Soluble LR11 as a Novel Biomarker in Acute Kawasaki Disease.

BACKGROUND: Intimal smooth muscle cells (SMCs) play an important role in the vasculitis caused by Kawasaki disease (KD). Lipoprotein receptor 11 (LR11) is a member of the low-density lipoprotein receptor family, which is expressed markedly in intimal vascular SMCs and secreted in a soluble form (sLR11). sLR11 has been recently identified as a potential vascular lesion biomarker. sLR11 is reportedly elevated in patients with coronary artery lesions long after KD, but there is no description of sLR11 in acute KD. Our aim was to determine the sLR11 dynamics in acute KD and to assess its usefulness as a biomarker.Methods and Results: 106 acute KD patients and 18 age-matched afebrile controls were enrolled. KD patients were classified into the following subgroups: intravenous immunoglobulin (IVIG) responders (n=85) and non-responders (n=21). Serum sLR11 levels before IVIG therapy were higher in non-responders (median, 19.6 ng/mL; interquartile range [IQR], 13.0-24.9 ng/mL) than in controls (11.9 ng/mL, 10.4-14.9 ng/mL, P<0.01) or responders (14.3 ng/mL, 11.7-16.5 ng/mL, P<0.01). Using a cutoff of >17.5 ng/mL, non-responders to initial IVIG therapy were identified with 66.7% sensitivity and 78.8% specificity. CONCLUSIONS: sLR11 can reflect the state of acute KD and might be a biomarker for patient response to IVIG therapy.

Novel electrocardiographic criteria for short QT syndrome in children and adolescents.

AIMS: Although shortening of the corrected QT interval (QTc) is a key finding in the diagnosis of short QT syndrome (SQTS), there may be overlap of the QTc between SQTS patients and normal subjects in childhood and adolescence. We aimed to investigate electrocardiographic findings for differentiation of SQTS patients. METHODS AND RESULTS: The SQTS group comprised 34 SQTS patients <20 years old, including 9 from our institutions and 25 from previous reports. The control group comprised 61 apparently healthy subjects with an QTc of <360 ms who were selected from 13 314 participants in a school-based screening programme. We compared electrocardiographic findings, including QT and Jpoint-Tpeak intervals (QT and J-Tpeak, respectively), those corrected by using the Bazett's and Fridericia's formulae (cB and cF, respectively) and early repolarization (ER) between the groups. QT, QTc by using Bazett's formula (QTcB), QTc by using Fridericia's formula (QTcF), J-Tpeak, J-Tpeak cB, and J-Tpeak cF were significantly shorter in the SQTS group than in the control group. On receiver operating characteristic curve analysis, the area under the curve (AUC) was largest for QTcB (0.888) among QT, QTcB, and QTcF, with a cut-off value of 316 ms (sensitivity: 79.4% and specificity: 96.7%). The AUC was largest for J-Tpeak cB (0.848) among J-Tpeak, J-Tpeak cB, and J-Tpeak cF, with a cut-off value of 181 ms (sensitivity: 80.8% and specificity: 91.8%). Early repolarization was found more frequently in the SQTS group than in the control group (67% vs. 23%, P = 0.001). CONCLUSION: A QTcB <316 ms, J-Tpeak cB < 181 ms, and the presence of ER may indicate SQTS patients in childhood and adolescence.

Soluble LR11 is a novel biomarker for vascular lesions late after Kawasaki disease.

OBJECTIVE: Coronary artery lesions (CALs) and a risk for early onset of atherosclerosis are major concerns following Kawasaki disease (KD). Intimal smooth muscle cells (SMCs) have an important role in vascular lesions in KD. It is known that soluble LR11 (sLR11) is a novel biomarker for vascular lesions and LR11 is markedly expressed in intimal SMCs in atherosclerotic lesions. In this study, we hypothesized that sLR11 reflects the presence of vascular lesions late after KD. METHODS: Twenty-three age-matched controls (group 1) and 59 patients with a history of KD were enrolled; 36 with KD had normal coronary arteries or regressed aneurysms (group 2), and 23 had CALs (group 3). RESULTS: Serum sLR11 levels in group 3 (median, interquartile range (IQR): 11.1 ng/mL, 9.3-13.9 ng/mL) were significantly higher than those in groups 1 (8.4 ng/mL, 7.1-10.2 ng/mL, p < 0.001) and 2 (9.0 ng/mL, 7.7-10.1 ng/mL, p < 0.01). Levels of sLR11 were positively correlated with levels of high-sensitivity C-reactive protein (r = 0.480, p < 0.01) and lipoprotein (a) (r = 0.486, p < 0.01). CONCLUSION: These findings suggest that sLR11 reflects the development of vascular lesions in patients with serious CALs.

Short QT syndrome in a boy diagnosed on screening for heart disease.

We report on an asymptomatic 10-year-old boy who had a short QT interval (corrected QT interval, 260 ms). Short QT syndrome (SQTS) was detected in a school screening program for heart disease and the patient was subsequently diagnosed as having N588K mutation in the KCNH2 gene. Quinidine prolonged the QT interval, but not the QU interval. During treadmill exercise stress test, QT and QU intervals responded differently to heart rate changes, suggesting a mechanoelectrical hypothesis for the origin of the U wave. Although rare, attention should be paid to SQTS, which is associated with potential fatal arrhythmias.

Characteristic alteration in the second derivative of photoplethysmogram in children.

BACKGROUND: The second derivative of the photoplethysmogram (SDPTG) has been verified as a useful method for analyzing pulse wave form in adults; however, there have been few studies on the SDPTG in children. METHODS: We examined age-related alteration of SDPTG (study 1) and the SDPTG response to a vasodilator (study 2). The subjects in study 1 were 36 healthy children aged 0.9-16.0 years. The subjects in study 2 were 13 children aged 5.4-18.9 years with a history of Kawasaki disease. Subjects received an i.v. infusion of 0.568 mg/kg dipyridamole. We assessed the SDPTG by d/a ratio, b/a ratio and aging index (AGI). RESULTS: The d/a ratio increased with advance of age (r= 0.636, P < 0.001), and the b/a ratio and AGI decreased with advance of age (r=-0.343, P < 0.05 and r=-0.678, P < 0.001, respectively). The d/a ratio and AGI were correlated with height (r= 0.523, P < 0.01 and r=-0.623, P < 0.001, respectively), but the b/a ratio was not significantly correlated with height. In study 2, the d/a ratio increased significantly (P≤ 0.05), but the b/a ratio and AGI did not alter. CONCLUSIONS: The SDPTG indices in children show characteristic alterations with advance of age and react to a vasodilator.

Massive pulmonary gas embolism in a neonate with ileal atresia and meconium peritonitis.

We presented the case of a neonate with portal venous gas and pulmonary gas embolism. The patient presented with severe respiratory distress and abdominal distension 12 hours after birth. An ultrasound revealed intravascular microbubbles moving into a pulmonary artery that were traveling from the portal venous system through a ductus venosus. Additional clinical observations were hypotension and a sudden decrease in end-tidal carbon dioxide with a markedly discrepant high Pco(2), indicating a massive pulmonary gas embolism. Operative findings revealed congenital ileal atresia and meconium peritonitis with abscess. Gas-forming Escherichia coli was recovered from the abscess contents. The patient had respiratory distress, shock, disseminated intravascular coagulation, and intractable diarrhea but eventually recovered and was discharged on the 131st postoperative day.