Plasma biomarkers levels, essential for diagnosing cardiovascular diseases, may vary by ethnicity. In this international prospective study, we compared plasma biomarker levels between European and Asian patients with clinically similar acute heart failure (AHF). Data were collected on emergency admission for acute dyspnea. Blood samples were obtained within 4 hrs of presentation and analyzed for N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin-T, growth differentiation factor 15, interleukin-6, and C-reactive protein levels. Overall, 907 AHF patients were enrolled; of which, 135 (15%) were Japanese, and 772 (85%) were European. NT-proBNP levels were significantly higher in Japanese than in Europeans [4,060 ng/L (interquartile range (IQR) 2,081-12,218) vs. 3,390 ng/L (IQR 1,410-7,682), P =0.004]. After propensity score matching (PSM), no biomarker levels differed significantly. After stratification according to left ventricular ejection fraction (LVEF) at admission, higher NT-proBNP levels were observed in Japanese AHF patients with LVEF > 50% (P =0.02) than in European patients. After PSM, the difference was insignificant (P =0.35). In Asian and Caucasian AHF patients with similar clinical profiles, plasma cardiovascular biomarker levels did not differ significantly, regardless of LVEF, suggesting that NT-proBNP and related biomarkers can be applied across these ethnicities.
{"title":"Comparison of Plasma N-Terminal Pro-B-Type Natriuretic Peptide Levels Between European and Japanese Patients with Acute Heart Failure: An International Study.","authors":"Jolie Bruno,Aziz Daghmouri,Ayu Asakage,Camille Gobeaux,Kamilė Čerlinskaitė-Bajorė,Jelena Čelutkienė,Naoki Sato,Koji Takagi,Alexandre Mebazaa,Benjamin Deniau,Shiro Ishihara","doi":"10.3343/alm.2025.0232","DOIUrl":"https://doi.org/10.3343/alm.2025.0232","url":null,"abstract":"Plasma biomarkers levels, essential for diagnosing cardiovascular diseases, may vary by ethnicity. In this international prospective study, we compared plasma biomarker levels between European and Asian patients with clinically similar acute heart failure (AHF). Data were collected on emergency admission for acute dyspnea. Blood samples were obtained within 4 hrs of presentation and analyzed for N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin-T, growth differentiation factor 15, interleukin-6, and C-reactive protein levels. Overall, 907 AHF patients were enrolled; of which, 135 (15%) were Japanese, and 772 (85%) were European. NT-proBNP levels were significantly higher in Japanese than in Europeans [4,060 ng/L (interquartile range (IQR) 2,081-12,218) vs. 3,390 ng/L (IQR 1,410-7,682), P =0.004]. After propensity score matching (PSM), no biomarker levels differed significantly. After stratification according to left ventricular ejection fraction (LVEF) at admission, higher NT-proBNP levels were observed in Japanese AHF patients with LVEF > 50% (P =0.02) than in European patients. After PSM, the difference was insignificant (P =0.35). In Asian and Caucasian AHF patients with similar clinical profiles, plasma cardiovascular biomarker levels did not differ significantly, regardless of LVEF, suggesting that NT-proBNP and related biomarkers can be applied across these ethnicities.","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":"32 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609921","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":"Reinterpreting National Whole-Genome Sequencing Data: Lessons from the First Korean Pilot Study.","authors":"In-Suk Kim","doi":"10.3343/alm.2025.0645","DOIUrl":"https://doi.org/10.3343/alm.2025.0645","url":null,"abstract":"","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":"8 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609922","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}
Namsoo Kim,Hyeon Ah Lee,Miri Park,Yehyun Kang,Dongju Won,Seung-Tae Lee,Jong Rak Choi,Yu Jin Park,Saeam Shin
BackgroundNext-generation sequencing (NGS) is increasingly applied in clinical diagnostics; however, standard workflows are frequently challenged by insufficient DNA yields in diverse clinical scenarios. Although whole-genome amplification (WGA) is used to overcome this limitation, comparative performance data on WGA kits based on different amplification mechanisms under low-input conditions remain scarce.MethodsWe systematically evaluated four commercial WGA platforms: REPLI-g (Qiagen), which employs multiple displacement amplification; PicoPLEX (Takara Bio) and SurePlex (Illumina), which utilize modified multiple annealing and looping-based amplification cycles (MALBAC); and ResolveDNA (BioSkryb Genomics), which uses primary template-directed amplification (PTA), using 100-pg and 1-ng DNA input. Performance was assessed by examining allelic dropout (ADO), chimerism, copy number variation (CNV), and the total DNA yield.ResultsResolveDNA showed the lowest ADO rates across input levels, whereas PicoPLEX offered the most accurate quantification for chimerism and CNV. REPLI-g had the highest DNA yield but exhibited marked amplification bias and ADO under ultra-low-input conditions. SurePlex demonstrated intermediate performance across all metrics. PicoPLEX and SurePlex showed consistent CNV detection and chimerism accuracy, whereas PTA-based ResolveDNA better preserved allelic balance.ConclusionsEach platform demonstrated specific strengths and limitations depending on analytical endpoints. Modified MALBAC-based platforms can perform optimally when quantitative accuracy is critical, such as in chimerism or CNV analysis, whereas PTA-based WGA can be preferred when allelic fidelity is essential. Our findings can help guide platform selection tailored to specific clinical applications using low-input NGS, including preimplantation testing or cell-free DNA analysis.
{"title":"Performance Evaluation of Whole-Genome Amplification Platforms for Clinical Next-Generation Sequencing with Minimal Nucleic Acid Input.","authors":"Namsoo Kim,Hyeon Ah Lee,Miri Park,Yehyun Kang,Dongju Won,Seung-Tae Lee,Jong Rak Choi,Yu Jin Park,Saeam Shin","doi":"10.3343/alm.2025.0348","DOIUrl":"https://doi.org/10.3343/alm.2025.0348","url":null,"abstract":"BackgroundNext-generation sequencing (NGS) is increasingly applied in clinical diagnostics; however, standard workflows are frequently challenged by insufficient DNA yields in diverse clinical scenarios. Although whole-genome amplification (WGA) is used to overcome this limitation, comparative performance data on WGA kits based on different amplification mechanisms under low-input conditions remain scarce.MethodsWe systematically evaluated four commercial WGA platforms: REPLI-g (Qiagen), which employs multiple displacement amplification; PicoPLEX (Takara Bio) and SurePlex (Illumina), which utilize modified multiple annealing and looping-based amplification cycles (MALBAC); and ResolveDNA (BioSkryb Genomics), which uses primary template-directed amplification (PTA), using 100-pg and 1-ng DNA input. Performance was assessed by examining allelic dropout (ADO), chimerism, copy number variation (CNV), and the total DNA yield.ResultsResolveDNA showed the lowest ADO rates across input levels, whereas PicoPLEX offered the most accurate quantification for chimerism and CNV. REPLI-g had the highest DNA yield but exhibited marked amplification bias and ADO under ultra-low-input conditions. SurePlex demonstrated intermediate performance across all metrics. PicoPLEX and SurePlex showed consistent CNV detection and chimerism accuracy, whereas PTA-based ResolveDNA better preserved allelic balance.ConclusionsEach platform demonstrated specific strengths and limitations depending on analytical endpoints. Modified MALBAC-based platforms can perform optimally when quantitative accuracy is critical, such as in chimerism or CNV analysis, whereas PTA-based WGA can be preferred when allelic fidelity is essential. Our findings can help guide platform selection tailored to specific clinical applications using low-input NGS, including preimplantation testing or cell-free DNA analysis.","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":"5 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145583436","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}
Michael Krigstein,Emily Jude,Aleisha Jaffrey,Stephen Bye,Bin Wang,Min Ru Qiu,David Ma
BackgroundOur genomic understanding of lymphomas, a heterogeneous group of neoplasms, has grown exponentially. The latest World Health Organization (WHO) and International Consensus classifications reflect the importance of genetic assessment in the diagnosis and prognostication of and therapeutic decision making in lymphoid neoplasms. To address this clinical need for routinely available and timely testing, we aimed to validate the Ion AmpliSeq Liverpool Lymphoid Network Panel (IALLNP; Thermo Fisher Scientific, Waltham, MA, USA).MethodsWe clinically validated the IALLNP on the Ion Torrent Genexus Sequencer (Thermo Fisher Scientific). The panel detects single-nucleotide variants (SNVs) and insertions/deletions (indels) in 60 clinically relevant genes. The validation set included a commercial control and 54 DNA samples covering the spectrum of clinically aggressive and indolent lymphomas.ResultsAfter optimizing for poor coverage regions, recurrent artifacts, and false-negative calls, the panel showed good performance in terms of depth of coverage, on-target reads, and uniformity. Its sensitivity for SNVs and indels at a lower limit of detection of 5% variant allele frequency (VAF) was 100%. Specificity in variant-negative samples was 100%, and the mean per-sample number of false-positive variants-which were easily identifiable and excluded upon interrogation of raw data-was 0.4. The panel demonstrated 92.8% reproducibility; however, all nonreproducible variants fell below the 5% VAF analytical threshold.ConclusionsThe IALLNP is an accurate and reproducible next-generation sequencing panel that delivers genetic results for lymphoid neoplasms in a clinically meaningful timeframe.
{"title":"Clinical Validation of a Rapid Automated Lymphoma Next-Generation Sequencing Panel.","authors":"Michael Krigstein,Emily Jude,Aleisha Jaffrey,Stephen Bye,Bin Wang,Min Ru Qiu,David Ma","doi":"10.3343/alm.2025.0254","DOIUrl":"https://doi.org/10.3343/alm.2025.0254","url":null,"abstract":"BackgroundOur genomic understanding of lymphomas, a heterogeneous group of neoplasms, has grown exponentially. The latest World Health Organization (WHO) and International Consensus classifications reflect the importance of genetic assessment in the diagnosis and prognostication of and therapeutic decision making in lymphoid neoplasms. To address this clinical need for routinely available and timely testing, we aimed to validate the Ion AmpliSeq Liverpool Lymphoid Network Panel (IALLNP; Thermo Fisher Scientific, Waltham, MA, USA).MethodsWe clinically validated the IALLNP on the Ion Torrent Genexus Sequencer (Thermo Fisher Scientific). The panel detects single-nucleotide variants (SNVs) and insertions/deletions (indels) in 60 clinically relevant genes. The validation set included a commercial control and 54 DNA samples covering the spectrum of clinically aggressive and indolent lymphomas.ResultsAfter optimizing for poor coverage regions, recurrent artifacts, and false-negative calls, the panel showed good performance in terms of depth of coverage, on-target reads, and uniformity. Its sensitivity for SNVs and indels at a lower limit of detection of 5% variant allele frequency (VAF) was 100%. Specificity in variant-negative samples was 100%, and the mean per-sample number of false-positive variants-which were easily identifiable and excluded upon interrogation of raw data-was 0.4. The panel demonstrated 92.8% reproducibility; however, all nonreproducible variants fell below the 5% VAF analytical threshold.ConclusionsThe IALLNP is an accurate and reproducible next-generation sequencing panel that delivers genetic results for lymphoid neoplasms in a clinically meaningful timeframe.","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":"223 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582977","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}
Sumi Yoon,Kye Won Choe,Hongkyung Kim,Yong Kwan Lim,Oh Joo Kweon
Accurate interpretation of whole-blood viscosity (WBV) requires population-specific reference intervals (RIs), as WBV is influenced by sex, age, and Hct. This study is the first to establish RIs for WBV using a fully automated scanning capillary tube viscometer, RHEOVIS 200 (Biorheologics, Jeonju, Republic of Korea), in Korean adults. WBV was measured in 438 adults at shear rates of 1 s-1 (diastolic WBV) and 300 s-1 (systolic WBV). RIs were determined using the non-parametric method according to CLSI guideline EP28-A3c, and median WBV values were compared by sex and age. At 1 s-1, the RIs were 20.83-38.50 millipascal-second (mPa·s) in all adults, 25.97-39.26 mPa·s in men, and 20.14-35.08 mPa·s in women. At 300 s-1, these were 3.74-5.50 mPa·s in all adults, 4.16-5.60 mPa·s in men, and 3.64-5.05 mPa·s in women. The median WBV was significantly higher in men than in women (P <0.01) and lower in the 20-30-yr group than in other groups (P ≤ 0.03). Sex-specific RIs are required for accurate WBV interpretation in Korean adults, and age-specific RIs require further validation. For WBV measurements using RHEOVIS 200, clinical laboratories should establish and continually verify their own RIs.
{"title":"Reference Intervals for Whole-Blood Viscosity Measured Using the Fully Automated Scanning Capillary Tube Viscometer RHEOVIS 200 in Korean Adults.","authors":"Sumi Yoon,Kye Won Choe,Hongkyung Kim,Yong Kwan Lim,Oh Joo Kweon","doi":"10.3343/alm.2025.0495","DOIUrl":"https://doi.org/10.3343/alm.2025.0495","url":null,"abstract":"Accurate interpretation of whole-blood viscosity (WBV) requires population-specific reference intervals (RIs), as WBV is influenced by sex, age, and Hct. This study is the first to establish RIs for WBV using a fully automated scanning capillary tube viscometer, RHEOVIS 200 (Biorheologics, Jeonju, Republic of Korea), in Korean adults. WBV was measured in 438 adults at shear rates of 1 s-1 (diastolic WBV) and 300 s-1 (systolic WBV). RIs were determined using the non-parametric method according to CLSI guideline EP28-A3c, and median WBV values were compared by sex and age. At 1 s-1, the RIs were 20.83-38.50 millipascal-second (mPa·s) in all adults, 25.97-39.26 mPa·s in men, and 20.14-35.08 mPa·s in women. At 300 s-1, these were 3.74-5.50 mPa·s in all adults, 4.16-5.60 mPa·s in men, and 3.64-5.05 mPa·s in women. The median WBV was significantly higher in men than in women (P <0.01) and lower in the 20-30-yr group than in other groups (P ≤ 0.03). Sex-specific RIs are required for accurate WBV interpretation in Korean adults, and age-specific RIs require further validation. For WBV measurements using RHEOVIS 200, clinical laboratories should establish and continually verify their own RIs.","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":"8 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531222","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}
Kiwook Jung,Hyun Jin Kim,Sunghwan Shin,Wookeun Lee,Jun Hyung Lee,Hee Sue Park,Qute Choi
BackgroundRecent advancements in large language models (LLMs) have accelerated their integration into clinical domains, including laboratory medicine. The performance of LLMs in answering board-level laboratory medicine questions has not been comprehensively evaluated. Given the importance of diagnostic accuracy in this field, rigorous and objective evaluations of LLM capabilities are essential.MethodsWe assessed 12 LLMs from OpenAI, Anthropic, and Google using 320 Korean Residency Examination questions (2021-2024) spanning six laboratory medicine subspecialties. Standardized prompts were provided via their application programming interfaces under deterministic settings (temperature=0). Questions were administered thrice to assess response reproducibility. Outputs were compared with validated answers and analyzed for accuracy, reasoning quality, and error typology.ResultsGoogle's Gemini 2.0 Pro achieved the highest accuracy (80.0%), followed by OpenAI's GPT-4.5 (77.2%) and Anthropic's Claude 3.7 Sonnet (74.1%). Accuracy decreased as the difficulty of questions increased (78.0% for easy vs. 45.1% for challenging). Subspecialty performance varied. Al models underperformed on questions on transfusion medicine (mean accuracy: 38.8%), primarily because of limitations in domain-specific and regional knowledge representations. Incorrect answers primarily resulted from reasoning errors. Reproducibility exceeded 95% for most models; however, some residual non-determinism appeared even with greedy decoding (temperature=0).ConclusionsLLMs demonstrated substantial potential for integration into laboratory medicine, particularly in clinical chemistry and immunology. Performance inconsistencies (particularly for high-difficulty questions) and knowledge gaps (notably for transfusion medicine) highlight the necessity for further development-potentially including domain-specific fine-tuning and retrieval-augmented generation integration-and robust expert oversight before clinical application.
{"title":"Evaluation of the Performance of Advanced Large Language Models in Laboratory Medicine Using Residency Examinations.","authors":"Kiwook Jung,Hyun Jin Kim,Sunghwan Shin,Wookeun Lee,Jun Hyung Lee,Hee Sue Park,Qute Choi","doi":"10.3343/alm.2025.0200","DOIUrl":"https://doi.org/10.3343/alm.2025.0200","url":null,"abstract":"BackgroundRecent advancements in large language models (LLMs) have accelerated their integration into clinical domains, including laboratory medicine. The performance of LLMs in answering board-level laboratory medicine questions has not been comprehensively evaluated. Given the importance of diagnostic accuracy in this field, rigorous and objective evaluations of LLM capabilities are essential.MethodsWe assessed 12 LLMs from OpenAI, Anthropic, and Google using 320 Korean Residency Examination questions (2021-2024) spanning six laboratory medicine subspecialties. Standardized prompts were provided via their application programming interfaces under deterministic settings (temperature=0). Questions were administered thrice to assess response reproducibility. Outputs were compared with validated answers and analyzed for accuracy, reasoning quality, and error typology.ResultsGoogle's Gemini 2.0 Pro achieved the highest accuracy (80.0%), followed by OpenAI's GPT-4.5 (77.2%) and Anthropic's Claude 3.7 Sonnet (74.1%). Accuracy decreased as the difficulty of questions increased (78.0% for easy vs. 45.1% for challenging). Subspecialty performance varied. Al models underperformed on questions on transfusion medicine (mean accuracy: 38.8%), primarily because of limitations in domain-specific and regional knowledge representations. Incorrect answers primarily resulted from reasoning errors. Reproducibility exceeded 95% for most models; however, some residual non-determinism appeared even with greedy decoding (temperature=0).ConclusionsLLMs demonstrated substantial potential for integration into laboratory medicine, particularly in clinical chemistry and immunology. Performance inconsistencies (particularly for high-difficulty questions) and knowledge gaps (notably for transfusion medicine) highlight the necessity for further development-potentially including domain-specific fine-tuning and retrieval-augmented generation integration-and robust expert oversight before clinical application.","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":"40 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145499563","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}
Kyung-Hwa Shin,Hyun-Woo Choi,Jihyang Lim,Eun-Suk Kang
BackgroundCurrent reference intervals for lymphocyte subpopulations are primarily based on Western populations, with limited data available for Korean children, particularly for extended subsets. We determined absolute cell counts and percentages of lymphocyte subpopulations in Korean children, according to age and sex.MethodsSamples from 92 children-stratified into two age groups, groups 1 (5-9 yrs) and 2 (10-17 yrs)-were obtained. Immunophenotyping was performed via flow cytometry using the Primary Immunodeficiency Orientation Tube (PIDOT) panel, primarily classifying the cells into T, B, and natural killer cell populations. T lymphocytes were divided into CD4+, CD8+, and CD4-CD8- subsets; T and B cells were further subdivided according to their maturation stage.ResultsChildren in group 1 exhibited higher absolute counts of total B cells, unswitched memory B cells/plasma cells, total T cells, CD4+ naïve cells, and TCRγδ+ T cells than those in group 2. In contrast, Group 2 children showed higher absolute counts of CD4+ effector memory (EM) T cells. Males had higher absolute counts of total B cells, particularly pregerminal center B cells, CD4+ EM cells, and CD8+ terminally differentiated T cells, whereas females showed higher proportions of CD4+, CD4+ naïve, and CD8+ central memory/transitional memory T cells.ConclusionsTo the best of our knowledge, this study is the first to establish reference values for extended lymphocyte subsets in Korean children using the PIDOT panel. Age, sex, and laboratory-related factors influenced lymphocyte subset distributions. These findings may serve as reference data for immune disorders and immunotherapy in pediatric populations.
{"title":"Reference Values for Extended Lymphocyte Subsets in Korean Children: A Multicenter Study Using the EuroFlow PIDOT Panel.","authors":"Kyung-Hwa Shin,Hyun-Woo Choi,Jihyang Lim,Eun-Suk Kang","doi":"10.3343/alm.2025.0241","DOIUrl":"https://doi.org/10.3343/alm.2025.0241","url":null,"abstract":"BackgroundCurrent reference intervals for lymphocyte subpopulations are primarily based on Western populations, with limited data available for Korean children, particularly for extended subsets. We determined absolute cell counts and percentages of lymphocyte subpopulations in Korean children, according to age and sex.MethodsSamples from 92 children-stratified into two age groups, groups 1 (5-9 yrs) and 2 (10-17 yrs)-were obtained. Immunophenotyping was performed via flow cytometry using the Primary Immunodeficiency Orientation Tube (PIDOT) panel, primarily classifying the cells into T, B, and natural killer cell populations. T lymphocytes were divided into CD4+, CD8+, and CD4-CD8- subsets; T and B cells were further subdivided according to their maturation stage.ResultsChildren in group 1 exhibited higher absolute counts of total B cells, unswitched memory B cells/plasma cells, total T cells, CD4+ naïve cells, and TCRγδ+ T cells than those in group 2. In contrast, Group 2 children showed higher absolute counts of CD4+ effector memory (EM) T cells. Males had higher absolute counts of total B cells, particularly pregerminal center B cells, CD4+ EM cells, and CD8+ terminally differentiated T cells, whereas females showed higher proportions of CD4+, CD4+ naïve, and CD8+ central memory/transitional memory T cells.ConclusionsTo the best of our knowledge, this study is the first to establish reference values for extended lymphocyte subsets in Korean children using the PIDOT panel. Age, sex, and laboratory-related factors influenced lymphocyte subset distributions. These findings may serve as reference data for immune disorders and immunotherapy in pediatric populations.","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":"89 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491482","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}
Kwangjin Ahn,Seong Jin Choi,Hye Gyung Bae,Hyukmin Lee,Jong Rak Choi,Young Uh,Yangsoon Lee,Kyungwon Lee
BackgroundAn increase of group B Streptococcus (GBS) colonization in pregnant women with a parallel rise in neonatal and infant infections, were observed in Korea. We characterized antimicrobial resistance (AMR) and molecular features of GBS isolates from reproductive-aged women between 1994-2000 and 2017-2022.MethodsWe collected 246 GBS isolates, 37 during 1994-2000 and 209 during 2017-2022, from cervical and/or anorectal swabs at three institutions. Antimicrobial susceptibility was tested using the MicroScan MicroSTREP Plus Panel (Beckman Coulter, Brea, CA, USA). Sequence types (STs), clonal complexes (CCs), cps genotypes by serotypes, and AMR genes were identified using whole-genome sequencing on the NovaSeq 6000 system (Illumina, San Diego, CA, USA).ResultsDuring 1994-2000, CC19 was predominant (35.1%, 13/37), whereas during 2017-2022, CC1 became the most common (35.4%, 74/209). cps genotype VIII, previously limited to one ST1 isolate, appeared in 32 ST2 isolates (P =0.037). All isolates remained susceptible to β-lactams and vancomycin. Tetracycline resistance decreased from 97.3% to 60.8% (P <0.001), with tetM prevalence decreasing from 91.7% to 72.4% (P <0.001) and tetO prevalence increasing from 2.8% to 29.9% (P =0.017). Levofloxacin resistance increased from 0% to 23.4% (P =0.001), with 98.0% of resistant isolates carrying both gyrA and parC. The number of resistance profiles increased from six to 16, including 11 newly identified patterns, covering 81.8% of levofloxacin resistant isolates.ConclusionsThe acquisition of diverse resistance genes has expanded AMR profiles in colonized GBS, emphasizing the need for sustained nationwide surveillance.
{"title":"Increasing Antimicrobial Resistance Profile Diversity of Colonizing Group B Streptococcus in Reproductive-aged Women in Korea.","authors":"Kwangjin Ahn,Seong Jin Choi,Hye Gyung Bae,Hyukmin Lee,Jong Rak Choi,Young Uh,Yangsoon Lee,Kyungwon Lee","doi":"10.3343/alm.2025.0439","DOIUrl":"https://doi.org/10.3343/alm.2025.0439","url":null,"abstract":"BackgroundAn increase of group B Streptococcus (GBS) colonization in pregnant women with a parallel rise in neonatal and infant infections, were observed in Korea. We characterized antimicrobial resistance (AMR) and molecular features of GBS isolates from reproductive-aged women between 1994-2000 and 2017-2022.MethodsWe collected 246 GBS isolates, 37 during 1994-2000 and 209 during 2017-2022, from cervical and/or anorectal swabs at three institutions. Antimicrobial susceptibility was tested using the MicroScan MicroSTREP Plus Panel (Beckman Coulter, Brea, CA, USA). Sequence types (STs), clonal complexes (CCs), cps genotypes by serotypes, and AMR genes were identified using whole-genome sequencing on the NovaSeq 6000 system (Illumina, San Diego, CA, USA).ResultsDuring 1994-2000, CC19 was predominant (35.1%, 13/37), whereas during 2017-2022, CC1 became the most common (35.4%, 74/209). cps genotype VIII, previously limited to one ST1 isolate, appeared in 32 ST2 isolates (P =0.037). All isolates remained susceptible to β-lactams and vancomycin. Tetracycline resistance decreased from 97.3% to 60.8% (P <0.001), with tetM prevalence decreasing from 91.7% to 72.4% (P <0.001) and tetO prevalence increasing from 2.8% to 29.9% (P =0.017). Levofloxacin resistance increased from 0% to 23.4% (P =0.001), with 98.0% of resistant isolates carrying both gyrA and parC. The number of resistance profiles increased from six to 16, including 11 newly identified patterns, covering 81.8% of levofloxacin resistant isolates.ConclusionsThe acquisition of diverse resistance genes has expanded AMR profiles in colonized GBS, emphasizing the need for sustained nationwide surveillance.","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":"12 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440656","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}
Monoclonal protein (M-protein) is a crucial biomarker for diagnosing and monitoring mono-clonal gammopathies, including multiple myeloma (MM). Traditionally, electrophoresis (EP)-based methods, such as protein EP and immunofixation EP, have been widely used for M-protein detection. However, these methods can show low sensitivity and inadequate quantification of small amounts of M-protein. To overcome these challenges, EP-based methods are often combined with the quantification of serum free light chains in auto-mated immunoassays. Advances in mass spectrometry (MS) have introduced three main approaches for sample preparation: top-down, middle-down, and bottom-up. Middle-down approaches are commonly used with matrix-assisted laser desorption/ionization time-of-flight MS and liquid chromatography-electrospray ionization (LC-ESI) quadrupole time-of-flight MS, whereas the bottom-up approach is typically applied with LC-ESI Orbitrap MS. A review of studies, conducted from 2014 to 2024, on plasma cell disorders that utilized MS-based methods demonstrate improvements in the sensitivity and accuracy of M-pro-tein identification and quantification. MM remains the most frequently studied disease, with significant therapeutic advancements leading to improved outcomes. Minimal resid-ual disease has gained attention because of its correlation with better prognoses. Mono-clonal gammopathy of undetermined significance and amyloid light-chain amyloidosis are occasionally addressed, while studies on other rare diseases remain limited. This review highlights the clinical applications and advancements in MS-based methods, particularly in assessing M-protein levels for treatment responses, risk factors, and prognostic moni-toring. Given their advantages-high sensitivity and specificity, automation, cost-effective-ness, and time efficiency-MS-based methods may eventually replace EP-based methods in clinical laboratories.
{"title":"Paradigm Shift in Monoclonal Protein Detection: From Electrophoresis-based to Mass Spectrometry-based Methods.","authors":"Jikyo Lee,Sangmi Yoo,Seojin Yang,Sang Hoon Song","doi":"10.3343/alm.2025.0133","DOIUrl":"https://doi.org/10.3343/alm.2025.0133","url":null,"abstract":"Monoclonal protein (M-protein) is a crucial biomarker for diagnosing and monitoring mono-clonal gammopathies, including multiple myeloma (MM). Traditionally, electrophoresis (EP)-based methods, such as protein EP and immunofixation EP, have been widely used for M-protein detection. However, these methods can show low sensitivity and inadequate quantification of small amounts of M-protein. To overcome these challenges, EP-based methods are often combined with the quantification of serum free light chains in auto-mated immunoassays. Advances in mass spectrometry (MS) have introduced three main approaches for sample preparation: top-down, middle-down, and bottom-up. Middle-down approaches are commonly used with matrix-assisted laser desorption/ionization time-of-flight MS and liquid chromatography-electrospray ionization (LC-ESI) quadrupole time-of-flight MS, whereas the bottom-up approach is typically applied with LC-ESI Orbitrap MS. A review of studies, conducted from 2014 to 2024, on plasma cell disorders that utilized MS-based methods demonstrate improvements in the sensitivity and accuracy of M-pro-tein identification and quantification. MM remains the most frequently studied disease, with significant therapeutic advancements leading to improved outcomes. Minimal resid-ual disease has gained attention because of its correlation with better prognoses. Mono-clonal gammopathy of undetermined significance and amyloid light-chain amyloidosis are occasionally addressed, while studies on other rare diseases remain limited. This review highlights the clinical applications and advancements in MS-based methods, particularly in assessing M-protein levels for treatment responses, risk factors, and prognostic moni-toring. Given their advantages-high sensitivity and specificity, automation, cost-effective-ness, and time efficiency-MS-based methods may eventually replace EP-based methods in clinical laboratories.","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":"19 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440585","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}
Dokyun Kim,SungYoung Lee,Jun Sung Hong,Min Hyuk Choi,Hyun Soo Kim,Young Ree Kim,Young Ah Kim,Young Uh,Kyeong Seob Shin,Jeong Hwan Shin,Jeong Su Park,Kyoung Un Park,Soo Hyun Kim,Jong Hee Shin,Jungsik Yu,Seok Hoon Jeong
BackgroundExtended-spectrum β-lactamase (ESBL)-producing Escherichia coli is among the most important multidrug-resistant pathogens causing bloodstream infections (BSIs). Cefotaximase (CTX-M) enzymes are the most common and highly diverse ESBL family in E. coli. CTX-M-15 in group CTX-M-1 and CTX-M-14 in group CTX-M-9 are the most extensively disseminated enzymes. Multidrug-resistant E. coli strains complicate empirical therapy and increase healthcare burden globally and in Korea. We investigated the molecular epidemiology, sequence types (STs), and ESBL genotypes of E. coli bloodstream isolates in Korea and identified clinical risk factors for cefotaxime resistance.MethodsWe collected all non-duplicated isolates of E. coli and related clinical information from patients with BSIs at eight sentinel hospitals in the Korean Global Antimicrobial Resistance Surveillance System (Kor-GLASS) collection network during 2017-2021. Duplicate isolates were removed to ensure representativeness of the data. Antimicrobial susceptibility was tested using disk diffusion tests, and multilocus sequence typing and beta-lactamase genotyping were performed.ResultsAmong 9,232 E. coli blood isolates, resistance rates to cefotaxime and ceftazidime were 36.4% and 11.4%, respectively. Among the clinical factors, age >65 yrs (adjusted odds ratio [aOR], 1.36), hospital-origin infection (aOR, 2.55), and admission type (intensive care unit [ICU] vs. general ward; aOR, 1.34) were significant cefotaxime resistance risk factors. ST131 was the most prevalent among cefotaxime-resistant E. coli (64.8%, 2,180/3,363), followed by ST1193 (5.3%, N=177), and ST69 (5.1%, N=170). ST131, ST648, ST405, and ST410 cefotaxime-resistant E. coli isolates frequently harbored blaCTX-M-15, whereas ST1193 and ST68 showed a high proportion of blaCTX-M-27 carriers, and most ST457 and ST5150 isolates carried blaCTX-M-55.ConclusionsContinuous monitoring of ESBL-producing E. coli is required to prevent further dissemination, guide empirical therapy, inform infection control policies, and ensure early detection of multidrug-resistant clones with the potential for widespread transmission.
{"title":"Molecular Epidemiology of Extended-Spectrum β-Lactamase-Producing Escherichia coli in South Korea: A Korean Global Antimicrobial Resistance Surveillance System Report.","authors":"Dokyun Kim,SungYoung Lee,Jun Sung Hong,Min Hyuk Choi,Hyun Soo Kim,Young Ree Kim,Young Ah Kim,Young Uh,Kyeong Seob Shin,Jeong Hwan Shin,Jeong Su Park,Kyoung Un Park,Soo Hyun Kim,Jong Hee Shin,Jungsik Yu,Seok Hoon Jeong","doi":"10.3343/alm.2025.0145","DOIUrl":"https://doi.org/10.3343/alm.2025.0145","url":null,"abstract":"BackgroundExtended-spectrum β-lactamase (ESBL)-producing Escherichia coli is among the most important multidrug-resistant pathogens causing bloodstream infections (BSIs). Cefotaximase (CTX-M) enzymes are the most common and highly diverse ESBL family in E. coli. CTX-M-15 in group CTX-M-1 and CTX-M-14 in group CTX-M-9 are the most extensively disseminated enzymes. Multidrug-resistant E. coli strains complicate empirical therapy and increase healthcare burden globally and in Korea. We investigated the molecular epidemiology, sequence types (STs), and ESBL genotypes of E. coli bloodstream isolates in Korea and identified clinical risk factors for cefotaxime resistance.MethodsWe collected all non-duplicated isolates of E. coli and related clinical information from patients with BSIs at eight sentinel hospitals in the Korean Global Antimicrobial Resistance Surveillance System (Kor-GLASS) collection network during 2017-2021. Duplicate isolates were removed to ensure representativeness of the data. Antimicrobial susceptibility was tested using disk diffusion tests, and multilocus sequence typing and beta-lactamase genotyping were performed.ResultsAmong 9,232 E. coli blood isolates, resistance rates to cefotaxime and ceftazidime were 36.4% and 11.4%, respectively. Among the clinical factors, age >65 yrs (adjusted odds ratio [aOR], 1.36), hospital-origin infection (aOR, 2.55), and admission type (intensive care unit [ICU] vs. general ward; aOR, 1.34) were significant cefotaxime resistance risk factors. ST131 was the most prevalent among cefotaxime-resistant E. coli (64.8%, 2,180/3,363), followed by ST1193 (5.3%, N=177), and ST69 (5.1%, N=170). ST131, ST648, ST405, and ST410 cefotaxime-resistant E. coli isolates frequently harbored blaCTX-M-15, whereas ST1193 and ST68 showed a high proportion of blaCTX-M-27 carriers, and most ST457 and ST5150 isolates carried blaCTX-M-55.ConclusionsContinuous monitoring of ESBL-producing E. coli is required to prevent further dissemination, guide empirical therapy, inform infection control policies, and ensure early detection of multidrug-resistant clones with the potential for widespread transmission.","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":"46 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440583","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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