Clinical chemistry最新文献

{"title":"B-165 Evaluation of a newly developed Access anti-HAV IgM immunoassay on the DxI 9000 Immunoassay Analyzer in the United States","authors":"Hannah Hartman, Saeed Jortani, Ian Gunsolus, Fred Apple, Stephanie Bord Romeu, Thomas Robin, Danielle Maher","doi":"10.1093/clinchem/hvag086.469","DOIUrl":"https://doi.org/10.1093/clinchem/hvag086.469","url":null,"abstract":"Background Beckman Coulter, Inc. recently developed a fully automated Access anti-hepatitis A Virus (HAV) IgM assay for the detection of IgM antibodies to HAV for use on the DxI 9000 Immunoassay Analyzer. The assay's analytical and clinical performances were evaluated. Methods Imprecision was evaluated using three replicates of eight samples including serum and plasma and two quality controls using multiple reagent packs and calibrator lots in 40 runs based on CLSI EP05-A3. Reproducibility was evaluated at three U.S clinical laboratories using one lot of reagent, with low and high negative and positive serum and plasma samples, and quality controls based on CLSI EP05-A3. Cross-reactivity was evaluated using 348 negative samples and a reference method across 25 categories including other viral infection and auto-immune diseases. Seroconversion panels were tested to evaluate sensitivity of the Access anti-HAV IgM Assay in early detection of hepatitis A IgM antibodies. Clinical performance on the DxI 9000 Analyzer was evaluated in comparison to commercially available FDA-cleared anti-HAV IgM reference assays at three U.S clinical laboratories to evaluate the assay’s ability as an aid in the diagnosis of acute or recent HAV infection. Results Within-Laboratory imprecision demonstrated = 7.7 % CV for samples = 1.00 S/CO, and standard deviation (SD) = 0.05 for samples < 1.00 S/CO while reproducibility demonstrated an overall imprecision = 8.8% for samples = 1.00 S/CO (n=360) and an SD of = 0.05 for samples < 1.00 S/CO (n=360). The cross-reactivity study demonstrated overall negative agreement of 100.0% versus the reference assay. In seroconversion testing, the Access anti-HAV IgM assay exhibited sensitivity equivalent to the reference assay across three panels, notably detecting anti-HAV IgM one bleed earlier on a fourth panel. The Access anti-HAV IgM assay demonstrated overall PPA of 100.0% (n=88/88; 95% CI: 95.8-100.0%) and NPA of 99.3% (n=762/767; 95% CI: 98.5-99.7%) in the diagnostic population. Conclusion The Access anti-HAV IgM assay consistently demonstrated excellent analytical and clinical performance, proving equivalent to currently FDA-cleared anti-HAV IgM assays. Given the recent shift in US hepatitis A outbreaks1 from predominantly food-borne to person-to-person transmission, the introduction of a new, high-throughput anti-HAV IgM assay is particularly significant, enabling robust and scalable serologic testing crucial for effective public health surveillance and outbreak management.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"4 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086396","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":"A-036 Comparison of formulas for LDL measurement in cancer patients with hypercholesterolemia and low triglyceride levels","authors":"Billy Sanchez-Jacinto, Olga Arroyo - Huanaco, Rommy Pizarro - Robles","doi":"10.1093/clinchem/hvag086.030","DOIUrl":"https://doi.org/10.1093/clinchem/hvag086.030","url":null,"abstract":"Background In recent years, cancer treatments have become highly effective, achieving high cure rates in the early stages of the disease and long-term remission. However, dyslipidemia may play a significant role in carcinogenesis by dysregulating lipid signaling, potentially leading to the development of cardiovascular disease. Furthermore, it has been associated with promoting tumor invasion and metastasis, as well as producing resistance to cancer medications. Low-density lipoproteins (LDL) are a biomarker for the diagnosis and treatment of dyslipidemia. Currently, primary care and specialized hospitals still rely on formula-based methods due to their accessibility and low cost compared to direct LDL measurement. Among these formulas, the Friedwald equation, proposed in 1972, stands out. In recent years, newer equations such as the Martin-Hopkins (MH) and Sampson equations have emerged, based on total cholesterol (TC), high-density lipoproteins (HDL), and triglycerides (TG). The objective was to compare LDL cholesterol measurement formulas in cancer patients with hypercholesterolemia and low triglyceride levels. Methods An observational, cross-sectional, analytical, and prospective study. The sample size was 265 lipid profiles, processed using an automated dry chemistry analyzer between January and March 2023 at a cancer institute in Lima, Peru. The population was divided into several triglyceride level groups (<100 mg/dL, 100–149 mg/dL), and LDL cholesterol was stratified according to the ATP III classification to assess patient classification with respect to the LDL cholesterol formulas. Statistical analysis included descriptive analysis of categorical and numerical variables; correlation was performed using Pearson's correlation coefficient, and the Bland-Altman test was used to compare LDL cholesterol formulas and determine bias and percentage bias. Clinical relevance was assessed by comparing the results with the biological variation in the Westgard table. A p-value <0.05 was considered significant, and the data were processed using Stata v.14 and MedCalc v23.2.1. Results Mean age of the patients was 57.30 ± 13.30 years, and the frequency of female sex was 78.87% (n = 209). The mean measured HDL and LDL levels were 57.32 ± 14.16 mg/dL and 135.21 ± 23.78 mg/dL, respectively, and the median total cholesterol (TC) level was 222.35 (211.13–241.30) mg/dL. While the calculated average LDL in Friedewald was 148.73 ± 23.73 mg/dL, in MH it was 148.61 ± 23.11 mg/dL, and in Sampson it was 151.39 ± 23.70 mg/dL. The correlation between measured and calculated LDL was strong (r > 0.85) at the different triglyceride levels; statistical (p < 0.05) and clinical relevance was observed in all three formulas evaluated overall and at both triglyceride levels. Furthermore, patients showed a reclassification using the Friedewald, Martin-Hopkins, and Sampson formulas of 43.4%, 44.5%, and 47.5%, respectively. Conclusion The LDL formulas","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"219 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086429","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":"B-055 A Multiplexed SERS Assay for Quantitative Protease Turnover Detection at Picomolar Levels","authors":"Kaitlyn Varela, Kaleb Byers, Mini Thomas, Michael Poderycki, Vincent Davisson","doi":"10.1093/clinchem/hvag086.382","DOIUrl":"https://doi.org/10.1093/clinchem/hvag086.382","url":null,"abstract":"Background Surface-Enhanced Raman Spectroscopy (SERS) allows for ultrasensitive detection of analytes in complex biofluids. This capability is particularly important when measuring analytes at low concentrations or when clinical sample volumes are limited. SERS improves workflows by eliminating complex sample-preparation steps and instead employs dilution to reduce matrix interference in analyte measurements. Amplified Sciences has previously used its proprietary dyes and automated BioMatra™ hardware platform to develop a low-volume assay panel (PanCystPro™) which is offered as a Lab Developed Test in a CLIA-certified lab. This multi-analyte test includes an ultra-low-volume SERS-based proteolytic activity measurement of the digestive enzyme gastricsin to differentiate mucinous and non-mucinous pancreatic cysts. Beyond this initial use, significant opportunities exist to apply protease activity biomarkers to other clinical conditions. However, highly accurate diagnostics often demand panels of biomarkers, not single markers, regardless of technology or analyte type. Advancing BioMatra’s multiplexing capabilities will enable additional efficiencies and cost-effective testing. A recently developed multiplexed protease assay panel featuring isotopically-labeled SERS-active dyes demonstrates the platform's potential to analyze complex biological matrices utilizing small sample volumes. Methods A variant of the CLIA laboratory-installed BioMatra was developed, integrating a Wasatch Photonics 785nm Raman spectrometer into a fully automated multi-axis plate reader system (Fig. 1A). The platform software enables high-throughput analysis of 384-well plates with ∼10 second/well acquisition to ensure reproducible readout. A molecular reporter system uses deuterated (d0/d8) isotope-labeled R19 dimer-conjugated SERS-active peptide substrates for neutrophil elastase and MMP9, producing partially overlapping but resolvable spectral signatures centered at 1327 cm-1 (d8, hNE) and 1353 cm-1 (d0, MMP9) (Fig. 1B). Commercial preparations of recombinant neutrophil elastase and MMP9 were mixed with their respective magnetic bead-bound peptide substrates and cleavage reactions terminated via bead removal. Samples for multiplex data acquisition were generated by mixing a portion of the collected supernatants, and analysis included a ratiometric correction factor based on Area Under the Curve of characteristic peaks within overlapping spectra. Results Increasing concentrations of recombinant enzymes were used to generate standard curves, and both activity assays demonstrated excellent linearity (R2 > 0.99), with coefficients of variation ranging from 1.5-9.7%. The limit of detection was 0.07 ng/mL (2.5 pM) for neutrophil elastase and 0.89 ng/mL (13.4 pM) for MMP9 (Fig. 1C and 1D). Dynamic range spanned approximately two orders of magnitude (0.2-25 ng/mL for neutrophil elastase; 0.7-125 ng/mL for MMP9). Multiplex measurements showed strong concordance with singlepl","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"11 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086432","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":"A-045 Comparing the patterns of some biochemistry laboratory parameters between healthy older and younger subjects","authors":"Sujata Wangkheimayum, Rashi Garg, Priya Saini","doi":"10.1093/clinchem/hvag086.038","DOIUrl":"https://doi.org/10.1093/clinchem/hvag086.038","url":null,"abstract":"Backgrond Ageing is associated with some decline in physiological functions. It is reported to be linked with dyslipidemia, insulin resistance and decrease in anti-oxidant defense etc. Lipoprotein lipase (LPL) is an important enzyme involved in lipoprotein metabolism. It hydrolyzes triglycerides (TG) in TG-rich lipoproteins in the circulation. Triglyceride glucose index (TyG), a relatively new marker of insulin resistance, TG/HDL ratio and non HDL cholesterol are important laboratory parameters which may provide information related to nutrient metabolism and hence, cardio-metabolic health in older subjects. The main focus of the work was to study the activities/concentrations of LPL, lipid profile and carbohydrate and lipid metabolism-related derived parameters in older subjects compared to younger group. Methods A total of 40 subjects in age group of 20-40 years and another 40 subjects in the age range of 40 to 60 years, all apparently healthy were taken for the study after informed consent. The study approved by our Institute Ethics Committee. LPL activity in blood samples were performed by manual, chemical methods, whereas, LPL mass was estimated by ELISA Fasting glucose, lipid profile, plasma proteins, bilirubin and other biochemistry parameters were performed in Cobas, Roche Diagnostics autoanalyzers TyG, non HDL cholesterol, TG/HDL, other lipid ratios and globulins were calculated Data was analyzed by IBM SPSS Version 26. Results The concentrations and activity of LPL were significantly decreased in the older age group compared to the younger group. There were increased fasting glucose, cholesterol, LDL and TG in older group. However, HDL showed no differences. Similarly, non-HDL cholesterol and TG/HDL ratio were observed to be higher (p=0.002 for both) in the older subjects. No significant correlations were observed between LPL and triglyceride in both groups. The ratios, cholesterol/HDL and LDL/HDL did not show any significant differences between the two groups. Significant increase in globulin (p=0.003), but decrease in albumin (p=0.006) were observed in the older group. Though albumin was decreased, total protein was observed to be more (p=0.016) in the older subjects in our study. The TyG index was significantly higher in healthy older group versus healthy younger group (4.71+/-0.18 vs 4.48+/- 0.20, p=<.001). Conclusions The significant increase in glucose, TyG index, non-HDL cholesterol, globulin and decrease in albumin in older group provides information of changes in biochemistry parameters with age. Though sex hormone binding globulin as well as corticosteroid-binding globulin are reported to be lower in older subjects, the finding of increased globulin but decreased albumin in older subjects in our study highlights the importance of determining globulin fraction(s).The enzyme activity and mass estimated by chemical method and ELISA lack precision and sample size was small. Though most laboratory parameters were within refer","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"12 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086434","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":"B-060 Comparing the Ability of PBS-Caffeine to Caffeine Buffers to Inhibit Exocytosis during the Horseshoe Crab Blood Collection Process and Produce a High Yield of Limulus Amebocyte Lysate for Endotoxin Detection","authors":"Jessica Zhang, Mengmeng Zhang, Sophia Zhang","doi":"10.1093/clinchem/hvag086.386","DOIUrl":"https://doi.org/10.1093/clinchem/hvag086.386","url":null,"abstract":"Background Limulus amoebocyte lysate (LAL) is widely used for endotoxin detection. Previous studies have shown that a caffeine-based collection solution inhibits degranulation, and caffeine-derived LAL remains functional in both chromogenic and turbidimetric assays. However, cell pellets collected in the caffeine mixture exhibited significant aggregation upon resuspension in 5 mM CaCl2, an issue not observed with PBS. To address this, we evaluated the clotting effects of PBS-based collection solutions and developed a novel PBS-caffeine bleeding solution. Our results demonstrate that both PBS-caffeine and caffeine buffers effectively prevent degranulation while yielding high LAL recovery. To identify the optimal bleeding solution, we compared PBS-caffeine and caffeine buffers, prepared Factor G lysate, and assessed its stability. Methods Experiments were carried out to compare the effects of both an 80 mM caffeine solution and a PBS-caffeine solution on degranulation during the bleeding process. Six or 12 crabs were bled once a week. A total of 121 crabs were bled. The blood of each crab was collected with a caffeine collection solution, PBS-caffeine collection solutions, and PBS-caffeine collection solutions supplemented with EDTA, EGTA, or both. The cell pellets were ultimately resuspended in 5 mM CaCl2. The final LAL activity of the supernatant was tested via both chromogenic and turbidimetric methods. To evaluate the stability of Factor G, the LAL lysate was treated with 10% PEG-8000 and stored in a 20 mM acetate buffer (pH 5.6). Factor G activity was tested via a chromogenic assay at different time intervals. Results Both the PBS-caffeine and caffeine-only collection mixtures prevented degranulation for over 1 hour. The yield of LAL obtained from the PBS-caffeine mixture was slightly higher than that from the caffeine-only mixture, but the difference was not statistically significant. The activity also varied slightly depending on the month of the bleeding season. Additionally, Factor G lysate prepared with 10% PEG-8000 remained stable for 27 months in 20 mM acetate buffer (pH 5.6). Conclusion Both PBS-caffeine and caffeine-only collection solutions effectively prevent amoebocyte degranulation during blood collection and processing. While the PBS-caffeine mixture additionally reduces cell aggregation/clotting, no statistically significant difference was observed in LAL activity between the 2 solutions. Furthermore, Factor G lysate prepared in 10% PEG-8000 and 20 mM acetate buffer (pH 5.6) exhibited stability for over 2 years.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"56 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086437","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":"B-195 Preliminary implementation of mass spectrometry (EXENT®) for the detection of oligoclonal bands in CSF","authors":"Nick Paciaroni, Marta Outón, José Luis Veiga, Mónica Pascual, Raúl Vidal, Teresa Cedena, Joaquín Martínez, Luisa María Villar, María Ángeles Iglesias, Rosa Pello","doi":"10.1093/clinchem/hvag086.496","DOIUrl":"https://doi.org/10.1093/clinchem/hvag086.496","url":null,"abstract":"Background Detection of IgG oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) by isoelectric focusing (IEF) with immunoblotting remains the reference laboratory method for demonstrating intrathecal immunoglobulin synthesis in multiple sclerosis (MS). Although analytically sensitive, IEF is labor-intensive, qualitative, and subject to interobserver variability. Mass spectrometry–based immunoglobulin profiling using the EXENT® Analyzer enables molecular-level detection of clonal intact light chains (iLC) through selective immunocapture and MALDI-TOF analysis, providing a digital and potentially more standardized readout. Methods Twelve paired CSF–serum samples previously characterized by IEF in a reference center were analyzed. Patterns included three mirror cases, three IgG+IgM positive cases, three IgG positive cases, and three negative cases. CSF samples were processed without external dilution; serum was analyzed both diluted and undiluted, with improved analytical performance observed in undiluted serum. The EXENT® workflow applies an internal ∼1:10 dilution during analytical processing. Independent expert interpretation was performed for both methodologies. Results EXENT® demonstrated 100% concordance with IEF for IgG OCB-positive and negative cases. Mirror-pattern cases showed limited agreement, with 1/3 fully concordant (33%). In one mirror case, only serum peaks were detected; in another, no differential signal was observed. Mirror-pattern cases were not associated with intrathecal synthesis or clinical MS diagnosis, consistent with their biological interpretation. These findings underscore the importance of appropriate alignment of serum and CSF immunoglobulin concentrations to minimize potential misclassification and preserve diagnostic specificity. No IgM oligoclonal patterns were detected by EXENT®, including samples classified as IgG+IgM positive by IEF. Analytical review indicated that IgG—and particularly IgM—concentrations in CSF were frequently near the system’s analytical limit of detection. The internal dilution step may reduce the effective concentration of intact light chains available for immunocapture, potentially influencing analytical sensitivity, especially for IgM detection. Conclusion In this preliminary evaluation, EXENT® mass spectrometry showed excellent agreement with IEF for IgG OCB-positive and negative classifications. However, reduced concordance in mirror patterns and absence of IgM detection suggest that analytical sensitivity in low-concentration CSF samples may be influenced by internal dilution. Further optimization of CSF-specific workflows and larger multicenter studies with formal statistical validation are needed to better define the role of mass spectrometry in CSF oligoclonal band assessment.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"6 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086466","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":"B-167 Combined Plasma H3.1 Nucleosomes with Creatinine and Lactate for Early Sepsis Detection in Emergency Department Patients","authors":"Terry Kelly, Aristotelis Kotronoulas, Andrew Retter, M I tchell Aicher, Marielle Herzog, Tom Soriano","doi":"10.1093/clinchem/hvag086.471","DOIUrl":"https://doi.org/10.1093/clinchem/hvag086.471","url":null,"abstract":"Background Early recognition of sepsis in the emergency department (ED) remains challenging, and existing clinical scores and routine biomarkers have limited sensitivity. Circulating nucleosomes containing histone H3.1 are biomarkers of cellular injury and organ dysfunction. We hypothesized that integrating plasma H3.1 nucleosomes with routine chemistry markers could improve early identification of sepsis at ED presentation. Methods We performed a retrospective analysis of 193 unselected adult ED patients. Plasma H3.1 nucleosome concentrations were measured at presentation using a chemiluminescent immunoassay, alongside routine creatinine and lactate testing. Sepsis diagnosis was adjudicated retrospectively by two senior clinicians according to Sepsis-3 criteria. A multivariable logistic regression model incorporating log-transformed H3.1, creatinine, and lactate was developed to discriminate sepsis from non-sepsis. Model performance was assessed by area under the receiver operating characteristic curve (AUC) with internal cross-validation. Sensitivity and specificity were calculated at the optimal Youden’s J threshold. Results Of 193 patients, 94 (49%) met Sepsis-3 criteria. The combined H3.1–creatinine–lactate model demonstrated strong discrimination with a cross-validated AUC of 0.863 (95% CI, 0.823–0.902). At the Youden-optimal threshold, sensitivity was 89.7% and specificity was 78.8%, enabling identification of the majority of sepsis cases while avoiding nearly four-fifths of false-positive classifications. The addition of H3.1 provided incremental diagnostic value beyond routine markers alone. Conclusions A logistic regression model integrating plasma H3.1 nucleosomes with creatinine and lactate achieved high early diagnostic accuracy for sepsis in a general ED population. This approach requires addition of only a single novel biomarker to existing laboratory workflows and may provide actionable diagnostic support at the frontline. Prospective multicenter validation is warranted.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"171 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086469","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":"A-122 STOP CULTURING EVERYTHING: A DATA-DRIVEN, FIVE-PARAMETER URINALYSIS SCORECARD TO TRIAGE SUSPECTED UTI","authors":"Leonardo Vasconcellos, Daniel Bücker, Victor Sampaio, Lucas Moreira, Lucas Rocha","doi":"10.1093/clinchem/hvag086.096","DOIUrl":"https://doi.org/10.1093/clinchem/hvag086.096","url":null,"abstract":"Background Urine culture remains the gold standard for diagnosing urinary tract infections (UTI), yet it is resource-intensive and often creates a significant laboratory burden due to high rates of negative results. Reliance on isolated urinalysis parameters is frequently insufficient for accurate triage. We aimed to develop a robust, multivariable clinical scorecard derived from machine learning to risk-stratify patients and reduce unnecessary urine cultures in a tertiary care setting. Methods We analyzed a retrospective dataset of 150,234 paired urinalysis and culture results (2011–2024). Data processing included specific gravity normalization and feature engineering to create clinically relevant categories (e.g., significant pyuria >10 WBC/hpf, male infants <1 year, and fertile-age women 14–45 years). We employed XGBoost with a 70/30 train/test split. The training set was balanced using undersampling, while the hold-out set retained real-world prevalence. A simplified, deployable scorecard was then generated using logistic regression coefficients based on the Sullivan’s health expectancy method. Results Machine learning analysis identified Nitrite, bacterial Flora, and Pyuria as the dominant predictors. Crucially, the model captured demographic interactions that adjusted risk: male infants received positive weighting (reflecting higher risk), while fertile-age women received negative weighting (adjusting for common non-UTI presentations). Parameters like protein and hemoglobin contributed negligible weight in the presence of stronger predictors. A final cutoff score of =3 demonstrated >82% sensitivity and >75% specificity in the hold-out validation set, providing an optimal balance for reflex culture screening. Conclusion Implementing this five-parameter scorecard can significantly streamline laboratory workflows, reducing unnecessary cultures while maintaining high diagnostic safety.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"20 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086470","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":"A-108 Comprehensive Performance Evaluation of a Rapid, Universal, Sepsis Diagnostic Workflow that identifies Pathogens and characterizes their Antimicrobial Resistance","authors":"Ramya VM, Thomas A Hall, Divya Sharma, Ishita Chakraborty, Deeksha Hebbar, Lisa Risen, Christine Marzan, Michael Mosel, James Hannis, Hila Roshanravan, Robert Bonomo, Megan Carpenter","doi":"10.1093/clinchem/hvag086.082","DOIUrl":"https://doi.org/10.1093/clinchem/hvag086.082","url":null,"abstract":"Background Rapid and accurate diagnosis of bloodstream infections (BSIs) is essential to initiate appropriate therapy in patients with sepsis, where mortality risk increases with every passing hour. The current gold standard, blood culture, requires approximately 15–72 hours for pathogen identification (ID), followed by an additional 8–15 hours for antimicrobial susceptibility testing (AST). In addition to its prolonged turnaround time (TAT), blood culture is susceptible to both false-positive and false-negative results. Furthermore, most nucleic acid–based assays available commercially rely on blood culture as the initial input material and/or are restricted to detecting a predefined panel of pathogens and antimicrobial resistance (AMR) genes. Therefore, a rapid, unbiased diagnostic approach capable of directly detecting pathogens and their associated AMR markers from whole blood within a clinically actionable TAT remains a significant unmet need in sepsis management. Towards advancing the field of sepsis diagnostics, we have developed a cutting-edge approach called ASPIRE: Agnostic Sepsis Pathogen Identification and REsistance determination. This workflow is rapid, agnostic, quantitative, automation amenable that can report pathogen ID and AMR determinants, directly from whole blood, within 6 to 8 hours using nanopore sequencing. The workflow is illustrated in Figure-1. Methods We evaluated analytical sensitivity of ASPIRE workflow using 3 to 5 mL contrived blood samples (n=50) spiked with typical BSI bacteria and fungi at 10 to 100 CFU/mL. We also tested 1.0 mL clinical samples (58 Blood cultures and 31 Whole blood samples) to evaluate the clinical concordance of the ASPIRE workflow with blood culture outcomes. In addition, ASPIRE workflow was tested with 31 clinical bacterial isolates which were pre-characterized for their antimicrobial signatures (19 confirmed positives and 12 confirmed negatives). A breadth of coverage (BoC) analysis for this workflow was also performed using 19 commercially procured bacterial isolates. Results AMR detection: The ASPIRE system displayed the ability to simultaneously identify multiple relevant AMR determinants in a panel of blinded multi drug resistant bacterial isolates with a high degree of confidence. Except for the specific variant IMP-13, all targeted markers identified in the truth key were correctly identified Analytical sensitivity: The ASPIRE system achieved detection of 5 to 10 CFU/mL for ESKAPE bacteria and Candida albicans using the ASPIRE workflow. Clinical sensitivity: Preliminary clinical studies showed substantial concordance between blood cultures and ASPIRE workflow at 87.8% (58 samples), sensitivity of 94% (47/50 confirmed positives) and specificity of 50% (4/8 confirmed negatives) when tested with 58 blood culture samples. We observe a PPA of 0.94 and NPA of 0.8. With ∼1mL of direct (uncultured) blood, we observed concordance of 83.9% (31 samples), sensitivity of 73.7% (14/19 confirmed po","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"27 16 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086475","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":"B-221 Development of a prototype Bridge ELISA for detection of anti-nephrin autoantibodies","authors":"Jackie Weiss, Andrea Deerberg, Sina Rhein, Christiane Radzimski, Swantje Mindorf, Viola Borchardt-Lohölter, Felicitas Hengel, Silke Dehde, Nicola Tomas, Tobias Huber","doi":"10.1093/clinchem/hvag086.520","DOIUrl":"https://doi.org/10.1093/clinchem/hvag086.520","url":null,"abstract":"Background Anti-nephrin autoantibodies bind at the slit diaphragm of podocytes in the kidney, leading to failure of the glomerular filtration barrier and inducing podocyte dysfunction leading to nephrotic syndrome [1]. Circulating anti-nephrin autoantibodies are common in patients with podocytopathies such as minimal change disease (MCD),primary focal segmental glomerulosclerosis (FSGS), and childhood idiopathic nephrotic syndrome, and their levels correlate with disease activity [2]. The current gold standard for anti-nephrin antibody detection is immunoprecipitation (IP) [2,3]. Conventional ELISAs have been ineffective in detecting these antibodies, possibly because of the low abundance or affinity of these autoantibodies, showing the need for a highly sensitive assay [2, 3]. Here we report on the development of a new prototype Bridge ELISA for the detection of anti-nephrin autoantibodies. The study evaluates the performance of the prototype assay. Methods The detection principle of the prototype Anti-Nephrin Bridge ELISA (Euroimmun) involves capturing bivalent anti-nephrin antibodies between two antigens, one capture and one detection antigen, forming a \"bridge\". The utilization of both antibody valences helps to increase the specificity that allows to apply serum samples at a significantly lower dilution. This in turn finally is the key to enable the detection of the low-abundance antibodies while still ensuring proper discrimination between anti-nephrin-positive and anti-nephrin-negative samples. The performance of the prototype Anti-Nephrin Bridge ELISA was evaluated using a panel (n=40) comprising 8 anti-nephrin-positive serum samples from MCD patients precharacterized by IP (using the recombinant human nephrin ectodomain [2]), 29 sera from healthy adult blood donors, and 3 anti-nephrin IgG positive control substances. Results were compared with those obtained with an in-house Anti-Nephrin ELISA with a conventional detection principle. From the blood donors, 9 samples were additionally tested for anti-nephrin autoantibodies using IP. Agreement of qualitative results (n=17, 8 patients + 9 blood donors) between ELISAs and IP was calculated using Cohen’s kappa (?). Results The prototype Anti-Nephrin Bridge ELISA detected all 40 samples correctly, which corresponds to an accuracy of 100%. The agreement between qualitative results of IP and the Bridge ELISA were perfect (?=1), but slight (?=0) between IP and the conventional in-house ELISA. All patient sera had higher optical densities when analyzed with the prototype Anti-Nephrin Bridge ELISA than with the conventional Anti-Nephrin ELISA, providing tentative initial evidence for a very high sensitivity of the prototype Anti-Nephrin Bridge ELISA. Conclusion The prototype Anti-Nephrin Bridge ELISA could be a valuable tool for supporting precise and sensitive detection of anti-nephrin autoantibodies. Autoantibody quantification can support treatment monitoring of glomerular diseases, enhance trea","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"11 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149086524","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}