Clinical symptoms of patients with Kawasaki disease include smoldering fever.

BACKGROUND: Persistent low-grade fever has been observed in some patients during intravenous immunoglobulin (IVIG) therapy for Kawasaki disease (KD); however, smoldering fever (SF) has not previously been reported in patients with KD. This study aimed to clarify the clinical characteristics of SF in patients with KD. METHODS: A single-center retrospective cohort study, which included a total of 621 patients who received IVIG therapy, was conducted. Patients with a fever of 37.5-38°C lasting ≥3 days after 2 days of the initial-IVIG were defined as the SF group. Patients were divided into four groups according to the fever course: SF (n = 14), biphasic fever (BF, n = 78), non-fever after initial-IVIG (NF, n = 384), and persistent fever (PF, n = 145). The clinical features of SF were described and compared between the groups. RESULTS: The median duration of fever in the SF group was 16 days, which was longer than that in any other group. The neutrophil fraction after IVIG therapy in the SF group was higher than that in the BF and NF groups but similar to that in the PF group. Repeated IVIG administration in the SF group resulted in increased IgG levels but decreased serum albumin levels. In the SF group, 29% of the patients had coronary artery lesions at 4 weeks. CONCLUSIONS: The frequency of SF in KD was 2.3%. Patients with SF continued to have moderate inflammatory responses. Repeated administration of IVIG doses was not effective in treating SF, and acute coronary artery lesions were occasionally observed. Active therapeutic intervention was needed.

New predictors to identify severe cases during intravenous immunoglobulin therapy in Kawasaki disease.

BACKGROUND: The purpose of this study was to predict which patients would require plasma exchange therapy (PEX) using laboratory findings during intravenous immunoglobulin (IVIG) therapy in Kawasaki disease. METHODS: A retrospective, single-center, cohort study was conducted. Of the 621 IVIG-treated patients, 166 patients who received a second IVIG dose on the second day after initiation of IVIG were included. The endpoint was PEX. Participants were divided into two groups: 10 patients who received PEX and 156 patients who did not. The variables were C-reactive protein (CRP), white blood cell count (WBC), and neutrophil fraction (NEUT) at three time points: pre-initial IVIG, pre-second IVIG, and post-second IVIG. The change ratio (post-IVIG value/pre-IVIG value) of each variable, with each IVIG dose, was calculated. Receiver operating characteristic analysis determined the area under the curve (AUC) and cut-off values. RESULTS: The variables with an AUC > 0.9 were CRP (post-second IVIG), change ratio of CRP (CRP value post-second IVIG/CRP value pre-second IVIG), NEUT (pre-second IVIG), and NEUT (post-second IVIG). Among these, the variables with high sensitivity were CRP (post-second IVIG) and the change ratio of CRP (second IVIG), with cut-off values of 9.52 mg/dL and 0.99, respectively. The sensitivity and specificity of these variables were 100% and 91%, and 100% and 80%, respectively. The combined sensitivity and specificity (95% confidence intervals) of these two variables were 100% (59-100) and 94% (89-97). CONCLUSION: High CRP levels and the change ratio of CRP after the second IVIG dose were associated with PEX.

Poor response to intravenous immunoglobulin in patients with a parental history of Kawasaki disease.

BACKGROUND: Patients whose parents had a history of Kawasaki disease (KD) often show a poor response to intravenous immunoglobulin (IVIG). There are very few reports describing the clinical characteristics and no reports on changes in C-reactive protein (CRP) level after IVIG administration in such cases. METHODS: A single-center cohort study including 950 patients hospitalized for KD and treated with IVIG was conducted. The patients were divided into two groups: patients whose parents had a history of KD (PHK) (N = 16) and patients whose parents had no history of KD (NPHK) (N = 934). The clinical characteristics and responsiveness to IVIG were compared between the two groups. RESULTS: The PHK group had higher CRP levels before administering IVIG than the NPHK group (P = 0.0010). CRP levels after IVIG administration were higher in the PHK group than in the NPHK group (P = 0.0094). The percentage of patients who received a second administration of IVIG on day 2 after the initial IVIG therapy was higher in the PHK group than in the NPHK group (P = 0.0016). The percentage of patients who required plasma exchange therapy in the PHK group was significantly higher than that in the NPHK group (P = 0.0010). CONCLUSIONS: Patients in the PHK group had severe KD before IVIG administration, and these patients showed poor responsiveness to IVIG therapy.

Ascending Aortic Aneurysm in a Child With Fibulin-4 Deficiency.

EFEMP2 (alias FBLN4) encodes extracellular matrix protein fibulin-4, and its mutation is associated with autosomal recessive cutis laxa type 1B and leads to severe aortopathy with aneurysm formation and vascular tortuosity. A 4-month-old child presented with a large ascending aortic aneurysm, and genetic testing revealed an EFEMP2 mutation. We achieved successful repair of the ascending aortic aneurysm at 33 months of age and report the macroscopic and microscopic findings.

Self-perception of children with autism spectrum disorders.

BACKGROUND: We aimed to evaluate self-perceived competence and self-esteem of primary school children with autism spectrum disorder (ASD) in Japan and compare to those of children with other chronic physical diseases and healthy controls. METHODS: Data were collected from 227 children: ASD (N.=91), nephrotic syndrome (NS) (N.=52) and asthma (N.=84), using Children's Perceived Competence Scale (CPCS) in 2012-2014. CPCS measures perceived competence in cognitive, social and physical domains, and a general self-worth domain as self-esteem. RESULTS: Scores in the social domain of the ASD group were lower than those of all other groups after adjusting for school age grades and gender. Scores of the ASD group negatively correlated with psychosomatic symptoms in all domains and IQ in the physical domain. CONCLUSIONS: These findings are the first data set in Japan on self-perceived competence and self-esteem in primary school children with ASD. Those results were comparable to previous researches in adolescents with ASD. Low social domain scores in the ASD group indicate the CPCS may be one of the useful tools to evaluate difficulty in social competence from the children's point of view. Correlations between CPCS scores and psychosomatic symptoms in the ASD group suggest development of psychosomatic symptoms may be addressed early by attention to low scores, especially in general self-worth.

Impact of rotavirus vaccination on the burden of acute gastroenteritis in Nagoya city, Japan.

BACKGROUND: In Nagoya city, Japan, rotavirus (RV) vaccination has been available since 2011 with estimated coverage reaching 92% by 2015 after the introduction of a public subsidy in 2012. This study assessed the impact of vaccination on the RV gastroenteritis (RVGE) burden in children aged <5 years old (y) by comparing RVGE hospitalizations and outpatient visits during pre-vaccination (2007-2011), transition (2011-2012) and subsidization (2012-2016) periods. METHODS: All hospitalizations and outpatient visits in children aged <5 y from 2 administrative districts of Nagoya city were identified from the hospital-based electronic databases of 4 hospitals. RVGE cases were identified by diagnostic code and/or positive results of diagnostic kits. RESULTS: Compared to the pre-vaccination period, there was a decrease in RVGE hospitalizations for children <5 y from 5.59 per 1000 person-year (kPY) to 3.65/kPY in the subsidization period (i.e. 34.69%). In children <1 y, the incidence of RVGE hospitalizations decreased continuously from 6.62/kPY in the pre-vaccination period to 1.84/kPY in the subsidization period (i.e. 72.19%). The highest decrease was observed in the subsidization season i.e. when high coverage was reached: 69% and 75.57% in the 2013/2014 season for 2-3 y and 3-4 y, and 74.03% in the 2014/2015 season for 4-5 y, respectively. Proportion of RVGE outpatient visits decreased by 87.44% for children <1 y and 57.05% for <5 y from the pre-vaccination to the subsidization period. This decrease started the first year of subsidization for children <1 y, 1-2 y and 2-3 y (78.89%, 18.86% and 5.80%) and the second year (2013/2014 season) for children 3-4 y and 4-5 y (87.73% and 51.78%). CONCLUSIONS: Although yearly fluctuations have been observed, the introduction of vaccination significantly decreased pediatric RVGE hospitalizations and outpatient visits, especially in the age group eligible for vaccination. During the second and third year of subsidization, we observed a herd protection effect on other age groups <5 y who were not eligible for vaccination. Clinicaltrial.gov.registered#:NCT01733862.

Children's Perceived Competence Scale: Reference values in Japan.

To support children with chronic diseases, reference values to measure developmental changes in self-perception and self-esteem are considered a useful yardstick. To develop reference values to measure self-perceived competence and self-esteem in Japanese children, the Children's Perceived Competence Scale (CPCS) was administered to 768 children of elementary school grade 1 (6 years) to grade 6 (11 years) at four public schools in Japan, from November to December 2012. After excluding 74 with chronic diseases and/or incomplete responses, 694 children were included. CPCS measures children's self-perceived competence in cognitive, social, physical domains, and general self-worth, namely self-esteem. There was a tendency for scores of cognitive and general self-worth to decrease with increasing grade. Scores among grade 5 respondents were significantly lower than those among grade 4 respondents for both social and physical domains. Scores among boys and girls differed significantly, with boys scoring higher for physical domain in grades 3 and 6 and for general self-worth domain in grade 6. The CPCS reference values to measure self-perceived competence and self-esteem in Japanese children were developed in this study. These reference values are useful to inform practitioners supporting children with psychological or psychiatric problems or those with chronic diseases.

A case of atypical hemolytic uremic syndrome due to anti-factor H antibody in a patient presenting with a factor XII deficiency identified two novel mutations.

A 9-year-old boy with pallor and macrohematuria showed hemolytic anemia, thrombocytopenia and renal failure. There was no history of diarrhea and the stool culture was negative. A diagnosis of atypical hemolytic uremic syndrome (HUS) was confirmed; however, the cause of the prolonged activated partial thromboplastin time (APTT) was unknown. Plasma exchange and hemodialysis were performed because of progressive hemolytic anemia and renal dysfunction. Fresh frozen plasma was administered frequently to correct the prolonged APTT after hemolysis was controlled and C3 levels had recovered. Factor H (FH) and factor I (IF) levels were normal and we did not detect mutations of FH, IF and membrane cofactor protein. Further investigation revealed the presence of anti-FH antibody in the patient's plasma and a deficiency of coagulation factor XII. Analysis of the patient's coagulation system displayed <3% functional activity of factor XII, whereas levels of other coagulation factors were within the normal range. Two novel mutations (W222G and R447S) were identified upon analysis of the factor XII gene in this patient. Moreover, further investigation revealed that compound heterozygous mutations were present in two of the patient's three siblings, while the third sibling only had a mutation at W222G. The patient was treated for atypical HUS; however, no treatment was required for factor XII deficiency as he did not display a hemorrhagic tendency. We report here a rare case of atypical HUS due to anti-FH antibody presenting with a coagulation factor XII deficiency.

Comprehensive genetic analysis of relevant four genes in 49 patients with Marfan syndrome or Marfan-related phenotypes.

In order to evaluate the contribution of FBN1, FBN2, TGFBR1, and TGFBR2 mutations to the Marfan syndrome (MFS) phenotype, the four genes were analyzed by direct sequencing in 49 patients with MFS or suspected MFS as a cohort study. A total of 27 FBN1 mutations (22 novel) in 27 patients (55%, 27/49), 1 novel TGFBR1 mutation in 1 (2%, 1/49), and 2 recurrent TGFBR2 mutations in 2 (4%, 2/49) were identified. No FBN2 mutation was found. Three patients with either TGFBR1 or TGFBR2 abnormality did not fulfill the Ghent criteria, but expressed some overlapping features of MFS and Loeys-Dietz syndrome (LDS). In the remaining 19 patients, either of the genes did not show any abnormalities. This study indicated that FBN1 mutations were predominant in MFS but TGFBRs defects may account for approximately 5-10% of patients with the syndrome.

Neonatal sudden death due to Legionella pneumonia associated with water birth in a domestic spa bath.

We report the first case of neonatal Legionnaires' disease associated with water birth in a spa bath at home. Legionella pneumophila serogroup 6 was detected from postmortem lung tissue.

Less invasive surgical closure of patent ductus arteriosus in extremely low birth weight infants.

Minimally invasive surgery is widely used in pediatric surgery. Extremely low birth weight infants (ELBWI) are literally so fragile to surgical stress that the minimum invasive procedures should be required. We report 15 ELBWI cases with patent ductus arteriosus (PDA), who underwent surgical closure. All of them had failed treatment with indomethacin to close PDA or had contraindicated to its use. The mean gestational age at birth was 26.0+/-2.7 weeks (24-34 weeks) and birth weight 702+/-140 g (479-966 g). The mean age at operation was 23+/-11 days (2-48 days) and body weight at operation 679+/-151 g (428-969 g). The surgery-related mortality was none. No complications were also encountered. Our surgical procedures consist of 2 modalities, one is clipping PDA, not ligation. Clipping technique attributes to minimize the dissection of surrounding tissue of PDA. The other is posterolateral muscle sparing thoracotomy, which would reduce long-term physical impairment and deformity. We believe our surgical technique can be accomplished safely and would be an alternative approach for ELBWI with a lower probability of PDA closure with indomethacin or an increased risk of complications for medical treatment.