors in assessing the high intraoperative bleeding risk in patients undergoing posterior lumbar decompression and fusion internal fixation surgery during outpatient visits. By evaluating individual risk, surgeons can develop an individualized treatment plan to reduce the risk of intraoperative bleeding for each patient.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"135 ","pages":"Article 110856"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serial secretoneurin measurement and risk of ventricular arrhythmias and death in patients with left ventricular systolic dysfunction","authors":"Torbjørn Omland ,&nbsp;Helge Røsjø ,&nbsp;Torbjørn Wisløff ,&nbsp;Michael L. Bernard ,&nbsp;A.Elise Hiltbold ,&nbsp;Sammy Khatib ,&nbsp;Glenn M. Polin ,&nbsp;Paul A. Rogers ,&nbsp;Daniel P. Morin","doi":"10.1016/j.clinbiochem.2024.110868","DOIUrl":"10.1016/j.clinbiochem.2024.110868","url":null,"abstract":"<div><h3>Background</h3><div>Secretoneurin, a member of the granin protein family, is associated with the risk of mortality in patients with acute and chronic heart failure. Secretoneurin may play an important role in cardiomyocyte calcium handling, suggesting that it may influence cardiac arrhythmia risk. We hypothesized that baseline and serial measurements of circulating secretoneurin are associated with the risk of incident ventricular tachyarrhythmias (VA) and death, and that serial measurement would provide prognostic information beyond baseline values.</div></div><div><h3>Methods</h3><div>We measured circulating secretoneurin concentrations in blood samples obtained at 3-month intervals for one year in a prospectively enrolled cohort of ambulatory patients with left ventricular ejection fraction (LVEF) ≤ 35 % and a primary-prevention implanted cardioverter defibrillator (ICD). Associations between secretoneurin modeled as a time-dependent variable and the incidences of VA and death were assessed.</div></div><div><h3>Results</h3><div>154 patients (66 ± 14 years, LVEF 23 ± 8 %) were included in the analysis. During one-year follow-up, 26 (17 %) patients experienced VA, and 16 (10 %) died. Adjusting for age, sex, eGFR, and LVEF, baseline secretoneurin concentration was associated with the risk of death (hazard ratio (HR) per 10 pmol/L increase: 1.14 (95 % CI: 1.02–1.27), p = 0.020) but not VA (HR: 0.98 (0.81–1.19), p = 0.856). Using serial measurements at 3-month intervals, time-varying secretoneurin was associated with a similarly higher risk of death (HR: 1.14 (1.02–1.27), p = 0.017) but not of VA (HR: 0.97 (0.81–1.17), p = 0.776).</div></div><div><h3>Conclusion</h3><div>In stable ambulatory patients with reduced LV systolic function and a primary prevention indication for ICD, secretoneurin concentration was associated with the risk of death but not ventricular tachyarrhythmia.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"135 ","pages":"Article 110868"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of three different cystatin C measurement procedures in a pediatric chronic kidney disease cohort: Calibration for longitudinal measurements and implications for clinical estimation of GFR","authors":"Derek K. Ng ,&nbsp;George J. Schwartz ,&nbsp;Bradley A. Warady ,&nbsp;Susan L. Furth ,&nbsp;Jesse C. Seegmiller ,&nbsp;for the CKiD Study Investigators","doi":"10.1016/j.clinbiochem.2024.110869","DOIUrl":"10.1016/j.clinbiochem.2024.110869","url":null,"abstract":"<div><h3>Introduction</h3><div>Serum cystatin C (CysC) is used to estimate glomerular filtration rate (eGFR), including in the Chronic Kidney Disease in Children (CKiD) Under 25 years (U25eGFR) equations. Several CysC measurement procedures available from diagnostic vendors include reference material for calibration, but the extent of heterogeneity across manufacturers is unclear. Since heterogeneity may have clinical and research implications for eGFR, we evaluated three CysC procedures in samples from the CKiD study representing a wide spectrum of kidney function.</div></div><div><h3>Materials and Methods</h3><div>The three CysC measurement procedures evaluated were: Siemens BN II N Latex CystatinC Assay; Gentian CystatinC Immunoassay; and Roche Tina-quant CystatinC Gen.2. Bland-Altman quantified agreement with Siemens as reference because that method was used for longitudinal CKiD samples from 2003 to 2023. We present derivation of the interquartile range (IQR) of U25eGFR as a measure of precision and describe differences outside this range.</div></div><div><h3>Results</h3><div>From 53 samples from 44 participants, Gentian measurements were 7 % higher than Siemens (95 %CI: +5.6 %,+8.5 %), while Roche measurements were 4.8 % lower on average (95 %CI: −6.2 %,-3.3 %). Both had very high correlation: 0.9926 and 0.9906, respectively. There was strong agreement across procedures, but a simple correction factor of 7 % reduction applied to Gentian yielded unbiased estimates (+0.03 %, 95 %CI: −1.3 %,+1.4 %) and strong performance in Deming regression. For precision, 98 % of U25eGFR values based on Gentian and Roche CysC were each within the IQR of the Siemens-based estimates.</div></div><div><h3>Conclusions</h3><div>Despite reference material calibration, heterogeneity across CysC measurement procedures was observed. Procedure variability was within the limits of U25eGFR estimates indicating that practically, all procedures are appropriate for clinical use. Clinicians may consider calculating IQR of U25eGFR estimates for pediatric chronic kidney disease management.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"136 ","pages":"Article 110869"},"PeriodicalIF":2.5,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re-evaluating the utility of iron indices in hereditary hemochromatosis genotyping: A retrospective study","authors":"Amy Lou ,&nbsp;Manal O. Elnenaei ,&nbsp;Julie Zhu ,&nbsp;Kevork Peltekian ,&nbsp;Eric Liu ,&nbsp;Jennifer A. Jamieson ,&nbsp;Hammam Said ,&nbsp;Bassam A. Nassar","doi":"10.1016/j.clinbiochem.2024.110860","DOIUrl":"10.1016/j.clinbiochem.2024.110860","url":null,"abstract":"<div><h3>Introduction</h3><div>Hereditary hemochromatosis (HH), associated with C282Y or H63D mutations in the HFE gene, is the commonest genetic disorder in Canada. The majority of HH cases are attributable to C282Y homozygosity which can precipitate iron overload and organ damage, but with low penetrance. Elevated transferrin saturation (TSat) and ferritin levels are key biochemical indicators of iron overload in C282Y homozygotes. This retrospective study examined TSat and ferritin levels as predictors of C282Y homozygosity in genotyped patients.</div></div><div><h3>Methods</h3><div>This study included 23,432 individuals from Maritime provinces who underwent HFE genotyping from 2009 to 2022. Those with available biomarkers (TSat, ferritin, ALT) were included in the study sample. C282Y and H63D variants were identified based on HFE genotying. Median values for each biomarker were compared across genotypes and their diagnostic performance in predicting C282Y homozygosity evaluated using ROC analysis.</div></div><div><h3>Results</h3><div>1241 individuals (5.3 %) showed C282Y homozygosity, marking the largest North American study cohort. C282Y homozygotes showed significantly higher median TSat and ferritin levels than wildtypes. TSat showed the best diagnostic performance in detecting C282Y homozygosity (AUC = 0.82, 95 % CI: 0.78–0.85), outperforming ferritin (AUC = 0.54, 95 % CI: 0.50–0.58) and ALT (AUC = 0.59, 95 % CI: 0.56–0.63). TSat thresholds of 32 % (females) and 35 % (males) had a 90 % sensitivity for C282Y homozygosity. Using thresholds of TSat ≤46 % and ferritin ≤370 µg/L (females), and TSat ≤49 % and ferritin ≤703 µg/L (males) reduced the need for genotyping by up to 50 % without missing significant biochemical iron overload cases. Implementing this strategy across 23,432 tests could save $1,701,163 and potentially reduce unnecessary downstream management.</div></div><div><h3>Conclusion</h3><div>Our study suggests significant efficiency savings by implementing an algorithm to reduce unnecessary HFE genotyping and alleviate unwarranted genetic testing anxiety.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"135 ","pages":"Article 110860"},"PeriodicalIF":2.5,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}