No association between inactivated influenza vaccination and influenza viral load at diagnosis among young Japanese children: An observational study of the 2013/2014 through 2017/2018 influenza seasons.

BACKGROUND: The association between inactivated influenza vaccination and viral load in young children remains unclear. METHODS: During the 2013/2014 to 2017/2018 influenza seasons in Japan, children under 6 years of age with pre-defined influenza-like illness and influenza-positive status by real-time RT-PCR were recruited at pediatric clinics for this observational study. Influenza viral load was measured for the most predominant subtype/lineage in each season. Using median dichotomized viral load as an outcome, a multilevel logistic regression model was applied to estimate the multivariable adjusted odds ratio (MOR) and 95% confidence interval (CI) for higher viral load. RESULTS: A total of 1,185 influenza-positive children were analyzed. The median log10 viral load copy number (copies per milliliter) was 5.5 (interquartile range, 4.6 to 6.1) and did not differ by vaccination status: 5.5 for unvaccinated, 5.7 for one dose, and 5.5 for two doses (p = 0.67). The MOR of vaccinated (one or two doses) versus unvaccinated children was 1.19 (95% CI: 0.86-1.64). Other factors showing significant associations with higher viral load were positive results for A(H1N1)pdm09 and A(H3N2) in comparison with B/Yamagata. The respective MORs were 3.25 (95% CI: 2.28-4.64) and 1.81 (95% CI: 1.32-2.49). Significantly elevated MORs against higher viral load were also observed for higher body temperature at influenza diagnosis and shorter duration from fever onset to specimen collection. CONCLUSION: No association was observed between inactivated-influenza vaccination and viral load at influenza-positive diagnosis. Influenza subtype/lineage, body temperature, and time elapsed since fever onset were significantly associated with viral load.

Influence of Prior Influenza Vaccination on Current Influenza Vaccine Effectiveness in Children Aged 1 to 5 Years.

BACKGROUND: Although annual influenza vaccination is an important strategy used to prevent influenza-related morbidity and mortality, some studies have reported the negative influence of prior vaccination on vaccine effectiveness (VE) for current seasons. Currently, the influence of prior vaccination is not conclusive, especially in children. METHODS: We evaluated the association between current-season VE and prior season vaccination using a test-negative design in children aged 1-5 years presenting at nine outpatient clinics in Japan during the 2016/17 and 2017/18 influenza seasons. Children with influenza-like illness were enrolled prospectively and tested for influenza using real-time RT-PCR. Their recent vaccination history was categorized into six groups according to current vaccination doses (0/1/2) and prior vaccination status (unvaccinated = 0 doses/vaccinated = 1 dose or 2 doses): (1) 0 doses in the current season and unvaccinated in prior seasons (reference group); (2) 0 doses in the current season and vaccinated in a prior season; (3) 1 dose in the current season and unvaccinated in a prior season; (4) 1 dose in the current season and vaccinated in a prior season; (5) 2 doses in the current season and unvaccinated in a prior season, and (6) 2 doses in the current season and vaccinated in a prior season. RESULTS: A total of 799 cases and 1196 controls were analyzed. The median age of the subjects was 3 years, and the proportion of males was 54%. Overall, the vaccination rates (any vaccination in the current season) in the cases and controls were 36% and 53%, respectively. The VEs of the groups were: (2) 29% (95% confidence interval: -25% to 59%); (3) 53% (6% to 76%); (4) 70% (45% to 83%); (5) 56% (32% to 72%), and (6) 61% (42% to 73%). The one- and two-dose VEs of the current season were significant regardless of prior vaccination status. The results did not differ when stratified by influenza subtype/lineage. CONCLUSION: Prior vaccination did not attenuate the current-season VE in children aged 1 to 5 years, supporting the annual vaccination strategy.

Hypoxia induces alteration of bone morphogenetic protein receptor signaling in pulmonary artery endothelial cell.

Reduced expression of bone morphogenetic protein receptors (BMPR) has been implicated in the pathogenesis of pulmonary hypertension (PH), but changes in the intracellular signaling pathway of BMPR have not been fully understood. We hypothesized that BMPR signaling in pulmonary endothelial cells is altered during the development of PH, such as hypoxia-induced PH. We examined the expression of BMPR, BMP-regulated Smads and Id-1 in lung tissues of Sprague-Dawley rats exposed to 2 wk of hypoxia and in isolated lung vascular endothelial cells exposed to hypoxia. BMPRII was predominantly expressed in the endothelial cells (EC) of pulmonary vasculature. In hypoxic rats, reduced expression of BMPRII was observed in the EC of resistance pulmonary arteries. The expression of phosphorylated-Smad1/5/8 and Id-1 in EC was also reduced, whereas the expression of Smad1 as well as activin receptor-like kinase 1 (ALK1) was up-regulated during the development of PH. In in vitro exposure to hypoxia, the expression of mRNA transcripts for BMPRII, Smad8, and Id-1 in EC was reduced, whereas mRNA of Smad1 was not diminished. Our results suggest that hypoxia induces alteration of intracellular BMPR signaling in the EC of resistance pulmonary artery, which is involved in the pathogenesis of PH.

Application of signal-averaged electrocardiogram to myocardial damage in the late stage of Kawasaki disease.

BACKGROUND: Myocardial damage occurs in the late stage of Kawasaki disease (KD) regardless of whether coronary artery lesions (CALs) are present. METHODS AND RESULTS: A signal-averaged electrocardiogram (ECG) was performed in 23 patients who were in the late stage of KD (CAL was found in 12 and no CAL (non-CAL) was found in 11) and 10 healthy controls. Filtered QRS duration and the root-mean-square voltage in the last 40 ms of the QRS complex were measured using time-domain analysis. Additionally, the area ratio (AR), (area of 20-50 Hz)/(area of 0-20 Hz) x100, was calculated by frequency domain analysis. These findings were compared with the clinical data and histopathological findings. In time-domain analysis, there were no significant differences among the 3 groups. In frequency domain analysis, the AR in CAL was significantly higher than that in the other 2 groups. Furthermore, all 4 patients who underwent an endomyocardial biopsy showed a high AR and abnormal histopathological features. CONCLUSIONS: The findings of the present study suggest that patients in the late stage of KD have abnormal findings on signal-averaged ECG even without stenotic lesions, arrhythmia or ischemia, a condition that might reflect histopathological changes in the myocardium in the late stage of KD.

Determination of timing for reoperation in patients after right ventricular outflow reconstruction.

After right ventricular (RV) outflow reconstruction, patients often develop postoperative outflow tract stenosis or pulmonary regurgitation, or both. The aim of this study was to assess the relation between RV hypertrophy, volume, pressure, and function and to provide indications for repeat surgery. We performed magnetic resonance imaging to measure RV volume, wall mass, and the ratio of mass to volume in 31 patients after RV outflow reconstruction and in 12 controls. Patients were divided into 2 groups, New York Heart Association class I and the repeat surgery group. The RV stress index was defined as RV peak systolic pressure/(mass to volume); RV ejection fraction (EF) was calculated by ventriculography. The RV stress index for the repeat surgery group was significantly higher than for the remaining groups (p <0.01). In the New York Heart Association class I and control groups, a significant inverse correlation was observed between RVEF and the RV stress index (r = -0.59, p <0.01). All patients in reoperation group whose RVEF decreased to <95% confidence limit of regression had symptoms of RV failure. The RV stress index decreased substantially after reoperation, but RVEF remained at <95% limits. These findings suggest that excess RV wall stress contributes to impaired RV performance. The RV stress-RVEF relation may be useful in assessing RV function and in establishing a surgical indication.

The clinical pathway for fast track recovery of school activities in children after minimally invasive cardiac surgery.

BACKGROUND: Minimally invasive cardiac surgery is now becoming standard in the correction of simple congenital cardiac malfbrmations. We introduced a clinical pathway for fast track recovery of school activities in children after minimally invasive cardiac surgery, and assessed the function of the pathway in children with atrial or ventricular septal defects, comparing minimally invasive surgery to repair through a conventional full sternotomy. METHODS: We studied 15 children of school age who underwent repair of an atrial or ventricular septal defect through a lower midline sternotomy, and 10 children undergoing repair through a full sternotomy. The clinical pathway was for extubation to take place in the operating room, echocardiographic evaluation on the 5th postoperative day, and discharge home on the 7th postoperative day, with return to school within 2 weeks, and resumption of all gymnastic activity within 6 weeks of the minimally invasive surgery. RESULTS: In those having a lower midline sternotomy, postoperative hospital stay was 7.4 +/- 0.8 days, with return to school 8.0 +/- 2.4 days after discharge. They resumed gymnastics 41 +/- 11 days after the minimally invasive surgery. In those having a full sternotomy, in contrast, these parameters were 13.5 +/- 2.7, 23.1 +/- 8.4, and 95 +/- 43 days, respectively. Of the 15 children undergoing a minimally invasive approach, 12 (80%) fulfilled the criterions of our clinical pathway. CONCLUSIONS: We conclude that minimally invasive cardiac surgery can safely be performed in children. In addition to its cosmetic role, the technique has added value in promoting early return to normal school life, including gymnastics.

P wave signal averaged electrocardiography in patients undergoing the Fontan operation.

OBJECTIVES: Supraventricular arrhythmias are one of the most common and fatal sequelae of the Fontan operation. P wave triggered signal averaged electrocardiography was performed in patients undergoing the Fontan operation to evaluate the presence of atrial degeneration, and to clarify which factors affected the development of atrial arrhythmias. METHODS: P wave triggered signal averaged electrocardiography was recorded in 14 patients after the Fontan-type operation (conventional atriopulmonary connection in 5 and total cavopulmonary connection in 9) and 15 healthy controls. The duration and area of the filtered P wave, and the signal magnitudes (M20, M30) at 20 Hz and 30 Hz obtained from the frequency domain analysis of the P wave (M20, M30) were evaluated and compared with the hemodynamic data. RESULTS: The duration and area of the filtered P wave, M20 and M30 in patients after atriopulmonary connection were significantly greater than in those after total cavopulmonary connection and the control subjects (p < 0.05). M20 was significantly greater in patients after total cavopulmonary connection than in the control subjects. Right atrial volume in patients after atriopulmonary connection was significantly (p < 0.001) larger than in patients after total cavopulmonary connection (p < 0.05). There were no significant differences in other indices including atrial pressure between the two groups. CONCLUSIONS: Our results suggest that the substrate for atrial arrhythmias such as atrial myocardial degeneration and fibrosis is frequently present in patients after the Fontan operation, especially after atriopulmonary connection. Thus, the enlarged right atrium may be involved in the presence of a substrate for atrial arrhythmias. The developmental risk for late atrial arrhythmias seems to be present even in patients after total cavopulmonary connection.