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INTRODUCTION: There are significant differences in the activated partial thromboplastin time (APTT) critical values reported in different studies, most of which does not make recommendations for any specific clear detection systems. The International Council for Standardization in Hematology (ICSH) recommends that APTT critical values be established based on the reagent type, coagulation factor sensitivity and heparin response. The objective of this study was to establish APTT critical values by using different reagents and based on single coagulation factor deficiencies. METHODS: The APTT values were determined in commercial endogenous coagulation factor-deficient plasma at concentrations of 1 IU/dL, 2 IU/dL, 5 IU/dL, 10 IU/dL, 20 IU/dL, and 30 IU/dL by using four assay systems. The retrospective collection of data from patients who lacked factor VIII (FVIII), FIX, or FXI alone was performed. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic accuracy of APTT for identifying patients with an endogenous coagulation factor activity < 5 IU/dL. RESULTS: The APTT values in the plasma samples with the same concentrations of endogenous coagulation factors were significantly different among the four assay systems (P < 0.001). The suggested critical values of APTT were 40.0 s for Sysmex CS5100 (Actin FSL), 58.0 s for Sysmex CS5100 (Actin), 51.8 s for STA-R Evolution (STA-PTTA), and 64.8 s for ACL TOP 700 (HemosIL SynthasIL). On the basis of the ROC curve, the optimal threshold values for APTT (STA-PTTA) were 55.8 s in patients with a simple deficiency of FVIII (sensitivity = 100%, specificity = 85.7%, area under the ROC curve (AUC) = 0.982), 54.3 s in patients with a simple deficiency of FIX (sensitivity = 100%, specificity = 92.9%, AUC = 0.986), and 71.7 s in patients with a simple deficiency of FXI (sensitivity = 100%, specificity = 94.1%, AUC = 0.992), which were closer (difference of 0.6-2.5 s) to the cutoff points for commercial plasma at equal factor levels. CONCLUSIONS: APTT critical values need to be established for different reagents based on the presence of a single coagulation factor deficiency.
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Factores de Coagulación Sanguínea , Humanos , Tiempo de Tromboplastina Parcial , Estudios Retrospectivos , Factores de Coagulación Sanguínea/análisis , Femenino , Masculino , Trastornos de las Proteínas de Coagulación/sangre , Trastornos de las Proteínas de Coagulación/diagnóstico , Curva ROC , Pruebas de Coagulación Sanguínea/métodos , Pruebas de Coagulación Sanguínea/normas , Indicadores y ReactivosAsunto(s)
Antineoplásicos/farmacología , Homólogo de la Proteína 1 Relacionada con la Autofagia/antagonistas & inhibidores , Homólogo de la Proteína 1 Relacionada con la Autofagia/genética , Autofagia/genética , Péptidos y Proteínas de Señalización Intracelular/antagonistas & inhibidores , Péptidos y Proteínas de Señalización Intracelular/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Animales , Autofagia/efectos de los fármacos , Bases de Datos Factuales , Modelos Animales de Enfermedad , Humanos , Leucemia Mieloide Aguda/patología , RatonesRESUMEN
Acute myeloid leukemia (AML) is an aggressive hematological malignancy that gradually develops resistance to current chemotherapy treatments. The available chemotherapy drugs show serious non-specific cytotoxicity to healthy normal cells, resulting in relapse and low survival rates. Natural small molecules with less toxicity and high selectivity for AML are urgently needed. In this study, we confirmed that pyridoxine (vitamin B6) selectively induces monocyte macrophages to undergo programmed cell death in two different modes: caspase-3-dependent apoptosis in U937 cells or GSDME-mediated pyroptosis in THP-1 cells. Further molecular analysis indicated that blocking the caspase pathway could switch the death to MLKL-dependent necroptosis and subsequent extensive inflammatory response. Pyridoxine also delayed the disease progression in a THP-1 leukemia mouse model. In addition, it induced the death of primary AML cells from AML patients by activating caspase-8/3. Overall, our results identify pyridoxine, a low-toxicity natural small molecule, as a potential therapeutic drug for AML treatment.
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Apoptosis/efectos de los fármacos , Leucemia Mieloide Aguda/tratamiento farmacológico , Macrófagos/efectos de los fármacos , Monocitos/efectos de los fármacos , Piridoxina/farmacología , Animales , Células Cultivadas , Humanos , Leucemia Mieloide Aguda/patología , Macrófagos/patología , Ratones , Ratones Endogámicos C57BL , Monocitos/patología , Oligopéptidos/farmacología , Piridoxina/uso terapéutico , Piroptosis/efectos de los fármacosRESUMEN
Breast cancer stem-like cells (BCSLCs) with a CD44+/CD24-/low phenotype initiate the invasion and metastasis of breast cancer. The expression of New York oesophageal squamous cell carcinoma 1 (NY-ESO-1), one of the most immunogenic cancer-testicular antigens, is largely restricted to cancer and germ cells/placental trophoblasts, with little to no expression in normal adult somatic cells. Currently, few studies have reported the expression or function of NY-ESO-1 in BCSLCs. In the present study, immunohistochemistry indicated enhanced expression levels of NY-ESO-1/CD44 (P<0.01) and decreased expression levels of CD24 (P<0.01) in metastatic breast cancer tissues (MBCT) compared with non-MBCT. Additionally, the co-localization of CD44, CD24 and NY-ESO-1 in tissue samples was determined using immunofluorescence analysis. The results revealed that the expression of NY-ESO-1/CD44/CD24 was associated with breast cancer metastasis. Moreover, Spearman's rank correlation analysis indicated that CD44/CD24 expression was significantly correlated with that of NY-ESO-1. In the present study, mammosphere culture, a valuable method of BCSLC enrichment, was used to enrich MCF-7 and SK-BR-3 BCSLCs; immunofluorescence, western blotting and flow cytometry demonstrated increased expression levels of NY-ESO-1 and CD44, and low expression levels of CD24 in BCSLCs. Furthermore, the cell migration and invasion assays verified that BCSLCs with an increased NY-ESO-1 expression level exhibited greater invasive and migratory capacity compared with parental breast cancer cells. In addition to previously reported findings from the Oncomine database, it was ascertained that CD44+/CD24-/low BCSLCs with an increased level of NY-ESO-1 expression initiated the invasion and metastasis of breast cancer; therefore, NY-ESO-1 may serve as a novel target for metastatic breast cancer immunotherapy.
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OBJECTIVE: To establish the reference value of high sensitive cardiac troponin T (hs-cTnT) and the efficiency of reference value in the diagnosis of chest pain. METHODS: Volunteers from eight independent communities in Chengdu,Sichuan were selected with detailed records of physical examination,electrocardiogram,ultrasound examination. The level of hs-cTnT for healthy volunteers was tested to determine ninety-ninth percentile references according to sex and ages. 2 249 patients with chest pain in the emergency department of Western China Hospital from July 2009 to July 2014 were enrolled to measure the efficiency of reference value for diagnosing acute myocardial infarction (AMI). RESULTS: There were 1 305 volunteers included finally. Among them,the mean hs-cTnT level of male was 4.3 (3.2-5.9) ng/L,which was significantly higher than that of female 3.0 (3.0-3.1) ng/L ( P<0.01) . The correlation coefficient between age and hs-cTnT level was 0.43 (male) and 0.29 (female),and the P-value was less than 0.01. The 99th percentile values of male were 10.8 ng/L,15.4 ng/L and 19.7 ng/L for <45 yr.,45-<60 yr. and ≥60 yr.,respectively. Those values of female were 4.6 ng/L,8.9 ng/L,18.8 ng/L,respectively. There was no difference in sensitivity and specificity between the value we figured out and manufactures provided (14.0 ng/L) for those<60 yr.. For the patients ≥60 yr.,the sensitivity and negative predictive value did not show diversity ( P>0.05) but the specificity and positive predictive value showed significant difference (male: 0.67 vs. 0.56 and 0.83 vs. 0.79, P<0.05;female:0.75 vs. 0.68 and 0.74 vs. 0.69, P<0.05). CONCLUSION: We recommends that the ninety-ninth percentile reference value of patients<60 yr. should be 14.0 ng/L,while 20.0 ng/L for those patients≥60 yr.
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Dolor en el Pecho/diagnóstico , Infarto del Miocardio/diagnóstico , Troponina T/sangre , Adulto , Biomarcadores/sangre , Dolor en el Pecho/sangre , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Valores de ReferenciaRESUMEN
CONTEXT: Cardiac troponins have become the gold standard for diagnosing acute myocardial infarction (AMI) in the general population; however, their diagnostic accuracy for hemodialysis (HD) patients presenting with chest pain or dyspnea is uncertain. OBJECTIVE: To examine the diagnostic accuracy of high-sensitivity cardiac troponin T (hs-cTnT) assay for AMI in HD patients. DESIGN: In this prospective study, we enrolled 670 consecutive stable HD patients presenting with chest pain or dyspnea on routine predialysis therapy in the nephrology department. Receiver operating characteristic (ROC) curves were used to examine the diagnostic accuracy of hs-cTnT levels at enrollment in HD patients presenting with chest pain or dyspnea, and the dynamic change in these levels after 3 hours. RESULTS: Acute myocardial infarction was the adjudicated final diagnosis in 12% of HD patients. Among patients with a final diagnosis other than AMI, 97% had a plasma hs-cTnT concentration above the 99th percentile. At the time of enrollment, the area under the ROC curve of hs-cTnT levels for diagnosis of AMI was 0.68 (95% confidence interval [CI], 0.62-0.74; P < .001) with a cutoff value of 107.7 ng/L; the relative change after 3 hours was 0.90 (95% CI, 0.82-0.96, P < .001) with a cutoff value of 24%, and the absolute change was 0.88 (95% CI, 0.82-0.94, P < .001) with a cutoff value of 32.6 ng/L. The prognostic value for 40-day mortality varied with the magnitude of elevation in hs-cTnT levels. CONCLUSIONS: Tracking the dynamic change in hs-cTnT levels during the short term significantly increased this measure's diagnostic accuracy for AMI in HD patients.
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Mediciones Luminiscentes/métodos , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Diálisis Renal/efectos adversos , Troponina T/sangre , Adulto , Anciano , Área Bajo la Curva , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etiología , Estudios Prospectivos , Curva ROC , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: In clinical work, patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) often have high-sensitivity cardiac troponin T (hs-cTnT) levels that surpass the 99th percentile of the normal reference population, a cutoff used to screen patients for acute myocardial infarction (AMI). However, a large proportion of these patients prove not to have AMI and are frequently misdiagnosed and overtreated. We analyzed whether the cutoff value of hs-cTnT for diagnosing AMI in AECOPD patients should be adjusted. METHODS: This was a prospective study of 873 consecutive patients with AECOPD who presented at the emergency department of West China Hospital of Sichuan University from January 2010 to December 2013. Conventional cardiac troponin (cTnT) was measured in patients' blood samples taken at presentation, and values were compared with their final diagnoses. RESULTS: Among patients with a final diagnosis other than AMI, 64.64% had a plasma hs-cTnT concentration above the 99th percentile of a normal reference population (14 ng/L). The median level of hs-cTnT in AECOPD patients without AMI was 16 ng/L. The area under the receiver-operating characteristic curve (AUC) of hs-cTnT for diagnosis of AMI was 0.92 (0.85 - 0.99, p < 0.001) with a cutoff value of 60.5 ng/L. CONCLUSIONS: The baseline levels of hs-cTnT were relatively high in AECOPD patients, and the optimal cutoff value of hs-cTnT for AMI diagnosis (60.5 ng/L) was also higher than that for non-AECOPD patients.
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Infarto del Miocardio/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Troponina T/sangre , Anciano , Área Bajo la Curva , Biomarcadores/sangre , China , Errores Diagnósticos , Progresión de la Enfermedad , Servicio de Urgencia en Hospital , Femenino , Humanos , Masculino , Infarto del Miocardio/sangre , Valor Predictivo de las Pruebas , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/sangre , Curva ROC , Valores de Referencia , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: The objective of this study was to examine the diagnostic accuracy of high-sensitivity cardiac troponin T (hs-cTnT) for acute myocardial infarction (AMI) in patients with renal insufficiency, since this population has a high incidence of non-AMI elevations of hs-cTnT. METHODS: In this prospective study, we enrolled 2249 consecutive patients presenting with chest pain in the emergency department (ED), of whom 19.5% had an estimated glomerular filtration rate (eGFR)cys of <60 mL·min-1 (1.73 m2)-1. Hs-cTnT levels were measured blindly at presentation. RESULTS: Of the patients, 1108 (49.3%) were diagnosed as having AMI [321 with non-ST segment elevation myocardial infarction (NSTEMI)]. In patients whose final diagnosis was not AMI, there was a low but significant correlation between hs-cTnT and renal function [eGFRcys, r=-0.43 (-0.48, -0.38), p<0.001; eGFRcreat, r=-0.33 (-0.38, -0.27), p<0.001]. The area under the curve of the receiver operating characteristic (AUC) for hs-cTnT to diagnose AMI was 0.93 in patients with eGFRcys levels of <30 mL·min-1 (1.73 m2)-1, and AUCs did not vary significantly according to eGFR categories. On the basis of the ROC curve, the optimal threshold value for hs-cTnT was 143.6 ng·L-1 to diagnose AMI in patients with eGFRcys of <30 mL·min-1 (1.73 m2)-1, with a sensitivity of 83% and a specificity of 91%; 54.1 ng·L-1 in patients with eGFRcys between 30 and 59 mL·min-1, with a sensitivity of 90% and a specificity of 87%; 30.0 ng·L-1 in patients with eGFRcys between 60 and 89 mL·min-1, with a sensitivity of 89% and a specificity of 85%; and 20.3 ng·L-1 in patients with eGFRcys ≥90 mL·min-1 (1.73 m2)-1, with a sensitivity of 92% and a specificity of 88%. The same observations were done for the diagnosis of NSTEMI. CONCLUSIONS: Using a higher hs-cTnT cut-off value based on eGFR level is necessary for accurate diagnosis of AMI or NSTEMI in patients with renal insufficiency.
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Infarto del Miocardio/complicaciones , Infarto del Miocardio/metabolismo , Insuficiencia Renal/complicaciones , Troponina T/metabolismo , Enfermedad Aguda , Adulto , Anciano , Femenino , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Infarto del Miocardio/fisiopatología , Miocardio/metabolismo , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Acute kidney injury (AKI) has been proposed as a leading cause of mortality for acute pancreatitis (AP) patients admitted to the intensive care unit (ICU). This study investigated the predictive value of procalcitonin (PCT) for AKI development and relevant prognosis in patients with AP, and compared PCT's predictive power with that of other inflammation-related variables. METHODS: Between January 2011 and March 2013, we enrolled 305 cases with acute pancreatitis admitted to ICU. Serum levels of PCT, serum amyloid A (SAA), interleukin-6 (IL-6), and C reactive protein (CRP) were determined on admission. Serum PCT was tested in patients who developed AKI on the day of AKI occurrence and on either day 28 after occurrence (for survivors) or on the day of death (for those who died within 28 days). RESULTS: Serum PCT levels were 100-fold higher in the AKI group than in the non-AKI group on the day of ICU admission (p<0.05). The area under the receiver-operating characteristic (ROC) curve of PCT for predicting AKI was 0.986, which was superior to SAA, CRP, and IL-6 (p<0.05). ROC analysis revealed all variables tested had lower predictive performance for AKI prognosis. The average serum PCT level on day 28 (2.67 (0.89, 7.99) ng/ml) was significantly (p<0.0001) lower than on the day of AKI occurrence (43.71 (19.24,65.69) ng/ml) in survivors, but the serum PCT level on death (63.73 (34.22,94.30) ng/ml) was higher than on the day of AKI occurrence (37.55 (18.70,74.12) ng/ml) in non-survivors, although there was no significant difference between the two days in the latter group (pâ=â0.1365). CONCLUSION: Serum PCT is superior to CRP, IL-6, and SAA for predicting the development of AKI in patients with AP, and also can be used for dynamic evaluation of AKI prognosis.