吉川 哲史

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital cardiovascular anomaly that occurs in approximately 1 in 300,000 live births. This study aimed at identifying preoperative predictors of immediate postoperative outcomes. We conducted a retrospective, cross-sectional, single-center study and reviewed echocardiographic and hemodynamic data from all patients before and after surgical repair of ALCAPA at our center from January 2004 to February 2018. In all cases, the left coronary artery arose from the main pulmonary artery or a major branch. A total of 10 patients (age 1 month to 10 years, median 3 months) underwent ALCAPA surgical repair during the study period. No patients required a left ventricular assist device (LVAD) before surgery, but 4 patients (40%) received an LVAD after the surgery. The left ventricular ejection fraction (LVEF) improved in all patients following surgery. The utility of preoperative factors associated with pre- and post-procedure LVEF was investigated. LV dimension, as well as right coronary artery (RCA) and left coronary circumflex artery (LCX) Z scores were associated with a higher LVEF in the preoperative state. Patients with larger RCA, left ascending artery (LAD), and LCX Z scores also had a shorter duration of mechanical ventilation and ICU stay following surgery. Patients with a RCA Z score < 4 required implantation of an LVAD postoperatively. ALCAPA patients with larger RCA and LCX demonstrated a higher preoperative LVEF, while those with larger RCA, LAD, and LCX had superior postoperative hemodynamics and clinical outcomes.

Introduction: Scholarship is an essential component of postgraduate education. This study's objective was to investigate the effect of a new reform requiring research publication experience before taking the pediatric board examination to promote scholarly activities among pediatric residents in Japan. Methods: We conducted an experimental study from 2015 to 2018 to investigate the effectiveness of this reform for promoting scholarly activities among Japanese pediatric residents. Results: Of all 2524 participants, the number of examinees before and after the reform was 1580 and 944, respectively. The yearly number of the residents' presentations and publications during their residency was 1.2 (SD 0.9) and 0.06 (SD 0.16), respectively, before the reform and 1.3 (SD 1.0) and 0.21 (SD 0.18), respectively, after the reform. Multiple regression showed the post-reform examinees (β = 0.37, p < 0.01) and the number of research presentations (β = 0.28, p < 0.01) were significantly associated with the number of research publications during the residency. While no contributive variables were found in the institution types, residents in the Kyushu and Okinawa area (i.e., southern island area in Japan) published fewer articles than those in the Tokyo area (β = -0.05, p = 0.03). Conclusions: The newly implemented policy requiring residents to publish research articles as a board examination prerequisite effectively promotes research activities among pediatric residents.

Objectives: Fetal human cytomegalovirus (HCMV) infection might be involved in fetal growth restriction (FGR). Maternal serostatus and the prevalence of congenital HCMV infection are affected by various factors, such as socioeconomic status and ethnicity. Therefore, the prevalence of congenital HCMV-related FGR should be examined in each region. Methods: Seventy-eight cases of FGR with delivery between January 2012 and January 2017 at Fujita Health University Hospital were studied. Twenty-one non-FGR cases were also included as a control group. Placental sections obtained from the FGR and control cases were immunostained with two primary antibodies for detecting immediate early antigens. Results: Nineteen placental samples from FGR cases with another etiology were excluded. Finally, 59 placental samples from FGR cases of unknown etiology were included in the pathological analysis. Four of 59 (6.8%) placental samples were positive for HCMV antigen. All four positive cases were stained with the M0854 antibody, and cases showed positivity for the MAB 810R antibody. Neither maternal nor infantile clinical features were different between the HCMV-positive and -negative FGR cases. A pathological examination showed a hematoma in three of four cases and infarction in two of four cases. Conclusions: HCMV antigen was detected in 6.8% of placental samples obtained from FGR cases without an obvious etiology. No remarkable maternal or neonatal clinical features discriminated HCMV-related FGR from FGR due to other causes. Vasculitis and inflammation might play important roles in the pathogenesis of HCMV-related FGR.

Objectives: To establish a point-of-care test for coronavirus disease 2019 (COVID-19), we developed a dry loop-mediated isothermal amplification (LAMP) method to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. Methods: We carried out reverse transcription (RT)-LAMP using the Loopamp SARS-CoV-2 Detection kit (Eiken Chemical, Tokyo, Japan). The entire mixture, except for the primers, is dried and immobilized inside the tube lid. Results: To determine the specificity of the kit, 22 viruses associated with respiratory infections, including SARS-CoV-2, were tested. The sensitivity of this assay, determined by either a real-time turbidity assay or colorimetric change of the reaction mixture, as evaluated by the naked eye or under illumination with ultraviolet light, was 10 copies/reaction. No LAMP product was detected in reactions performed with RNA from any pathogens other than SARS-CoV-2. After completing an initial validation analysis, we analyzed 24 nasopharyngeal swab specimens collected from patients suspected to have COVID-19. Of the 24 samples, 19 (79.2%) were determined by real-time RT-PCR analysis as being positive for SARS-CoV-2 RNA. Using the Loopamp SARS-CoV-2 Detection kit, we detected SARS-CoV-2 RNA in 15 (62.5%) of the 24 samples. Thus, the sensitivity, specificity, positive predictive value, and negative predictive values of the Loopamp 2019-CoV-2 detection reagent kit were 78.9%, 100%, 100%, and 55.6%, respectively. Conclusions: The dry LAMP method for detecting SARS-CoV-2 RNA is fast and easy to use, and its reagents can be stored at 4°C, solving the cold chain problem; thus, it represents a promising tool for COVID-19 diagnosis in developing countries.

Severe combined immunodeficiency (SCID) is an inborn error of immunity that occurs in approximately 1 in 50,000 births, mainly due to impaired lymphocyte differentiation. Without curative treatment, such as hematopoietic cell transplantation (HCT) or gene therapy, severe infection in the first year of life could make this condition fatal. The results of HCT are poor when patients have active infections, thus requiring early diagnosis before onset of infection. In five cases of SCID diagnosed in Japan, the oral rotavirus vaccine had been administered before diagnosis. In this study, we demonstrated that the rotavirus from their stools was a vaccine-derived strain. In some cases, severe gastroenteritis triggered the diagnosis of SCID. However, newborn screening for SCID is available before the first rotavirus vaccination using assays for the detection of T-cell receptor excision circles (TRECs). Therefore, to improve the prognosis of patients with SCID in Japan, we should establish a screening system of TRECs for newborns throughout Japan.

BACKGROUND: The COVID-19 pandemic has affected the lives of people of all ages. Most reports on pediatric cases suggest that children experience fewer and milder symptoms than do adults. This is the first nationwide study in Japan focusing on pediatric cases reported by pediatricians, including cases with no or mild symptoms. METHODS: We analyzed the epidemiological and clinical characteristics and transmission patterns of 840 pediatric (<16 years old) COVID-19 cases reported between February and December 2020 in Japan, using a dedicated database which was maintained voluntarily by members of the Japan Pediatric Society. RESULTS: Almost half of the patients (47.7%) were asymptomatic, while most of the others presented mild symptoms. At the time of admission or first outpatient clinic visit, 84.0% of the cases were afebrile (<37.5°C). In total, 609 cases (72.5%) were exposed to COVID-19-positive household members. We analyzed the influence of nationwide school closures that were introduced in March 2020 on COVID-19 transmission routes among children in Japan. Transmission within households occurred most frequently, with no significant difference between the periods before and after declaring nationwide school closures (70.9% and 74.5%, respectively). CONCLUSIONS: COVID-19 symptoms in children are less severe than those in adults. School closure appeared to have a limited effect on transmission. Controlling household transmission from adult family members is the most important measure for prevention of COVID-19 among children.

Maturity-onset diabetes of the young (MODY) is a form of diabetes mellitus characterized by autosomal dominant inheritance, early onset, and the absence of pancreatic autoimmune markers. MODY-causing mutations have been identified in 14 genes, and carboxyl ester lipase (CEL) has been implicated in MODY8. We report a Japanese patient with MODY who harbored a heterogeneous mutation in CEL exon 2 (NM_001807.4:c.146_147delCT; NP_001798.2:p.Ser49CysfsTer52). A 13-year-old girl experienced her first episode of diabetic ketoacidosis, during which her endogenous insulin secretion was poor. However, her insulin secretion had apparently recovered 2 months after the commencement of insulin treatment, and no further treatment was required for the following 2 years. Diabetic ketoacidosis recurred when the patient was 15 years old, when her insulin secretion was again poor. Since that time, the patient, who is now 18 years old, has been undergoing continuous insulin treatment. The large fluctuations in her insulin secretory capacity led us to suspect MODY. MODY8 patients that carry a mutation in the variable number of tandem repeats in the last exon of the CEL gene typically show pancreatic exocrine dysfunction. However, in the present case, which features premature termination, there is no involvement of exocrine dysfunction, potentially demonstrating a genotype-phenotype correlation.

The full spectrum of human herpesviruses (HHV)-associated neuroinfectious diseases in immunocompetent adults remains unclear. Hence, we sought to elucidate the epidemiology and clinical features of these diseases. The study subjects were patients over 16 years old suspected of neuroinfectious diseases who underwent spinal tap performed by neurologists in our university hospital between April 2013 and March 2018. The presence of seven HHV DNAs in cerebrospinal fluid (CSF) was determined by real-time PCR. HHV DNAs were detected in 33 (10.2%) of the 322 patients. The most frequently detected herpesvirus was varicella zoster virus (VZV) (19 patients), followed by HHV-6 (four patients), herpes simplex virus (HSV)-1 (three patients), HSV-2 (three patients), and Epstein-Barr virus (two patients). HHV DNAs were detected in CSF collected from patients with various neuroinfectious diseases, including myelitis, peripheral neuritis, encephalitis, and meningitis. All patients with HSV-1 DNA had encephalitis, whereas all patients with HSV-2 DNA had meningitis. Eleven of the 19 patients with VZV DNA had meningitis. Patients with VZV-associated encephalitis (median age, 80 years) were significantly older than non-encephalitis patients (median age, 60.5 years) (P = 0.046). Although post-herpetic neuralgia was observed in seven (54%) of the 13 patients with VZV and without encephalitis, no such neurological sequela was observed in the four encephalitis patients. In conclusion, HHVs were associated with approximately 10% of neuroinfectious diseases in this cohort. VZV was the most common pathogen, probably due to the large number of VZV meningitis patients. In addition, patients with VZV-associated meningitis were significantly younger than patients with VZV-associated encephalitis.

<title>Abstract</title>We report a case of a 13-year<bold>-</bold>old boy with arginase 1 deficiency carrying a new variant in <italic>ARG1</italic>. Sanger sequencing identified the compound heterozygous variants: NM_000045.4: c.365G&gt;A (p.Trp122*)/c.820G&gt;A (p.Asp274Asn). Although not previously reported, the p.Asp274Asn variant is predicted to have strong pathogenicity because it is located in a highly conserved domain in the protein core and arginase activity in the patient was below measurement sensitivity.

Varicella vaccine meningitis is an uncommon delayed adverse event of vaccination. Varicella vaccine meningitis has been diagnosed in 12 children, of whom 3 were immunocompromised. We now report two additional cases of vaccine meningitis in twice-immunized immunocompetent children and we perform further testing on a prior third case. We used three methods to diagnose or investigate cases of varicella vaccine meningitis, none of which have been used previously on this disease. These include metagenomic next-generation sequencing and cytokine multiplex profiling of cerebrospinal fluid and immunology exome analysis of white blood cells. In one new case, the diagnosis was confirmed by metagenomic next-generation sequencing of cerebrospinal fluid. Both varicella vaccine virus and human herpesvirus 7 DNA were detected. We performed cytokine multiplex profiling on the cerebrospinal fluid of two cases and found ten elevated biomarkers: interferon gamma, interleukins IL-1RA, IL-6, IL-8, IL-10, IL-17F, chemokines CXCL-9, CXCL-10, CCL-2, and G-CSF. In a second new case, we performed immunology exome sequencing on a panel of 356 genes, but no errors were found. After a review of all 14 cases, we concluded that (i) there is no common explanation for this adverse event, but (ii) ingestion of an oral corticosteroid burst 3-4 weeks before onset of vaccine meningitis may be a risk factor in some cases.

Chronic active Epstein-Barr virus (CAEBV) disease is a rare condition characterised by persistent EBV infection in previously healthy individuals. Defective EBV genomes were found in East Asian patients with CAEBV. In the present study, we sequenced 14 blood EBV samples from three UK patients with CAEBV, comparing the results with saliva CAEBV samples and other conditions. We observed EBV deletions in blood, some of which may disrupt viral replication, but not saliva in CAEBV. Deletions were lost overtime after successful treatment. These findings are compatible with CAEBV being associated with the evolution and persistence of EBV+ haematological clones that are lost on successful treatment.

The theme of the 24th Annual Meeting of the Japanese Society for Vaccinology was "Sustainable Future Medical Care Created by Vaccines." This theme includes topics such as the proposal to reduce the medical costs incurred by societies with aging populations through prophylactic vaccination. The coronavirus disease 2019 (COVID-19) pandemic alerted us to the important roles that preventive measures, such as vaccines, play in fighting infectious diseases. In order to inform the public of the benefits of vaccines, it is important to provide society with information regarding new vaccine developments, adjuvants, the cost-benefit ratio of vaccine introduction, and vaccine effectiveness and safety. Clinical research is essential for obtaining evidence of vaccine effectiveness and safety. The United States Centers for Disease Control and Prevention (CDC) conducts active surveillance in defined areas before and after the introduction of vaccines and documents the reduction in infection rates as a measure of vaccine effectiveness. However, vaccine efficacy and side effects may vary by country and ethnicity. Therefore, it is necessary for individual countries to develop their own evidence-based surveillance programs. We have studied vaccine efficacy and documented side-effects observed in patients for the varicella and rotavirus vaccines in Japan. This review outlines the importance of providing scientific evidence for vaccine effectiveness and safety.

Here, we present a previously healthy adolescent with aseptic meningitis without skin rash caused by varicella vaccine derived from the Oka/Biken strain; the patient received a single dose of varicella vaccine at 1 year of age. Pediatricians should be aware of the potential for reactivation of varicella vaccine derived from the Oka/Biken strain, which can cause aseptic meningitis in vaccinated children even in the absence of a skin rash.

HHV-6 and HHV-7 can reactivate in the salivary gland in response to various host stresses. Lactococcus lactis strain Plasma (LC-Plasma) can activate plasmacytoid dendritic cells (pDCs) and decrease viral infection. We investigated whether LC-Plasma intake could decrease HHV-6 and HHV-7 reactivation in the salivary gland. A total of 54 healthy volunteers were enrolled in this study. Participants took LC-Plasma granules daily for 6 weeks. Saliva samples were collected from subjects weekly for 4 weeks before (first), during (second), and after (third period) LC-Plasma intake. There was a 2-week interval between the first and second periods and a 3-week interval between the second and third periods. Mean salivary HHV-6 and HHV-7 DNA loads were compared among the three observation periods. In the first period (baseline data of viral DNA shedding), HHV-6 DNA shedding was significantly higher in subjects under 40 years old, and HHV-7 DNA shedding was significantly higher in males. HHV-6 and HHV-7 DNA loads did not significantly differ between periods. Meanwhile, in a subgroup analysis of the subjects under 40 years old, HHV-6 DNA load was significantly lower in the second period than in the first period. LC-Plasma decreases HHV-6 reactivation in the salivary glands in younger adults.

The exact evolutionary patterns of human G4P[6] rotavirus strains remain to be elucidated. Such strains possess unique and strain-specific genotype constellations, raising the question of whether G4P[6] strains are primarily transmitted via independent interspecies transmission or human-to-human transmission after interspecies transmission. Two G4P[6] rotavirus strains were identified in fecal specimens from hospitalized patients with severe diarrhea in Thailand, namely, DU2014-259 (RVA/Human-wt/THA/DU2014-259/2014/G4P[6]) and PK2015-1-0001 (RVA/Human-wt/THA/PK2015-1-0001/2015/G4P[6]). Here, we analyzed the full genomes of the two human G4P[6] strains, which provided the opportunity to study and confirm their evolutionary origin. On whole genome analysis, both strains exhibited a unique Wa-like genotype constellation of G4-P[6]-I1-R1-C1-M1-A8-N1-T1-E1-H1. The NSP1 genotype A8 is commonly found in porcine rotavirus strains. Furthermore, on phylogenetic analysis, each of the 11 genes of strains DU2014-259 and PK2015-1-0001 appeared to be of porcine origin. On the other hand, the two study strains consistently formed distinct clusters for nine of the 11 gene segments (VP4, VP6, VP1-VP3, and NSP2-NSP5), strongly indicating the occurrence of independent porcine-to-human interspecies transmission events. Our observations provide important insights into the origin of zoonotic G4P[6] strains, and into the dynamic interaction between porcine and human rotavirus strains.

BACKGROUND: Children receiving home medical care need special attention to prevent unexpected death. The aim of this study was to clarify the factors contributing to death in children receiving home medical care from the child death review database. METHODS: Children receiving home medical care were enrolled from the child death review database from 2014 to 2016 in Aichi prefecture, Japan, with a population of one million children. Types of medical care and factors contributing to death were examined. RESULTS: Of the 631 children who died, 40 children (6%) were receiving home medical care (21: tracheostomy; 19: ventilator; 26: suctioning of naso-oral secretions; 19: oxygen inhalation; 32: tube feeding; 6: urethral catheterization; and 1: peritoneal dialysis). The death rate was 50 times that in the general population of children. Ten children had contributory factors that seemed to be preventable. In four children, the families could not replace the tracheostomy tubes during an accident. In three, oxygen saturation or ventilator alarms were not set appropriately. In two, an oxygen cylinder became empty. One child fell down from a seat in a car. CONCLUSIONS: Improvement of devices and correct guidance to caregivers may reduce the death rate in children receiving home medical care. IMPACT: Children receiving home medical care, such as tracheostomy care, mechanical ventilation, or tube feeding, need special attention to prevent unexpected death. In this population-based child death review, 6% of children received home medical care, and it was estimated that 1 of 100 children receiving home medical care died per year. One-quarter of the deaths could be preventable by caregiver education or development of devices.

OBJECTIVE: The aim of this study was to elucidate vaccine effectiveness (VE) during varicella outbreaks in schools and nurseries in Japan. METHODS: An outbreak was defined as emergence of three or more cases of varicella within 21 days at the same institute. Clinical information such as varicella vaccination status, and history of varicella was collected. If a child had varicella during the outbreak, information about absences, fever, and disease severity was collected. RESULTS: From September 2018 to January 2020, four outbreaks were reported around our institute from three elementary schools and one nursery. A total of 676 children were analyzed in this study. Seventy-six children (11.2%) were unvaccinated, 309 (45.7%) had received one dose of vaccine, and 291 (43.0%) had received two doses. Most children in Pre-K2 (1-2 years old) to Pre-K6 (5-6 years old), who were the targets of the national immunization schedule, received two doses. Meanwhile, most children older than third grade received single dose. Seventy-five children (11.1%) had varicella. Varicella prevalence from Pre-K5 to the third grade was greater than 10%. The adjusted VEs of single- and two-dose of varicella vaccine were 57.8% and 89.0%. The number of days absent was significantly longer in unvaccinated children than single-dose recipients (P = 0.0145). Unvaccinated children had significantly more severe skin eruptions than single-dose recipients (P = 0.0046) and two-dose recipients (P = 0.0258). CONCLUSIONS: Although VEs of single-dose varicella vaccination during outbreaks was not high, the VE of two-dose vaccination was similar to that in a previously reported case-control study.

Kawasaki disease (KD) is an acute systemic vasculitis that most commonly causes acquired cardiac disease in children in developed countries. The most highly recommended treatment for KD is 2 g/kg intravenous immunoglobulin (IVIG). There are two types of IVIG, sodium-containing (high-Na) and sodium-trace (low-Na) preparations. However, few studies have compared the effects of these two preparations for superiority. The purpose of this study was to compare outcomes between high and low-Na IVIG preparations in KD children using a national inpatient database in Japan. We used the Diagnostic Procedure Combination database to identify KD patients treated with IVIG between 2010 and 2017. We identified those receiving high and low-Na preparations of IVIG as an initial treatment. Outcomes included proportion of coronary artery abnormalities (CAA), IVIG resistance, adverse effects, length of stay, and medical cost. Propensity score-matched analyses were conducted to compare the outcomes between the two groups. Instrumental variable analyses were performed to confirm the results. We identified 42,345 patients with KD. There were significant differences in proportions of CAA (2.8% vs. 3.2%; p = 0.031) and IVIG resistance (17% vs. 18%, p = 0.001) between the two groups. However, there were no significant differences in length of stay or medical cost. The instrumental variable analysis confirmed the same results as the propensity score analysis.Conclusion: The present study suggests that high-Na IVIG is potentially effective for reducing the proportion of CAA in KD patients. Prospective studies are warranted to confirm the effectiveness observed in this study. What is Known: • For treatments of Kawasaki Disease in acute phase, intravenous immunoglobulin have been the most recommended to reduce fever early and prevent complications of coronary artery abnormalities. There are two types of IVIG preparations, sodium-containing IVIG and sodium-trace IVIG. However, few studies have performed comparisons to determine which preparation of IVIG is superior. What is New: • The present findings suggest that high-Na IVIG is associated with reductions in the proportions of CAAs and IVIG resistance in KD patients.

The aim of this study was to determine whether human herpesvirus 6B (HHV-6B) infection can impair the hippocampus in pediatric hematopoietic stem cell transplant (HSCT) recipients. Study subjects were pediatric HSCT recipients monitored for HHV-6B infection who underwent brain MRI before and after transplantation. Volumetric analysis of the hippocampus was performed. Of the 107 patients that received HSCT at Nagoya University Hospital Between July 2008 and April 2014, 20 were eligible for volumetric analysis. Eight patients had HHV-6B infection, of whom two had encephalopathy at the time of HHV-6B infection. None of the 12 patients without HHV-6B infection had encephalopathy. The median ratio of the right hippocampal volume from before to after transplantation was 0.93 in patients with HHV-6B infection and 1.02 in without HHV-6B infection (p = 0.007). The median ratio of the left hippocampal volume ratio in patients with and without HHV-6B infection was 0.92 and 1.00, respectively (p = 0.003). Among the eight patients with HHV-6B infection, four had a marked reduction in hippocampal volume (volume ratio < 0.90). Only one of these patients had neurological symptoms at the time of HHV-6B infection. The reduction in the hippocampal volume ratio was higher in pediatric HSCT recipients with HHV-6B infection than those without viral infection. Neurological follow-up may be required for pediatric HSCT recipients with HHV-6B infection.

Pediatric cases of the coronavirus disease 2019 (COVID-19) are generally mild or asymptomatic, and are usually detected by virological examination following close contact with COVID-19 patients, often the children's parents. The detailed clinical features and virological data of pediatric patients with COVID-19, particularly young infants, remain unclear. Here, the clinical and virological characteristics of four children with COVID-19 including two young infants were investigated. One- and 4-month-old boys with COVID-19 were both asymptomatic, and seroconversion was demonstrated. These findings suggest that even young infants can mount an immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), despite having weaker immune defenses than adolescents and adults. Three-year-old boy, who was SARS-CoV-2-negative, was admitted to the same room as his SARS-CoV-2-positive father due to the lack of caregivers. Although he was asymptomatic, he had seroconverted to SARS-CoV-2. Eleven-year-old boy, who was sibling of the 3-year-old boy, was also SARS-CoV-2-negative. He was isolated in his own room and did not seroconvert. If young children are SARS-CoV-2 negative, they should be isolated from their SARS-CoV-2-positive parents. This may be difficult in practice, if parents with COVID-19 are the only available caregivers. In such situations, the most appropriate measures should be taken for each patient.

BACKGROUND: Examining the predictors of summative assessment performance is important for improving educational programs and structuring appropriate learning environments for trainees. However, predictors of certification examination performance in pediatric postgraduate education have not been comprehensively investigated in Japan. METHODS: The Pediatric Board Examination database in Japan, which includes 1578 postgraduate trainees from 2015 to 2016, was analyzed. The examinations included multiple-choice questions (MCQs), case summary reports, and an interview, and the predictors for each of these components were investigated by multiple regression analysis. RESULTS: The number of examination attempts and the training duration were significant negative predictors of the scores for the MCQ, case summary, and interview. Employment at a community hospital or private university hospital were negative predictors of the MCQ and case summary score, respectively. Female sex and the number of academic presentations positively predicted the case summary and interview scores. The number of research publications was a positive predictor of the MCQ score, and employment at a community hospital was a positive predictor of the case summary score. CONCLUSION: This study found that delayed and repeated examination taking were negative predictors, while the scholarly activity of trainees was a positive predictor, of pediatric board certification examination performance.

OBJECTIVE: The Japanese national immunization program recommends that children receive 4 doses of acellular pertussis vaccine between 3 months and 2 years of age. Nevertheless, the number of pertussis cases is increasing in elementary school children aged 6-12 years. Therefore, a test-negative case-control study was conducted to assess the effectiveness of the pertussis vaccine program. METHODS: Subjects included children aged ≥3 months who visited a collaborating hospital due to pertussis-specific cough between October 2017 and November 2019. All subjects underwent diagnostic tests for pertussis, and those diagnosed as positive were regarded as cases. Subjects diagnosed as pertussis-negative were classified as controls. Vaccination history was collected using a questionnaire administered to parents with reference to immunization records. Logistic regression models were employed to calculate the odds ratio (OR) and 95% confidence interval for laboratory-confirmed pertussis. RESULTS: Of 187 recruited subjects (120 cases and 67 controls), questionnaire responses were obtained for 145 subjects (95 cases and 50 controls). Compared with unvaccinated subjects, the vaccine effectiveness (VE) of 4 doses was 70% among all subjects and reached to 90% with marginal significance among subjects under 6 years of age. However, among school-aged subjects, the VE was not suggestive of protection against pertussis (VE: 8%). For vaccinees given 4 doses, the OR for developing pertussis increased significantly with longer duration since the fourth dose (compared with <4.5 years, OR of 6.0-8.2 years = 5.74; OR of ≥8.3 years = 3.88; P for trend by duration < 0.01). CONCLUSION: Effectiveness of administering 4 doses of pertussis vaccine during infancy decreases with time passed since the fourth dose. This regimen does not protect school-aged children against pertussis.

Little is known whether 2-g/kg IVIG is necessary for older children with Kawasaki disease (KD), because they could have more complications and financial burden. The purpose of this study was to compare outcomes between high- and low-dose IVIG in KD children with higher body weight (25 kg or more), using a national inpatient database in Japan from 2010 to 2017. We identified those receiving 2-g/kg and 1-g/kg IVIG as an initial treatment. Outcomes included the proportions of coronary artery abnormality (CAA) formation, IVIG resistance, adverse effects, length of stay, and medical costs. A propensity score matching analysis was conducted to compare the outcomes between the groups. We identified 1332 patients with KD and created 4:1 propensity score-matched pairs between high- and low-dose IVIG groups. There were no significant differences in the proportions of CAA (5.3% vs. 4.1%; p = 0.587), IVIG resistance, and length of stay. Medical costs were significantly higher in the high-dose group than in the low-dose group (p < 0.001).Conclusion: No significant difference was shown between the high- and low-dose IVIG groups in the proportions of outcomes, while medical costs were higher in the high-dose group. Further studies are needed to ascertain the appropriate IVIG dose in older patients with KD. What is Known: • For treatments of Kawasaki disease at any age in the acute phase, 2-g/kg single-dose intravenous immunoglobulin and aspirin have been the most recommended to reduce fever early and prevent complications of coronary artery abnormalities. What is New: • There was no significant difference in outcomes between children with Kawasaki disease weighing ≥ 25 kg treated with high-dose or low-dose IVIG in terms of coronary artery abnormalities, IVIG resistance, adverse effects, and length of stay, except for medical costs.

BACKGROUND: Aggressive systemic mastocytosis (ASM) is a rare malignant disease characterized by disordered mast cell accumulation in various organs. We here describe a female ASM patient with a previous history of ovarian dysgerminoma. METHODS: Molecular cytogenomic analyses were performed to elucidate an etiological link between the ASM and dysgerminoma of the patient. RESULTS: This patient was affected by ovarian dysgerminoma which was treated by chemotherapy and surgical resection. Having subsequently been in complete remission for 2 years, she developed symptoms of ASM. A somatic D816A mutation in the KIT gene was detected in her bone marrow, which facilitated the diagnosis of ASM. Unexpectedly, this KIT D816A variant was also detected in the prior ovarian dysgerminoma sample. Whole-exome sequencing allowed us to identify a somatic nonsense mutation of the TP53 gene in the bone marrow, but not in the dysgerminoma. Microarray analysis of the patient's bone marrow revealed a copy-number-neutral loss of heterozygosity at the TP53 locus, suggestive of the homozygous nonsense mutation in the TP53 gene. In addition, the loss of heterozygosity at the TP53 locus was also detected in the dysgerminoma. CONCLUSIONS: These results indicated that either the mast cells causing the ASM in this case had originated from the preceding ovarian dysgerminoma as a clonal evolution of a residual tumor cell, which acquired the TP53 mutation, or that both tumors developed from a common cancer stem cell carrying the KIT D816A variation.

水痘ワクチン接種後に水痘ワクチン株による帯状疱疹を発症することはあるが、本邦での発症報告は少ない。また、帯状疱疹発症時に運動麻痺を伴う例が稀にある。運動麻痺を伴った水痘ワクチン株による帯状疱疹例を提示する。症例は生来健康な8歳男児。3歳時に右上腕に1回水痘ワクチン接種歴がある。第1病日から右上肢の脱力感があり、第2病日から右上肢に疼痛を伴う水疱が出現、第4病日に当科紹介された。右上肢C5-6領域に水疱を認め、同領域の筋力はMMT4に低下していた。帯状疱疹と診断し、アシクロビル投与を行った。第5病日に右上肢の筋力は改善し、第10病日にすべての水疱が痂皮化し後遺症なく改善した。ペア血清での水痘・帯状疱疹ウイルス(VZV)抗体価(EIA)はIgG32.2/128、IgM0.06/0.87であった。水疱内容液のVZV LAMP法が陽性で、増殖産物のRFLP解析でワクチン株と判明した。本邦では水痘ワクチンが定期接種となり、今後は帯状疱疹発症者のうちワクチン接種者の割合が増加する可能性がある。水痘ワクチン接種歴のある者が帯状疱疹を発症した場合、VZVの由来がワクチン株か野生株かを鑑別する必要がある。(著者抄録)