Loss-of-function mutations in cardiac ryanodine receptor channel cause various types of arrhythmias including long QT syndrome.

AIMS: Gain-of-function mutations in RYR2, encoding the cardiac ryanodine receptor channel (RyR2), cause catecholaminergic polymorphic ventricular tachycardia (CPVT). Whereas, genotype-phenotype correlations of loss-of-function mutations remains unknown, due to a small number of analysed mutations. In this study, we aimed to investigate their genotype-phenotype correlations in patients with loss-of-function RYR2 mutations. METHODS AND RESULTS: We performed targeted gene sequencing for 710 probands younger than 16-year-old with inherited primary arrhythmia syndromes (IPAS). RYR2 mutations were identified in 63 probands, and 3 probands displayed clinical features different from CPVT. A proband with p.E4146D developed ventricular fibrillation (VF) and QT prolongation whereas that with p.S4168P showed QT prolongation and bradycardia. Another proband with p.S4938F showed short-coupled variant of torsade de pointes (scTdP). To evaluate the functional alterations in these three mutant RyR2s and p.K4594Q previously reported in a long QT syndrome (LQTS), we measured Ca2+ signals in HEK293 cells and HL-1 cardiomyocytes as well as Ca2+-dependent [3H]ryanodine binding. All mutant RyR2s demonstrated a reduced Ca2+ release, an increased endoplasmic reticulum Ca2+, and a reduced [3H]ryanodine binding, indicating loss-of-functions. In HL-1 cells, the exogenous expression of S4168P and K4594Q reduced amplitude of Ca2+ transients without inducing Ca2+ waves, whereas that of E4146D and S4938F evoked frequent localized Ca2+ waves. CONCLUSION: Loss-of-function RYR2 mutations may be implicated in various types of arrhythmias including LQTS, VF, and scTdP, depending on alteration of the channel activity. Search of RYR2 mutations in IPAS patients clinically different from CPVT will be a useful strategy to effectively discover loss-of-function RYR2 mutations.

Prevention Measures for COVID-19 and Changes in Kawasaki Disease Incidence.

BACKGROUND: Kawasaki disease is suspected to be triggered by previous infection. The prevention measures for coronavirus disease 2019 (COVID-19) have reportedly reduced transmission of certain infectious diseases. Under these circumstances, the prevention measures for COVID-19 may reduce the incidence of Kawasaki disease. METHODS: We conducted a retrospective study using registration datasets of patients with Kawasaki disease who were diagnosed in all 11 inpatient pediatric facilities in Yamanashi Prefecture. The eligible cases were 595 cases that were diagnosed before the COVID-19 pandemic (from January 2015 through February 2020) and 38 cases that were diagnosed during the COVID-19 pandemic (from March through November 2020). Incidence of several infectious disease were evaluated using data from the Infectious Disease Weekly Report conducted by the National Institute of Infectious Diseases. RESULTS: Epidemics of various infectious diseases generally remained at low levels during the first 9 months (March through November 2020) of the COVID-19 pandemic. Moreover, the incidence of COVID-19 was 50-80 times lower than the incidence in European countries and the United States. The total number of 38 cases with Kawasaki disease for the 9 months during the COVID-19 pandemic was 46.3% (-3.5 standard deviations [SDs] of the average [82.0; SD, 12.7 cases] for the corresponding 9 months of the previous 5 years. None of the 38 cases was determined to be triggered by COVID-19 based on their medical histories and negative results of severe acute respiratory syndrome coronavirus 2 testing at admission. CONCLUSION: These observations provide a new epidemiological evidence for the notion that Kawasaki disease is triggered by major infectious diseases in children.

Mediastinal and hilar soft tissue mass-like lesions in congenital unilateral pulmonary vein atresia: A retrospective review of seven pediatric patients.

BACKGROUND: Congenital unilateral pulmonary vein atresia (CUPVA) is known to lead to the formation of an abnormal confluent mediastinal and hilar soft tissue mass, thoracic hypoplasia, and interlobular septal thickening on the affected side. The purpose of the present study is to investigate the frequency and severity of mediastinal soft tissue mass-like lesions and examine other abnormal findings associated with CUPVA. METHODS: We retrospectively reviewed seven children with CUPVA who underwent contrast-enhanced CT scans and measured the soft tissue mass volume in the bilateral mediastinum (affected and normal side). The location of abnormal soft tissue was divided into three anatomical sections (paratracheal, peribronchial, and the dorsal aspect of the left atrium). The relationships among soft tissue volume and anatomical section were statistically evaluated. Also, the presence of thoracic hypoplasia, small ipsilateral pulmonary arteries, interlobular septal thickening, and ground-glass opacities were investigated. RESULTS: In all cases, CT scans confirmed the presence of confluent soft tissue mass-like lesions in the affected mediastinum. The soft tissue volume on the affected side was 5.5-fold greater than the volume on the normal side (average: 18.0 cm3 and 4.25 cm3 respectively, P < 0.01). Thoracic hypoplasia and interlobular septal thickening were found in all patients. Small pulmonary arteries and ground-glass opacities were present in six of the seven patients. CONCLUSION: Abnormal mediastinal and hilar soft tissue is commonly found in patients with CUPVA. So, if we encounter the mediastinal soft tissue mass in patients with CUPVA, no further test will be indicated.

Correction to: Outcomes of plasma exchange for severe dilated cardiomyopathy in children.

In original publication of the article, some of the co-author's names were not included. The correct author group is published in this article.

Infliximab regulates monocytes and regulatory T cells in Kawasaki disease.

BACKGROUND: The effect of infliximab (IFX) on immune cells has not been fully reported in Kawasaki disease (KD). To investigate the mechanism of IFX in KD, we examined changes in the abundance of CD14+ CD16+ activated monocytes, regulatory T cells (Treg ) cells, and T-helper type 17 (Th17) cells following treatment with IFX. METHODS: We collected peripheral blood from patients with i.v. immunoglobulin (IVIG)-resistant KD and analyzed absolute CD14+ CD16+ monocyte, Treg (CD4+ CD25+ FOXP3+ ) and Th17 cell (CD4+ IL-17A+ ) counts on flow cytometry. We also measured changes in serum soluble interleukin (IL)-2 receptor (IL-2R), IL-6, and tumor necrosis factor (TNF)-α on enzyme-linked immunosorbent assay. RESULTS: Treg cells and Th17 cells significantly increased after IFX treatment compared with baseline (126 ± 85 cells/µL vs 62 ± 53 cells/µL, P < 0.01; 100 ± 111 cells/µL vs 28 ± 27 cells/µL, P < 0.05, respectively). In contrast, in a subgroup of patients with CD14+ CD16+ monocytes above the normal range before IFX, the CD14+ CD16+ monocytes significantly decreased following IFX treatment (72 ± 51 cells/µL vs 242 ± 156 cells/µL, P < 0.05).. Serum TNF-α did not change, but soluble IL-2R and IL-6 decreased after IFX treatment. CONCLUSION: IFX could downregulate activated monocytes and upregulate Treg cells towards the normal range. IFX treatment thus contributes to the process of attenuating inflammation in KD.

Outcomes of plasma exchange for severe dilated cardiomyopathy in children.

Antimyocardial autoantibodies are a cause of dilated cardiomyopathy (DCM). Immunoabsorption therapy for eliminating autoantibodies can improve cardiac function in adult DCM. The purpose of this study was to investigate the indication and efficacy of plasma exchange in children with DCM and their outcomes. We performed a single-center, retrospective study in children with DCM who had received plasma exchange (PE). Six patients in various degrees of heart failure (three patients in acute exacerbation phase, one patient in early phase, and two patients in chronic phase) received PE. The effects of first PE were that the left ventricular ejection fraction (LVEF) and New York Heart Association (NYHA) functional class were transiently increased in five of six patients (83 %) and in four of five patients (80 %), respectively. The median duration of improved cardiac function after first PE was 8 months. PE was performed a total of two times in two patients and three times in one patient. The effect of repeated PE was attenuated when compared with first PE. Improved LVEF and NYHA functional class were observed in two of four courses (50 %) and in one of four courses (25 %), respectively. The median duration of improved cardiac function was 1 month. PE can transiently improve cardiac function and clinical symptoms of DCM in children. PE may be an additional therapeutic option in children with refractory DCM. However, PE should only be considered as a bridge to ventricular assist device implantation or heart transplantation.

Plasma exchange for the patients with dilated cardiomyopathy in children is safe and effective in improving both cardiac function and daily activities.

Autoantibodies against cardiac proteins play an important role in the development of dilated cardiomyopathy (DCM). The efficacy and safety of apheresis such as immunoadsorption (IA) or plasma exchange (PE) to remove such antibodies have been reported in adult DCM patients. However, apheresis for pediatric DCM has not been performed because of technical difficulty due to relatively low blood volume and instability of hemodynamics. As we have experiences of preforming apheresis on hemodynamically unstable children, we have preformed ten courses of PE on seven child DCM patients including both patients in chronic and acute phase to assess the safety and efficacy to PE. Under general anesthesia, the patients were administered PE three times during 3 days as 1 course. Simultaneously, continuous hemodiafiltration (CHDF) was performed in series with the PE circuit to stabilize hemodynamic status and to minimize the adverse effects of PE. The changes in LVEF, CTR, mBP, the dosage of furosemide and NYHA were assessed before and after the procedure of PE. There were no severe adverse effects such as systemic bleeding or refractory hypotension due to apheresis. Echocardiography showed that mean baseline LVEF was 24.3 ± 7.8%. Mean LVEF significantly increased 1 week after PE to 30.5 ± 12.5%. CTR significantly decreased after PE. Mean BP significantly increased 1 month after PE (54.5 ± 10.7 to 60.7 ± 9.8 mmHg). NYHA improved after PE significantly (NYHA; 3.4 ± 1.1 to 2.5 ± 1.1). PE is safe and effective in improving both cardiac function and daily activities.

The development of a pseudo-chamber after balloon pulmonary angioplasty: long-term complications of balloon pulmonary angioplasty.

We experienced a rare complication where extravasation developed a pseudo-chamber long after the balloon pulmonary angioplasty for supravalvular pulmonary stenosis. A 3-month-old girl was diagnosed with an anomalous origin of the left coronary artery from the pulmonary artery. She underwent the Takeuchi procedure at 10 months of age. During the follow-up, the supravalvular pulmonary stenosis deteriorated, and was treated by balloon pulmonary angioplasty with the double balloon technique catheter at 6 years of age. Angiography at the main pulmonary artery showed a small amount of extravasation contrast medium after the procedure. Follow-up echocardiography showed a diminished extravasation hemorrhage. Twelve years later, right ventricular enlargement due to pulmonary regurgitation had been observed on echocardiography. In addition, abnormal echo free space was detected at the left posterior of the left atrium. Enhanced computed tomography clearly demonstrated there was an orifice and extent of the pseudo-chamber. Surgical findings revealed a large tear just distal to the coronary tunnel. We speculated that extravasation blood was limited in the perivascular area early after the procedure but eventually reached the non-adhesive oblique pericardial sinus with age. Consequently, pulmonary to oblique pericardial sinus communication was established and looked like a pseudo-chamber long after the procedure. In conclusion, even if extravasation seems to be limited immediately after the balloon pulmonary angioplasty, it could expand for non-adhesive space and could develop a huge blood space like chamber. Long-term careful observation should be necessary for extravasation of pulmonary artery even with surgical adhesion.

Co-occurrence of hypertrophic cardiomyopathy and myeloproliferative disorder in a neonate with Noonan syndrome carrying Thr73Ile mutation in PTPN11.

Most cases of Noonan syndrome (NS) result from mutations in one of the RAS-MAPK signaling genes, including PTPN11, SOS1, KRAS, NRAS, RAF1, BRAF, SHOC2, MEK1 (MAP2K1), and CBL. Cardiovascular diseases of varying severity, such as pulmonary stenosis and hypertrophic cardiomyopathy (HCM), are common in NS patients. RAF1 mutations are most frequent in NS with HCM, while PTPN11 mutations are also well known. Thr73Ile is a gain-of-function mutation of PTPN11, which has been highly associated with juvenile myelomonocytic leukemia and NS/myeloproliferative disease (MPD), but has not previously been reported in HCM. Here, we report a Japanese female infant with NS carrying the PTPN11 T73I mutation with NS/MPD, complete atrio-ventricular septal defect, and rapidly progressive HCM. No other HCM-related mutations were detected in PTPN11, RAF1, KRAS, BRAF, and SHOC2. This patient provides additional information regarding the genotype-phenotype correlation for PTPN11 T73I mutation in NS.

Benefits of Balloon-Dilatable Bilateral Pulmonary Artery Banding in Patients With Hypoplastic Left Heart Syndrome and Other Complex Cardiac Anomalies.

OBJECTIVES: The purpose of this study was to evaluate the potential of balloon-dilatable bilateral pulmonary artery banding (b-PAB) and its impact on the configuration of the pulmonary artery (PA). BACKGROUND: We have previously used balloon-dilatable b-PAB as first-stage palliation for patients with hypoplastic left heart syndrome (HLHS) and other complex cardiac anomalies. METHODS: Two pliable tapes were placed around each branch of the PA and tightened with 7-0 polypropylene sutures in a manner that allowed for the subsequent adjustment of PA diameters. We retrospectively examined the adjustability of PA diameters by balloon dilation and the need for surgical PA angioplasty at later stages. RESULTS: From January 2010 to October 2013, we performed b-PAB in 8 patients, including 3 borderline cases between biventricular repair (BVR) and univentricular repair (UVR). The b-PAB procedures were performed at a median age of 6.5 days (range, 2-10 days). Balloon dilations were performed in 10 lesions in 4 patients. All of the procedures were performed safely. Two patients reached definite BVR. The remaining 6 patients underwent open palliative procedures with univentricular physiologies that resulted in 2 deaths unrelated to the initial b-PAB. In all but 1 of the patients, the PA configuration was properly maintained and did not require surgical pulmonary angioplasty. CONCLUSIONS: Balloon-dilatable b-PAB can be performed safely and prevents PA distortion at later stages. This technique should be considered for patients with complex cardiac anomalies if uncertainty exists regarding the optimal surgical strategy (BVR or UVR) in early infancy.

Novel curved balloon catheter for dilating postoperative angled lesions associated with congenital heart disease.

OBJECTIVES: This study aimed to analyze the surface stress generated by a novel curved balloon and assess its efficacy for treating angular lesions associated with congenital heart disease. BACKGROUND: Obstructions at the anastomosis of aortopulmonary shunts and cavopulmonary connections may occur postoperatively. Catheter interventions are often performed for such lesions; however, acute angulation may cause balloon slippage or inappropriate stress on the vessel wall. METHODS: We dilated the curved balloon in a curved vessel model and measured the resultant wall stress and its distribution. Clinical evaluations were performed using this balloon in angled lesions. RESULTS: In the curved vessel model, curved balloons generated uniform stress on the lesser and greater curvatures (curved type, lesser/greater = 0.343 MPa/0.327 MPa; P = 0.61), whereas straight balloons caused disproportionate stress (straight type, lesser/greater = 0.358 MPa/0.254 MPa; P = 0.19). However, the difference in average stress was not statistically significant. Furthermore, the stress was uniform along the entire length of the curved balloon, but differed between the mid and end portions of the straight balloon. Curved balloon dilations were performed for 10 lesions in 7 patients. The curved balloon conformed well to the angulated lesion without slipping. The median percent change in the minimal lumen diameter (MLD) was 64% (range, 0-206%). In 5 lesions, MLD increased by ≥50%. Oxygen saturation increased by 5% (0-9%). CONCLUSIONS: Although further clinical evaluation is necessary, this novel curved balloon may be a reasonable alternative in angled lesions, providing better conformability and preventing excessive stress to the vessel wall adjacent to the stenosis.

Correlation between the Closure Time of Patent Ductus Arteriosus in Preterm Infants and Long-Term Neurodevelopmental Outcome.

In patent ductus arteriosus (PDA) in preterm infants, the relationship between treatment timing and long-term developmental prognosis remains unclear. The purpose of this study was to clarify the relationship between the age in days when ductus arteriosus closure occurred and long-term development. Preterm infants with a birth weight of less than 1500 g who were admitted to our NICU over a period of 9 years (2011-2019) and were diagnosed with PDA were included. A new version of the K-type developmental test for corrected ages of 1.5 and 3 years was used as an index of development. The relationship between the duration of PDA and the developmental index was evaluated using Pearson's correlation coefficient, and multiple regression analysis was performed. Development quotient (DQ) at the ages of 1.5 and 3 years showed a correlation with the PDA closure date and the standard deviation (SD) value of the term birth weight. Multiple regression analysis showed a positive correlation of the DQ at 1.5 and 3 years with the SD value of the term birth weight and a negative correlation with the PDA closure date. In addition, a stronger correlation was found in the "posture/motor" sub-item at 3 years. On the other hand, the analysis including preterm infants without PDA showed that preterm infants with PDA closure on the 6th day or later after birth had a significantly lower 3-year-old DQ than preterm infants with a PDA exposure within 5 days. In conclusion, it is suggested that the decrease in cerebral blood flow due to PDA in preterm infants has an adverse effect on long-term neurodevelopment. Appropriate interventions, including surgical treatment for PDA in preterm infants without delay, ideally within 5 days of birth, may be effective in improving the developmental prognosis.

Transoral traumatic perforation of the pyriform sinus by a marker pen: report of an infant case.

BACKGROUND: Perforation of the pyriform sinus, included in hypopharyngeal injury, is a rare condition typically caused by iatrogenic factors. We present a case of an infant who developed deep cervical and mediastinal abscesses due to a traumatic pyriform sinus perforation caused by accidentally falling with a marker pen in the mouth. CASE PRESENTATION: An 11-month-old healthy male infant fell on a trampoline with a marker pen in his mouth. The patient developed swelling in the neck 3 h after the incident and was taken to a regional general hospital. Although a laryngoscopy showed no perforation in the oral cavity or posterior pharynx, a computed tomography (CT) scan revealed significant emphysema extending from the cervix to the mediastinum. The patient was transferred to our tertiary hospital and admitted to the intensive care unit, where he was mechanically ventilated, and antibiotic therapy was initiated. On day 3 of admission, a CT scan revealed deep abscesses in the cervical and upper posterior mediastinum with pneumomediastinum. Although his respiratory status stabilized and he was temporarily weaned, the fever recurred. Pharyngoesopagography revealed significant leakage of contrast from the left pyriform sinus to the mediastinum. Consequently, surgical drainage of the abscess was performed on day 10. Two low-pressure continuous suction drains were placed, one in the posterior mediastinum and the other close to the pyriform sinus. Pharyngoesophagography on postoperative day (POD) 7 demonstrated decreased contrast leakage into the posterior mediastinum. The patient was initiated on enteral nutrition through a nasogastric tube. The patient was discharged on POD 31 after the suction drains were replaced with open Penrose drains, and enteral nutrition via nasogastric tube was continued at home. The Penrose drains were removed on POD 54, and salivary leakage ceased on POD 111. CONCLUSIONS: Although injuries to the oral cavity and posterior pharynx are more easily recognized, the existence of injury in the pyriform sinus can be challenging to evaluate. However, prompt and appropriate management, including intubation, antibiotic therapy, surgical drainage, and nutritional support, is critical in preventing life-threatening complications.

A simple scoring model based on machine learning predicts intravenous immunoglobulin resistance in Kawasaki disease.

INTRODUCTION: In Kawasaki disease (KD), accurate prediction of intravenous immunoglobulin (IVIG) resistance is crucial to reduce a risk for developing coronary artery lesions. OBJECTIVE: To establish a simple scoring model predicting IVIG resistance in KD patients based on the machine learning model. METHODS: A retrospective cohort study of 1002 KD patients diagnosed at 12 facilities for 10 years, in which 22.7% were resistant to initial IVIG treatment. We performed machine learning with diverse models using 30 clinical variables at diagnosis in 801 and 201 cases for training and test datasets, respectively. SHAP was applied to identify the variables that influenced the prediction model. A scoring model was designed using the influential clinical variables based on the Shapley additive explanation results. RESULTS: Light gradient boosting machine model accurately predicted IVIG resistance (area under the receiver operating characteristic curve (AUC), 0.78; sensitivity, 0.50; specificity, 0.88). Next, using top three influential features (days of illness at initial therapy, serum levels of C-reactive protein, and total cholesterol), we designed a simple scoring system. In spite of its simplicity, it predicted IVIG resistance (AUC, 0.72; sensitivity, 0.49; specificity, 0.82) as accurately as machine learning models. Moreover, accuracy of our scoring system with three clinical features was almost identical to that of Gunma score with seven clinical features (AUC, 0.73; sensitivity, 0.53; specificity, 0.83), a well-known logistic regression scoring model. CONCLUSION: A simple scoring system based on the findings in machine learning seems to be a useful tool to accurately predict IVIG resistance in KD patients.

Postoperative hyperthermia-induced multiple organ failure in a child with Down syndrome: a case report.

BACKGROUND: Psychological stress has been reported to cause hyperthermia. Persistent excessive hyperthermia can, in turn, cause hypercytokinemia and organ damage. We report a case of postoperative severe hyperthermia leading to a systemic inflammatory response and multiple organ failure in a child with Down syndrome. CASE PRESENTATION: A 10-month-old native Japanese boy with Down syndrome and Hirschsprung's disease is described. Newborn screening showed congenital hypothyroidism and a ventricular septal defect, but these conditions were stable upon administration of levothyroxine and furosemide. His development was equivalent to that of a child with Down syndrome. He developed a noninfectious high fever twice after preoperative preparations at age 8 months and again at 9 months. He was readmitted to hospital at age 10 months to undergo the Soave procedure to correct Hirschsprung's disease. However, he contracted a fever immediately after the surgical procedure. Hyperthermia (42 °C) was refractory to acetaminophen treatment and deteriorated to multiple organ failure due to hypercytokinemia, with increased serum levels of interleukin-6 (44.6 pg/mL) and interleukin-10 (1010 pg/mL). He died on postoperative day 2 with hypoxemia, respiratory/metabolic acidosis, increased serum levels of transaminases, reduced coagulation, and pancytopenia. Various infectious and noninfectious causes of hyperthermia could not be identified clearly by culture or blood tests. CONCLUSIONS: We speculated that the proximate cause of the fever was psychological stress, because he suffered repeated episodes of hyperthermia after the invasive procedure. Hyperthermia, together with the immune-system disorders associated with Down syndrome, may have induced hypercytokinemia and multiple organ failure. This rare case of noninfectious postoperative hyperthermia leading to multiple organ failure may help to shed further light on the currently unclear pathogenic mechanism of hyperthermia and associated multiple organ failure during the perioperative period in children.

Giant pulmonary bulla causing respiratory compromise in a very low-birthweight infant.

Acquired cystic lung disease in premature infants is a serious respiratory complication, and pulmonary interstitial emphysema (PIE) has been widely reported. We report a rare case of giant pulmonary bulla in an infant treated with bullectomy where chest computed tomography was useful in directing treatment.

Plasma exchange for removal of antibeta1-adrenergic receptor antibody in a small child with dilated cardiomyopathy.

A 5-year-old boy was diagnosed with dilated cardiomyopathy (DCM) at 8 months of age. He underwent plasma exchange (PE) three times during 4 days because his antibeta1-adrenergic receptor antibody titer was 160 times the background density on enzyme-linked immunosorbent assay. BNP titer decreased from 1320 pg/ml before to 506 pg/ml after PE. Dobutamine infusion was discontinued after PE because of improving cardiac function. After PE, his antibeta1-adrenergic receptor antibody titer was < 20 times the background density. When patients have a high titer of antibeta1-adrenergic receptor antibody, PE should be considered, even in small children, as an alternative treatment.

A de novo gain-of-function KCND3 mutation in early repolarization syndrome.

BACKGROUND: Early repolarization syndrome (ERS) is characterized by J-point elevation on electrocardiograms and ventricular fibrillation (VF). Early repolarization arises from augmentation of the transmural electrical gradient in the cardiac action potential; therefore, the transient outward potassium current (Ito) has been regarded as a key candidate current for elucidating the mechanism of ERS. KCND3 encoding Kv4.3, an α-subunit of the Ito channel, is considered as one of target genes. OBJECTIVE: The purpose of this study was to search for novel KCND3 mutations associated with ERS and to clarify the pathogenesis. METHODS: We performed genetic screening for 11 unrelated probands with ERS and analyzed the electrophysiological properties of detected mutations by patch-clamp methods. RESULTS: A novel de novo KCND3 heterozygous mutation, Gly306Ala (c.917g>c), was found in 1 proband. The proband was a 12-year-old boy, who suffered VF storm and showed significant J-point elevation in multiple leads. Intravenous isoproterenol and subsequent administration of quinidine were effective in preventing VF recurrence and restored the J-point elevation. In electrophysiological analysis, cultured cells expressing mutant Kv4.3 showed significantly increased current densities, slow inactivation, and slow recovery from inactivation compared to wild type. Extracellular application of quinidine significantly restored the inactivation time course in mutant Kv4.3. A simulation study confirmed the relationship between the novel KCND3 mutation and early repolarization on electrocardiograms. CONCLUSION: A novel KCND3 heterozygous mutation was found to be associated with ERS. The pathogenesis can be explained by the increased Ito. Genetic screening for KCND3 could be useful for understanding the pathogenesis and selecting effective treatment.

Plasma Exchange Downregulates Activated Monocytes and Restores Regulatory T Cells in Kawasaki Disease.

In Kawasaki disease (KD), the effect of plasma exchange (PE) on immune cells has not been fully elucidated. Therefore, we examined the changes in the number of CD14+ CD16+ activated monocytes, regulatory T (Treg ), and T-helper type 17 (Th17) cells in KD patients treated with PE. The percentage of total monocytes and subclasses of lymphocytes, including CD4+ and CD8+ T cells, and CD19+ B cells, showed no significant difference before and after PE. However, the percentage of CD14+ CD16+ monocytes in total leukocytes decreased significantly after PE (1.1% ± 1.5% vs. 2.1% ± 2.3%, P < 0.05). Furthermore, while the percentage of Th17 cells in CD4+ T cells did not change, the percentage of Treg cells in CD4+ T cells increased significantly after PE (11.1% ± 5.1% vs. 8.0% ± 4.4%, P < 0.05). Therefore, PE downregulates activated monocytes and upregulates Treg cells toward normal levels and thus attenuates inflammation in KD.