Han-Ik Cho

Correlation between plasma activity of ADAMTS-13 and coagulopathy, and prognosis in disseminated intravascular coagulation

INTRODUCTION In disseminated intravascular coagulation (DIC), widespread activation of intravascular coagulation accompanied with florid endothelial activation results in release of unusually large von Willebrand factor (ULvWF) from endothelium. Circulating a disintegrin-like and metalloprotease with thrombospondin type 1 repeats (ADAMTS)-13 may be consumed through the ongoing cleavage of ULvWF, resulting in a secondary deficiency of ADAMTS-13 in DIC. We determined whether ADAMTS-13 activity showed a significant correlation with the activation status of the coagulation system and hospital mortality in DIC. MATERIALS AND METHODS ADAMTS-13 activity was assayed by fluorescence resonance energy transfer assay in 97 patients who were clinically suspected to have DIC. RESULTS ADAMTS-13 activity gradually decreased based on the DIC score and D-dimer levels and was correlated with the antithrombin level, representing the consumption of ADAMTS-13 during the ongoing coagulation process. There were no correlation between ADAMTS-13 activity and neutrophil CD64 expression as a neutrophil activation marker and circulating IL-6 level as an inflammatory marker. Patients with a low activity of ADAMTS-13 (< or = 56.4%) had a poor survival rate compared to patients with a high activity of ADAMTS-13. CONCLUSIONS We conclude that ADAMTS-13 activity is strongly correlated with the severity of coagulopathy and hospital mortality. ADAMTS-13 may serve as a diagnostic and prognostic marker of DIC.

Erythrocyte Sedimentation Rate Measurements by TEST 1 Better Reflect Inflammation Than Do Those by the Westergren Method in Patients With Malignancy, Autoimmune Disease, or Infection

We compared the TEST 1 (Alifax, Padova, Italy) and Westergren methods of measuring the erythrocyte sedimentation rate (ESR) to assess inflammation. The ESR was measured by both methods in 154 blood samples from patients with malignancy (n = 69), autoimmune disease (n = 44), or infection (n = 41). Total protein, albumin, and C-reactive protein (CRP) levels were measured in each plasma sample, and albumin and alpha(1)-, alpha(2)-, beta(1)-, beta(2)-, and gamma-globulin fractions were measured by capillary electrophoresis. TEST 1 ESR values were significantly lower than the Westergren values, by 10.9 mm/h. We found that the correlations of TEST 1 ESR values with inflammatory protein levels (total protein, globulin, CRP, and alpha(1)-, alpha(2)-, beta(2)-, and gamma-globulin) were better than those obtained using the Westergren method. These findings indicate that ESR measurements by TEST 1 reflect inflammation better than do those by the Westergren method in patients with malignancy, autoimmune disease, or infection.

Prognostic values of the factor Xa-activated clotting time and endogenous thrombin potential in patients suspected of having disseminated intravascular coagulation.

BACKGROUND Widespread coagulation activation and intravascular fibrin formation are clinical features of disseminated intravascular coagulation (DIC). The endogenous thrombin potential (ETP) has been shown to be a useful marker for hypo- or hypercoagulability. The factor Xa-activated clotting time (XACT) represents plasma levels of procoagulant phospholipids. We investigated whether the ETP and XACT would be good prognostic markers in patients suspected of having DIC and whether these markers would show a significant correlation with the thrombin-antithrombin complex (TAT), a marker of in vivo coagulation activation. METHODS One hundred twenty-nine patients suspected of having DIC were enrolled for the study. The TAT was measured by ELISA. The ETP and XACT were measured by calibrated automated thrombinography. The 28-day mortality was used as a predictor of clinical outcomes. RESULTS In overt DIC, higher XACT (9.67 vs. 7.33 min) and higher TAT (26.15 vs. 11.56 ng/ml) results were obtained from the nonsurvivors than from the survivors. ETP levels were lower in the overt DIC group than in the no overt DIC group. In receiver operating characteristic analysis, which was conducted to predict the 28-day mortality, the areas under the receiver operating characteristic analysis curve were as follows: 0.71 (95% CI: 0.62-0.78) for the XACT, 0.70 (0.61-0.77) for the TAT, and 0.64 (0.55-0.72) for the ETP. For the diagnosis of overt DIC, the area under the curve of XACT, TAT and ETP were 0.77 (0.69-0.84), 0.64 (0.55-0.72) and 0.73 (0.64-0.80), respectively. The odds ratio of the XACT for the relative risk of 28-day mortality was 9.60 (3.53-26.11), and that of the TAT was 5.18 (2.11-12.72) and that of the ETP 7.66 (1.67-35.17). For the diagnosis of overt DIC, the odds ratio of XACT, TAT and ETP were 37.35 (4.86-286.89), 4.89 (1.93-12.43) and 4.89 (1.98-12.09), respectively. There was a negative correlation between the TAT and ETP (r=-0.223, P=0.012) and a positive correlation between the TAT and XACT (r=0.251, P=0.004). CONCLUSION Our results suggest that the XACT and ETP may be useful diagnostic and prognostic markers for the DIC. Among various markers, the XACT serves as a good prediction of the 28-day mortality in patients suspected of having DIC.

Utility of the Fibrinogen/C-Reactive Protein Ratio for the Diagnosis of Disseminated Intravascular Coagulation

Although the presence of decreased plasma fibrinogen has been regarded as an indicator of ongoing disseminated intravascular coagulation (DIC), fibrinogen, which is one of the acute phase reactants, is often increased in the patients with DIC. We investigated the diagnostic and prognostic utility of a new parameter [the fibrinogen/C-reactive protein (CRP) ratio] for predicting DIC in 1,056 patients with suspected DIC and who also had underlying disorders associated with DIC. Among the 535 patients with overt DIC, 46 patients (8.6%) showed low plasma fibrinogen (<100 mg/dl), suggesting that the plasma fibrinogen level is not a sensitive marker for DIC. There was a strong correlation between the increased DIC scores and increased number of patients with low (<104) fibrinogen/CRP ratios. Among the three groups with different serum fibrinogen/fibrin degradation product levels, the fibrinogen/CRP ratio showed a higher difference than did the fibrinogen level. The DIC score was highly correlated with the 28-day mortality and the number of patients with low fibrinogen/CRP ratios. The odds ratio (the relative risk of 28-day mortality) of the low fibrinogen/CRP ratio was 6.15, while the odds ratio of the low fibrinogen level was 2.13. The area under the receiver-operating characteristic curve of the fibrinogen/CRP ratio, when this was used for predicting mortality, showed significantly better discriminative power than did that of the fibrinogen level. This study demonstrates that the fibrinogen/CRP ratio may provide more discriminating power for identifying the patients with active coagulation consumption, and the fibrinogen/CRP ratio has a good predictive value concerning the 28-day mortality in the patients suspected of having DIC. The results of our study suggest that replacement of fibrinogen by the fibrinogen/CRP ratio for calculating the DIC score may lead to enhance diagnostic and prognostic power for DIC.

Protective Role of CYP1A1*2A in the Development of Multiple Myeloma

We had previously reported the association of the NQO1*2/*2 polymorphism with a decreased risk for multiple myeloma (MM) in Koreans (odds ratio, OR, 0.24; 95% confidence interval, CI, 0.01–0.68). The associations of polymorphisms of other metabolizing enzymes (CYP1A1, GSTM1 and GSTT1) with the MM risk were investigated in 116 Korean MM patients and 176 Korean controls using TaqMan allelic discrimination and multiplex polymerase chain reaction. The ORs for CYP1A1*1/*2A and CYP1A1*1/*2B genotypes were 0.43 (95% CI, 0.19–0.98) and 0.51 (95% CI, 0.26–0.98), respectively, which was significantly associated with a decreased MM risk. With regard to CYP1A1 alleles, the OR for the CYP1A1*2A allele was 0.57 (95% CI, 0.326–0.995), which was also significantly associated with a decreased MM risk. However, null types of GSTM1 and GSTT1 polymorphisms were not associated with the MM risk. These results were different from those of a previous report on Caucasians which suggested the association of the GSTT1 polymorphism with an increased MM risk and no association of CYP1A1 with the MM risk. The associations of polymorphisms of metabolizing enzymes with the risk for MM differed between Koreans and Caucasians, suggesting an ethnic variation in the susceptibility to MM.

Improvements in the Metabolic Syndrome and Stages of Change for Lifestyle Behaviors in Korean Older Adults

Objectives This study aims to examine the effectiveness of a 6-month lifestyle modification program on the improvement in metabolic syndrome (MetS) status and in stages of change for lifestyle behaviors associated with MetS among Korean older adults. Methods A lifestyle modification program was developed based on the transtheoretical model. The program consisted of health counseling, education classes, a self-management handbook, newsletters and a health diary. Older adults aged ≥60 (n = 480) with MetS were randomly assigned to the intervention group (IG) or the comparison group (CG). The IG received a comprehensive 6-month lifestyle modification intervention, while the CG received minimal information on MetS and lifestyle modification. Health examination and selfadministered survey were conducted before and after the intervention to determine the effectiveness of the program. Results After the intervention, the prevalence of MetS decreased to 38.1% in the IG and 52.4% in the CG (p = 0.046). The IG improved abdominal obesity (p = 0.016), blood pressure (p = 0.030), and triglyceride (p = 0.005) more than the CG did. The IG demonstrated significant improvements in the behavioral stages for portion control (p = 0.021), balanced diet (p < 0.001) and adequate intake of fruits and vegetables (p = 0.012). The IG reduced the prevalence of abdominal obesity (OR = 2.34) and improved MetS status (OR = 1.79) better than the CG. The IG were more likely to advance from preaction stages at baseline to action stage at post-intervention for portion control (OR = 3.29) and adequate intake of fruits and vegetables (OR = 2.06). Conclusion Lifestyle modification can improve the MetS status and behavioral stages in older adults.

Prognostic value of immature platelet fraction and plasma thrombopoietin in disseminated intravascular coagulation.

Although platelet count is a good parameter for the diagnosis of disseminated intravascular coagulation (DIC), a single measurement of platelet is not enough to reflect the ongoing platelet consumption because of compensatory synthesis of circulating platelet number. Increased thrombopoiesis owing to peripheral destruction is expected in patients with DIC. Reticulated platelet, measured as immature platelet fraction (IPF), and plasma thrombopoietin (TPO) are markers of platelet production. We investigated the potential usefulness of circulating IPF and TPO in 222 patients suspected of having DIC. Both IPF and TPO levels were significantly increased in overt DIC patients and well correlated with DIC score. IPF also correlated with fibrin-related marker such as fibrinogen degradation product and D-dimer. Both IPF and TPO showed better mortality prediction than platelet count with the multivariate logistic regression and Kaplan–Meier survival analysis. These results suggest that IPF and TPO are new potential candidates to detect the severity of DIC and to predict DIC mortality.

Heterogeneity in Obesity Status and Cardiovascular Risks in Multiethnic Asian Female Immigrants in South Korea

The present study investigated the prevalence of obesity and the associated health conditions of multiethnic Asian female immigrants in Korea. Data were collected from 2246 immigrant wives in 7 largest ethnic groups in a national health examination program. The mean body mass index was 21.9 ± 3.3 kg/m2. Prevalence of obesity (body mass index ≥25 kg/m2) among immigrant women was 15.4%. Age-adjusted prevalence of obesity varied among groups by native country (from 10.4% for Japanese to 36.3% for Thai women). The likelihood of obesity significantly increased with years of residence in Korea (odds ratio [OR] = 1.44 for 5.0-9.9 years; 1.85 for ≥10 years), physical inactivity (OR = 1.84), and eating spicy and/or salty food (OR = 1.45). Prevalence of chronic health conditions also differed by country of origin. Significant associations were observed between obesity and elevated blood pressure (OR = 1.87), obesity and elevated cholesterol level (OR = 2.83), and obesity and prediabetes/diabetes (OR = 2.44) after adjusting for age, country of origin, and years of residence in Korea.

Efficacy and tolerability of mirtazapine in treating major depressive disorder with anxiety symptoms: an 8-week open-label randomised paroxetine-controlled trial

Aims:  Prominent anxiety symptoms are related to poor clinical course and outcome in major depressive disorder (MDD). The aim of this randomised, open‐label, controlled study is to compare the efficacy and tolerability of mirtazapine in the form of orally disintegrating tablets against paroxetine in treating MDD patients with anxiety symptoms.

Native ETV6 deletions accompanied by ETV6-RUNX1 rearrangements are associated with a favourable prognosis in childhood acute lymphoblastic leukaemia: a candidate for prognostic marker

Junzo Nojima Yukari Motoki Hidehiro Tsuneoka Hirohiko Kuratsune Tomohiro Matsui Misa Yamamoto Masashi Yanagihara Yuji Hinoda Kiyoshi Ichihara Department of Laboratory Science, Faculty of Health Science, Yamaguchi University Graduate School of Medicine, Yamaguchi, Department of Health Science, Faculty of Health Science for Welfare, Kansai University of Welfare Science, Kashihara, Osaka, and Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan E-mail: nojima-j@yamaguchi-u.ac.jp