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The early detection of lung cancer (LC) improves patient outcomes, but current methods have limitations. Autoantibodies against tumor-associated antigens have potential as early biomarkers. This study evaluated the 9G testTM Cancer/Lung, measuring circulating complexes of two antigen-autoantibody immune complexes (AIC) against their respective free antigens (CYFRA 21-1 and p53) for LC diagnosis. We analyzed 100 LC patients and 119 healthy controls using the 9G testTM Cancer/Lung, quantifying the levels of AICs (CYFRA 21-1-Anti-CYFRA 21-1 autoantibody immune complex (CIC) and p53-Anti-p53 autoantibody immune complex (PIC)), free antigens (CYFRA 21-1 and p53), and ratios of AICs/antigens (LC index). The levels of the CICs and PICs were significantly elevated in LC compared to the controls (p < 0.0062 and p < 0.0026), while free antigens showed no significant difference. The CIC/CYFRA 21-1 and PIC/p53 ratios were also significantly higher in LC (all, p < 0.0001). The LC index, when combining both ratios, exhibited the best diagnostic performance with an area under the curve (AUC) of 0.945, exceeding individual CICs, PICs, and free antigens (AUCs ≤ 0.887). At a cut-off of 3.60, the LC index achieved 81% sensitivity and 95% specificity for LC diagnosis. It detected early-stage (Stage I-II) LC with 87.5% sensitivity, exceeding its performance in advanced stages (72.7%). The LC index showed no significant differences based on age, gender, smoking status (former, current, or never smoker), or pack years smoked. The LC index demonstrates promising potential for early LC diagnosis, exceeding conventional free antigen markers.
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Background: In 2022, the WHO and International Consensus Classification (ICC) published diagnostic criteria for myelodysplastic neoplasms (MDSs). We examined the influence of the revised diagnostic criteria on classifying MDSs in a large population. Methods: We retrieved an open-source pre-existing dataset from cBioPortal and included 2,454 patients with MDS in this study. Patients were reclassified based on the new diagnostic 2022 WHO and ICC criteria. Survival analysis was performed using Cox regression to validate the new criteria and to assess risk factors. Results: Based on the 2022 WHO criteria, 1.4% of patients were reclassified as having AML. The 2022 WHO criteria provide a superior prognostic/diagnostic model to the 2017 WHO criteria (Akaike information criterion, 14,152 vs. 14,516; concordance index, 0.705 vs. 0.681). For classifying MDS with low blast counts and SF3B1 mutation, a variant allele frequency cut-off of 5% (2022 WHO criteria) and the absence of RUNX1 co-mutation (2022 ICC criteria) are diagnostically relevant. For classifying MDSs with mutated TP53, a blast count cut-off of 10% (2022 ICC criteria) and multi-hit TP53 (2022 WHO criteria) are independent risk factors in cases with ≥10% blasts. Conclusions: Our findings support the refinements of the new WHO criteria. We recommend the complementary use of the new WHO and ICC criteria in classifying SF3B1- and TP53-mutated MDSs for better survival prediction.
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Few studies have focused on the association between clonal hematopoiesis of indeterminate potential (CHIP) and ß-amyloid (Aß) deposition in the brain, which causes Alzheimer's disease. We aimed to investigate the potential role of CHIP in brain Aß deposition in Korean patients. We enrolled 58 Korean patients over 50 yrs of age with cognitive impairment who underwent brain Aß positron emission tomography. We explored CHIP in their peripheral blood using deep-targeted next-generation sequencing. Irrespective of the presence or absence of brain Aß deposition, mutations in DNMT3A and the C:G>T:A single-nucleotide variants were identified as the primary characteristics, which reflect aged hematopoiesis in the study population. Multivariate logistic regression revealed that the presence of CHIP was not associated with brain Aß deposition. As both CHIP and brain Aß deposition are associated with aging, further research is required to elucidate their possible interplay.
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BACKGROUND: Thrombi retrieved from patients with acute ischemic stroke may contain prognostic information. OBJECTIVE: To investigate the relationship between the immunologic phenotype of thrombi and future vascular events in patients with a stroke. METHODS: This study included patients with acute ischemic stroke who underwent endovascular thrombectomy at Chung-Ang University Hospital in Seoul, Korea, between February 2017 and January 2020. Laboratory and histological variables were compared between patients with and without recurrent vascular events (RVEs). Kaplan-Meier analysis followed by the Cox proportional hazards model was used to identify factors related to RVE. Receiver operating characteristic (ROC) analysis was conducted to evaluate the performance of the immunologic score by combining immunohistochemical phenotypes to predict RVE. RESULTS: A total of 46 patients were included in the study with 13 RVEs (mean±SD age, 72.8±11.3 years; 26 (56.5%) men). Thrombi with a lower percentage of programmed death ligand-1 expression (HR=11.64; 95% CI 1.60 to 84.82) and a higher number of citrullinated histone H3 positive cells (HR=4.19; 95% CI 0.81 to 21.75) were associated with RVE. The presence of high-mobility group box 1 positive cell was associated with reduced risk of RVE, but the association was lost after adjustment for stroke severity. The immunologic score, which consists of the three immunohistochemical phenotypes, showed good performance in predicting RVE (area under the ROC curve, 0.858; 95% CI 0.758 to 0.958). CONCLUSIONS: The immunological phenotype of thrombi could provide prognostic information after stroke.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Trombosis , Masculino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Accidente Cerebrovascular Isquémico/cirugía , Accidente Cerebrovascular Isquémico/complicaciones , Trombosis/patología , Infarto Cerebral/complicaciones , Accidente Cerebrovascular/complicaciones , Trombectomía , Fenotipo , Isquemia Encefálica/complicacionesRESUMEN
Autoantibodies against specific lung cancer-associated antigens have been suggested for the performance of lung cancer diagnosis. This study aimed to evaluate the diagnostic performance of the antigen-autoantibody immune complex (AIC) against its free antigens for CYFRA21-1, ProGRP, neutrophil gelatinase-associated lipocalin (NGAL), and neuron-specific enolase (NSE) in non-small cell lung cancer (NSCLC). In total, 85 patients with NSCLC and 120 healthy controls (HCs) were examined using a 9-guanine DNA chip method. The ratios of AICs to their antigens and the combinations of ratios consisting of two to four markers were calculated. The levels of AICs for CYFRA21-1, ProGRP, NGAL, and NSE were higher than those for their free antigens in all participants. The levels of each free antigens distinguished patients with NSCLC from the HCs. The ratios of the AIC to its antigen and seven combinations of two to four ratios were significantly higher in patients with NSCLC than in the HCs. Excellent diagnostic performance was observed for all combination ratios (C4-1), with 85.9% sensitivity and 86.7% specificity at a 3.51 cut-off. Higher sensitivity was observed in the early stages (0-I) and adenocarcinoma than in stages II-IV and other pathological types. Combining all ratios of AICs and their antigens for all four markers was useful when diagnosing NSCLC.
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Osimertinib is a third-generation epidermal growth factor receptor (EGFR)1 tyrosine kinase inhibitor (TKI) approved for the treatment of EGFR-positive patients exhibiting a T790 M resistance mutation after treatment with an earlier generation of EGFR TKIs. However, resistance to osimertinib inevitably develops despite its efficacy, and the resistance mechanisms are complex and not fully understood. We established cell lines with acquired resistance to osimertinib from gefitinib- or erlotinib-resistant NSCLC cells using a dose-escalation method, and found that they had upregulated levels of phosphorylated ERK1/2. Targeted next-generation sequencing of 143 genes was performed, and interestingly, amplification of KRAS was observed in osimertinib-resistant cells. Transfection of siRNA against the KRAS gene notably reduced the activation of ERK1/2 and AKT and significantly enhanced the induction of apoptosis by osimertinib treatment in osimertinib-resistant cells. LY3009120, a RAF inhibitor, showed a significant synergistic effect with osimertinib on apoptotic cell death in osimertinib-resistant cells. Combined treatment with osimertinib and LY3009120 also demonstrated remarkable synergistic anti-tumor activity in mouse xenografts of these cells. This could be a potential new treatment option for KRAS amplification-induced osimertinib failure.
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Neoplasias Pulmonares , Proteínas Proto-Oncogénicas p21(ras) , Humanos , Animales , Ratones , Proteínas Proto-Oncogénicas p21(ras)/genética , Resistencia a Antineoplásicos/genética , Línea Celular Tumoral , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Compuestos de Anilina/farmacología , Receptores ErbB/genética , Inhibidores de Proteínas Quinasas/farmacología , MutaciónRESUMEN
BACKGROUND: Sysmex DI-60 (Sysmex, Kobe, Japan) is a digital morphology (DM) analyzer widely used in clinical laboratories and supports body fluid (BF) applications. We evaluated analytical performance of DI-60 compared with XN-350 (Sysmex) and manual counting for BF cell differential counts. METHODS: A total of 213 BF samples were collected (47 cerebrospinal fluid [CSF], 80 pleural fluid, and 86 ascites samples). The analytical performance of DI-60 for BF cell differential counts was evaluated based on sensitivity, specificity, accuracy, and agreement. BF cell differential counts obtained by DI-60 were compared with those obtained by XN-350 and manual counting. RESULTS: The overall sensitivity was high for neutrophils, lymphocytes, and macrophages (range, 83.1-99.4%). The overall specificity and overall accuracy were high for all cell types (range, 95.3-99.7% and 94.3-99.3%, respectively). The agreement between DI-60 pre-classification and verification was strong (κ = 0.89). The absolute mean differences between DI-60 verification and XN-350 ranged from 0.26 to 11.05, and differences between DI-60 verification and manual counting ranged from 0.01 to 4.76. CONCLUSIONS: This is the first study to evaluate the performance of DI-60 compared with XN-350 and manual counting for BF cell differential counts. DI-60 showed reliable performance with CSF, pleural fluid, and ascites samples. For BF cell differential counts, DI-60 may be a better option than XN-350 and could be used for screening purposes in understaffed laboratories. To improve the hematology workflow for BF cell differential counting, the DM analyzer needs to be optimized by taking into account the laboratory situation and unmet needs, and the clinical laboratory needs to establish criteria for verification and manual slide review.
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Líquidos Corporales , Hematología , Humanos , Ascitis , Leucocitos , Linfocitos , Reproducibilidad de los Resultados , Recuento de LeucocitosRESUMEN
This corrects the article on p. 28 in vol. 19, PMID: 36606643.
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BACKGROUND: Measurement uncertainty (MU) estimation has become an important process in clinical laboratories; however, calculating the MUs of the international sensitivity index (ISI) of thromboplastins is difficult because of the complex mathematical calculations required in calibration. Therefore, this study quantifies the MUs of ISIs through the Monte Carlo simulation (MCS), which involves random sampling of numerical values to solve a complex mathematical calculation. METHODS: Eighty blood plasmas and commercially available certified plasmas (ISI Calibrate) were used to assign the ISIs of each thromboplastin. Prothrombin times were measured using reference thromboplastin and 12 commercially available thromboplastins (Coagpia PT-N, PT Rec, ReadiPlasTin, RecombiPlasTin 2G, PT-Fibrinogen, PT-Fibrinogen HS PLUS, Prothrombin Time Assay, Thromboplastin D, Thromborel S, STA-Neoplastine CI Plus, STA-Neoplastine R 15, and STA-NeoPTimal) with two automated coagulation instruments: ACL TOP 750 CTS (ACL TOP; Instrumentation Laboratory, Bedford, MA, USA) and STA Compact (Diagnostica Stago, Asnières-sur-Seine, France). Then, the MUs of each ISI were simulated through MCS. RESULTS: The MUs of ISIs ranged from 9.7 % to 12.1 % and 11.6 % to 12.0 % when blood plasma and ISI Calibrate were used, respectively. For some thromboplastins, the ISI claimed by manufacturers significantly differed from the estimated results. CONCLUSIONS: MCS is adequate to estimate the MUs of ISI. These results would be clinically useful for estimating the MUs of the international normalized ratio in clinical laboratories. However, the claimed ISI significantly differed from the estimated ISI of some thromboplastins. Therefore, manufacturers should provide more accurate information about the ISI value of thromboplastins.
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Fibrinógeno , Tromboplastina , Humanos , Método de Montecarlo , Incertidumbre , Tiempo de Protrombina , Relación Normalizada Internacional/métodos , CalibraciónRESUMEN
BACKGROUND AND PURPOSE: We investigated whether circulating microRNAs (miRNAs) is associated with arterial stiffness in patients with acute ischemic stroke. METHODS: We recruited patients with acute ischemic stroke who were admitted to a university hospital stroke center and underwent carotid-femoral pulse wave velocity (cfPWV) measurement using SphygmoCor (AtCor Medical, Sydney, Australia) and brachial-ankle PWV using a volume-plethysmography device (VP-1000, Omron Colin, Komaki, Japan). Circulating miRNAs were measured in venous blood samples stored in EDTA. We selected five miRNAs (miR-17, miR-93, miR-450, miR-629, and let-7i) related to atherosclerosis based on a literature review. Pearson's correlation analysis was applied to the correlations between miRNAs and arterial stiffness parameters. Finally, multivariable linear regression analysis was performed to identify the independent factors for cfPWV. RESULTS: This study included 70 patients (age=71.1±10.3 years [mean±SD], 29 females). The expression levels of miR-93 (r=-0.27, p=0.049) and let-7i (r=-0.27, p=0.039) were inversely correlated with cfPWV. Multivariable linear regression analysis including age, hypertension, and estimated glomerular filtration rate showed that let-7i was independently related with cfPWV (standardized coefficient=-0.262, p=0.036). Correlation analysis indicated that let-7i was positively associated with visceral muscle Hounsfield units on computed tomography (r=0.264, p=0.043). CONCLUSIONS: The expression level of let-7i was independently related to arterial stiffness in patients with cerebral infarction, suggesting that it plays a pathophysiological role in atherosclerosis.
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ChAdOx1 nCoV-19 , Vacunación , Humanos , Femenino , Prevalencia , Vacunación/efectos adversos , Anticuerpos AntiviralesRESUMEN
Cytokeratin 19 fragment antigen 21-1 (CYFRA 21-1) is useful for predicting and monitoring non-small cell lung cancer prognosis. We established reference intervals (RIs) of CYFRA 21-1 in Korean adults, including those older than 60 years. Data of 4,098 apparently healthy subjects (age range, 20-87 years) were analyzed after excluding those with a history of malignancy, high tumor marker concentrations (except CYFRA 21-1), and/or abnormal findings on a chest computed tomography scan through medical chart review. After removing two outliers, RIs of CYFRA 21-1 were determined using data of 4,096 subjects based on the non-parametric method (2.5th and 97.5th percentiles) according to CLSI guidelines EP28-A3c. The subjects were divided into two and four groups according to sex and age (20-40, 41-50, 51-60, and >60 years), respectively, and the median CYFRA 21-1 concentration was compared between the groups. The RI of CYFRA 21-1 was 0.66-3.84 ng/mL, applicable to both men and women. Regardless of sex, the CYFRA 21-1 concentration increased with age, suggesting that age-dependent RIs of CYFRA 21-1 should be applied. Rather than using a single RI provided by the manufacturer, the RI of CYFRA 21-1 should be continually verified and established in each clinical laboratory.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias , Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Queratina-19 , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , República de Corea , Adulto JovenRESUMEN
BACKGROUND: The prevalence of Tropheryma whipplei varies depending on age, region, and underlying disease. We estimated the prevalence of T. whipplei in the stools of Korean patients with diarrhea using real-time PCR (RT-PCR) and compared three RT-PCR targets, rpoB, hsp65, and Dig15. METHODS: A total of 1404 nucleic acid samples extracted from the stools of Korean patients with diarrhea were tested using an initial RT-PCR targeting T. whipplei-specific regions of 16S-23S rRNA intergenic spacer. Subsequently, the samples positive for the initial RT-PCR were tested using the follow-up RT-PCRs targeting rpoB, hsp65, and Dig15 and analyzed by sequencing to confirm the presence of T. whipplei. We estimated the prevalence of T. whipplei and compared them according to gender and age. We also compared the performance of three targets in the follow-up RT-PCRs. RESULTS: T. whipplei was detected in 1.4% of all samples (20 of 1404), and there were no differences according to gender and age. In pediatric samples (≤ 19 years), T. whipplei was detected higher in children aged 6-19 than in those aged 1-5 (2.7% vs. 0.7%, P = 0.01). Sensitivities of the rpoB, hsp65, and Dig15 RT-PCR were 50.0%, 85.0%, and 95.0%, respectively; specificities were 100.0%, 100.0%, and 84.6%, respectively. CONCLUSIONS: This is the first study that estimated the prevalence of T. whipplei in the stools of Korean patients with diarrhea. This study demonstrated the presence of T. whipplei in stools of Koreans, even though the bacterium was detected low. The RT-PCRs targeting hsp65 and Dig15 showed reliable performance, and a multiplex PCR including these targets is expected to be useful for T. whipplei detection.
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Tropheryma , Humanos , Niño , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
BACKGROUND: The tendency of amyloid-ß to form oligomers in the blood as measured with Multimer Detection System-Oligomeric Amyloid-ß (MDS-OAß) is a valuable biomarker for Alzheimer's disease and has been verified with heparin-based plasma. The objective of this study was to evaluate the performance of ethylenediaminetetraacetic acid (EDTA)-based MDS-OAß and to develop machine learning algorithms to predict amyloid positron emission tomography (PET) positivity. METHODS: The performance of EDTA-based MDS-OAß in predicting PET positivity was evaluated in 312 individuals with various machine learning models. The models with various combinations of features (i.e., MDS-OAß level, age, apolipoprotein E4 alleles, and Mini-Mental Status Examination [MMSE] score) were tested 50 times on each dataset. RESULTS: The random forest model best-predicted amyloid PET positivity based on MDS-OAß combined with other features with an accuracy of 77.14 ± 4.21% and an F1 of 85.44 ± 3.10%. The order of significance of predictive features was MDS-OAß, MMSE, Age, and APOE. The Support Vector Machine using the MDS-OAß value only showed an accuracy of 71.09 ± 3.27% and F-1 value of 80.18 ± 2.70%. CONCLUSIONS: The Random Forest model using EDTA-based MDS-OAß combined with the MMSE and apolipoprotein E status can be used to prescreen for amyloid PET positivity.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Ácido Edético , Péptidos beta-Amiloides , Enfermedad de Alzheimer/diagnóstico por imagen , Tomografía de Emisión de Positrones , Biomarcadores , Aprendizaje Automático , Algoritmos , Disfunción Cognitiva/diagnósticoRESUMEN
Antigen rapid diagnostic tests (RDTs) became the most important tool for the diagnosis of the coronavirus disease 2019 (COVID-19), however there have been very few evaluations of the accuracy of the RDTs in actual use. In this study, we investigated the performance accuracy of the RDT, the STANDARD Q COVID-19 Ag (STANDARD Q), in the Republic of Korea. We collected a total of 5,792 results that underwent both RDT and reverse transcription polymerase chain reaction simultaneously, and overall sensitivity and specificity of the STANDARD Q were 57.6% and 99.9%, respectively. With binomial logistic regression analysis, we estimated that about half of the COVID-19 patients with a cycle threshold value of 25 for E and RdRP were RDT-negative. These results suggest that the clinical sensitivity of RDTs against severe acute respiratory syndrome coronavirus 2 is considerably low in a real-world setting, and we recommend that limitations of RDTs should be considered when setting up COVID-19 test strategies.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , Pruebas Diagnósticas de Rutina , Sensibilidad y Especificidad , República de Corea , Antígenos ViralesRESUMEN
BACKGROUND: We investigated the neutralization performance of various automated blood culture systems for antifungal agents with regard to the most commonly isolated Candida species. METHODS: In this study, we evaluated the time to detection (TTD) of simulated candidemia for 6 Candida spp. (C. albicans, C. auris, C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis) in 3 automated blood culture systems (BACTEC™ FX, BACT/ALERT® 3D, and BACT/ALERT® VIRTUO®), with or without trough and peak levels of eight antifungal agents (amphotericin B, anidulafungin, caspofungin, fluconazole, itraconazole, micafungin, posaconazole, and voriconazole). RESULTS: Caspofungin and micafungin significantly prolonged the TTDs for most of the tested strains in the 3 blood culture instruments, especially at peak concentrations. CONCLUSION: Peak concentrations of caspofungin and micafungin influence the performance of blood culture detection systems. Therefore, one should be careful about the possibility of prolonged TTDs for candidemia when using the abovementioned antifungal agents.
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Candidemia , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Candida , Candida albicans , Candida glabrata , Candida parapsilosis , Candida tropicalis , Candidemia/diagnóstico , Candidemia/tratamiento farmacológico , Candidemia/prevención & control , Caspofungina , Fluconazol , Humanos , Micafungina , Pruebas de Sensibilidad MicrobianaRESUMEN
A Gram-stain-positive coccus was isolated from the blood of a paediatric patient suffering from gastroenteritis. The taxonomic position of this catalase-positive, non-motile, non-spore-forming facultative anaerobe designated as strain MKL-02T was investigated using a polyphasic approach. Colonies grown on tryptic soy agar with 10â% sheep blood were circular, creamy yellow, and convex. Phylogenetic analysis based on 16S rRNA gene and whole-genome sequences revealed that this strain was most closely related to Arsenicicoccus bolidensis CCUG 47306T within the cluster of the genus Arsenicicoccus. Average nucleotide identity and digital DNA-DNA hybridization values between strain MKL-02T and A. bolidensis DSM 15745T, A. dermatophillus DSM 25571T and A. piscis DSM 22760T were 89.5 and 37.0â%, 79.6 and 22.4â%, and 75.9 and 21.0â%, respectively. The genomic size of strain MKL-02T was 3â423â857 bp with a 72.7âmol% G+C content. Growth was observed at 10-45 °C (optimum, 37-40 °C) and pH 6.0-10.0 (optimum, pH 7.0), in the presence of 0-10â% (w/v) NaCl (optimum, 0.5â%). Cells of strain MKL-02T were non-motile cocci and 0.50-0.60 µm long, as determined by transmission electron microscopy. The strain was catalase-positive and oxidase-negative. The major fatty acid type (>10â% of total) was C15â:â0. The polar lipid profile consisted of two unidentified phospholipids, three unidentified lipids and an unidentified aminophospholipid. The strain contained MK-8 (H4) as the predominant menaquinone. Based on phylogenetic and phenotypic considerations, it is proposed that strain MKL-02T be classified as a new species, named Arsenicicoccus cauae sp. nov. The type strain is MKL-02T (=NCCP 16967T=JCM 34624T).
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Infecciones por Actinomycetales , Actinomycetales , Gastroenteritis , Actinomycetales/aislamiento & purificación , Infecciones por Actinomycetales/sangre , Infecciones por Actinomycetales/microbiología , Animales , Técnicas de Tipificación Bacteriana , Composición de Base , Catalasa/genética , Niño , ADN Bacteriano/genética , Ácidos Grasos/química , Gastroenteritis/sangre , Gastroenteritis/microbiología , Humanos , Hibridación de Ácido Nucleico , Fosfolípidos/química , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , OvinosRESUMEN
BACKGROUND: The Sysmex DI-60 digital morphology analyzer is a fully automated, cell-locating image analysis system. This study aimed to evaluate the analytical performance of DI-60. METHODS: A total of 822 peripheral blood smears were used. The diagnostic performance of DI-60 in terms of red blood cell (RBC) morphology characterization, white blood cell (WBC) differentials, and the total assay time including hands-on time was evaluated. RESULTS: In comparison with manual slide review, DI-60 demonstrated acceptable accuracy in recognizing polychromasia, target cells, and ovalocytes. However, for schistocytes, DI-60 demonstrated low specificity (10.4%) despite the high sensitivity (97.2%). In the precision analysis of RBC morphology characterization, borderline samples harboring specific RBCs showed inconsistencies in the positive results among 20 replicates. Particularly, 6 of 10 samples showed inconsistencies in the precision for schistocytes. For WBC differentials, the overall agreement between pre-classification results and user-verified results was 89.4%. Except for basophils, normal WBCs showed a good correlation between DI-60 (after user verification) and manual counts. The sensitivities in detecting immature granulocytes, blasts, atypical lymphocytes, and normoblasts were 85.9%, 92.0%, 37.5%, and 77.6%, respectively. Although the total assay time of DI-60 was longer than that of manual review, the hands-on time was considerably shorter with a difference of 144.1 s/slide for abnormal samples. CONCLUSION: DI-60 demonstrated acceptable performance for normal samples. However, for abnormal WBC differentials and RBC morphology characterization, it should be utilized carefully. DI-60 may contribute to an improvement in laboratory efficiency with increased feasibility.
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Pruebas Hematológicas , Leucocitos , Recuento de Células Sanguíneas/métodos , Recuento de Eritrocitos , Recuento de LeucocitosRESUMEN
There is a global demand for rapid diagnostic tests (RDTs) for Coronavirus disease 2019 (COVID-19), and the interest in their clinical compliance is growing. In this study, we evaluated the clinical compliance of seven different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen RDTs. Nasopharyngeal/oropharyngeal swab specimens from COVID-19-confirmed cases and reverse-transcription PCR (RT-PCR) screening were used to evaluate the performance of seven RDTs. Using the RT-PCR and RDT results, we predicted the cycle threshold (Ct) of each target gene (E, RdRP, and N genes) which 50% (Ct50) and 95% (Ct95) detection rates were achieved in the RDTs. A total of 482 specimens were enrolled in our study: 316 specimens from COVID-19-confirmed cases and 166 RT-PCR-negative specimens. The median values of Ct50 and Ct95 for the seven RDTs were in the ranges of ranged 24.3-30.9 and 19.3-22.6 for E, 25.5-31.5 and 20.9-24.0 for RdRP, and 26.8-32.3 and 22.7-25.7 for N, respectively. The RDTs showed acceptable compliance only for specimens with high viral burdens (Ct < 20). However, the false-negative rate increased by more than 50% for most of the RDTs in low-viral burden specimens (Ct> 30). These results suggest that RDTs should not be used without molecular assays for COVID-19 screening for asymptomatic patients because of their high false-negative rates.
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COVID-19 , SARS-CoV-2 , Antígenos Virales , Humanos , Nasofaringe , Sensibilidad y Especificidad , Carga ViralRESUMEN
BACKGROUND: We investigated the microRNA expression pattern from thrombus retrieved by mechanical thrombectomy in acute stroke patients to understand the stroke mechanism. METHODS: This study included acute ischemic stroke patients who had undergone intra-arterial thrombectomy at Chung-Ang University Hospital in Seoul, Korea between February 2016 and March 2019. The thrombus was retrieved and stored at -70â after obtaining informed consent. MicroRNA microarray analysis was performed for the patients with identified stroke mechanisms including (1) large artery atherosclerosis, (2) cardioembolism with atrial fibrillation, and (3) cardioembolism with valvular heart disease. The microRNAs derived from microarray analysis were validated by quantitative real-time polymerase chain reaction (qRT-PCR) from different patient populations. The correlation analysis was performed between microRNA levels and laboratory data to understand the functional relevance of the altered microRNA. RESULTS: In total, 55 thrombi were obtained from 74 patients, and the microRNAs were analyzed in 45 samples. Microarray analysis of 2578 microRNAs revealed that 50 microRNAs were significantly altered among the three groups. Validation using qRT-PCR showed that miR-378f and miR-450b-5p were significantly elevated among the cardioembolic thrombi; both microRNAs were inversely correlated with the ejection fraction from echocardiography. Thrombi from patients with early neurological deterioration exhibited higher levels of miR-93-5p and lower levels of miR-629-5p than those from neurologically stable patients. CONCLUSIONS: The microRNA expression pattern can provide information regarding the mechanism of stroke by reflecting the underlying pathological status of the organ from which the thrombus was derived.