RESUMEN
This study aimed to identify plasma proteins that could serve as potential biomarkers for microbial invasion of the amniotic cavity (MIAC) or intra-amniotic inflammation (IAI) in women with preterm labor (PTL). A retrospective cohort comprised singleton pregnant women with PTL (24-34 weeks) who underwent amniocentesis. Pooled plasma samples were analyzed by label-free liquid chromatography-tandem mass spectrometry for proteome profiling in a nested case-control study (concomitant MIAC/IAI cases vs. non-MIAC/IAI controls [n = 10 per group]). Eight target proteins associated with MIAC/IAI were further verified by immunoassays in a large cohort (n = 230). Shotgun proteomic analysis revealed 133 differentially expressed proteins (fold change > 1.5, P < 0.05) in the plasma of MIAC/IAI cases. Further quantification confirmed that the levels of AFP were higher and those of kallistatin and TGFBI were lower in the plasma of women with MIAC and that the levels of kallistatin and TGFBI were lower in the plasma of women with IAI than in those without these conditions. The area under the curves of plasma AFP, kallistatin, and TGFBI ranged within 0.67-0.81 with respect to each endpoint. In summary, plasma AFP, kallistatin, and TGFBI may represent valuable non-invasive biomarkers for predicting MIAC or IAI in women with PTL.
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Biomarcadores , Proteínas Sanguíneas , Trabajo de Parto Prematuro , Proteómica , Humanos , Femenino , Embarazo , Trabajo de Parto Prematuro/sangre , Adulto , Proteínas Sanguíneas/análisis , Proteínas Sanguíneas/metabolismo , Biomarcadores/sangre , Estudios de Casos y Controles , Estudios Retrospectivos , Proteómica/métodos , Corioamnionitis/sangre , Corioamnionitis/microbiología , Inflamación/sangre , Amniocentesis , Proteoma/análisisRESUMEN
PURPOSE: To determine whether various inflammatory-, angiogenic/anti-angiogenic-, and extracellular matrix remodeling-associated proteins in plasma, alone or in combination with conventional blood-based markers, can predict intra-amniotic inflammation and/or microbial invasion of the amniotic cavity (IAI/MIAC) in women with spontaneous preterm labor (PTL). METHODS: A total of 193 singleton pregnant women with PTL (23-33 weeks) were included in this retrospective cohort study. Plasma samples were obtained at the time of amniocentesis. Amniotic fluid (AF) was cultured for microorganism detection and consequent MIAC diagnosis. IL-6 levels were determined in AF and used to identify IAI (AF IL-6 ≥ 2.6 ng/mL). Endostatin, haptoglobin, IGFBP-2/3, LBP, M-CSF, MMP-2/8, pentraxin 3, PlGF, S100A8/A9, and VEGFR-1 levels were assayed in plasma samples by ELISA. CRP levels and neutrophil-to-lymphocyte ratio (NLR) were measured. RESULTS: Plasma LBP, MMP-8, and S100A8/A9 levels, CRP levels, and NLR were significantly higher, and plasma IGFBP-2 and MMP-2 levels were significantly lower in women with IAI/MIAC than in those without this condition, whereas no baseline variables differed significantly between the two groups. Using a stepwise regression analysis, a noninvasive prediction model for IAI/MIAC was developed, which included plasma LBP, MMP-2, and MMP-8 levels (area under the curve [AUC], 0.785). The AUC for this prediction model was significantly or borderline greater than that of any single factor included in the model. CONCLUSIONS: IGFBP-2, LBP, MMP-2, MMP-8, and S100A8/A9 may represent valuable plasma biomarkers for predicting IAI/MIAC in women with PTL. Combination of LBP, MMP-2, and MMP-8 expression data can significantly improve the predictive potential for IAI/MIAC.
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Líquido Amniótico , Biomarcadores , Proteína C-Reactiva , Corioamnionitis , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina , Metaloproteinasa 2 de la Matriz , Metaloproteinasa 8 de la Matriz , Trabajo de Parto Prematuro , Humanos , Femenino , Embarazo , Estudios Retrospectivos , Adulto , Trabajo de Parto Prematuro/microbiología , Trabajo de Parto Prematuro/sangre , Líquido Amniótico/microbiología , Líquido Amniótico/metabolismo , Metaloproteinasa 8 de la Matriz/sangre , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Biomarcadores/sangre , Corioamnionitis/microbiología , Corioamnionitis/sangre , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Metaloproteinasa 2 de la Matriz/sangre , Calgranulina A/sangre , Endostatinas/sangre , Proteínas de Fase Aguda/análisis , Interleucina-6/sangre , Amniocentesis , Componente Amiloide P Sérico/análisis , Componente Amiloide P Sérico/metabolismo , Haptoglobinas/análisis , Haptoglobinas/metabolismo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Valor Predictivo de las Pruebas , Matriz Extracelular/metabolismo , Angiogénesis , Calgranulina BRESUMEN
Background: Several T-cell response assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are available; however, their comparability and correlations with antibody responses remain unclear. We compared four SARS-CoV-2 T-cell response assays and two anti-SARS-CoV-2 spike antibody assays. Methods: We enrolled 89 participants who had received a booster dose of the BNT162b2 vaccine after two doses of the ChAdOx1 or BNT162b2 vaccine. Fifty-six participants without breakthrough infection (BI) (ChAdOx1/BNT162b2 group: N=27; BNT162b2 group: N=29) and 33 with BI were included. We evaluated two whole-blood interferon-gamma release assays (IGRAs) (QuantiFERON and Euroimmun), T-SPOT.COVID, an in-house enzyme-linked immunospot (ELISPOT) assay (targeting the spike and nucleocapsid peptides of wild-type and Omicron SARS-CoV-2), Abbott IgG II Quant, and Elecsys Anti-S, using Mann-Whitney U, Wilcoxon signed-rank, and Spearman's correlation tests. Results: The correlations between the IGRAs and between the ELISPOT assays (ρ=0.60-0.70) were stronger than those between the IGRAs and ELISPOT assays (ρ=0.33-0.57). T-SPOT.COVID showed a strong correlation with Omicron ELISPOT (ρ=0.70). The anti-spike antibody assays showed moderate correlations with T-SPOT.COVID, Euroimmun IGRA, and ELISPOT (ρ=0.43-0.62). Correlations tended to be higher in the BI than in the noninfected group, indicating that infection induces a stronger immune response. Conclusions: T-cell response assays show moderate to strong correlations, particularly when using the same platform. T-SPOT.COVID exhibits potential for estimating immune responses to the Omicron variant. To accurately define SARS-CoV-2 immune status, both T-cell and B-cell response measurements are necessary.
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Vacuna BNT162 , COVID-19 , Humanos , Infección Irruptiva , SARS-CoV-2 , Linfocitos T , Anticuerpos AntiviralesRESUMEN
BACKGROUND: In Korea, during the early phase of the coronavirus disease 2019 (COVID-19) pandemic, we responded to the uncertainty of treatments under various conditions, consistently playing catch up with the speed of evidence updates. Therefore, there was high demand for national-level evidence-based clinical practice guidelines for clinicians in a timely manner. We developed evidence-based and updated living recommendations for clinicians through a transparent development process and multidisciplinary expert collaboration. METHODS: The National Evidence-based Healthcare Collaborating Agency (NECA) and the Korean Academy of Medical Sciences (KAMS) collaborated to develop trustworthy Korean living guidelines. The NECA-supported methodological sections and 8 professional medical societies of the KAMS worked with clinical experts, and 31 clinicians were involved annually. We developed a total of 35 clinical questions, including medications, respiratory/critical care, pediatric care, emergency care, diagnostic tests, and radiological examinations. RESULTS: An evidence-based search for treatments began in March 2021 and monthly updates were performed. It was expanded to other areas, and the search interval was organized by a steering committee owing to priority changes. Evidence synthesis and recommendation review was performed by researchers, and living recommendations were updated within 3-4 months. CONCLUSION: We provided timely recommendations on living schemes and disseminated them to the public, policymakers and various stakeholders using webpages and social media. Although the output was successful, there were some limitations. The rigor of development issues, urgent timelines for public dissemination, education for new developers, and spread of several new COVID-19 variants have worked as barriers. Therefore, we must prepare systematic processes and funding for future pandemics.
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COVID-19 , Niño , Humanos , Adenosina-5'-(N-etilcarboxamida) , República de Corea , SARS-CoV-2 , Guías de Práctica Clínica como AsuntoRESUMEN
HLA-DQA1*05:75 differs from DQA1*05:05:01:01 by a single substitution at nucleotide 701 (G/A) in exon 4.
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Donantes de Sangre , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Alelos , Análisis de Secuencia de ADN , Cadenas alfa de HLA-DQ/genética , República de CoreaRESUMEN
HLA-B*15:656 differs from B*15:27:01:01 by two nucleotide substitutions in codon 163 (CTG > GAG).
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Genes MHC Clase I , Antígenos HLA-B , Humanos , Alelos , Antígenos HLA-B/genética , Secuenciación de Nucleótidos de Alto Rendimiento , República de CoreaRESUMEN
BACKGROUND: The epidemiology of pathogenic bacteria varies according to the socioeconomic status and antimicrobial resistance status. However, longitudinal epidemiological studies to evaluate the changes in species distribution and antimicrobial susceptibility of pathogenic bacteria nationwide are lacking. We retrospectively investigated the nationwide trends in species distribution and antimicrobial susceptibility of pathogenic bacteria over the last 20 years in Korea. METHODS: From 1997 to 2016, annual cumulative antimicrobial susceptibility and species distribution data were collected from 12 university hospitals in five provinces and four metropolitan cities in South Korea. RESULTS: The prevalence of Staphylococcus aureus was the highest (13.1%) until 2012 but decreased to 10.3% in 2016, consistent with the decrease in oxacillin resistance from 76.1% in 2008 to 62.5% in 2016. While the cefotaxime resistance of Escherichia coli increased from 9.0% in 1997 to 34.2% in 2016, E. coli became the most common species since 2013, accounting for 14.5% of all isolates in 2016. Pseudomonas aeruginosa and Acinetobacter baumannii rose to third and fifth places in 2008 and 2010, respectively, while imipenem resistance increased from 13.9% to 30.8% and 0.7% to 73.5% during the study period, respectively. Streptococcus agalactiae became the most common pathogenic streptococcal species in 2016, as the prevalence of Streptococcus pneumoniae decreased since 2010. During the same period, pneumococcal penicillin susceptibility decreased to 79.0%, and levofloxacin susceptibility of S. agalactiae decreased to 77.1% in 2016. CONCLUSION: The epidemiology of pathogenic bacteria has changed significantly over the past 20 years according to trends in antimicrobial resistance in Korea. Efforts to confine antimicrobial resistance would change the epidemiology of pathogenic bacteria and, consequently, the diagnosis and treatment of infectious diseases.
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Antibacterianos , Escherichia coli , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Estudios Retrospectivos , Farmacorresistencia Bacteriana , Bacterias , Pruebas de Sensibilidad Microbiana , Bacterias GramnegativasRESUMEN
PROBLEM: To investigate whether altered expression of various inflammation-, angiogenesis-, and extracellular matrix-related mediators in cervicovaginal fluid (CVF) could be independently associated with acute histological chorioamnionitis (HCA), microbial-associated HCA, and funisitis in women with preterm premature rupture of membranes (PPROM). METHOD OF STUDY: Clinical data of 102 consecutive singleton pregnant women with PPROM at 23+0 to 34+0 weeks were retrospectively analyzed. CVF samples were collected upon admission. Levels of APRIL, DKK-3, IGFBP-1/2, IL-6/8, lipocalin-2, M-CSF, MIP-1α, MMP-8/9, S100A8A9, TGFBI, TIMP-1, TNFR2, uPA, and VDBP were determined by ELISA. Placentas were histologically examined after birth. RESULTS: Multivariate logistic regression analyses showed that: (1) elevated CVF levels of IL-8 and TNFR2 were independently associated with acute HCA; (2) elevated CVF levels of IL-6, IL-8, M-CSF, MMP-8, and TNFR2 were independently associated with microbial-associated HCA; and (3) elevated CVF IL-8 and MMP-8 levels were independently associated with funisitis when adjusted for gestational age. Areas under the curves of the aforementioned CVF biomarkers ranged within 0.61-0.77, thereby demonstrating poor to fair diagnostic capacity for these clinical endpoints. HCA risk significantly increased as the CVF levels of each inflammatory mediator increased (P for trend < 0.05). CONCLUSIONS: Herein, we identified several inflammatory biomarkers (IL-6/8, M-CSF, MMP-8, and TNFR2) in the CVF that are independently associated with acute HCA, microbial-associated HCA, and funisitis in women with PPROM. Furthermore, the degree of inflammatory response in the CVF, based on the levels of these proteins, demonstrated a direct relationship with HCA risk (especially risk severity).
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Corioamnionitis , Rotura Prematura de Membranas Fetales , Recién Nacido , Femenino , Embarazo , Humanos , Corioamnionitis/patología , Factor Estimulante de Colonias de Macrófagos , Receptores Tipo II del Factor de Necrosis Tumoral/metabolismo , Estudios Retrospectivos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Metaloproteinasa 8 de la Matriz/metabolismo , Rotura Prematura de Membranas Fetales/metabolismo , Biomarcadores/metabolismo , Líquido Amniótico/metabolismoRESUMEN
Data on HLA genotype distribution, including DQA1 and DPA1, in the Korean population are limited. We aimed to investigate the allele and haplotype frequencies of 11 HLA loci in 339 Korean subjects using next-generation sequencing (NGS)-based HLA typing. A total of 339 samples from unrelated healthy subjects were genotyped for HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQB1, -DQA1, -DPB1, and -DPA1 using two different NGS-based HLA typing kits (166 tested using the NGSgo-MX11-3 kit [GenDx, Netherlands] and 173 by the AllType NGS 11 Loci Amplification kit [One Lambda, USA]). PyPop software was used to estimate allele and haplotype frequencies and linkage disequilibrium between the loci. Additionally, a principal component analysis was performed to compare the allele distribution of Koreans with that of other populations. A total of 214 HLA alleles (97 class I and 117 class II alleles) were assigned. The most frequent alleles for each locus were A*24:02:01 (24.78%), B*15:01:01 (10.18%), C*01:02:01 (18.44%), DRB1*04:05:01 (9.59%), DRB3*02:02:01 (13.72%), DRB4*01:03:01 (25.81%), DRB5*01:01:01 (9.0%), DQA1*01:02:01 (16.96%), DQB1*03:01:01 (14.31%), DPA1*01:03:01 (44.4%), and DPB1*05:01:01 (35.1%), respectively. The most frequent haplotypes were A*33:03:01-C*03:02:02-B*58:01:01 for HLA class I (5.01%) and DRB1*04:05:01-DQA1*03:03:01-DQB1*04:01:01-DPA1*02:02:02-DPB1*05:01:01 for HLA class II (6.23%). The total allelic ambiguities by NGS were estimated to be minimal and considerably decreased compared with those by Sanger sequencing. The Japanese population had the most similar allele distribution to Koreans, followed by the Chinese population. Frequency data of 11 HLA loci in Koreans can provide essential data for population genetics and disease association studies.
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Pueblos del Este de Asia , Antígenos de Histocompatibilidad Clase II , Humanos , Haplotipos , Antígenos de Histocompatibilidad Clase II/genética , Alelos , Frecuencia de los Genes , Secuenciación de Nucleótidos de Alto Rendimiento , Cadenas HLA-DRB1/genéticaRESUMEN
HLA-DPA1*01:106 differs from DPA1*01:03:01:01 by a single substitution at nucleotide 5 (G/A) in exon 1.
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Donantes de Sangre , Humanos , AlelosRESUMEN
Clinical guidelines recommend several risk factors to identify women in early pregnancy at high risk of developing pregnancy-associated hypertension. However, these variables result in low predictive accuracy. Here, we developed a prediction model for pregnancy-associated hypertension using graph-based semi-supervised learning. This is a secondary analysis of a prospective study of healthy pregnant women. To develop the prediction model, we compared the prediction performances across five machine learning methods (semi-supervised learning with both labeled and unlabeled data, semi-supervised learning with labeled data only, logistic regression, support vector machine, and random forest) using three different variable sets: [a] variables from clinical guidelines, [b] selected important variables from the feature selection, and [c] all routine variables. Additionally, the proposed prediction model was compared with placental growth factor, a predictive biomarker for pregnancy-associated hypertension. The study population consisted of 1404 women, including 1347 women with complete follow-up (labeled data) and 57 women with incomplete follow-up (unlabeled data). Among the 1347 with complete follow-up, 2.4% (33/1347) developed pregnancy-associated HTN. Graph-based semi-supervised learning using top 11 variables achieved the best average prediction performance (mean area under the curve (AUC) of 0.89 in training set and 0.81 in test set), with higher sensitivity (72.7% vs 45.5% in test set) and similar specificity (80.0% vs 80.5% in test set) compared to risk factors from clinical guidelines. In addition, our proposed model with graph-based SSL had a higher performance than that of placental growth factor for total study population (AUC, 0.71 vs. 0.80, p < 0.001). In conclusion, we could accurately predict the development pregnancy-associated hypertension in early pregnancy through the use of routine clinical variables with the help of graph-based SSL.
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Hipertensión Inducida en el Embarazo , Aprendizaje Automático Supervisado , Biomarcadores , Femenino , Humanos , Hipertensión Inducida en el Embarazo/diagnóstico , Factor de Crecimiento Placentario , Embarazo , Estudios ProspectivosRESUMEN
BACKGROUND: We aimed to identify changes in the diagnosis and subtype classification of Korean patients with BCR-ABL1-negative MPN related to the revision of the WHO classification in 2016. METHODS: We evaluated 76 Korean patients with BCR-ABL1-negative MPN who underwent diagnostic work-ups, including bone marrow (BM) examinations and JAK2 V617F mutation analysis, from January 2013 to June 2018. Additionally, we reclassified the subtype of 43 patients who were diagnosed based on the WHO 2008 classification. RESULTS: From January 2013 to April 2016, 43 patients were diagnosed with BCR-ABL1-negative MPN (12 PV, 17 ET, 14 PMF) according to the 2008 WHO classification, and from May 2016 to June 2018, 33 patients were diagnosed according to the 2016 classification (15 PV, 11 ET, 7 PMF). With the application of 2016 classification, 3 cases of ET were reclassified as pre-PMF, and the proportion of PV increased from 27.9% to 45.5%. There were significant differences in CBC between pre-PMF and overt PMF, between ET and overt-PMF, but no difference between ET and pre-PMF. CONCLUSIONS: The overall characteristics of BCR-ABL1-negative MPN patients were not significantly different from those of previous reports. 'Masked PV', which could not be diagnosed according to the WHO 2008 classification, may have been diagnosed as PV since 2016 due to the increase in the diagnostic value of the BM findings and the lowering of the hemoglobin (Hb) threshold.
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Trastornos Mieloproliferativos , Neoplasias , Proteínas de Fusión bcr-abl/genética , Humanos , Janus Quinasa 2/genética , Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/genética , República de Corea , Organización Mundial de la SaludRESUMEN
Rapid antigen tests (RATs) for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are widely used in the Coronavirus disease 2019 (COVID-19) pandemic caused by diverse variants. Information on the real-world performance of RATs for variants is urgently needed for decision makers. Systematic searches of the available literature and updates were conducted in PubMed, Ovid-MEDLINE, Ovid-EMBASE, CENTRAL, and KMBASE for articles evaluating the accuracy of instrument-free RATs for variants up until 14 March 2022. A bivariate random effects model was utilized to calculate pooled diagnostic values in comparison with real-time reverse transcription-polymerase chain reaction as the reference test. A total of 7562 samples from six studies were available for the meta-analysis. The overall pooled sensitivity and specificity of RATs for variants were 69.7% (95% confidence interval [CI] = 62.5% to 76.1%) and 100.0% (95% CI = 98.8% to 100.0%), respectively. When an additional 2179 samples from seven studies reporting sensitivities only were assessed, the pooled sensitivity dropped to 50.0% (95% CI = 44.0% to 55.0%). These findings suggest reassessment and monitoring of the diagnostic utility of RATs for variants, especially for the sensitivity aspect, to facilitate appropriate diagnosis and management of COVID-19 patients.
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COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , Humanos , Pandemias , Sistemas de Atención de Punto , SARS-CoV-2/genética , Sensibilidad y EspecificidadRESUMEN
PROBLEM: To identify potential proteins in the amniotic fluid (AF) that may be associated with histologic chorioamnionitis (HCA) in patients with preterm premature rupture of membranes (PPROM) using antibody-based microarray analysis. METHOD OF STUDY: This was a retrospective cohort study involving 100 singleton pregnant women with PPROM at 24-34 weeks who underwent amniocentesis and delivered within 120 h of amniocentesis. First, the AF proteomes of 15 patients with PPROM and HCA were compared with those of 15 gestational age-matched patients without HCA using a protein microarray. Next, 12 candidate proteins associated with HCA were further validated in 100 consecutive patients with PPROM by ELISA. RESULTS: Of 507 proteins assessed in the microarray analysis, 46 showed significant intergroup differences. Further quantification confirmed that the levels of EN-RAGE, IL-6, MMP-9, TNFR2, SPARC, TSP2, and uPA were higher in the AF of PPROM patients with HCA than in those without. Multivariate analyses also showed that elevated AF EN-RAGE, IL-6, MMP-9, and TNFR2 levels were independently associated with HCA when adjusted for baseline variables. The frequency of the highest quartile of the aforementioned proteins significantly increased as the total grade of HCA increased; the risk of HCA significantly increased with increasing AF levels of each protein (P for trend < .001). CONCLUSIONS: Using protein-antibody microarray technology, we discovered several potential AF proteins (EN-RAGE, IL-6, MMP-9, and TNFR2) independently associated with HCA in patients with PPROM. Furthermore, we demonstrated a direct correlation between the gradation of the intra-amniotic inflammatory response and HCA severity.
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Corioamnionitis , Rotura Prematura de Membranas Fetales , Líquido Amniótico/metabolismo , Corioamnionitis/metabolismo , Femenino , Humanos , Recién Nacido , Interleucina-6/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Análisis por Micromatrices , Embarazo , Receptores Tipo II del Factor de Necrosis Tumoral/metabolismo , Estudios RetrospectivosRESUMEN
Background: Adoptive cell therapy using umbilical cord blood (UCB)-derived allogeneic natural killer (NK) cells has shown encouraging results. However, because of the insufficient availability of NK cells and limited UCB volume, more effective culture methods are required. NK cell expansion and functionality are largely affected by the culture medium. While human serum is a major affecting component in culture media, the way it regulates NK cell functionality remains elusive. We elucidated the effects of different culture media and human serum supplementation on UCB NK cell expansion and functionality. Methods: UCB NK cells were cultured under stimulation with K562-OX40L-mbIL-18/21 feeder cells and IL-2 and IL-15 in serum-containing and serum-free culture media. The effects of the culture media and human serum supplementation on NK cell expansion and cytotoxicity were evaluated by analyzing the expansion rate, activating and inhibitory receptor levels, and the cytotoxicity of the UCB NK cells. Results: The optimal medium for NK cell expansion was Dulbecco's modified Eagle's medium/Ham's F12 with supplements and that for cytotoxicity was AIM V supplemented with Immune Cell Serum Replacement. Shifting media is an advantageous strategy for obtaining several highly functional UCB NK cells. Live cell imaging and killing time measurement revealed that human serum enhanced NK cell proliferation but delayed target recognition, resulting in reduced cytotoxicity. Conclusions: Culture medium supplementation with human serum strongly affects UCB NK cell expansion and functionality. Thus, culture media should be carefully selected to ensure both NK cell quantity and quality for adoptive cell therapy.
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Células Asesinas Naturales , Proliferación Celular , Medios de Cultivo/farmacología , HumanosRESUMEN
Despite strict guidelines for coronavirus disease 2019 (COVID-19), South Korea is facing its fourth pandemic wave. In this study, by using an automated electrochemiluminescence immunoassay assay, we tracked anti-spike protein receptor-binding domain (anti-S-RBD) antibody titer from the second dose to 2 weeks after the booster dose vaccination. After the second dose, 234 participants had their anti-S-RBD antibody titers decrease over time. We also showed the booster dose (the third dose) increased antibody titer by average 14 (min-max, 2-255)-fold higher compared to the second dose among the 211-booster group participants, therefore, the booster dose could be recommended for low responders to the second dose. Our findings showed a distinct humoral response after booster doses of BNT162b2 mRNA vaccines and may provide further evidence of booster vaccination efficacy. These data will also be helpful in vaccination policy decisions that determine the need for the booster dose.
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COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , Formación de Anticuerpos , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19 , Personal de Salud , Humanos , Vacunas Sintéticas , Vacunas de ARNmRESUMEN
BACKGROUND: There have been reports of increases in the incidence and prevalence of nontuberculous mycobacterial pulmonary disease (NTM-PD) in several countries, but no studies have analyzed claims data using laboratory tests. This study aimed to estimate the nationwide epidemiology and medical treatments of NTM-PD according to laboratory tests run in Korea. METHODS: Using claims data from the Health Insurance Review and Assessment Service, we analyzed patients with nontuberculous mycobacterium (ICD-10: A31) who were diagnosed from Jan 2007 to Jun 2019. The incidence and prevalence of NTM-PD and whether related laboratory tests were performed were analyzed. Diagnostic code-based NTM-PD patients were defined as patients who had NTM as a diagnosis on at least 2 occasions within 180 days. Clinically refined NTM-PD patients were defined as those excluding hospital-diagnosed patients with acid-fast bacilli (AFB) culture rates less than 5%. Laboratory tests included AFB smears, AFB culture, NTM identification, and drug susceptibility tests (DSTs). RESULTS: A total of 60,071 diagnostic code-based NTM-PD patients were evaluated. Clinically refined NTM-PD included 45,321 patients, excluding 14,750 (24.6%) patients diagnosed in hospitals with low AFB culture rates. The annual incidence per 100,000 population increased from 2.9 cases in 2008 to 12.3 cases in 2018. The annual prevalence per 100,000 population increased from 5.3 cases in 2008 to 41.7 cases in 2018. After removing outliers according to the AFB culture rate, a significant decrease in incidence was observed in women younger than 50 years. Among patients with clinically refined NTM-PD, the test rates for AFB culture, NTM identification, and DST were 84.3%, 59.1%, and 40.4%, respectively. From the outpatient clinic, 17,977 (39.7%) patients were prescribed drugs related to NTM treatment, with a median number of prescriptions of 7 (interquartile range (IQR) 3-11) and a median duration from the diagnosis to end of treatment of 330 (IQR 118-578) days. CONCLUSIONS: Although the incidence and prevalence of NTM-PD are on the rise, the recent surge in women 50 years of age is overestimated in patients not adequately tested. In claim-based studies, there may be limitations in estimating the epidemiological data with only the diagnostic codes.
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Enfermedades Pulmonares , Infecciones por Mycobacterium no Tuberculosas , Femenino , Humanos , Pulmón , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/microbiología , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Micobacterias no Tuberculosas , República de Corea/epidemiología , Estudios RetrospectivosRESUMEN
ABSTRACT: Medical care should be equally provided to the public regardless of their financial capability. In the real world, expenditures directly out from the patient sector decide the medical journey, even in a country with national health insurance. The aim of this study was to investigate whether there are differences in the diagnostic and treatment processes in hematologic malignancies based on patient characteristics, such as health insurance status.Through the review of 5614 "CBCs with differential count" results with abnormal cells from 358 patients from January 2010 to June 2017, 238 patients without past medical histories of hematologic malignancies were enrolled. Excluding reactive cases, 206 patients with hematologic malignancy were classified into 8 disease categories: acute leukemia, myelodysplastic syndrome, myeloproliferative neoplasm (MPN), myelodysplastic syndrome/MPN, lymphoid neoplasm, plasma cell neoplasm, r/o hematologic malignancy, and cancer.The patients' age, sex, disease categories and follow-up durations showed associations with the clinical course. The "refusal of treatment" group was the oldest and had a relatively higher percentage of females, whereas those who decided to transfer to a tertiary hospital were younger. The age, clinical course, and follow-up durations were different across health insurance statuses. The medical aid group was the oldest, and the group whose status changed from a medical insurance subscriber to a medical aid beneficiary during treatment was the youngest. The majority of patients who refused treatment or wished to be transferred to a tertiary hospital were medical insurance subscribers. The percentage of patients who were treated in this secondary municipal hospital was higher in the medical-aid beneficiaries group than in the medical insurance group. Follow-up durations were longest in the status change group and shortest in the medical insurance group.Almost all medical aid beneficiaries with hematologic malignancies opted to continue treatment at this secondary/municipal hospitals, indicating that this category of medical institutions provides adequate levels and qualified healthcare services to those patients. The secondary municipal hospital provides qualified healthcare services for medical aid beneficiaries with hematologic malignancies.