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BACKGROUND: The World Health Organization (WHO) has set targets to eliminate viral hepatitis, including hepatitis C virus (HCV) infection, by 2030. We present the results of the in-hospital Reflex tEsting ALarm-C (REAL-C) model, which incorporates reflex HCV RNA testing and sending alerts to physicians. METHODS: We conducted a retrospective study analysing the data of 1730 patients who newly tested positive for anti-HCV between March 2020 and June 2023. Three distinct periods were defined: pre-REAL-C (n = 696), incomplete REAL-C (n = 515) and complete REAL-C model periods (n = 519). The primary outcome measure was the HCV RNA testing rate throughout the study period. Additionally, we assessed the referral rate to the gastroenterology department, linkage time for diagnosis and treatment and the treatment rate. RESULTS: The rate of HCV RNA testing increased significantly from 51.0% (pre-REAL-C) to 95.6% (complete REAL-C). This improvement was consistent across clinical departments, regardless of patients' comorbidities. Among patients with confirmed HCV infection, the gastroenterology referral rate increased from 57.1% to 81.1% after the REAL-C model. The treatment rate among treatment-eligible patients was 92.4% during the study period. The mean interval from anti-HCV positivity to HCV RNA testing decreased from 45.1 to 1.9 days. The mean interval from the detection of anti-HCV positivity to direct-acting antiviral treatment also decreased from 89.5 to 49.5 days with the REAL-C model. CONCLUSION: The REAL-C model, featuring reflex testing and physician alerts, effectively increased HCV RNA testing rates and streamlined care cascades. Our model facilitated progress towards achieving WHO's elimination goals for HCV infection.
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Hepatitis C Crónica , Hepatitis C , Humanos , Hepacivirus/genética , Antivirales/uso terapéutico , Estudios Retrospectivos , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C/tratamiento farmacológico , Hospitales , ARN ViralRESUMEN
BACKGROUND AND OBJECTIVES: The Writing Committee of American Society for Apheresis released the ninth edition of guidelines for therapeutic apheresis in 2023. Categories have been a part of the guidelines since the first edition, and the grading system was introduced in the fifth edition, with updates in every new edition. In this study, we investigated the category and grade change trends through the latest five editions, focusing on therapeutic plasma exchange, to suggest future directions as part of evidence-based medicine. MATERIALS AND METHODS: Categories and grades for therapeutic plasma exchange (TPE) were collected and analysed from the fifth through ninth editions. We aligned classification changes to the ninth edition's clinical context and compared its categories and grades with those introduced in the guideline. RESULTS: Among 166 total indications in the ninth edition, 118 included TPE procedure, either as a sole treatment or as one of the therapeutic apheresis techniques. The total number of indications changed, but Category III remained predominant throughout the editions. Similarly, Grade 2C consistently emerged as the most prevalent grade. Notably, 24 cases had grade changes. Of the 16 cases with evidence quality changes, the quality weakened in six and improved in 10. Evidence levels were not improved throughout the study period for 102 clinical conditions. CONCLUSION: To address gaps in evidence quality, international collaboration is imperative to establish comprehensive large-scale studies or randomized controlled trials. This will refine the use of therapeutic apheresis, including TPE, to foster evidence-based advancements in clinical practice.
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Eliminación de Componentes Sanguíneos , Medicina Basada en la Evidencia , Intercambio Plasmático , Humanos , Intercambio Plasmático/métodos , Eliminación de Componentes Sanguíneos/métodos , Guías de Práctica Clínica como Asunto , Sociedades Médicas , Estados Unidos , Femenino , MasculinoRESUMEN
BACKGROUND: The immunogenicity of a blood group antigen is a measure of its likelihood of inducing alloantibodies. Although the immunogenicity of blood group antigens has been analyzed in Caucasian populations, immunogenicity to date has not been analyzed in Asian subjects. The present study therefore evaluated the relative immunogenicity of blood group antigens in a Korean population. STUDY DESIGN AND METHODS: All available data of unexpected antibody identification tests performed at Asan Medical Center between 1997 and 2021 were analyzed. The relative immunogenicity of a blood group antigen relative to K antigen was calculated based on relative numbers of alloantibodies and the probabilities of antigen-negative recipients receiving antigen-positive RBC units. RESULTS: A total of 3898 antibody identification results were included, with 1632 (41.9 %) from male patients. The ranking of antigen immunogenicity was: E > c > e > C > K > Jk(a) > Lu(a) > S > Fy(a) > Fy(b) > Jk(b) > Di(b) > Di(a) in the total population and E > c > e > C > Jk(a) > Fy(a) > Fy(b) > S > K > Lu(a) > Jk(b) > Di(b) > Di(a) in male patients. DISCUSSION: The rank order of immunogenicity for blood group antigens in this study provides information about relative immunogenecity in Koreans. These findings also provide supporting evidence regarding antigen selection for extended antigen-matched transfusions in recipients of multiple transfusions.
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Antígenos de Grupos Sanguíneos , Humanos , Masculino , Isoanticuerpos , Transfusión Sanguínea , Pueblo Asiatico , República de Corea , EritrocitosRESUMEN
INTRODUCTION: The unexpected antibody test is an essential for ensuring the safety of blood transfusions. In infants, different pre-transfusion tests and transfusion strategies are needed due to their immature antigen/antibody system. This study aims to analyze the pattern of unexpected antibodies and their clinical significance in infants. METHODS: A retrospective analysis was conducted on the results of unexpected antibody identification tests performed on infants under one year of age at Asan Medical Center from 1999 to 2022. Patients' unexpected antibody identification test results and clinical information were investigated. The results of unexpected antibody identification and phenotype of each patient's mother were collected. RESULTS: 45 cases of antibody results were studied. 25 cases were found in infants under 4 months of age, and 18 cases (76%) were associated with hemolytic disease of the fetus and newborn (HDFN). The most common unexpected antibody in infants was anti-M (17 cases). There was one case of severe HDFN caused by anti-M. In 10 cases, anti-E and anti-c were found together, and 9 of these cases were associated with HDFN. There were four cases with a history of previous transfusion. CONCLUSIONS: Non-ABO antibodies found in infants showed a different pattern compared to adults. Interpreting unexpected antibody tests in infants, it is important to consider the clinical status of the infant and the test results of the mother, due to possibility of HDFN. To our knowledge, this is the first study to reveal the distribution and clinical significances of unexpected antibodies found in infants in Korea.
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Antígenos de Grupos Sanguíneos , Eritroblastosis Fetal , Humanos , Lactante , Recién Nacido , Relevancia Clínica , Isoanticuerpos , Estudios RetrospectivosRESUMEN
Clonal cytopenia of undetermined significance (CCUS) is characterized by persistent cytopenias with genetic aberrations, which do not meet the diagnostic criteria for myelodysplastic syndrome (MDS). We aimed to compare the clinical and genetic characteristics of CCUS with lower-risk MDS and identify patients with CCUS with a high risk of progression. We performed targeted sequencing of bone marrow (BM) samples from patients with idiopathic cytopenia of undetermined significance (ICUS) (n = 139) and MDS (n = 226). Overall survival (OS) of patients with CCUS (n = 78) was worse than non-clonal ICUS (n = 61) and superior to lower-risk MDS (n = 99). Patients with CCUS showed similar characteristics to those with lower-risk MDS, except for higher haemoglobin, lower BM cellularity, and less frequent SF3B1 mutations. Lower haemoglobin, DDX41 (biallelic germline and somatic), ETV6, and RUNX1 mutations were independent prognostic factors for worse OS. Lower haemoglobin and DDX41 mutations were also associated with lower progression-free survival. Patients with CCUS with high-risk features showed similar or worse OS than patients with lower-risk MDS. Our findings suggest that patients with CCUS having certain clinical or genetic features should be regarded and treated as lower-risk MDS despite lacking significant dysplasia or MDS-associated chromosomal abnormalities.
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Hematopoyesis Clonal , Síndromes Mielodisplásicos , Aberraciones Cromosómicas , Hemoglobinas/genética , Humanos , Mutación , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/genéticaRESUMEN
DDX41 mutations are associated with hematologic malignancies including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but the incidence in idiopathic cytopenia of undetermined significance (ICUS) is unknown. We investigated the incidence, genetic characteristics, and clinical features of DDX41 mutations in Korean patients with ICUS, MDS, or AML. We performed targeted deep sequencing of 61 genes including DDX41 in 457 patients with ICUS (n=75), MDS (n=210), or AML (n=172). Germline DDX41 mutations with causality were identified in 28 (6.1%) patients, of whom 27 (96.4%) had somatic mutations in the other position of DDX41. Germline origins of the DDX41 mutations were confirmed in all of the 11 patients in whom germline-based testing was performed. Of the germline DDX41 mutations, p.V152G (n=10) was most common, followed by p.Y259C (n=8), p.A500fs (n=6), and p.E7* (n=3). Compared with non-mutated patients, patients with a DDX41 mutation were more frequently male, older, had a normal karyotype, low leukocyte count, and hypocellular marrow at diagnosis. Three of the four ICUS patients with germline DDX41 mutations progressed to MDS. The incidence of DDX41 mutations in Korean patients was high and there was a distinct mutation pattern, in that p.V152G was a unique germline variant. ICUS harboring germline DDX41 mutations may be regarded as a hereditary myeloid neoplasm. Germline DDX41 mutations are not uncommon and should be explored when treating patients with myeloid malignancies.
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ARN Helicasas DEAD-box , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Trastornos Mieloproliferativos , ARN Helicasas DEAD-box/genética , Etnicidad/genética , Enfermedades Hematológicas/genética , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Masculino , Mutación , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/patología , Trastornos Mieloproliferativos/genéticaRESUMEN
ABO antibodies occur naturally and usually exist as alloantibodies. They are the most clinically significant in cases of transfusions. However, there are very few reports on auto-anti-A or B. A 58-year-old man visited our hospital for evaluation of an inguinal mass. Blood typing was performed, while preparing the patient for an excisional biopsy. Forward and reverse typing showed a typical AB and A pattern. Results of the direct antiglobulin and unexpected antibody screening tests were negative. The serum did not react with AB3 cells. The biopsy revealed a diffuse large B-cell lymphoma. After completing four cycles of R-CHOP chemotherapy, the patient achieved complete remission. There were no anti-B antibodies found on repeat ABO typing. This report shares our experience on unexpected anti-B antibody findings in a patient with an A1B blood type. To the best of our knowledge, this is the first report of anti-B antibodies in a patient with an A1B blood type in Korea.
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Sistema del Grupo Sanguíneo ABO , Linfoma de Células B Grandes Difuso , Masculino , Humanos , Persona de Mediana Edad , Isoanticuerpos , Tipificación y Pruebas Cruzadas Sanguíneas , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Anticuerpos AntiidiotiposRESUMEN
Background and objectives: The ABO antibody (Ab) titration tests are used in monitoring in ABO-incompatible (ABOi) solid organ transplantation (SOT). However, currently developed ABO Ab tests show Ab binding reactions. This study attempted to measure ABO Ab level using complement-dependent cytotoxicity (CDC). Materials and methods: We studied 93 blood group O serum samples from patients who underwent ABOi SOT from January 2019 to May 2021. Patients' sera were incubated with A1 or B cells and added to a human complement solution. Supernatants were collected after centrifugation, and free hemoglobin (Hb) was measured by spectrophotometry. We converted plasma Hb value to hemolysis (%), which were compared with ABO Ab titer. Results: We found a mild correlation between hemolysis and ABO Ab titers. In simple regression analysis, the correlation coefficients were within 0.3660−0.4968 (p < 0.0001) before transplantation. In multiple linear regression analysis, anti-A hemolysis (%) was higher in immunoglobulin M (IgM) (ß = 12.9) than in immunoglobulin G (IgG) (ß = −3.4) (R2 = 0.5216). Anti-B hemolysis was higher in IgM (ß = 8.7) than in IgG (ß = 0.0) (R2 = 0.5114). There was a large variation in hemolysis within the same Ab titer. Conclusions: CDC can be used in a new trial for ABO Ab measurement. Furthermore, IgM rather than IgG seems to play a significant role in vivo activity, consistent with previous knowledge. Thus, this study may help in the development of the ABO Ab titration supplement test for post-transplant treatment policy establishment and pre-transplant desensitization.
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Sistema del Grupo Sanguíneo ABO , Trasplante de Riñón , Hemólisis , Humanos , Inmunoglobulina G , Inmunoglobulina MRESUMEN
BACKGROUND: Criteria for selection of FFP blood type has not been clearly established and use of group AB plasma is preferred by numerous transplantation protocols. AIMS: This study assesses the safety and efficacy of alternative group A or B plasma in ABO incompatible solid organ transplantation. MATERIALS & METHODS: Alternative use of group A or B plasma (incompatible plasma) was inevitable during the shortage of group AB plasma. Experience from select number of patients during the period of extreme group AB plasma shortage is described. RESULTS: The result of alternative use of group A or B plasma was within expectation, showing effective reduction of isoagglutinin titers for pre-operative desensitization and efficacy for treatment of post-operative patients. No immediate hemolytic transfusion reaction was reported. DISCUSSION: While validation in a larger cohort of patients is necessary, our limited experience have shown satisfactory clinical outcomes without adverse events. CONCLUSIONS: Use of incompatible group A or B plasma is a viable option when group AB plasma is limited.
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Sistema del Grupo Sanguíneo ABO , Incompatibilidad de Grupos Sanguíneos/terapia , Intercambio Plasmático/métodos , Trasplante/métodos , Aglutininas/química , Bancos de Sangre/provisión & distribución , Supervivencia de Injerto , Hemólisis , Humanos , Trasplante de Riñón/efectos adversos , Seguridad del Paciente , Plasma/inmunología , Plasmaféresis , Reacción a la Transfusión , Resultado del TratamientoRESUMEN
For the best results in quantitative polymerase chain reaction (qPCR) experiments, it is essential to design high-quality primers considering a multitude of constraints and the purpose of experiments. The constraints include many filtering constraints, homology test on a huge number of off-target sequences, the same constraints for batch design of primers, exon spanning, and avoiding single nucleotide polymorphism (SNP) sites. The target sequences are either in database or given as FASTA sequences, and the experiment is for amplifying either each target sequence with each corresponding primer pairs designed under the same constraints or all target sequences with a single pair of primers. Many websites have been proposed, but none of them including our previous MRPrimerW fulfilled all the above features. Here, we describe the MRPrimerW2, the update version of MRPrimerW, which fulfils all the features by maintaining the advantages of MRPrimerW in terms of the kinds and sizes of databases for valid primers and the number of search modes. To achieve it, we exploited GPU computation and a disk-based key-value store using PCIe SSD. The complete set of 3 509 244 680 valid primers of MRPrimerW2 covers 99% of nine important organisms in an exhaustive manner. Free access: http://MRPrimerW2.com.
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Cartilla de ADN/química , Reacción en Cadena en Tiempo Real de la Polimerasa , Programas Informáticos , Animales , Bovinos , Exones , Humanos , Ratones , Polimorfismo de Nucleótido Simple , Ratas , Análisis de SecuenciaRESUMEN
Affordable point-of-care (POC) CD4 + T lymphocyte counting techniques have been developed as alternatives to flow cytometry-based instruments caring for patients with human immunodeficiency virus (HIV)-1. However, POC CD4 enumeration technologies can be inaccurate. Here, we developed a microparticle-based visual detector of CD4 + T lymphocytes (ImmunoSpin) using microparticles conjugated with anti-CD4 antibodies, independent of microfluidic or fluorescence detection systems. Visual enumeration of CD4 + T cells under conventional light microscope was accurate compared to flow cytometry. Microparticle-tagged CD4 + T cells were well-recognized under a light microscope. ImmunoSpin showed very good precision (coefficients of variation of ImmunoSpin were ≤ 10%) and high correlation with clinical-grade flow cytometry for the enumeration of CD4 + T cells (y = 0.4232 + 0.9485 × for the %CD4 + T cell count, R2 = 0.99). At thresholds of 200 and 350 cells/µL, there was no misclassification of the ImmunoSpin system compared to the reference flow cytometry. ImmunoSpin showed clear differential classification of CD4 + T lymphocytes from granulocytes and monocytes. Because non-fluorescence microparticle-tags and cytospin slides are used in ImmunoSpin, they can be applied to an automatic digital image analyzer. Slide preparation allows long-term storage, no analysis time limitations, and image transfer in remote areas.
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Linfocitos T CD4-Positivos/inmunología , Micropartículas Derivadas de Células/metabolismo , Sistemas de Atención de Punto/normas , Diferenciación Celular , HumanosRESUMEN
OBJECTIVE: To evaluate whether HPV DNA in urine has potential advantages as an alternative biomarker for HPV-based cervical cancer screening. METHODS: Among patients with Cobas HPV test results, a total of 67 HPV-positive (n = 42) and -negative (n = 25) women who agreed to participate in this study were willing to provide paired cervical and urine samples, and we observed concordance between sample types from each patient in identifying HPV genotypes using the nanowire assay. RESULTS: We detected high-risk strains of HPV DNA in unprocessed urine specimens using polyethyleneimine-conjugated nanowires (PEI-NWs). Concordance for high-risk HPV (hrHPV) between paired urine and cervical samples was 90.4% (κ = 0.90; 95% CI: 0.80-100.00). The virological sensitivity and specificity for detection of HPV DNA from a small urine sample (200 µL) were 81.3% (κ = 0.83; 95% CI: 62.1-100.0) and 98.0% (κ = 0.83; 95% CI: 94.2-100.0) for HPV16 group, 100.0% (κ = 0.65; 95% CI: 100.0-100.0) and 95.3% (κ = 0.65; 95% CI: 90.1-100.0) for HPV18 group, and 96.4% (κ = 0.97; 95% CI: 89.6-100.0) and 100.0% (κ = 0.97; 95% CI: 100.0-100.0) for other hrHPV group, respectively. CONCLUSIONS: The nanowire assay demonstrated excellent ability to identify HPV DNA from urine specimens. We observed an excellent agreement in the detection of high-risk HPV between paired urine and cervical samples, even with small urine sample volume.
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ADN Viral/orina , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/virología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/orina , Ácidos Nucleicos Libres de Células/orina , Citodiagnóstico/instrumentación , Citodiagnóstico/métodos , ADN Viral/genética , Detección Precoz del Cáncer/métodos , Femenino , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/aislamiento & purificación , Humanos , Nanocables , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/orina , Polietileneimina , Espectrofotometría Ultravioleta , Neoplasias del Cuello Uterino/orinaRESUMEN
The Jra antigen of the JR blood group system is a highly prevalent red blood cell antigen. Although anti-Jra-associated hemolytic disease of the fetus and newborn (HDFN) is generally considered mild-to-moderate, a rare fatal case was recently reported. We report the third example of HDFN-related anti-Jra with fatal outcomes. The clinical significance of anti-Jra antibody as a cause of HDFN should be reassessed.
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Antígenos de Grupos Sanguíneos/inmunología , Eritroblastosis Fetal/diagnóstico , Isoanticuerpos/inmunología , Adulto , Femenino , Humanos , Recién Nacido , EmbarazoRESUMEN
BACKGROUND: Anti-blood group antibody titers (ABTs) reported in titer values are variable depending on the testing method used. The introduction of new test methods such as automated methods requires proper method comparison. In this study, the automated blood bank system and manual tube method for ABT were compared using a log-transformed dataset to evaluate the alternative statistical approach. METHODS: ABT was conducted using specimens referred for solid organ transplantation. Methods for comparison were conventional manual tube method and IH-500 automated blood bank system using column agglutination (CAT). Criteria for agreement were exact match and 1-titer match. Measured titer values were log-transformed into interval scale for Deming regression analysis. RESULTS: From the comparison of the tube and CAT methods using titer values and the two criteria, the exact and 1-titer match were 15.9-41.5 % and 65.9-97.6 %, respectively. Deming regression was used to demonstrate the presence of both proportional and constant difference between the two methods. CONCLUSION: The method comparison using conventional statistical approaches had limits due to the semi-quantitative value of the test. Log-transformed interval scale values for comparison were useful for interpretation of method comparison datasets. This alternative statistical approach could contribute to a more accurate comparison between assays and standardization of ABT testing.
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Sistema del Grupo Sanguíneo ABO/inmunología , Almacenamiento de Sangre/métodos , Estudios de Evaluación como Asunto , HumanosRESUMEN
BACKGROUND: Exchange transfusion (ET) is an established, efficacious, and reliable practice for severe neonatal hyperbilirubinemia, hemolytic disease of the newborn, and neonatal sepsis. This study assessed the indications and clinical outcomes of ET performed in a tertiary hospital in Korea. MATERIALS AND METHODS: We studied 64 ET sessions performed on 23 neonates between March 1999 and March 2018. ET was performed based on estimated double volume exchange transfusion using fresh red blood cells and fresh frozen plasma. Patients' clinical information, including demographic data and ET indication, and laboratory data were collected pre- and post-ET. RESULTS: The most common ET indication was hyperbilirubinemia with hemolytic anemia due to non-ABO maternal blood group discrepancies. In three preterm babies, ETs were performed for severe anemia, leukocytosis, and hyperkalemia cases. Before ET, the patients showed slightly high WBC counts, low hemoglobin levels, and low platelet counts. After ET, blood examination revealed normal WBC counts, increased hemoglobin levels, and decreased platelet counts (all P < 0.001). Bilirubin levels decreased immediately after ET (P < 0.001). Electrolyte and C-reactive protein levels showed no significant changes after ETs. Adverse events occurred in 11 (47.8 %) patients; the most common were hypoxemia and hypotension. One infant experienced cardiorespiratory arrest due to hypercalcemia and was successfully resuscitated. No one died within 24 h of ET. However, five infants showed hyperbilirubinemia aggravation. CONCLUSIONS: ET is an effective treatment modality for leukocytosis and hyperbilirubinemia with low mortality but involves common adverse events post-ET. This report provides an overview of current ET practices in Korea.
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Anemia/terapia , Recambio Total de Sangre/métodos , Hiperbilirrubinemia Neonatal/terapia , Recambio Total de Sangre/efectos adversos , Femenino , Humanos , Recién Nacido , Masculino , República de CoreaRESUMEN
BACKGROUND: Although plasma free hemoglobin (fHb) test is important for assessing intravascular hemolysis, it is still dependent on the gold standard Harboe method using manual and labor-intensive spectrometric measurements at the wavelength of 380-415-450 nm. We established an automated fHb assay using a routine chemistry autoanalyzer that can be tuned to a wavelength of 380-416-450 nm. METHODS: The linearity, precision, accuracy, correlation, and sample carryover of fHb measurement using TBA200FRneo method and manual Harboe method were evaluated, respectively. fHb values measured by manual Harboe method were compared with those measured by our new automated TBA200FRneo method. RESULTS: fHb measurements were linear in the range of 0.05~38.75 µmol/L by TBA200FRneo and 0.05~9.69 µmol/L by manual Harboe method. Imprecision analysis (%CV) revealed 0.9~2.8% for TBA200FRneo method and 5.3~13.6% for the manual Harboe method. Comparison analysis showed 0.9986 of correlation coefficient (TBA200FRneo = 0.970 × Harboe + 0.12). In analytical accuracy analysis, the manual Harboe method revealed about 4 times higher average total error % (12.2%) than the TBA200FRneo automated method (2.8%). The sample carryover was -0.0016% in TBA200FRneo method and 0.0038% in Harboe method. CONCLUSIONS: In the measurement of fHb, the automated TBA200FRneo method showed better performance than the conventional Harboe method. It is expected that the automated fHb assay using the routine chemistry analyzer can replace the gold standard Harboe method which is labor-intensive and need an independent spectrophotometry equipment.
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Análisis Químico de la Sangre/métodos , Hemoglobinas/análisis , Espectrofotometría/métodos , Automatización de Laboratorios , Análisis Químico de la Sangre/instrumentación , Humanos , Espectrofotometría/instrumentaciónRESUMEN
Natural killer (NK) cells are cytotoxic innate lymphocytes endowed with a unique ability to kill a broad spectrum of cancer and virus-infected cells. Given their key contribution to diverse diseases, the measurement of NK cell activity (NKA) has been used to estimate disease prognosis or the effect of therapeutic treatment. Currently, NKA assays are primarily based on cumbersome procedures related to careful labeling and handling of target cells and/or NK cells, and they require a rapid isolation of peripheral blood mononuclear cells (PBMCs) which often necessitates a large amount of blood. Here, we developed an ELISA-based whole blood (WB) NKA assay involving engineered target cells (P815-ULBP1+CD48) providing defined and synergistic stimulation for NK cells via NKG2D and 2B4. WB collected from healthy donors (HDs) and patients with multiple myeloma (MM) was stimulated with P815-ULBP1+CD48 cells combined with IL-2. Thereafter, it utilized the serum concentrations of granzyme B and IFN-γ originating in NK cells as independent and complementary indicators of NKA. This WB NKA assay demonstrated that MM patients exhibit a significantly lower NKA than HDs following stimulation with P815-ULBP1+CD48 cells and had a good correlation with the commonly used flow cytometry-based PBMC NKA assay. Moreover, the use of P815-ULBP1+CD48 cells in relation to assessing the levels of NKG2D and 2B4 receptors on NK cells facilitated the mechanistic study and led to the identification of TGF-ß1 as a potential mediator of compromised NKA in MM. Thus, our proposed WB NKA assay facilitates the reliable measurement of NKA and holds promise for further development as both a clinical and research tool.
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Células Asesinas Naturales/inmunología , Leucocitos Mononucleares/inmunología , Mieloma Múltiple/inmunología , Receptores de Células Asesinas Naturales/metabolismo , Estudios de Casos y Controles , Citometría de Flujo , Humanos , Células Asesinas Naturales/metabolismo , Leucocitos Mononucleares/metabolismo , Mieloma Múltiple/metabolismoRESUMEN
BACKGROUND: The rhesus (Rh) system is the second most important blood group system after ABO, with highly immunogenic antigens. Although the anti-E Rh antibody has been reported to cause hemolytic disease of the newborn and delayed hemolytic transfusion reactions, acute hemolytic transfusion reactions (AHTR) have been rarely reported. METHODS: Peripheral blood (PB) samples were screened for irregular antibodies using a commercial ID-Diacell I - II antibody screening Panel (Bio-Rad Laboratories, Glattbrugg, Switzerland) and ID-cards "LISS/Coombs" (Bio-Rad, Switzerland). The antibody was confirmed using ID DiaPanel, an antibody identification panel (Bio-Rad, Switzerland). Rh phenotyping was performed for RhC/c and RhE/e antigens using an immediate-spin tube test with monoclonal anti-C, -c, -E, and -e (OrthoClinical Diagnostics, High Wycombe, UK) in saline-filled test-tubes. RESULTS: The patient was negative for antibody screening test before transfusion. After receiving a total of 6 units of cross-matching negative RBC transfusion, the antibody screening test result increased to 2+ after showing traces and the antibody was confirmed as anti-E Rh antibody. The Rh phenotype of the patient was C (+), c (+), E (-), and e (+). In addition, we verified that all the six units of RBCs transfused were E (+) except for the two units transfused before surgery. CONCLUSIONS: Here is an unusual case of an AHTR due to the anti-E Rh antibody after E-positive RBC transfusion in a patient with Crohn's disease. Because anemia is common in patients with Crohn's disease, it is important to determine the cause of the anemia and necessary to examine the Rh phenotype before transfusions because of the high need for transfusion due to any cause. Awareness of this possibility will ensure safe blood transfusion with special care to screen for antibodies and perform Rh phenotyping, thereby minimizing morbidity and preventing potential mortality.
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Antígenos de Grupos Sanguíneos/inmunología , Enfermedad de Crohn/terapia , Transfusión de Eritrocitos/métodos , Sistema del Grupo Sanguíneo Rh-Hr/inmunología , Reacción a la Transfusión/sangre , Adulto , Enfermedad de Crohn/sangre , Enfermedad de Crohn/inmunología , Humanos , Masculino , Reacción a la Transfusión/inmunologíaRESUMEN
Para-Bombay phenotypes are rare blood groups that have inherent defects in producing H antigens associated with FUT1 and/or FUT2. We report the first case of para-Bombay blood type in a Southeast Asian patient admitted at a tertiary hospital in Korea. A 23-year-old Indonesian man presented to the hospital with fever and was diagnosed with a disseminated nontuberculous mycobacterium infection and anemia. During blood group typing for blood transfusion, cell typing showed no agglutination with both anti-A and anti-B reagents. Serum typing showed strong reactivity against B cells and trace agglutination pattern with A1 cells. His red blood cells failed to react with anti-H reagents. Direct sequencing of FUT1 and FUT2 revealed a missense variation, c.328G>A (p.Ala110Thr, rs56342683, FUT1*01W.02), and a synonymous variant, c.390C>T (p.Asn130=, rs281377, Se357), respectively. This highlights the need for both forward and reverse grouping.
Asunto(s)
Sistema del Grupo Sanguíneo ABO/genética , Fucosiltransferasas/genética , Pueblo Asiatico/genética , Transfusión Sanguínea , Humanos , Indonesia , Masculino , Mutación Missense , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , República de Corea , Análisis de Secuencia de ADN , Centros de Atención Terciaria , Adulto Joven , Galactósido 2-alfa-L-FucosiltransferasaRESUMEN
OBJECTIVES: This study aimed to evaluate the impact of seasonal variations in climate on the performance of the fecal immunochemical test (FIT) in screening for colorectal cancer in the National Cancer Screening Program in Korea. METHODS: Data were extracted from the National Cancer Screening Program databases for participants who underwent FIT between 2009 and 2010. We compared positivity rates, cancer detection rates, interval cancer rates, positive predictive value, sensitivity, and specificity for FIT during the spring, summer, fall, and winter seasons in Korea. RESULTS: In total, 4,788,104 FIT results were analyzed. FIT positivity rate was lowest during the summer months. In the summer, the positive predictive value of FIT was about 1.1 times (adjusted odds ratio (aOR) 1.08, 95% confidence interval (CI) 1.00-1.16) higher in the overall FIT group and about 1.3 times (aOR 1.29, 95% CI 1.10-1.50) higher in the quantitative FIT group, compared to those in the other seasons. Cancer detection rates, however, were similar regardless of season. Interval cancer risk was significantly higher in the summer for both the overall FIT group (aOR 1.16, 95% CI 1.07-1.27) and the quantitative FIT group (aOR 1.31, 95% CI 1.12-1.52). In addition, interval cancers in the rectum and distal colon were more frequently detected in the summer and autumn than in the winter. CONCLUSIONS: The positivity rate of FIT was lower in the summer, and the performance of the FIT screening program was influenced by seasonal variations in Korea. These results suggest that more efforts to reduce interval cancer during the summer are needed in population-based screening programs using FIT, particularly in countries with high ambient temperatures.