Immunoglobulin profiling identifies unique signatures in patients with Kawasaki disease during intravenous immunoglobulin treatment.

Identifying the causes of high fever syndromes such as Kawasaki disease (KD) remains challenging. To investigate pathogen exposure signatures in suspected pathogen-mediated diseases such as KD, we performed immunoglobulin (Ig) profiling using a next-generation sequencing method. After intravenous Ig (IVIG) treatment, we observed disappearance of clonally expanded IgM clonotypes, which were dominantly observed in acute-phase patients. The complementary-determining region 3 (CDR3) sequences of dominant IgM clonotypes in acute-phase patients were commonly observed in other Ig isotypes. In acute-phase KD patients, we identified 32 unique IgM CDR3 clonotypes shared in three or more cases. Furthermore, before the IVIG treatment, the sums of dominant IgM clonotypes in IVIG-resistant KD patients were significantly higher than those of IVIG-sensitive KD patients. Collectively, we demonstrate a novel approach for identifying certain Ig clonotypes for potentially interacting with pathogens involved in KD; this approach could be applied for a wide variety of fever-causing diseases of unknown origin.

CXCL10/IP-10 is a biomarker and mediator for Kawasaki disease.

RATIONALE: Kawasaki disease (KD), an acute febrile vasculitis, is the most common cause of acquired heart disease in childhood; however, diagnosing KD can be difficult. OBJECTIVE: To identify unique proteomic biomarkers that can be used to facilitate earlier diagnosis of KD. METHODS AND RESULTS: We enrolled 214 children with fever and clinical features suggestive of KD. Of those, only 100 were diagnosed with KD. Their plasma samples were globally analyzed for cytokines, chemokines, and cell adhesion molecules using an unbiased, large-scale, quantitative protein array. This study was conducted in 3 stages: discovery, replication, and blinded validation. During the discovery phase (n [KD]=37; n [control]=20), the expression of interleukin-17F, sCD40L, E-selectin, CCL23 (myeloid progenitor inhibitory factor 1), and CXCL10 (IFN-γ-inducible protein 10 [IP-10]) were upregulated during the acute phase in patients with KD when compared with that in the controls. A notable increase was observed in the IP-10 levels (KD, 3037 ± 226.7 pg/mL; control, 672 ± 130.4 pg/mL; P=4.1 × 10(-11)). Receiver-operating characteristic analysis of the combined discovery and replication data (n [KD]=77; n [control]=77) showed that the IP-10 level had high area under the curve values (0.94 [95% confidence interval, 0.9055-0.9778]; sensitivity, 100%; and specificity, 77%). With 1318 pg/mL as the optimal cutoff, the blinded validation study confirmed that the IP-10 levels were a good predictor of KD. With intravenous immunoglobulin treatment, the IP-10 levels returned to normal. The downstream receptor of IP-10, CXCR3, was activated in the T cells of patients with acute KD. CONCLUSIONS: IP-10 may be used as a biomarker to facilitate KD diagnosis, and it may provide clues about the pathogenesis of KD.

Regression of Neonatal Cardiac Rhabdomyoma in Two Months Through Low-Dose Everolimus Therapy: A Report of Three Cases.

Cardiac rhabdomyoma (CR) is the most common cardiac tumor in newborns. Approximately 75% of cases are associated with tuberous sclerosis complex. Although these tumors usually spontaneously regress after 2 years of age, they can be life-threatening when they obstruct major cardiac inflow or outflow pathways. Everolimus is an inhibitor of the mammalian target of rapamycin, reducing its production of the proteins harmartin and tuberin. Everolimus has demonstrated a remarkable suppression effect in children with tuberous sclerosis complex at doses of 4.7-5.6 mg/M2/day and serum trough levels of 5-15 ng/mL. Since 2012, five case reports of neonates with CR have also reported the tumor-regressing effect of everolimus. However, the optimal dosage for neonates is still unknown. Over the past 2 years, we have deliberately used a low dose everolimus regimen (0.3-0.67 mg/M2/day) in three neonates with large CRs, in an effort to maintain serum trough levels at 3-7 ng/mL. In all three cases, the tumors regressed smoothly within 2 months. Regarding the drug's side effect of predisposing patients to infection, we observed that adenovirus pneumonia occurred in one case at 3 months of age, and chicken pox occurred in another case at 9 months of age; both recovered smoothly. Our three cases of neonatal CR demonstrate that a low-dose everolimus regimen is an effective treatment for tumor regression.

Comparison of severe pediatric complicated influenza patients with and without neurological involvement.

ABSTRACT: Although influenza is generally an acute, self-limited, and uncomplicated disease in healthy children, it can result in severe morbidity and mortality. The objectives of this study were to analyze and compare the clinical features and outcome of severe pediatric influenza with and without central nervous system (CNS) involvement.We conducted a retrospective observational study of children admitted to the pediatric intensive care unit (PICU) of China Medical University Children's Hospital in Taiwan with a confirmed diagnosis of influenza. The demographic data, clinical and laboratory presentations, therapeutic strategies, and neurodevelopmental outcomes for these patients were analyzed. Furthermore, comparison of patients with and without CNS involvement was conducted.A total of 32 children with severe influenza were admitted during the study periods. Sixteen children were categorized as the non-CNS (nCNS) group and 16 children were categorized as the CNS group. Nine of them had underlying disease. The most common complication in the nCNS group was acute respiratory distress syndrome, (n = 8/16), followed by pneumonia (n = 7/16, 44%). In the CNS group, the most lethal complication was acute necrotizing encephalopathy (n = 3/16) which led to 3 deaths. The overall mortality rate was higher in the CNS group (n = 6) than in the nCNS group (n = 1) (37.5% vs 6.25%, P = .03).The mortality rate of severe complicated influenza was significantly higher with CNS involvement. Children with primary cardiopulmonary abnormalities were at high risk of developing severe complicated influenza, while previously healthy children exhibited risk for influenza-associated encephalitis/encephalopathy.

Lack of effects of oral probiotics on growth and neurodevelopmental outcomes in preterm very low birth weight infants.

OBJECTIVE: To evaluate growth and neurodevelopmental outcomes in preterm very low birth weight (PVLBW) infants treated with oral probiotics for the prevention of necrotizing enterocolitis (NEC). STUDY DESIGN: A prospective follow-up study was performed in a cohort of PVLBW infants enrolled in a single center with a masked randomized control trial to evaluate the efficacy of oral probiotics in preventing NEC. Growth measures included weight, length, and head circumference. Neurologic and sensory performance was evaluated with standard techniques. Psychometric parameters were measured used the Bayley Scales of Infant Development II (BSID-II). The studies were performed at 3 years corrected age. The primary outcome was death or neurodevelopmental impairment. RESULTS: Of the 367 subjects enrolled in trial, 301 (89.9%) were evaluated (153 in the probiotics group and 148 in the control group). There were no significant differences in growth or in any of the neurodevelopmental and sensory outcomes between the 2 groups. CONCLUSIONS: Oral probiotics given to PVLBW infants at 1 week after birth to reduce the incidence of NEC did not affect growth and neurodevelopmental and sensory outcomes at 3 years corrected age.

BTNL2 gene polymorphisms may be associated with susceptibility to Kawasaki disease and formation of coronary artery lesions in Taiwanese children.

The butyrophilin-like 2 (BTNL2) gene is a member of the B7 receptor family that probably functions as a T cell costimulatory molecule. Because altered T cell functions are implicated in dysregulation of the immune response seen in Kawasaki disease (KD), it is reasonable to speculate that BTNL2 gene is involved in the pathophysiology of KD. The purpose of this study was to investigate whether polymorphisms of the BTNL2 gene are associated with KD and the development of coronary artery lesions (CALs) in Taiwanese children. Nine-three patients with KD and 669 ethnically matched healthy controls were genotyped for BTNL2 gene rs1555115 C/G and rs2395158 A/G polymorphisms. The frequency of GG genotype of rs 1555115 was significantly higher in KD patients compared with controls (2.2% vs 0.2%, P = 0.012). The odds ratio for developing KD in individuals with rs 1555115 GG genotype was 14.7 (95% confidence interval, 2.04-105.5, P = 0.003) compared with individuals with rs 1555115 CG and CC genotypes. No significant difference was observed in the genotype and allelic frequencies of rs 2395158 polymorphism between KD patients and controls. However, the frequency of the G allele of rs 2395158 was significantly higher in KD patients with CALs than in those without CALs (P = 0.001). No significant difference was observed in the genotype and allelic frequencies of rs 1555115 polymorphism between KD patients with and without CALs. In conclusion, our results suggest that BTNL2 gene polymorphisms might be genetic markers of KD susceptibility and risk of coronary artery complication in Taiwanese children.

Congenital heart disease with pulmonary artery hypertension in an Asian cohort-initial report from TACHYON (TAiwan congenital heart disease associated with pulmonarY arterial hypertension) registry.

BACKGROUND: Prospective registry studies of congenital heart disease (CHD)-associated pulmonary artery hypertension (PAH) are rare. We established a multicenter registry of CHD-PAH: the TACHYON (TAiwan Congenital Heart disease associated with pulmonarY arterial hypertension) registry. METHODS: The prospective TACHYON registry was initiated in January 2016. Nine pediatric cardiology centers with 99 patients were included. Using this database, we evaluated clinical characteristics and outcomes. RESULTS: Twelve patients with incomplete data were excluded. For the remaining 87 patients, mean age of enrollment was 37.4(SD 18.2) years, and the male to female ratio was 60:27. PAH after defect closure accounted for 46 (52.9%) and Eisenmenger syndrome for 30 (34.5%) cases. Atrial septal defect was the most common (48.3%) disease, followed by ventricular septal defect. Mean pulmonary artery pressure was 56.7 (SD 19.4) mmHg. PAH-targeted therapy was used in 95.4% of patients. Sildenafil and bosentan were the most common drugs. After mean 23.9 months of follow-up, the 2-year Kaplan-Meier survival rate was 93.2%. According to univariate Cox regression analysis, significant risk factors included right heart failure signs, symptom progression, high-risk baseline N-terminal pro-brain natriuretic peptide (BNP)/BNP, high-risk baseline 6-min walking distance (6MWD), and high baseline hemoglobin/hematocrit level. Using the three noninvasive parameters (functional class, 6MWD, NT-pro BNP/BNP) proposed by the European Society of Cardiology, the total number of high-risk criteria predicted survival rate reliably. CONCLUSIONS: Using the TACHYON registry is feasible, but the physicians' adherences to guidelines are unsatisfactory. Midterm outcomes of PAH-target therapy are favorable and predictable using noninvasive parameters.

Interleukin-18 gene 105A/C genetic polymorphism is associated with the susceptibility of Kawasaki disease.

Interleukin-18 (IL-18)-656T/G, -607A/C, and -137C/G promoter polymorphisms had been reported associated with Kawasaki disease (KD). An IL-18 genetic A/C polymorphism at coding position 105 (rs549908) has been linked with asthma, rheumatoid, and systemic lupus erythematosus. We tested a hypothesis that the IL-18 105A/C genetic polymorphism confers KD susceptibility. Study participants were Taiwanese KD patients and a healthy control group. Our data indicated that the frequency of C allele was significantly higher in the patient group (13.9%) than in the control group (2.7%; P<0.0001, odds ratio [OR]=5.93; 95% confidence interval [CI]=2.57-13.73). Therefore, persons with the C allele may have higher risk of developing KD. In addition, compared with the haplotype frequencies between case and control groups, the KD patients with TACC haplotype appeared to be a significant "at-risk" haplotype compared with other haplotypes (OR: 4.62, 95% CI: 1.71-12.43; P=0.001). KD patient with the TAGA haplotype appeared to be a significant "protective" haplotype compared with other haplotypes (OR: 0.51, 95% CI:0.29-0.89; P=0.017). Our results suggest that 105A/C polymorphism and the haplotypes in IL-18 gene are associated with the risk of KD in Taiwanese population.

Association of interleukin-10 A-592C polymorphism in Taiwanese children with Kawasaki disease.

Elevated serum levels of interleukin-10 (IL-10) have been reported in patients with Kawasaki disease (KD). IL-10 reduces the inflammatory actions of macrophages and T cells and it may play a significant role in the regulation of inflammatory vascular damage associated with systemic vasculitis. The aim of this study was to examine whether -592 IL-10 promoter polymorphism is a susceptibility or severity marker of KD in Chinese patients in Taiwan. The study included 105 KD patients and 100 normal controls. Genotype and allelic frequencies for the IL-10 gene polymorphism in both groups were compared. There were no significant between-group differences in the genotype distribution of IL-10 A-592C gene polymorphism (P=0.08). However, the frequency of the -592*A allele was significantly increased in the patients with KD compared with controls (71.9% vs. 61.0%, P=0.019). The odds ratio for developing KD in individuals with IL-10-592*A allele was 1.64 (95% confidence interval, 1.06-2.52) compared to individuals with the IL-10-592*C allele. No significant difference was observed in the genotype and allelic frequencies for the IL-10 A-592C polymorphism between patients with and without coronary artery lesions. The IL-10-592*A allele may be involved in the development of KD in Taiwanese children.

Update on thalassemia treatment in Taiwan, including bone marrow transplantation, chelation therapy, and cardiomyopathy treatment effects.

Over the past few decades, Taiwan has seen striking improvements in the life expectancy of its 400 registered beta-thalassemia major (beta-TM) patients due mainly to adequate transfusion regimens and effective iron chelation therapy. Since 1995, Taiwanese citizens have enjoyed universal health care through National Health Insurance (NIH), receiving comprehensive treatment at minimal cost. In 1984, a national program for thalassemia prevention, control, and hematopoietic stem cell transplantation (HSCT) was initiated. Recent data show 1- and 2-year event-free survival rates of 85 and 78%, respectively. Chelation agents like deferoxamine (DFO), deferiprone (L1) and deferasirox (DFRA) are available in Taiwan, and therapy is tailored to individuals based on drug availability and tissue distribution of iron load. Intensive chelation regimens combining L1 and DFO are recommended in patients with cardiac complications, while DFRA has been found to be effective in reducing serum ferritin, with acceptable side effects. Here, we report advances in thalassemia treatment in Taiwan and suggest treatment guidelines.

Clinical manifestation of pediatric mediastinal tumors, a single center experience.

Medical decisions should be well-planned to improve prognosis and reduce complications of mediastinal tumors. In this study, we analyzed the clinical presentations of pediatric mediastinal tumors and their correlation with long-term clinical outcome.Forty patients under 18 years of age diagnosed with mediastinal tumors at China Medical University Children's Hospital between 2001 and 2016 were enrolled. The patients' sex, age of onset, initial clinical symptoms, and treatment outcomes were analyzed.75% of the patients with mediastinal tumors in this study were men, and the median age of onset was 13 years old (age range: 0-17 years). The overall mortality rate was 40%. The most common tumors were lymphoma (47.5%), followed by germ cell tumors (12.5%), neuroblastoma (12.5%), and thymoma (7.5%). Neuroblastoma was more prevalent in girls younger than 5 years old. The initial presentations of these patients included breathing difficulty (65%), productive cough (47.5%), pleural effusion (54.5%), superior vena cava (SVC) syndrome (35%), neck mass (35%), airway compression (32.5%), fever (30%), chest pain (27.5%), and pericardial effusion (25%). Lymphomas were more likely to be accompanied by neck mass (52.6% vs19.0%, P = .04) and SVC syndrome (52.6% vs 19.0%, P = .026), yet also had a better 1-year-survival rate (68.4% vs 52.4%, P = .02).Overall, lymphoma should be suspected when children present with neck mass and SVC syndrome. Neuroblastoma with a posterior mediastinal origin should be suspected among children younger than 5 years old. Tumor-related airway obstruction, pleural effusion, and pericardial effusion were leading cause of cardiopulmonary instability during sedation for invasive procedures, which should be managed cautiously.

Genome-wide transcriptome analysis to further understand neutrophil activation and lncRNA transcript profiles in Kawasaki disease.

Kawasaki disease (KD) is the most common cause of acquired cardiac disease in children in developed countries. However, little is known regarding the role of transcriptomic targets of KD in the disease progression and development of complications, especially coronary artery aneurysms (CAA). The aim of our study was to identify transcripts affected by KD and their potential role in the disease. We enrolled 37 KD patients and collected blood samples along a comprehensive time-course. mRNA profiling demonstrated an abundance of CD177 transcript in acute KD, and in the intravenous immunoglobulin (IVIG)-resistant group compared to in the IVIG-sensitive group. lncRNA profiling identified XLOC_006277 as the most highly expressed molecule. XLOC_006277 expression in patients at acute stage was 3.3-fold higher relative to patients with convalescent KD. Moreover, XLOC_006277 abundance increased significantly in patients with CAA. XLOC_006277 knockdown suppressed MMP-8 and MMP-9 expression, both associated with heart lesions. Our result suggested that the increase of CD177pos neutrophils was associated with KD. Moreover, this study provided global long non-coding RNA transcripts in the blood of patients with KD, IVIG-resistant KD, or CAA. Notably, XLOC_006277 abundance was associated with CAA, which might contribute to further understanding of CAA pathogenesis in KD.

Mechanisms of and obstacles to iron cardiomyopathy in thalassemia.

Thalassemia is anemia of variable severity, arising from mutations of genes encoding the hemoglobin alpha and beta chains. Severe thalassemia is associated with iron overload, tissue lesions, and high risk for cardiovascular complications, and iron-mediated cardiomyopathy is the main cause of death in this condition. Thalassemia major (TM) patients exhibit cardiovascular abnormalities consistent with chronic anemia; these include enlargement of the ventricular chambers, increased cardiac output, and reduced total vascular resistance. Cardiac iron overload in TM patients due to long-term transfusion can cause further chamber dilation, decreased contractility, and arrhythmia. Paradoxically, many such patients remain asymptomatic until decompensation occurs. For decades, magnetic resonance imaging and echocardiography have been performed to detect advanced cardiac dysfunction; however, reliable evaluation tools for the early detection of cardiac abnormalities are currently in demand. This article reviews the mechanisms underlying the development of heart disease in thalassemia and strategies for therapeutic intervention in TM patients with congestive heart failure.

Upper aerodigestive tract sequelae in severe enterovirus 71 infection: predictors and outcome.

OBJECTIVE: Enterovirus 71 (EV71) infection sequelae can be severe and life-threatening, and long-term follow-up outcomes remain unknown. Therefore, we conducted a retrospective follow-up study to review airway and neurological sequelae development in patients with severe EV71 infection. We also studied the incidence and risk factors for tracheotomy and gastrostomy requirement. PATIENTS AND METHODS: We investigated 202 EV71-infected children according to their disease stage. Seventy-two of them were diagnosed to have EV71 encephalitis, which was characterized by myoclonus, ataxia, nystagmus, oculomotor palsy and bulbar palsy or combinations of these conditions. All the 72 patients required endotracheal intubation due to respiratory failure or ventilator dependence; among these, 14 underwent tracheostomy and 10 underwent gastrostomy. All patients were followed-up for at least 3 years after discharge. Predictors of tracheostomy and gastrostomy requirement were age <2 years, body weight <10th percentile, pulmonary hemorrhage or edema, meningeal symptoms and magnetic resonance imaging (MRI) findings of upper spinal cord and brainstem. We determined outcome based on persistent tracheostomy or gastrostomy requirement and whether patients developed positive neurological sequelae. RESULTS: Significant tracheostomy and gastrostomy predictors were age <2 years, pulmonary edema or hemorrhage, hypotension, hemiparesis and positive MRI findings. Statistical analysis revealed pulmonary edema and hypotension as index predictors of tracheostomy requirement and pulmonary edema as the significant risk factor for gastrostomy. CONCLUSIONS: Long-term neuropsychological impact was observed on children who present the signs of the pulmonary edema or hypotension in the early onset of the EV71 infection. EV71-infected patients who develop neurological pulmonary edema or hypotension should be hemodynamically stabilized and undergo early tracheostomy to prevent further complications. This may improve the decannulation success rate after the brainstem function recovers.

Pheochromocytoma complicated with severe ventricular tachycardia: report of one case.

Pheochromocytoma in children shows much worse complications than that in the adult patients. An 11-year-old girl was transferred to our emergency room after suffering from headache, dizziness, cold sweating and palpitation for 3 days. Severe hypertension, remarkable blood pressure fluctuation between 260/160 and 65/50 mmHg, decrease of cardiac contractility, as well as abnormal electrocardiogram findings including ST-T segment elevation and QT interval prolongation were noted soon after admission. Later, a 4x4.5x2.5 cm tumor in the right adrenal gland area was found by computed axial tomogram study. Assessment of the urine catecholamine metabolites showed high levels of vanillylmandelic acid, normetanephrine and norepinephrine indicating an active adrenal pheochromocytoma produced mainly norepinephrine. Although several antihypertensive drugs were used, ventricular tachycardia and Torsade de pointe still occurred on her for 3 times, each was preceded by a period of blood pressure fluctuation and burst out concomitantly at the peak of a hypertension crisis. From this case, we found that when the specific alpha-blocker like phenoxybenzamine or phentolamine was not available to us, labetalol by continuous intravenous infusion was the only effective drug to protect the patient from attacks of hypertensive crisis and ventricular tachycardia. Her right adrenal gland was resected smoothly when BP was well under control. Histological examination showed the adrenal medulla was full of pheochromocytoma cells.

Presentations and management of different causes of chylothorax in children: one medical center's experience.

BACKGROUND: Chylothorax in children is a relatively rare cause of pleural effusion. However, it is usually a common complication of cardiothoracic operations like open-heart surgery. Other etiologies for chylothorax, such as trauma or malignancy, occur more common in adults and rare in children. To explore the etiologies of chylothorax in children, this study analyzed the pediatric patients that were admitted in to onea medical center. METHODS: We retrospectively reviewed the medical records of the pediatric patients that were admitted to this tertiary transfer center with a diagnosis of chylothorax during the period of 1995 to 2005. RESULTS: A total of 22 patients (15 females and 7 males) with chylothorax were enrolled in our study. The etiologies for chylothorax were the following: a complication of cardiothoracic surgery in 14 patients (63.6%), congenital chylothorax in 5 patients (22.7%), association with neuroblastoma in 2 patients (9.1%), and congenital nephrotic syndrome in 1 patient (4.6%). All patients required medical therapy. Chest tube drainage was necessary to provide for twenty patients (90.9%), and surgical intervention was necessary to perform for 3 patients (13.6%). Four patients (18.2%) expired due to other causes. CONCLUSION: Cardiothoracic surgery was the most common cause of chylothorax in children at the institution surveyed. Medication and chest tube drainage were effective in treating most of these chylothorax-afflicted patients. In addition, early recognition, medication, and performing surgical intervention when necessary are important measures to avoid a catastrophe.

Vein of Galen aneurysm complicated with pulmonary hypertension: report of one newborn case.

The vein of Galen aneurysm is a rarely seen congenital intracranial vascular malformation with abnormal aneurysmal dilation of the vein of Galen in neonatal stage. We report a full- term female newborn presented with intractable heart failure, pulmonary artery hypertension, and respiratory distress soon after birth, in whom persistent pulmonary hypertension of newborn was suspected initially. Further study by ultrasound revealed turbulent blood flow in the cerebral vascular lesion in the region of vein of Galen; therefore, secondary pulmonary artery hypertension complicated with 'steal' phenomenon was impressed. With the advancement of diagnostic technique, ultrasound provides a rapid and noninvasive method for diagnosing the condition.

The rescue of acute fulminant myocarditis by extracorporeal membrane oxygenation in pediatric patients.

The severity of acute myocarditis varies between subclinical to lethal. For fulminant myocarditis, the mortality rate can be as high as 75% when shock occurs. Extracorporeal membrane oxygenation (ECMO) support to revert this fulminant course has been introduced into the management in recent years. Six such pediatric cases rescued with ECMO in our hospital over a 3-year period were reviewed. Femoral venoarterial cannulated ECMO was undertaken in 5 patients and right atrium and ascending aorta cannulated ECMO in one. All patients had histories and clinical findings consistent with fulminant myocarditis. Median age was 12 years old (range 9 to 14 years). Median duration of ECMO support was 61.5 hours (range 36 to 90 hours). Three patients survived. Two of them complicated with deep vein thrombosis or peripheral neuropathy. The survivors showed normal cardiac function after follow-up periods of 0.8-4.3 years. Early recognition and immediate establishment of an ECMO circuit are crucial to rescue a patient with fulminant myocarditis. Every effort to avoid the complications associated with ECMO should then be stressed.

Genetic variants in PLCB4/PLCB1 as susceptibility loci for coronary artery aneurysm formation in Kawasaki disease in Han Chinese in Taiwan.

Kawasaki disease (KD) is an acute, inflammatory, and self-limited vasculitis affecting infants and young children. Coronary artery aneurysm (CAA) formation is the major complication of KD and the leading cause of acquired cardiovascular disease among children. To identify susceptible loci that might predispose patients with KD to CAA formation, a genome-wide association screen was performed in a Taiwanese KD cohort. Patients with both KD and CAA had longer fever duration and delayed intravenous immunoglobulin treatment time. After adjusting for these factors, 100 susceptibility loci were identified. Four genes were identified from a single cluster of 35 using the Ingenuity Pathway Analysis (IPA) Knowledge Base. Silencing KCNQ5, PLCB1, PLCB4, and PLCL1 inhibited the effect of lipopolysaccharide-induced endothelial cell inflammation with varying degrees of proinflammatory cytokine expression. PLCB1 showed the most significant inhibition. Endothelial cell inflammation was also inhibited by using a phospholipase C (PLC) inhibitor. The single nucleotide polymorphism rs6140791 was identified between PLCB4 and PLCB1. Plasma PLC levels were higher in patients with KD and CC+CG rs6140791genotypes, and these genotypes were more prevalent in patients with KD who also had CAA. Our results suggest that polymorphism of the PLCB4/B1 genes might be involved in the CAA pathogenesis of KD.

Total anomalous pulmonary venous return complicated by progressive pulmonary venous stenosis after total repair: report of one case.

Total repair of an infracardiac type total anomalous pulmonary venous return was performed on a 3-day-old female newborn. Echocardiogram study showed a smooth connection between the pulmonary veins and the left atrium one week after the operation, however, later echocardiograms showed a progressive obstruction of the pulmonary veins. The patient died at 50 days of age due to lung congestion. The autopsy revealed severe intima hypertrophy and upstream obstruction in every pulmonary vein, while the anastomosis between the left atrium and the pulmonary venous confluence remained well patent. In view of the high rate of progressive pulmonary venous stenosis after total repair in patients with infracardiac type total anomalous pulmonary venous return, it is advised that the operator should try to mobilize every pulmonary vein, make larger areas of anastomosis with pericardial patch augmentation and avoid using continuous suture. When the progressive pulmonary venous stenosis occurred during the follow-up period, a 'sutureless neoatrium' procedure can be used to resolve the obstructions.