Tom Dehaemers, Birthe Michiels, Rita Derua, Yves Piette, Carolien Bonroy, Jonas De Leeuw, Doreen Dillaerts, Nele Peersman, Maaike Cockx, Tom De Waal, Pieter Vermeersch, Takashi Matsushita, Vanessa Smith, Jean-Baptiste Vulsteke, Ellen De Langhe, Xavier Bossuyt
{"title":"Detection of Anti-RuvBL1/2 Autoantibodies by Targeted Liquid Chromatography-Tandem Mass Spectrometry.","authors":"Tom Dehaemers, Birthe Michiels, Rita Derua, Yves Piette, Carolien Bonroy, Jonas De Leeuw, Doreen Dillaerts, Nele Peersman, Maaike Cockx, Tom De Waal, Pieter Vermeersch, Takashi Matsushita, Vanessa Smith, Jean-Baptiste Vulsteke, Ellen De Langhe, Xavier Bossuyt","doi":"10.1093/jalm/jfaf072","DOIUrl":"https://doi.org/10.1093/jalm/jfaf072","url":null,"abstract":"<p><strong>Background: </strong>Anti-RuvBL1/2 autoantibodies are found in patients with systemic sclerosis and systemic sclerosis-myositis overlap syndrome. Anti-RuvBL1/2 antibodies recognize conformational epitopes of the RuvBL1/2 complex, which complicates detection by solid phase assays. Here, we propose a method for detection of anti-RuvBL1/2 autoantibodies based on liquid phase immunoprecipitation combined with quantification of the precipitated RuvBL1/2 by LC-MS/MS.</p><p><strong>Methods: </strong>Serum antibodies of patients (n = 13) and controls (n = 60) were captured by and cross-linked to protein A/G magnetic beads and incubated with HeLa nuclear cell extract. Captured proteins were eluted and digested with trypsin. The digested antigen peptides were analyzed by liquid chromatography linked to a triple quadrupole mass spectrometer operating in multiple reaction monitoring (MRM) acquisition mode. Detected signals (peak areas) were quantified. Synthetic proteotypic peptides were used for quality control and quantification purposes.</p><p><strong>Results: </strong>The MRM analysis was based on 6 proteotypic peptides (3 for RuvBL1, 3 for RuvBL2) that are unique to each protein. The immunoprecipitation LC-MS/MS MRM approach allowed differentiation between anti-RuvBL1/2 positive and anti-RuvBL1/2 negative samples.</p><p><strong>Conclusions: </strong>We propose an immunoprecipitation-based LC-MS/MS MRM method for anti-RuvBL1/2 autoantibody testing. This technology is a promising detection method for autoantibodies targeting conformational epitopes.</p>","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Healthcare Excellence is a Global Phenomenon.","authors":"Melissa Ryan, Colleen Strain, Tricia Ravalico","doi":"10.1093/jalm/jfaf065","DOIUrl":"https://doi.org/10.1093/jalm/jfaf065","url":null,"abstract":"","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heather A Nelson, Chad Condie, Kelly Doyle, Joseph W Rudolf, Lauren N Pearson
{"title":"On-Cell Stability of Digoxin, Lithium, Phenytoin, Valproic Acid, and Vancomycin for Therapeutic Drug Monitoring.","authors":"Heather A Nelson, Chad Condie, Kelly Doyle, Joseph W Rudolf, Lauren N Pearson","doi":"10.1093/jalm/jfaf076","DOIUrl":"https://doi.org/10.1093/jalm/jfaf076","url":null,"abstract":"<p><strong>Background: </strong>A common problem in clinical laboratories and outpatient clinics is processing specimens rapidly to comply with specimen stability criteria. Currently, for therapeutic drug monitoring, the laboratory must centrifuge specimens and remove the serum or plasma from cells within 2 hours. Many of these drugs are monitored in the outpatient setting, which may require longer transportation times. This creates challenges for the laboratory in processing samples within 2 hours and may result in unnecessary rejection of otherwise acceptable specimens if blood is left on cells too long. The objective of this study was to determine the effect of storage time before centrifugation on the stability of digoxin, lithium, phenytoin, valproic acid, and vancomycin in blood.</p><p><strong>Methods: </strong>The concentration of 5 therapeutic drugs was examined following extended on-cell storage at room temperature (RT). For each drug studied, 3 red-top, no gel serum tubes per patient were collected and maintained at RT for 0.5, 6, and 12 hours after collection. Statistically significant changes from the 0.5-hour control were determined using repeated-measures ANOVA. Phenytoin studies were supplemented with spiked specimens. The spiked whole blood samples were mixed and left at RT for 0.5, 2, 4, 6, or 12 hours after collection.</p><p><strong>Results: </strong>The concentration of digoxin, lithium, phenytoin, valproic acid, and vancomycin were all within ±10% of the baseline concentration when left at RT on cells up to 12 hours.</p><p><strong>Conclusion: </strong>All 5 drugs showed adequate stability in unprocessed clotted blood for up to 12 hours at RT. This data can alleviate constraints on processing samples for therapeutic drug monitoring in the clinical laboratory.</p>","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael H Kanter, Wahid Wakach, Royann Timmins, Jasmine E Mitchell, Ariel R Silverman, Tracy M Imley
{"title":"An Electronic Clinical Surveillance System to Reduce Failure to Follow Up Abnormal Lab Results and Failure to Order Needed Tests: Description and Methods.","authors":"Michael H Kanter, Wahid Wakach, Royann Timmins, Jasmine E Mitchell, Ariel R Silverman, Tracy M Imley","doi":"10.1093/jalm/jfaf073","DOIUrl":"https://doi.org/10.1093/jalm/jfaf073","url":null,"abstract":"<p><strong>Background: </strong>Failure to follow up abnormal test results in a timely manner is a widespread issue in outpatient settings. The etiologies of this problem are multidimensional and vary across settings. While there is currently no widely used intervention to address these issues, multiple studies have noted that there is a need for multifaceted monitoring systems and quality improvement collaboratives to approach this problem.</p><p><strong>Methods: </strong>Kaiser Permanente Southern California (KPSC) implemented a program called SureNet, which addresses the issue of missed laboratory results. KPSC is an integrated healthcare delivery system serving approximately 4.8 million members across 14 hospitals and 200 medical offices. SureNet operates as an electronic clinical surveillance system to detect lapses in care, with a particular focus on ambulatory tests. The functions of SureNet interventions include prompting a specific treatment, a follow-up laboratory test, or a specialist referral.</p><p><strong>Results: </strong>Since its implementation in 2006, SureNet has grown to encompass more than 80 distinct programs, 39 of which focus on missed laboratory tests. The median number of measured interventions in a program was 4971 (range 60-182 249), and the measured percentage of successful interventions was 61% (range 4%-93%). Outcomes demonstrate that SureNet effectively closes care gaps that may have otherwise been missed.</p><p><strong>Conclusion: </strong>KPSC's SureNet represents a potentially generalizable example of an electronic clinical surveillance program that can effectively mitigate the problem of lack of timely follow-up on abnormal laboratory results at scale. SureNet provides a blame-free approach that prioritizes patient care and outcomes.</p>","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RhDnostics: A Machine Learning-Based Predictive Algorithm Model for RhD-Negative and DEL Blood Group Screening.","authors":"Meechoke Choodoung, Charuporn Promwong, Ketsaraporn Wongba, Arunsri Choodoung, Usanee Kerdpin, Peeradech Thichanpiang, Chotiros Plabplueng, Yann Fichou, Pornlada Nuchnoi","doi":"10.1093/jalm/jfaf074","DOIUrl":"https://doi.org/10.1093/jalm/jfaf074","url":null,"abstract":"<p><strong>Background: </strong>The D-elution (DEL) phenotype is serologically mislabeled as Rh-negative because of the very low amount of D antigen on red blood cells. The adsorption-elution test and genotyping are recommended tests for confirmation. However, turnaround time and the availability of instruments, reagents, and budget, as well as technical issues are challenging factors of DEL identification in laboratory practice and patient safety.</p><p><strong>Methods: </strong>To develop a screening predictive algorithm for DEL and Rh-negative, the serological tests of RhCcEe antigen and adsorption-elution tests were computed using a machine learning model.</p><p><strong>Results: </strong>The machine learning algorithm computed the data based on RhCcEe antigen with or without a DEL confirmative serological test like the adsorption-elution test. The predictive accuracy gave >90% for RhD-negative identification in a Thai blood donor dataset. To screen for RhD-negative, we provided the web application named RhDnostics at https://rnp-project-1.streamlit.app/.</p><p><strong>Conclusion: </strong>Our machine learning algorithm could be used as a predictive tool for RhD-negative screening in the laboratory with no confirmative serological test or RHD molecular testing available.</p>","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jillian Kodger, Rohit B Sangal, Aldo J Peixoto, Dennis G Moledina, Dustin Miconi, Joe M El-Khoury
{"title":"Creatinine Delta: Improving Critical Call Thresholds for Acute Kidney Injury Detection.","authors":"Jillian Kodger, Rohit B Sangal, Aldo J Peixoto, Dennis G Moledina, Dustin Miconi, Joe M El-Khoury","doi":"10.1093/jalm/jfaf075","DOIUrl":"https://doi.org/10.1093/jalm/jfaf075","url":null,"abstract":"","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144162750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Riona Singh-Gansan, Jean Pienaar, Dee Mary Blackhurst, Adrian David Marais
{"title":"Atypical Appearance of Lipoprotein X on Agarose Gel Electrophoresis.","authors":"Riona Singh-Gansan, Jean Pienaar, Dee Mary Blackhurst, Adrian David Marais","doi":"10.1093/jalm/jfaf070","DOIUrl":"https://doi.org/10.1093/jalm/jfaf070","url":null,"abstract":"","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical Drug Testing Supporting Patients with Substance Use Disorder: A Review.","authors":"Alec Saitman","doi":"10.1093/jalm/jfaf069","DOIUrl":"https://doi.org/10.1093/jalm/jfaf069","url":null,"abstract":"<p><strong>Background: </strong>Drug testing ordered to evaluate patients with substance use disorder (SUD) is not standardized. This may make drug testing difficult to interpret by the medical staff who order it.</p><p><strong>Content: </strong>In this review, a general overview of common drug testing strategies and potential knowledge gaps is discussed. This content is followed by discussion of how clinical laboratorians can support patients with SUD, through test offering optimization, development of drug interpretation services, and education on drug interpretation best practices.</p><p><strong>Summary: </strong>Clinical laboratorians are essential partners in healthcare delivery, particularly when providing interpretation of drug testing results. This review is intended to provide laboratorians with drug testing best practices to elevate their contribution to the healthcare system in supporting patients with SUD.</p>","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Disease Associations of Cluster of Differentiation (CD) 5+ Peripheral B Cells in a Diagnostic Flow Cytometry Laboratory.","authors":"Adrian Y S Lee","doi":"10.1093/jalm/jfaf066","DOIUrl":"https://doi.org/10.1093/jalm/jfaf066","url":null,"abstract":"<p><strong>Background: </strong>Cluster of differentiation (CD) 5+ B cells comprise approximately 15% of peripheral blood B cells and are commonly encountered in diagnostic flow cytometry. However, their disease associations have not been systematically reviewed before, particularly in non-CD5+ B-cell malignancy cases. The aim of this study was to ascertain the prevalence and clinical associations of nonmalignant-associated peripheral blood CD5+ B cells in the diagnostic flow cytometry laboratory.</p><p><strong>Methods: </strong>Over a period of 3 months, we undertook a single-laboratory cross-sectional study to examine disease associations of CD5+ B cells. B cells were assessed by flow cytometry using our standard B-cell panel. Medical records were reviewed to ascertain disease associations.</p><p><strong>Results: </strong>In the audit period, there were 426 consecutive B-cell panels excluding duplicate patients, CD5+ B-cell malignancies, and B-cell-depleted samples. The highest percentage of CD5+ B cells were noted in patients with autoimmune diseases and was, in general, higher than patients who had infections or other hematological disorders.</p><p><strong>Conclusions: </strong>CD5+ B cells are common in the periphery of patients with a variety of medical conditions and may reflect a degree of B-cell hyperreactivity. It would be important for future studies to examine the functional role and consequences of these B cells, and whether they may hold any prognostic or monitoring value.</p>","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christopher DiPasquale, Robert H Christenson, James G Donnelly, Susan A Evans, Alan H B Wu, Eric G Olson, Roy Barr, Nicolas Kosa, Hattie McKenzie, Melissa Abigania, James W Jacobson
{"title":"Equivalence between Capillary Blood and Venous Blood Test Results Using Miniaturized Assays and Novel Collection Methods to Support Routine Bloodwork.","authors":"Christopher DiPasquale, Robert H Christenson, James G Donnelly, Susan A Evans, Alan H B Wu, Eric G Olson, Roy Barr, Nicolas Kosa, Hattie McKenzie, Melissa Abigania, James W Jacobson","doi":"10.1093/jalm/jfaf059","DOIUrl":"https://doi.org/10.1093/jalm/jfaf059","url":null,"abstract":"<p><strong>Background: </strong>Capillary blood testing has potential to improve accessibility and adherence for routine tests. Due to historical challenges with sample volume and quality, capillary blood is rarely used for diagnostic testing. These studies provide objective evidence that miniaturized assays and novel capillary collection technologies can enable equivalent results for important panels.</p><p><strong>Methods: </strong>The studies evaluated equivalence of capillary blood testing using miniaturized assays and novel collection methods. We verified the performance of 20 miniaturized assays vs their unmodified versions. We then evaluated specimen equivalence across 39 analytes by comparing samples collected with novel capillary technologies vs samples collected with conventional technologies. For 38 analytes, specimen equivalence was evaluated vs conventional venous samples, and vs conventional capillary samples for 2 analytes with biological gradients (glucose and total CO2).</p><p><strong>Results: </strong>Equivalence of miniaturized assays and novel capillary methods to conventional testing was demonstrated across all analytes. Method comparison of all 20 miniaturized assays highly correlated (Pearson r > 0.95) to unmodified versions of each test. Capillary blood collected with the novel collection procedure produced results equivalent to conventional methods, with 37 analytes performing equivalently to venous serum, glucose to both venous and conventional capillary serum, and total CO2 to conventional capillary serum.</p><p><strong>Conclusions: </strong>Capillary blood can be utilized for routine bloodwork. Issues with sample volume can be overcome by miniaturizing assays without compromising performance. Issues with sample quality can be overcome by novel capillary collection technologies, which additionally enable non-phlebotomist sample collection in a broad scope of healthcare settings.</p>","PeriodicalId":46361,"journal":{"name":"Journal of Applied Laboratory Medicine","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}