Biomarkers of intravenous immunoglobulin resistance and coronary artery lesions in Kawasaki disease.

BACKGROUND: Currently, there are no reliable indicators for predicting intravenous immunoglobulin resistance and coronary artery lesions in the early stage of Kawasaki disease. METHODS: A total of 300 patients with Kawasaki disease were studied retrospectively. Laboratory data were compared between the intravenous immunoglobulin resistant (29 patients) and responsive groups, and between the groups with coronary artery lesions (48 patients) and without coronary artery lesions. RESULTS: The intravenous immunoglobulin resistant group had significantly higher D-dimer, globulin, interleukin-6 and serum ferritin levels in comparison to the intravenous immunoglobulin responder group. D-dimer level had a sensitivity of 87.0% and a specificity of 56.3% for predicting intravenous immunoglobulin resistance at a cutoff point of 1.09 mg/L. Globulin had a sensitivity of 62.1% and a specificity of 82.3% for predicting intravenous immunoglobulin resistance at a cutoff point of 34.7 g/L. Serum ferritin level had a sensitivity of 42.9% and a specificity of 88.8% for predicting intravenous immunoglobulin resistance at a cutoff point of 269.7 ng/mL. The patients with coronary artery lesions had higher D-dimer and tumor necrosis factor-α level. D-dimer level had a sensitivity of 50% and a specificity of 78.6% for predicting coronary artery lesions at a cutoff point of 1.84 mg/L. Based on analysis by multivariate logistic regression, serum ferritin and globulin were independent risks for intravenous immunoglobulin resistance, D-dimer was independent risk for coronary artery lesions. CONCLUSIONS: Elevated serum ferritin, globulin and D-dimer levels are significantly associated with intravenous immunoglobulin resistance in Kawasaki disease. Moreover, serum D-dimer is significantly increased in Kawasaki disease with coronary artery lesions.

Efficacy and safety of lenalidomide for the treatment of acute myeloid leukemia: a systematic review and meta-analysis.

BACKGROUND: Lenalidomide is effective for the treatment of low-risk myelodysplastic syndromes with deletion 5q abnormalities. However, whether lenalidomide leads to a significant improvement in treatment response and overall survival (OS) in cases of acute myeloid leukemia (AML) remains controversial. A systematic review and a meta-analysis were performed to evaluate the efficacy and safety of lenalidomide in the treatment of AML. METHODS: Clinical studies were identified from the Cochrane Central Register of Controlled Trials, PubMed, Embase, and ClinicalTrials.gov. Efficacy outcomes included overall response rate (ORR), complete remission (CR), and OS. Safety was evaluated based on the incidence of grade 3 and 4 treatment-related adverse events (AEs). RESULTS: Eleven studies were included in our meta-analysis; collectively these studies featured 407 AML patients. Pooled estimates for overall ORR and CR were 31% (95% CI: 26%-36%) and 21% (95% CI: 16%-27%), respectively. Thrombocytopenia, anemia, neutropenia, and infection were the most common grade 3 and 4 AEs. CONCLUSION: Lenalidomide may have some clinical activity in AML, but the population that would benefit from lenalidomide and incorporating lenalidomide into combination drug strategies need to be better defined.

Hypercoagulation and elevation of blood triglycerides are characteristics of Kawasaki disease.

BACKGROUND: Cardiovascular damages poses risks to children with Kawasaki disease (KD). Although hypertriglyceridemia and hypercholesteremia are risk factors of cardiovascular damages, studies on the blood lipid metabolism in KD are still limited. This study aims to analyze the blood lipids and coagulation in KD. METHODS: Triglyceride (TG) and cholesterol levels in the plasma and serum from 20 children with KD were examined in comparison with 10 healthy children (HC) as well as 10 children with high fever from identified bacterial infections (BT). Using electrospray ionization mass spectrometry, we profiled the lipid species. Blood coagulation was analyzed. Statistics was analyzed by one-way ANOVA using SigmaStat. RESULTS: We found that in KD, plasma TG level was significantly increased, but not serum TG. A total of 19 molecular species of TG were identified, and they were all increased in KD and BT patients, and more pronounced in KD. On the other hand, major molecular species of plasma phosphotidylcholine and lyso-phosphotidylcholine were decreased in KD and BT. Pronounced hypercoagulation was found in KD blood. CONCLUSION: Our data indicate hyperlipidemia in KD, especially for TG, which contributes to the hypercoagulation and the potential risk of cardiovascular damages. Evaluation of blood lipid levels in severe KD patients could provide valuable information for treatment and prognosis, thus would be worthy of consideration.

Correlation between rs198388 and rs198389 polymorphismsin brainnatriuretic peptide (NPPB) gene and susceptibility to congenital heart diseases in a Chinese population.

OBJECTIVE: We discussed the correlation between SNP loci (rs198389 and rs198388) in brain natriuretic peptide gene (NPPB) and susceptibility to congenital heart diseases (CHD). METHOD: Multiplex SNaPshot technique was adopted for profiling of SNP genotypes at loci rs198389 and rs198388 in NPPB gene among 150 cases of CHDand 150 normal controls. RESULTS: The distribution frequency of 3 genotypes (AA, AG and GG) at locus rs198389 was 40.7%, 36.0% and 23.3% in CHD group, respectively, showing significant differences compared with the normal controls (P<0.001). Gallele was associated with higher risk of CHD (OR=2.48, 95% CI=1.77-3.48). The distribution frequency of CC, CTand TT genotypes at locus rs198388 was 60.7%, 17.3% and 22.0% in CHD group, respectively, also showing significant differences compared with the normal controls (P<0.001). C allele could increase the risk of CHD (OR=1.92, 95% CI=1.48-2.48). CONCLUSION: SNP loci rs198389 and rs198388 in NPPB gene were correlated with genetic susceptibility to CHD.

[Relationship between 22q11 microdeletion syndrome and congenital heart disease].

OBJECTIVE: To investigate the relationship between 22q11 microdeletion syndrome and congenital heart disease. METHODS: Clinical screening assessment and genetic testing using standard fluorescence in-situ hybridization (FISH) were applied in 207 subjects suspected for 22q11 microdeletion syndrome. Patients with 22q11 microdeletion syndrome were examined by echocardiography, patients with complicated congenital heart disease were examined further by cardiac catheterization. RESULTS: 22q11 microdeletion syndrome was detected in 39 subjects. The incidence of 22q11 microdeletion syndrome was 1.6% in suspects with simple congenital heart disease without extracardiac manifestations, 53.0% in suspects with congenital heart disease combined with at least two extracardiac manifestations, 3.8% in suspects without congenital heart disease. The incidence of congenital heart disease in 22q11 microdeletion syndrome patient and non 22q11 microdeletion syndrome patient was 94.9% and 54.2% (P < 0.01). The incidence of congenital heart disease combined with at least two extracardiac manifestations in 22q11 microdeletion syndrome patient and non 22q11 microdeletion syndrome patient was 89.7% and 18.5% (P < 0.01). In 22q11 microdeletion syndrome patients, Tetralogy of Fallot was the most common type of congenital heart disease. Dysmorphic faces, learning difficulties and retarded physical development were the most common extracardiac manifestations of the congenital heart disease patients. CONCLUSION: 22q11 microdeletion syndrome is related to congenital heart disease.

Charting the developmental trajectories of attention and executive function in Chinese school-aged children.

Attention is a complex domain that has reawakened research interest in recent years. There are relatively few studies that have examined age-related changes across different attention subcomponents, such as selection, maintenance, and control, using large samples covering a wide age range. The present study assessed performance in 466 participants in order to identify the ages at which mature performance was reached across differing attention subcomponents. Furthermore, we investigated whether the nature of the attentional demands or task difficulty predicted the age at which stable levels of performance were reached. The results supported the former rather than the latter alternative.

Interventional occlusion of congenital vascular malformations.

BACKGROUND: New materials and devices have been used in the management of cardiac malformations. In this paper, we present our experience with interventional occlusion of congenital vascular malformations. METHODS: Between January 1997 and December 2005, 139 patients with congenital vascular malformations who had undergone interventional occlusion in the Children's Hospital, Zhejiang University School of Medicine were studied. The clinical data of the patients were retrospectively reviewed including pre-operative evaluation, surgical procedures, immediate complete closure rate, short-term complications, and short-term outcome. RESULTS: Of the 139 patients, 126 had patent ductus arteriosus, and successful deployment was achieved in 121 of the 126 patients (96%, 121/126). Six patients had coronary artery fistula and 14 different coils were used for embolization; the immediate complete closure rate was 83.3%, and the complete closure rate after one month was 100%. The abnormal vessels of 3 patients with pulmonary sequestration were completely occluded using four 0.038-inch Gianturco coils. In 3 patients with aortopulmonary collaterals, 14 abnormal vessel branches were occluded with sixteen 0.038-inch Gianturco coils, reaching a closure rate of 100%. One patient with pulmonary arteriovenous fistula was occluded successfully with two 0.038-inch Gianturco coils. CONCLUSIONS: Transcatheter closure using coils is a safe and effective alternative to surgical ligation in the management of congenital vascular malformations in children. Selection of appropriate coils is important to achieve a better outcome.

[Visual search attention in children with Williams syndrome].

OBJECTIVE: To explore the characteristics of visual search attention in children with Williams syndrome (WS). METHODS: Twenty-two children with WS, 13 male and 9 female, aged 12 (6-16), 25 chronological age (CA) and mental age (MA)-matched children with Down's syndrome (DS), 45 biological age-matched children, and 43 mental age-matched children, aged 4 +/- 2 (2-8) underwent Peabody picture vocabulary test (PPVT). Visual search attention including selective, switch, and sustained attention, was tested using a set of computerized visual search tasks via a touch-screen. In the dual target tasks, participants were required to alternate between two different targets. Sustained attention was investigated with vigilance task test. RESULTS: (1) In the single-target searching task with no target similar distractor, the accurate response rate of the WS patients was 71% +/- 25%, significantly lower than that of the CA-matched children (87% +/- 14%, P = 0. 001). The searching time of the WS children was 5 s, significantly longer than that of the CA-matched children (3 s, P = 0.000). The distance for touch of the WS children was 25 relative units, significantly longer than that of the CA-matched children (18 relative units, P = 0.000). The mean reaction time of the WS children was 5 s, significantly longer than that of the children with Down's syndrome (3 s, P = 0.022). The shape error rate of the WS children was 15%, significantly higher than that of the CA-matched children (0, P = 0.000). When non-targets similar to the targets were added, the accurate response rate of the WS group was 39% +/- 20%, significantly lower than those of the CA-matched and MA-matched children (77% +/- 23% and 66% +/- 23% respectively, both P = 0.000); the mean searching time of the WS children was 13 s, significantly longer than those of the CA-matched and MA-matched children (3 s and 5 s respectively, both P = 0. 000); and the distance per touch of the WS children was 41 relative units, significantly longer than those of the CA-matched and MA-matched children (20 and 27 relative units, P = 0.000 and P = 0.004). (2) The results of the dual target tasks showed that the accurate response rate of the WS children was 52% +/- 28%, significantly lower than that of the CA-matched children (78% +/- 22%, P = 0. 000), the mean searching time of the WS children was 11 s, significantly longer than that of the CA-matched children (4 s, P = 0.000); and the distance per touch of the WS children was 54 +/- 27 relative units, significantly longer than that of the CA-matched children (31 +/- 13 relative units, P = 0.000). However, there were not significant differences in the accurate response rate, mean searching time, and distance per touch between the WS and DS children. The switching error rate of the WS children was 13%, significantly higher than those of the CA and MA-matched children (0 and 4% respectively, P = 0.000 and P = 0.004). (3) The vigilance task test showed that the accurate response rate of the WS children was 52% +/- 25%, significantly lower than that of the CA-matched children (80% +/- 21%, P = 0.000); the mean searching time of the WS children was 4 s +/- 1 s, significantly longer than that of the CA-matched children (3 s +/- 1 s, P = 0.000); and the error hit number of the WS children was 8, significantly more than that of the CA-matched children (3, P = 0.000). However, there were not significant differences in the accurate response rate, mean searching time, and error hit number between the WS and DS children. Conclusion Distinct visual search deficits exist in WS children.

Patent ductus arteriosus and pulmonary valve stenosis in a patient with 18p deletion syndrome.

We report on a patient with a partial deletion on the short arm of chromosome 18 (del 18p), who presented with dysmorphic features and delayed developmental milestones as well as with a patent ductus arteriosus (PDA) and pulmonary valve stenosis (PS). Several forms of congenital heart disease (CHD) are found in about 10% of patients with del (18p), but coexisting PDA and PS have not been reported. Del (18p) must be considered in patients with characteristic phenotypic abnormalities and congenital heart disease, including a combination of PDA and PS.

[A study on the social adjustment and its affective factors in Down syndrome children].

OBJECTIVE: To explore the social adjustment status and affected factors thereof in Down syndrome children. METHODS: The family environment, cognitive development and social adjustment were examined in 36 Down syndrome children aged 52 - 167 months, 30 mental age-matched children aged 20 - 65 months, and 40 chronological age-matched children aged 43 - 144 months with questionnaire of family influential factors, Peabody Picture Vocabulary Test (PPVT) and Infants-Junior Middle School Students' Social-Life Abilities Scale from September 2004 to July 2006. The gender and general family environment were matched among the three groups. The information about the mode of delivery, history of newborn, family structure, income of family, and parents' education could be gathered from the questionnaire (used by parents). PPVT was adopted as research tool of cognitive development. Infants-Junior Middle School Students' Social-Life Abilities Scale was adopted as research tool of social adjustment. RESULTS: There were no differences between the Down syndrome children and mental age-matched group in communication and socialization. The Down syndrome children were better than the mental age-matched group in self-help [(20.0 +/- 4.8) vs (13.3 +/- 4.7), t = 5.72, P = 0.000]; locomotion [(7.5 +/- 1.4) vs (6.4 +/- 1. 6), t = 3.10, P = 0.003]; occupation [(8.2 +/- 2.4) vs (6.2 +/- 2.0), t = 3.68, P = 0.000], and self-direction [(5.9 +/- 2.6) vs (4.6 +/- 2.0), t = 2. 28, P = 0.026]. The chronological age-matched group were much better than the Down syndrome children in all factors of social-life abilities, including self-help [(20.0 +/- 4.8) vs (26.5 +/- 4.9), t = 5.84, P = 0.000]; locomotion [(7.5 +/- 1.4) vs (11.4 +/- 3.3), t = 6.76, P = 0.000]; occupation [(8.2 +/- 2.4) vs (14.4 +/- 3.9), t = 8.55, P = 0.000]; communication [(8.3 +/- 3.6) vs (18.3 +/- 4.8), t = 10.38, P = 0.000]; socialization [(9.6 +/- 2.3) vs (17.1 +/- 4.2), t = 9.76, P = 0.000], and self-direction [(5.9 +/- 2.6) vs (13. 8 +/- 4.6), t = 9.25, P = 0.000]. There was a relationship between the raw score of PPVT and social-life abilities in these children. Even after controlling effect of age, it was still associated with self-help (r = 0.70, P = 0.000), locomotion (r = 0.74, P = 0.000), occupation (r = 0.77, P = 0.000), communication (r = 0.86, P = 0.000), socialization (r = 0.80, P = 0.000), and self-direction (r = 0.76, P = 0.000). Multiple stepwise regression showed that the main factor influencing self-help was family structure. Family structure and mother's education influenced locomotion. Family structure and newborn history influenced occupation, communication, socialization and self-direction. CONCLUSION: Down syndrome children have better social adjustment than the mental age-matched group, yet worse than the chronological age-matched group. Cognition development, family environment and newborn history differently influence the Down syndrome child, which means proper intervention can improve their social adjustment.

Study on the social adaptation of Chinese children with down syndrome.

PURPOSE: To evaluate social adjustment and related factors among Chinese children with Down syndrome (DS). PATIENTS AND METHODS: A structured interview and Peabody Picture Vocabulary Test (PPVT) were conducted with a group of 36 DS children with a mean age of 106.28 months, a group of 30 normally-developing children matched for mental age (MA) and a group of 40 normally-developing children matched for chronological age (CA). Mean scores of social adjustment were compared between the three groups, and partial correlations and stepwise multiple regression models were used to further explore related factors. RESULTS: There was no difference between the DS group and the MA group in terms of communication skills. However, the DS group scored much better than the MA group in self-dependence, locomotion, work skills, socialization and self-management. Children in the CA group achieved significantly higher scores in all aspects of social adjustment than the DS children. Partial correlations indicate a relationship between social adjustment and the PPVT raw score and also between social adjustment and age (significant r ranging between 0.24 and 0.92). A stepwise linear regression analysis showed that family structure was the main predictor of social adjustment. Newborn history was also a predictor of work skills, communication, socialization and self-management. Parental education was found to account for 8% of self-dependence. Maternal education explained 6% of the variation in locomotion. CONCLUSION: Although limited by the small sample size, these results indicate that Chinese DS children have better social adjustment skills when compared to their mental-age-matched normally-developing peers, but that the Chinese DS children showed aspects of adaptive development that differed from Western DS children. Analyses of factors related to social adjustment suggest that effective early intervention may improve social adaptability.

[Percutaneous balloon aortic valvuloplasty for congenital valvular aortic stenosis in children].

OBJECTIVE: To assess the effect of the balloon valvuloplasty for congenital valvular aortic stenosis (AS) in children. METHODS: A total of twenty one children with AS accepted the treatment of percutaneous balloon aortic valvuloplasty (PBAV). One of them complicated with PDA underwent PDA closure by using Amplatzer occluder in the mean time. PBAV could not be accomplished in 3 cases because the catheter could not be advanced into left ventricle and PBAV was not performed in 2 cases due to the gradient pressures across aortic valves less than 50 mm Hg (1 mm Hg = 0.133 kPa). The procedure was completed in 16 cases. The ratios of balloon/valve were 0.98 +/- 0.04 (0.92 - 1.10). RESULTS: 13 cases had more than 50% gradient reduction (81.25%), 2 had 40% - 50% gradient reduction. The follow up period ranged from 3 months to 5 years. The gradient pressures rose to more than 50 mm Hg after follow up in 3 cases and they underwent repeat balloon valvuloplasty procedure or were operated successfully. There was no moderate to severe aortic insufficiency (AI). CONCLUSION: The result of balloon aortic valvuloplasty showed the significant hemodynamic improvement with relative safety in pediatric patients. PBAV provides another choice in comparison with surgery.

[Study on clinical features and fluorescence in situ hybridization detections of 22q11 microdeletion syndrome].

OBJECTIVE: To investigate clinical features and the diagnosis by fluorescence in situ hybridization (FISH) of 22q11 microdeletion syndrome (22q11 DS). METHODS: The clinical data of suspects were analyzed, and their peripheral blood samples were tested by FISH for microdeletion of 22q11. The diagnosis and correlated clinical factors of 22q11 DS were investigated by using the multiple factor Logistic regression analysis and Chi-square test. RESULTS: In 64 suspects, 14 were shown to have 22q11 microdeletion with many different types of malformation, and the percentage was 21.9%. The Logistic regression predictive equation for 22q11 DS was: y=-8.206+2.324x1+2.725x2+1.674x3, P=exp(y)/[1+exp(y)], in which the concomit ant variables were facial dysmorphic features (x1), congenital heart defects (x2), thymus scarcity/infection problem (x3), the P value meant the probability of diagnosis of 22q11 DS. CONCLUSION: Accurate clinical evaluation is just as preliminary screening to patients at risk for del22q11. The results of FISH test can be predicted by using the suitable Logistic regression equation.

[Cardiovascular manifestations in 40 patients with Williams syndrome].

OBJECTIVE: To evaluate the cardiovascular manifestations of Williams syndrome (WS) confirmed by fluorescence in situ hybridization (FISH). METHODS: Between July 2004 and January 2007, FISH was used to confirm diagnosis in 71 suspected WS cases by detecting chromosome 7q microdeletion. Cardiovascular abnormalities were assessed by echocardiography and Doppler echocardiography. RESULTS: Forty out of 71 patients were detected to have Elastin gene locus microdeletion, 25 patients (25/40, 62.5%) had at least one cardiac anomaly; among these patients, supravalvular aortic stenosis (SVAS) was diagnosed in 18 patients (18/25, 72%) and 6 of them had complex abnormalities. Patent ductus arteriosus was diagnosed in 3 patients (3/25, 12%, 1 was associated with other malformations), isolated pulmonary stenosis in 1 patient (1/25, 4%), isolated coarctation of aorta in 2 patients (2/25, 8%), and hypertension in 2 patients (2/25, 8%), mild aortic regurgitation in 2 patients, mild mitral regurgitation and moderate mitral regurgitation in 3 patients respectively. CONCLUSION: A detailed cardiac evaluation should be performed in all patients with Williams syndrome due to the high frequency of cardiovascular abnormalities.

[Transcatheter closure of perimembranous ventricular septal defects in children following transthoracic echocardiography].

OBJECTIVE: To evaluate the efficacy and safety of transcatheter closure of perimembranous ventricular septal defects (VSD) in children following transthoracic echocardiography (TTE). METHODS: From September 2002 to December 2005, eighty-nine children (47 males and 42 females) with perimembranous (VSD) underwent an attempt of transcatheter interventional occlusion. Among the 89 children, one of them was diagnosed with patent ductus arterious (PDA) and six with VSD leakage after the surgical repair (three with leakage after the surgical repair of tetralogy of Fallot and three with leakage after the surgical repair of VSD). The mean age of patients was (6.4 +/- 3.9) years (ranged from 1 to 18 years). The mean body weight of patients was (22 +/- 11 )kg (ranged from 9 to 78 kg). The mean diameter of VSD measured by TTE was (4.3 +/- 1.5) mm(ranged from 2 to 8.5mm). The path of artery to vein was established following X-rays and TTE. Occluder was released through the right heart system. All patients were followed up in 1, 3, 6 and 12 months after procedure of TTE, X-ray and electrocardiography. RESULT: The devices were deployed successfully in 85 patients, the rate of success was 95.5%. No death occurred during and after the procedure. There was trivial residual shunt in 12 patients immediately after the closure by TTE and angiography. Twenty-four hours later, only 3 patients had trivial residual and no shunt existed after 6 months follow-up. Convulsion occurred in 1 case due to serious cardiac arrhythmias. Hemolysis was found in 2 cases. Other complications included 2 cases of complete left bundle branch block, 1 cases of left anterior fascicular block and 3 cases of incomplete right bundle branch block. They recovered after 3 to 7 days of corticosteroid treatment. After 1 to 36 months (mean 9 months) follow-up, none of occluders displacement occurred and no valve was involved. CONCLUSION: Transcatheter closure of membranous VSD using occluder would be safe and effective for children, and the results of short-term was satisfied. Transcatheter closure of VSD following TTE is a feasible method. TTE has the potential benefit of avoiding general anesthesia and esophageal intubation in children.

[Transcatheter therapy of combined congenital heart diseases in children].

OBJECTIVE: To investigate the methods of interventional catheterization for combined congenital heart disease and to evaluate its efficacy in children. METHODS: From March 1994 to December 2003, 15 cases (6 boys, 9 girls) underwent transcatheter intervention for combined congenital heart diseases. The procedure of transcatheter intervention was as follows: for pulmonary stenosis (PS) and atrial septal defect (ASD) or patent ductus arteriosus (PDA), PBPV first, occlusion of ASD or PDA later; for coarctation of aorta (COA) and PDA, dilation of COA first, occlusion of PDA 4-15 months later; for aortic stenosis (AS) and PDA, PBAV first, occlusion of PDA later; for ventricular septal defect (VSD) and PDA, all occlusions with detachable coils. RESULT: Transcatheter intervention for combined congenital heart diseases was successful in all patients. There was no residual shunt after occlusion immediately apart from 2 cases of PDA which were little residual after occlusion immediately. Follow-up for (3.57 +/-2.61) years, the systolic pressure gradients across pulmonary valve and coarctation were normal by ultrasonic or transcatheter, except AS. There was 3 cases presented postoperative complications: 1 with mechanical haemolysis, 1 with fall off of coil and 1 with arterial embolism, respectively. CONCLUSION: Transcatheter intervention for combined congenital heart diseases could obtain satisfactory results with appropriate indications and procedure manipulations.