• Korean Journal of Clinical Laboratory Science
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• v.52 no.3
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• pp.172-180
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• 2020

This study investigated retrospectively the correlation between the results of the N-terminal pro-brain natriuretic peptide (NT-proBNP) and a routine blood test using a hospital information system. The NT-proBNP is involved in the pathophysiology of heart failure. The results show that the relationship between age and NT-proBNP was significant (P<0.01) with a positive correlation (r=0.163). The peptide concentration showed a negative correlation between the total protein (r=-0.250) and albumin (r=-0.270), and a negative correlation between the erythrocyte count and hemoglobin and hematocrit (P<0.01). NT-proBNP had a positive correlation with neutrophils (r=0.227) and a negative correlation with lymphocytes (r=-0.236), showing significant results (P<0.01). NT-proBNP and creatinine showed a positive correlation (r=0.594, P<0.01), and it was the most influential factor according to multiple regression analysis (B=0.53, t=7.65). P<0.01). The concentrations of NT-proBNP and uric acid showed a positive correlation (r=0.180, P<0.05). Lactate dehydrogenase was observed as a factor affecting the NT-proBNP (B=0.20, t=3.28, P<0.01). This explanatory power had an influence of 43%. Therefore, the accurate test and related factors of the NT-proBNP have significant clinical value.

• Clinical and Experimental Pediatrics
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• v.61 no.5
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• pp.167-173
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• 2018

Purpose: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome with many causes, including Kawasaki disease (KD). The purpose of this study was to identify the laboratory tests needed to easily differentiate KD with HLH from incomplete KD alone. Methods: We performed a retrospective study on patients diagnosed with incomplete KD and incomplete KD with HLH (HLH-KD) between January 2012 and March 2015. We compared 8 secondary HLH patients who were first diagnosed with incomplete KD with all 247 incomplete KD diagnosed patients during the study period. The complete blood count, erythrocyte sedimentation rate, platelet count, and serum total protein, albumin, triglyceride, C-reactive protein, N-terminal pro-brain natriuretic peptide (NT-proBNP), and ferritin levels were compared. Clinical characteristics and echocardiography findings were also compared between the 2 groups. Results: The total duration of fever was longer in the HLH-KD group than in the KD group. White blood cell and platelet counts were higher in the KD group. Alanine aminotransferase, ferritin, and coronary artery diameter were increased in the HLH-KD group compared with those in the KD group. The median of NT-proBNP was significantly higher in the HLH-KD group than in the KD group at 889.0 (interquartile range [IQR], 384.5-1792.0) pg/mL vs. 233.0 (IQR, 107.0-544.0) pg/mL. Conclusion: The NT-proBNP level may be helpful in distinguishing incomplete KD from KD with HLH. The NT-proBNP level should be determined in KD patients with prolonged fever, in addition to the white blood cell count, platelet count, and ferritin level, to evaluate secondary HLH.

• Clinical and Experimental Pediatrics
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• v.61 no.1
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• pp.12-16
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• 2018

Purpose: To differentiate adenoviral pharyngoconjunctival fever (PCF) from acute Kawasaki disease (KD) using laboratory tests before results of virus-real time polymerase chain reaction and ophthalmologic examination are obtained. Methods: Baseline patient characteristics and laboratory measurements were compared between 40 patients with adenovirus infection and 123 patients with KD. Results: The patients with adenovirus infection were generally older than those with KD (median: 3.9 years vs. 2 years, P=0.000). White blood cell and, platelet count, and aspartate aminotransferase, alanine aminotransferase, and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels showed significant differences between the 2 groups, but the C-reactive protein (CRP) levels did not ($6.8{\pm}3.0mg/dL$ vs. $8.3{\pm}5.8mg/dL$, P=0.126). In the adenovirus infection group, the CRP levels were <1, <3, <10, and ${\geq}10mg/dL$ in 2 (5%), 3 (7.5%), 30 (75%), and 5 patients (12.5%), respectively. The cutoff NT-proBNP level was 265 pg/mL. Discrepancy was defined as CRP and NT-proBNP levels of ${\geq}3$ or <3 mg/dL, and <265 or ${\geq}265pg/mL$, respectively. Among the 35 patients with adenovirus infection whose CRP levels were ${\geq}3mg/dL$, 29 (82.9%) showed a discrepancy. Conversely, of the 103 patients with KD whose CRP levels were ${\geq}3mg/dL$, 83 (80.6%) showed no discrepancy. Between the groups, a significant difference in discrepancy rate was observed (P=0.000). None of the patients with adenovirus infection had CRP and NT-proBNP levels of <3 mg/dL and ${\geq}265pg/mL$, respectively. Conclusion: With a sensitivity of 82.9% and a specificity of 80.6%, CRP and NT-proBNP levels may differentiate between adenoviral PCF and acute KD.

• Clinical and Experimental Pediatrics
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• v.59 no.12
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• pp.477-482
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• 2016

Purpose: We conducted a study to determine which factors may be useful as predictive markers in identifying Kawasaki disease (KD) patients with a high risk of resistance to intravenous immunoglobulin (IVIG) and developing coronary artery lesions (CAL). Methods: We enrolled 287 patients in acute phase of KD at a single center. The demographic, clinical and laboratory data were collected retrospectively. Results: There were 34 patients in the IVIG resistant group. The IVIG resistant group had significantly higher serum N-terminal-pro-brain natriuretic protein (NT-proBNP) levels (P<0.01) and polymorphonuclear neutrophil (PMN) percentage (P<0.01) in comparison to the IVIG responders. The results yielded sensitivity (78.8%, 60.6%), specificity (58.2%, 90%) and cutoff value (628.6 pg/mL, 80.3%) of NT-proBNP and PMN respectively, in predicting IVIG resistance. Despite IVIG administration, 13 of the 287 patients developed CAL. The patients in the CAL group had higher NT-proBNP levels (P<0.01) and higher PMN percentage (P<0.01). In these patients, the results yielded sensitivity (73.3%, 56.7%), specificity (67.9%, 88.9%) and cutoff value (853.4 pg/mL, 80.3%) of NT-proBNP and PMN respectively, for predicting CAL. The area under the curve (AUC) for predicting resistance to IVIG was NT-proBNP 0.712, PMN 0.802. The AUC for predicting CAL was NT-proBNP 0.739, and PMN 0.773. Conclusion: Serum NT-proBNP levels and PMN percentage were significantly elevated in patients with KD with IVIG resistance and CAL. Thus, they may be useful predicting markers for IVIG resistance and development of CAL in KD patients.

• Clinical and Experimental Pediatrics
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• v.59 no.7
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• pp.298-302
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• 2016

Purpose: Recent reports showed that plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) could be a useful biomarker of intravenous immunoglobulin (IVIG) unresponsiveness and coronary artery lesion (CAL) development in Kawasaki disease (KD). The levels of these peptides are critically influenced by age; hence, the normal range and upper limits for infants and children are different. We performed an age-adjusted analysis of plasma NT-proBNP level to validate its clinical use in the diagnosis of KD. Methods: The data of 131 patients with KD were retrospectively analyzed. The patients were divided into 2 groups-group I (high NT-proBNP group) and group II (normal NT-proBNP group)-comprising patients with NT-proBNP concentrations higher and lower than the 95th percentile of the reference value, respectively. We compared the laboratory data, responsiveness to IVIG, and the risk of CAL in both groups. Results: Group I showed significantly higher white blood cell count, absolute neutrophil count, C-reactive protein level, aspartate aminotransferase level, and troponin-I level than group II (P<0.05). The risk of CAL was also significantly higher in group I (odds ratio, 5.78; P=0.012). IVIG unresponsiveness in group I was three times that in group II (odds ratio, 3.35; P= 0.005). Conclusion: Age-adjusted analysis of plasma NT-proBNP level could be helpful in predicting IVIG unresponsiveness and risk of CAL development in patients with KD.

• Journal of Chest Surgery
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• v.56 no.5
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• pp.295-303
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• 2023

Background: The use of Adriamycin (ADR), also known as doxorubicin, as a chemotherapy agent is limited by its detrimental adverse effects, especially cardiotoxicity. Recent studies have emphasized the crucial role of angiotensin II (Ang-II) in the development of ADR-induced cardiomyopathy. This study aimed to explore the potential cardioprotective effects of losartan in a rat model of ADR-induced cardiomyopathy. Methods: Male Sprague-Dawley rats were randomly divided into 3 groups: a control group (group C), an ADR-treated group (ADR 5 mg/kg/wk for 3 weeks via intraperitoneal injections; group A), and co-treatment of ADR with losartan group (same dose of ADR and losartan; 10 mg/kg/day per oral for 3 weeks; group L). Western blot analysis was conducted to demonstrate changes in brain natriuretic peptide, collagen 1, tumor necrosis factor (TNF)-α, interleukin-6, matrix metalloproteinase (MMP)-2, B-cell leukemia/lymphoma (Bcl)-2, Bcl-2-associated X (Bax), and caspase-3 protein expression levels in left ventricular (LV) tissues from each group. Results: Losartan administration reduced LV hypertrophy, collagen content, and the expression of pro-inflammatory factors TNF-α and MMP-2 in LV tissue. In addition, losartan led to a decrease in the expression of the pro-apoptotic proteins Bax and caspase-3 and an increase in the expression of the anti-apoptotic protein Bcl-2. Moreover, losartan treatment induced a reduction in the apoptotic area compared to group A. Conclusion: In an ADR-induced cardiomyopathy rat model, co-administration of ADR with losartan presented cardioprotective effects by attenuating LV hypertrophy, pro-inflammatory factors, and apoptosis in LV tissue.

• Clinical and Experimental Pediatrics
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• v.58 no.10
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• pp.374-379
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• 2015

Purpose: Incomplete Kawasaki disease (KD) is frequently associated with delayed diagnosis and treatment. Delayed diagnosis leads to increasing risk of coronary artery aneurysm. Anterior uveitis is an important ocular signs of KD. The purpose of this study was to assess differences in laboratory findings, including echocardiographic measurements, clinical characteristics such as fever duration and treatment responses between KD patients with and those without uveitis. Methods: We conducted a prospective study with 110 KD patients from January 2008 to June 2013. The study group (n=32, KD with uveitis) was compared with the control group (n=78, KD without uveitis). Laboratory data were obtained from each patient including complete blood count (CBC), erythrocyte sedimentation rate (ESR), platelet count, and level of alanine aminotransferase, aspartate aminotransferase, serum total protein, albumin, C-reactive protein (CRP), and N-terminal probrain natriuretic peptide (NT-pro BNP). Echocardiographic measurements and intravenous immunoglobulin responses were compared between the two groups. Results: The incidence of uveitis was 29.0%. Neutrophil counts and patient age were higher in the uveitis group than in the control group. ESR and CRP level were slightly increased in the uveitis group compared with the control group, but the difference between the two groups was not significant. No significant differences in coronary arterial complication and treatment responses were observed between the two groups. Conclusion: Uveitis is an important ocular sign in the diagnosis of incomplete KD. It is significantly associated with patient age and neutrophil count.

• Clinical and Experimental Pediatrics
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• v.59 no.2
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• pp.80-90
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• 2016

Purpose: Studies have been conducted to identify predictive factors of resistance to intravenous immunoglobulin (IVIG) for Kawasaki disease (KD). However, the results are conflicting. This study aimed to identify laboratory factors predictive of resistance to high-dose IVIG for KD by performing meta-analysis of available studies using statistical techniques. Methods: All relevant scientific publications from 2006 to 2014 were identified through PubMed searches. For studies in English on KD and IVIG resistance, predictive factors were included. A meta-analysis was performed that calculated the effect size of various laboratory parameters as predictive factors for IVIG-resistant KD. Results: Twelve studies comprising 2,745 patients were included. Meta-analysis demonstrated significant effect sizes for several laboratory parameters: polymorphonuclear leukocytes (PMNs) 0.698 (95% confidence interval [CI], 0.469-0.926), C-reactive protein (CRP) 0.375 (95% CI, 0.086-0.663), pro-brain natriuretic peptide (pro-BNP) 0.561 (95% CI, 0.261-0.861), total bilirubin 0.859 (95% CI, 0.582-1.136), alanine aminotransferase (AST) 0.503 (95% CI, 0.313-0.693), aspartate aminotransferase (ALT) 0.436 (95% CI, 0.275-0.597), albumin 0.427 (95% CI, -0.657 to -0.198), and sodium 0.604 (95% CI, -0.839 to -0.370). Particularly, total bilirubin, PMN, sodium, pro-BNP, and AST, in descending numerical order, demonstrated more than a medium effect size. Conclusion: Based on the results of this study, laboratory predictive factors for IVIG-resistant KD included higher total bilirubin, PMN, pro-BNP, AST, ALT, and CRP, and lower sodium and albumin. The presence of several of these predictive factors should alert clinicians to the increased likelihood that the patient may not respond adequately to initial IVIG therapy.

• Clinical and Experimental Pediatrics
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• v.56 no.12
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• pp.519-522
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• 2013

Timely diagnosis of hyponatremia is important for preventing potential morbidity and mortality as it is often an indicator of underlying disease. The most common cause of eurvolemic hyponatremia is the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Recent studies have demonstrated that proinflammatory cytokines such as interleukin (IL) $1{\beta}$ and IL-6 are involved in the development of hyponatremia, a condition that is associated with severe inflammation and is related to antidiuretic hormone (ADH) secretion. Serum sodium levels in hyponatremia are inversely correlated with the percentage of neutrophils, C-reactive protein, and N-terminal-pro brain type natriuretic peptide. Additionally, elevated levels of serum IL-6 and IL-$1{\beta}$ are found in inflammatory diseases, and their levels are higher in patients with hyponatremia. Because it is significantly correlated with the degree of inflammation in children, hyponatremia could be used as a diagnostic marker of pediatric inflammatory diseases. Based on available evidence, we hypothesize that hyponatremia may be associated with inflammatory diseases in general. Understanding the mechanisms responsible for augmented ADH secretion during inflammation, monitoring patient sodium levels, and selecting the appropriate intravenous fluid treatment are important components that may lower the morbidity and mortality of patients in a critical condition.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.4
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• pp.256-264
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• 2022

Ischemic stroke is caused by an occlusion by a thrombus or embolus in a cerebral artery, preventing oxygenated blood from reaching the brain and causing the necrosis of nerve cells. This paper summarizes the serum candidate markers associated with cardiovascular disease and atrial fibrillation (AF) disease that enable an early diagnosis of ischemic stroke studied thus far and compares the odds ratio (OR) of each marker. This study examined the effect size of these serum candidate markers using meta-analysis techniques. The academic database search screening for articles containing the keywords "cardiovascular disease," "atrial fibrillation," "ischemic stroke," and "serum marker" was limited to results for patients with ischemic stroke. The most derived markers in this study were N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), D-dimer, C-reactive protein (CRP), and glial fibrillary acidic protein (GFAP), the rest being investigated individually. In conclusion, NT-pro-BNP appears to be very useful for the early diagnosis of ischemic stroke. Primarily, it is a marker of AF, and more AF markers will be uncovered and studied in the future.