Detection of Subclinical Anthracyclines' Cardiotoxicity in Children with Solid Tumor.

BACKGROUND: Cardiotoxicity is one of the most serious chronic complications of anthracyclines therapy. Assessment of the left ventricular ejection fraction (LVEF) fails to detect subtle cardiac dysfunction of left ventricular (LV). This study aimed to detect and evaluate new parameters of subclinical anthracyclines' cardiotoxicity in children with solid tumor. METHODS: A detailed echocardiographic examination was performed in 36 children with hepatoblastoma or rhabdomyosarcoma after receiving anthracyclines' chemotherapy and 36 healthy controls from January 2015 to December 2016. The LVEF, ratio of early diastolic peak velocity of transmitral flow (E) and septal diastolic e' mitral annular peak velocity (e'), tricuspid annular plane systolic excursion (TAPSE), and LV global longitudinal strain (GLS) were evaluated using M-mode, tissue Doppler imaging (TDI), and two-dimensional speckle tracking echocardiography (2D-STE), respectively. Echocardiographic parameters were compared between patient group and healthy controls. All patients were divided into two subgroups based on their anthracyclines' cumulative dosage (<300 mg/m2 subgroup and ≥300 mg/m2 subgroup). RESULTS: All patients had no presentation of heart failure and LVEF within normal range (65.7 ± 5.1%). Compared with healthy controls, the mean E/e' increased significantly (7.9 ± 0.7 vs. 10.2 ± 3.5, t = 3.72, P < 0.01), mean TAPSE decreased significantly (17.2 ± 1.3 mm vs. 14.2 ± 3.0 mm, t = -4.03, P < 0.01), and mean LV GLS decreased significantly (-22.2% ± 1.9% vs. -17.9% ± 2.9%, t = -5.58, P < 0.01) in patient group. Compared with subgroup with anthracyclines' cumulative dosage < 300 mg/m2, mean LV GLS decreased significantly (-18.7 ± 2.7% vs. -16.5 ± 2.1%, t = 2.15, P = 0.04), the mean E/e' increased significantly (9.1 ± 1.5 vs. 11.5 ± 4.9, t = -2.17, P = 0.04), and mean TAPSE decreased significantly (14.2 ± 2.1 mm vs. 12.5 ± 2.2 mm, t = -2.82, P = 0.02) in subgroup with anthracyclines' cumulative dosage ≥300 mg/m2. CONCLUSIONS: LV GLS is helpful in the early detection of subclinical LV dysfunction using 2D-STE. E/e' and TAPSE are other sensitive parameters in detecting subclinical cardiac dysfunction of both ventricles by TDI. These parameters show significant change with different anthracyclines' cumulative dosage, so cumulative dosage should be controlled in clinical treatment.

Qing Re Liang Xue Decoction Alleviates Hypercoagulability in Kawasaki Disease.

Objective. Kawasaki disease (KD) is a multisystemic autoimmune vasculitis. Intravenous immunoglobulin (IVIG) is the first-line treatment for KD. It is unclear whether traditional Chinese medicine (TCM) has an effect on KD. We aimed to observe the clinical efficacy of TCM on acute KD via serum interleukin-33 (IL-33) and tumor necrosis factor alpha (TNF-α) measurements. Methods. Thirty-one KD patients were treated with Qing Re Liang Xue decoction and Western medicine (integrative medicine treatment group), while 28 KD patients were treated with Western medicine only (Western medicine treatment group). Thirty patients were included in a febrile group and 28 healthy children were included in the control group. Clinical characteristics and laboratory findings were gathered and compared. Serum IL-33 and TNF-α levels were measured by multiplex Luminex assay. Results. The platelet count in the integrative medicine treatment group was significantly lower than that in the Western medicine treatment group. The integrative medicine group had a shorter fever duration and lower IL-33 and TNF-α levels than those in the Western medicine group, but there were no significant differences between the two KD groups after treatment. Conclusion. Qing Re Liang Xue decoction improved the hypercoagulable state of KD patients. Potential myocardial protective effects require further research.

Salvianolic Acid B Down-regulates Matrix Metalloproteinase-9 Activity and Expression in Tumor Necrosis Factor-α-induced Human Coronary Artery Endothelial Cells.

BACKGROUND: Salvianolic acid B (Sal B) is a bioactive water-soluble compound of Salviae miltiorrhizae, a traditional herbal medicine that has been used clinically for the treatment of cardiovascular diseases. This study sought to evaluate the effect of Sal B on matrix metalloproteinase-9 (MMP-9) and on the underlying mechanisms in tumor necrosis factor-α± (TNF-α±)-activated human coronary artery endothelial cells (HCAECs), a cell model of Kawasaki disease. METHODS: HCAECs were pretreated with 1-10 αµmol/L of Sal B, and then stimulated by TNF-α± at different time points. The protein expression and activity of MMP-9 were determined by Western blot assay and gelatin zymogram assay, respectively. Nuclear factor-κB (NF-κB) activation was detected with immunofluorescence, electrophoretic mobility shift assay, and Western blot assay. Protein expression levels of mitogen-activated protein kinase (c-Jun N-terminal kinase [JNK], extra-cellular signal-regulated kinase [ERK], and p38) were determined by Western blot assay. RESULTS: After HCAECs were exposed to TNF-α±, 1-10 αµmol/L Sal B significantly inhibited TNF-α±-induced MMP-9 expression and activity. Furthermore, Sal B significantly decreased IκBα± phosphorylation and p65 nuclear translocation in HCAECs stimulated with TNF-α± for 30 min. In addition, Sal B decreased the phosphorylation of JNK and ERK1/2 proteins in cells treated with TNF-α± for 10 min. CONCLUSIONS: The data suggested that Sal B suppressed TNF-α±-induced MMP-9 expression and activity by blocking the activation of NF-κB, JNK, and ERK1/2 signaling pathways.

Endothelial progenitor cell transplantation ameliorates elastin breakdown in a Kawasaki disease mouse model.

BACKGROUND: Coronary artery damage from Kawasaki disease (KD) is closely linked to the dysfunction of endothelial progenitor cells (EPCs). The aim of the present study was to evaluate the therapeutic effect of EPCs transplantation in KD model. METHODS: Lactobacillus casei cell wall extract (LCWE)-induced KD model in C57BL/6 mice was established. The model mice were injected intravenously with bone marrow-derived in vitro expanded EPCs. Histological evaluation, number of circulating EPCs and the function of bone marrow EPCs were examined at day 56. RESULTS: Inflammation was found around the coronary artery of the model mice after 14 days, Elastin breakdown was observed after 56 days. CM-Dil labeled EPCs incorporated into vessel repairing foci was found. At day 56, the number of peripheral EPCs in the KD model group was lower than in EPCs transplanted and control group. The functional index of bone marrow EPCs from the KD model group decreased in proliferation, adhesion and migration. Increased number of circulating EPCs and improved function were observed on the EPCs transplanted group compared with model group. CONCLUSION: Exogenously administered EPCs, which represent a novel strategy could prevent the dysfunction of EPCs, accelerate the repair of coronary artery endothelium lesion and decrease the occurrence of aneurysm.

[Diagnosis of unexplained syncope in children: a multi-center study].

OBJECTIVE: To examine the diagnostic value of head-up tilt test in children with unexplained syncope (UPS). METHODS: A total of 379 children (171 males, 208 females) aged 3-18 years, mean age (12 +/- 3) years with unexplained syncope from Beijing, Hunan, Hubei and Shanghai and undergoing baseline head-up tilt tests (BHUTT) or head-up tilt tests potentiated with nitroglycerine (SNHUTT) under a quiet circumstance were selected as the syncope group. Ten healthy children (5 males, 5 females) aged 9-15 years with a mean age of (11.4 +/- 2.1) years, were recruited as the control group. SPSS 10.0 software was used for data analysis. RESULTS: In 379 children with unexplained syncope, 67 (17.7%) were of postural orthostatic tachycardia syndrome (POTS), 157 (41.4%) of vasovagal syncope vasoinhibitory pattern, 14 (3.7%) of vasovagal syncope cardioinhibitory pattern, 47 (12.4%) of vasovagal syncope mixed pattern, 1 (0.3%) of orthostatic hypotension (OH) and 93 children (24.5%) of UPS. In syncope group and control group, the positive rate of BHUTT was 55.9% and 0 respectively and it was 75.5% and 20.0% respectively for SNHUTT. During BHUTT, the mean time of positive response occurrence was (16 +/- 12) minutes, and the posture when positive response appeared was at a tilt angle of 60 degrees. For SNHUTT, the mean time of positive response occurrence was (6 +/- 4) minutes and the posture was at a tilt angle of 60 degrees when potentiated with nitroglycerine. CONCLUSION: HUTT is an objective diagnostic tool of UPS. With a high diagnostic positive rate, SNHUTT can improve the diagnostic positive rate of BHUTT. Meanwhile the time of positive response occurrence during SNHUTT is markedly shorter than BHUTT.

Comparison between transcatheter and surgical closure of secundum atrial septal defect in children and adults: results of a multicenter nonrandomized trial.

OBJECTIVES: This study sought to compare the safety, efficacy and clinical utility of the Amplatzer septal occluder (ASO) for closure of secundum atrial septal defect (ASD) with surgical closure. BACKGROUND: The clinical utility of a device such as the ASO can only be judged against the results of contemporaneous surgery. METHODS: A multicenter, nonrandomized concurrent study was performed in 29 pediatric cardiology centers from March 1998 to March 2000. The patients were assigned to either the device or surgical closure group according to the patients' option. Baseline physical exams and echocardiography were performed preprocedure and at follow-up (6 and 12 months for device group, 12 months for surgical group). RESULTS: A total of 442 patients were in the group undergoing device closure, whereas 154 patients were in the surgical group. The median age was 9.8 years for the device group and 4.1 years for the surgical group (p < 0.001). In the device group, 395 (89.4%) patients had a single ASD; in the surgical group, 124 (80.5%) (p = 0.008) had a single ASD. The size of the primary ASD was 13.3 +/- 5.4 mm for the device group and 14.2 +/- 6.3 mm for the surgery group (p = 0.099). The procedural attempt success rate was 95.7% for the device group and 100% for the surgical group (p = 0.006). CONCLUSIONS: The early, primary and secondary efficacy success rates were 94.8%, 98.5% and 91.6%, respectively, for the device group, and 96.1%, 100% and 89.0% for the surgical group (all p > 0.05). The complication rate was 7.2% for the device group and 24.0% for the surgical group (p < 0.001). The mean length of hospital stay was 1.0 +/- 0.3 day for the device group and 3.4 +/- 1.2 days for the surgical group (p < 0.001). Mortality was 0% for both groups. The early, primary and secondary efficacy success rates for surgical versus. device closure of ASD were not statistically different; however, the complication rate was lower and the length of hospital stay was shorter for device closure than for surgical repair. Appropriate patient selection is an important factor for successful device closure. Transcatheter closure of secundum ASD using the ASO is a safe and effective alternative to surgical repair.