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Aims Post-extubation dysphagia (PED), an often overlooked problem, is a common and serious complication associated with mortality and major morbidity after cardiovascular surgery. Dysphagia is considered an age-related disease, and evaluating its long-term effects is a pressing issue with rapidly progressing ageing worldwide. Therefore, we examined the effect of PED on functional status and long-term cardiovascular events in patients undergoing cardiovascular surgery. Methods and results This single-centre, retrospective cohort study included 712 patients who underwent elective cardiovascular surgery and met the inclusion criteria. Patients were divided into PED and non-PED groups based on their post-operative swallowing status. The swallowing status was assessed using the Food Intake Level Scale. Functional status was evaluated as hospital-associated disability (HAD), defined as a decrease in activities of daily living after hospital discharge compared with preoperative values. The patients were subsequently followed up to detect major adverse cardiac and cerebrovascular events (MACCEs). Post-extubation dysphagia was present in 23% of the 712 patients and was independently associated with HAD (adjusted odds ratio, 2.70). Over a 3.5-year median follow-up period, MACCE occurred in 14.1% of patients. Multivariate Cox proportional hazard analysis revealed HAD to be independently associated with an increased risk of MACCE (adjusted hazard ratio, 1.85), although PED was not significantly associated with MACCE. Conclusion Post-extubation dysphagia was an independent HAD predictor, with the odds of HAD occurrence being increased by 2.7-fold due to PED. Hospital-associated disability accompanied by PED is a powerful predictor of poor prognosis. Perioperative evaluation and management of the swallowing status, and appropriate therapeutic interventions, are warranted. [ABSTRACT FROM AUTHOR]

• A test-negative case-control study examined an effectiveness of pertussis vaccine. • 4 doses of vaccine provided a high effectiveness in subjects under 6 years of age. • Vaccine effectiveness declines with time passed since the fourth dose. • 4 doses of pertussis vaccine have no preventive effect for school-aged children. 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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

The article presents guidelines on working group for revision of guidelines for the use of Palivizumab in Japan. Topics include the precautions and indications on the drug's information leaflet, the appropriate use of this agent should be used on a patient by patient basis; and referring to guidelines issued by healthcare societies and other professional academic organizations.

Background Japanese encephalitis (JE) is the leading cause of viral encephalitis with high mortality and morbidity in Asia. In Japan, however, the active recommendation of JE vaccine was retracted in 2005 because of the potential risk of acute disseminated encephalomyelitis. We aimed to determine the recent incidence of childhood-onset JE after the domestic change of vaccination policy in Japan, and to analyze the clinical features of affected children. Methods A retrospective nationwide survey was conducted for pediatric patients with JE in Japan from 1995 to 2015. The national surveillance system was used to identify the pediatric patients with JE. Follow-up questionnaires were sent to analyze their clinical and neuroimaging profiles. Results Among a total of 109 patients registered to the national surveillance, 10 (9%) were less than age 15 years. The annual incidence rate of childhood-onset JE was higher during 2005–15 than that during 1995–2004 (4.3 × 10–3 vs 1.1 × 10–3 per 100000, respectively; P =.04). Endemic regions overlapped with prefectures that farmed pigs harboring antibodies against JE virus with high prevalence. Detailed clinical data were collected from 9 patients. None of them died, but 5 of 9 patients (56%) had neurological sequelae after recovery. One patient who was partially vaccinated with 2 doses of JE vaccine fully recovered from a coma. The age of 3 years or less was associated with unfavorable neurological prognosis. Conclusions Our data provide evidence for the importance and prophylactic effect of the JE vaccine in young children in the endemic area. [ABSTRACT FROM AUTHOR]

Introduction: We have been developing a closed-circuit cardiopulmonary bypass (CPB) system ("Dihead CPB") for application during coronary artery bypass grafting (CABG) and valve surgery. To strive for minimal hemolysis during Dihead CPB, we compared the hemolysis caused by three different suction systems and performed a clinical study with the newly applied suction system. Materials & Methods: We evaluated the hemolysis caused by roller-pump suction, the SmartSuction® Harmony® and wall suction systems with respect to suction speed and compared the systems by means of in vitro studies. A clinical study was also performed on 15 volunteers to assess hemolysis and the adequacy of the newly applied suction system with Dihead CPB. Results: Pressure inside the suction cannula was −22.5 ± 0.1 mmHg at a maximum flow of 1.5 L/min for roller-pump suction and −43.4 ± 0.1 mmHg at −150 mmHg of the set vacuum pressure of wall suction. With the SmartSuction, the pressure inside the cannula varied from −76.3 ± 1.0 to −130.3 ± 1.5 mmHg, depending on suctioning conditions. Suction speed (to suction 50 ml of blood) was fastest with the SmartSuction (69.7 ± 3.58 s) whereas, with roller suction, it was 117.3 ± 8.47 s and with wall suction 96.9 ± 7.10 s. The SmartSuction had the highest hemolysis rate (2.00 ± 0.33%) vs. 0.61 ± 0.10% for roller suction and 0.41 ± 0.11% for wall suction (p<0.001). The clinical study with wall suction showed no significant increase in plasma free hemoglobin during or after CPB compared with before surgery. Conclusions: Wall suction had less hemolysis than roller suction or the SmartSuction in the in vitro study and the clinical study with wall suction showed efficient suction speed and acceptable hemolysis, suggesting that Dihead CPB with wall suction is feasible for CABG. [ABSTRACT FROM AUTHOR]

Pediatric Rheumatology Association of Japan has developed evidence-based guideline of vaccination in pediatric rheumatic diseases (PRDs) as a part of Guideline of Vaccination for Pediatric Immunocompromised Hosts. Available articles on vaccination in both adult rheumatic diseases and PRDs were analyzed. Non-live vaccines are generally safe and effective in patients with PRDs on corticosteroid, immunosuppressant, and/or biologics, although efficacy may be attenuated under high dose of the drugs. On the other hand, efficacy and safety of live-attenuated vaccine for the patients on such medication have not been established. Thus, live-attenuated vaccines should be withheld and, if indicated, may be considered as a clinical trial under the approval by Institutional Review Board. All patients with PRDs anticipating treatment with immunosuppressants or biologics should be screened for infection of hepatitis B and C and tuberculosis before the commencement of medication. Varicella vaccine should be considered in sensitive patients ideally 3 weeks or longer before the commencement of immunosuppressants, corticosteroids, or biologics. Bacille Calmette-Guérin should be withheld at least for 6 months after birth, if their mothers have received anti-tumor necrosis factor-α antibodies during the second or third trimester of pregnancy. [ABSTRACT FROM AUTHOR]

In 2008, the number of pertussis cases increased substantially among Japanese adolescents, despite high coverage with acellular pertussis vaccine (DTaP). This study examined the effectiveness of DTaP vaccine in the routine immunization program in Japan. Between April 2009 and October 2012, we conducted a multicenter, case-control study, and compared the history of DTaP vaccination between 55 newly diagnosed pertussis cases and 90 age- and sex-matched controls. DTaP vaccine history was obtained by a self-administered questionnaire completed by their parents or guardians. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for development of pertussis. DTaP vaccination of ≥1 dose revealed a significantly lower OR for pertussis (OR = 0.20, 95%CI, 0.04–0.97), and the OR of complete vaccination (4 doses) was 0.22 (0.04–1.05). Even after limiting subjects to those whose vaccination status could be confirmed by the immunization records, the negative associations were observed. The decreasing ORs of 4-dose vaccinees remained, even among subjects who had received the fourth dose ≥9.2 years earlier (OR = 0.11, 95%CI, 0.01–1.02). In conclusion, DTaP vaccination had a preventive effect for pertussis. Effectiveness was observed even 9 or more years after the final dose. [ABSTRACT FROM AUTHOR]

A new version of the Japanese pediatric guideline for the treatment and management of bronchial asthma was published in Japanese at the end of 2011. The guideline sets the pragmatic goal for clinicians treating childhood asthma as maintaining a 'well-controlled level' for an extended period in which the child patient can lead a trouble-free daily life, not forgetting the ultimate goal of obtaining remission and/or cure. Important factors in the attainment of the pragmatic goal are: (i) appropriate use of anti-inflammatory drugs; (ii) elimination of environmental risk factors; and (iii) educational and enlightening activities for the patient and caregivers regarding adequate asthma management in daily life. The well-controlled level refers to a symptom-free state in which no transient coughs, wheezing, dyspnea or other symptoms associated with bronchial asthma are present, even for a short period of time. As was the case in the previous versions of the guideline, asthmatic children younger than 2 years of age are defined as infantile asthma patients. Special attention is paid to these patients in the new guideline: they often have rapid exacerbation and easily present chronic asthmatic conditions after the disease is established. [ABSTRACT FROM AUTHOR]

Abstract: Freeze dried, cell culture-derived Japanese encephalitis vaccine (Inactivated) (JEBIK®V) is approved for a three-dose primary immunization followed by a one-dose booster immunization in Japan. We conducted a multicenter, double-blinded, randomized controlled trial of the safety and immunogenicity of the vaccine in 370 healthy children who received three doses of 5, 2.5 or 1.25μg of virus protein per 0.5mL formulation subcutaneously. Children received two doses of test vaccine 7–28 days apart followed by a dose 6–12 months after the second vaccination. The three-dose regimen showed a good safety profile with no serious vaccine-related adverse events. Fever and reactions at the injection site were common adverse reactions at each dose of vaccine. The seroconversion rates were 100%, 99.2% and 95.0% after two doses in the 5, 2.5 and 1.25μg groups, respectively, and 100.0% after three doses in all groups. The geometric mean titers were high for all three formulations after the second and third doses, with a very clear dose–response relationship. These results indicate that JEBIK®V is likely to be a useful vaccine. [Copyright &y& Elsevier]

Background: This study was performed to investigate the early and late outcomes of total aortic arch replacement (TAR) with or without coronary artery bypass grafting (CABG). Methods: From October 1999 to December 2010, 200 consecutive patients underwent elective TAR for nondissecting aneurysm through a median sternotomy. Of this number, 131 (65.5%) had isolated TAR (TAR group) and 69 (34.5%) underwent concomitant CABG (TAR/CABG group). Patients in the TAR/CABG group were older and had more advanced chronic kidney disease and higher additive/logistic European System for Cardiac Operative Risk Evaluation and Japan scores than patients in the TAR group. Results: Overall 30-day mortality was 0.5% (1 of 200) and hospital mortality was 3.5% (7 of 200). Hospital mortality was 1.5% (2 of 131) in the TAR group and 7.2% (5 of 69) in the TAR/CABG group (p = 0.036). Multivariate analysis showed that operation time (odds ratio [OR] 1.01, p = 0.013) was a risk factor for hospital mortality, but failed to demonstrate concomitant CABG as a risk factor. Cox proportional hazard analysis showed that age (OR 1.08, p = 0.05), female sex (OR 3.58, p = 0.0004), chronic kidney disease (OR 7.70, p < 0.0001), and operation time (OR 1.01, p = 0.0002) were risk factors for midterm mortality, whereas concomitant CABG was not (OR 0.92, p = 0.87). There was a significant difference in midterm survival and freedom from major cerebrocardiovascular events in the TAR group versus the TAR/CABG group. Conclusions: Concomitant CABG was not a risk factor for hospital morality with TAR. However, patients with concomitant CABG have more preoperative comorbidities, which may adversely affect outcomes, and which may therefore deserve special attention. [ABSTRACT FROM AUTHOR]

Background: Young infants with influenza virus infection are frequently hospitalized, and are at risk of serious complications including death. With the emergence of pandemic influenza A/H1N1 2009, oseltamivir was approved for use in Europe and the USA, including use in infants aged < 3 months. However, few data are available regarding the safety of oseltamivir treatment for influenza in infants aged < 3 months. Methods: The clinical data from Japanese infants aged < 3 months with laboratory-confirmed influenza virus infections, who were treated with oseltamivir between October 2009 and April 2011, were collected and analyzed. Results: Forty-four infants were included in the study. The median age was 1 month (range 4 days to 2 months) and median body weight was 4.5 kg (range 2.6-7.6 kg). Thirty-eight infants (86%) had no underlying diseases. The most common presenting symptom was fever (42 infants, 95%). There were no cases of influenza-associated encephalopathy or myocarditis. The median time between the onset of influenza symptoms and initiation of oseltamivir treatment was 0 days (range 0-7 days), with treatment initiated within 1 day in 40 infants (91%). The oseltamivir dose was 1.5-2 mg/kg twice daily in 98% of infants. No serious adverse events were identified during treatment. All infants recovered completely. Conclusions: Treatment of influenza with oseltamivir 1.5-2 mg/kg twice daily may be safe in infants aged < 3 months. [ABSTRACT FROM AUTHOR]

Members of the Japanese Society of Pediatric Pulmonology and the Japanese Society for Pediatric Infectious Diseases developed the Guidelines for the Management of Respiratory Infectious Diseases in Children with the objective of facilitating the appropriate diagnosis and treatment of childhood respiratory infections. To date, a first edition (2004) and a revised edition (2007) have been issued. Many problems complicate the diagnosis of the pathogens responsible for bronchopulmonary infections in children. The Guidelines were the first pediatric guidelines in the world to recommend treatment with antimicrobials suited to causative pathogens as identified from cultures of sputum and other clinical specimens collected from infection sites and satisfying assessment criteria. The major causative microorganisms for pneumonia in infants and children were revealed to be Streptococcus pneumoniae, Haemophilus influenzae and Mycoplasma pneumoniae. This manuscript describes the Guidelines for the Management of Respiratory Infectious Diseases in Children in Japan 2007, with a focus on pneumonia. [ABSTRACT FROM AUTHOR]

Abstract: The incidence of reported cases with pertussis has increased in young adults in Japan and the lack of additional booster immunizations containing pertussis components is suspected to be one of the causal reasons. Instead of DT immunization at 11–12 years of age, safety and immunogenicity were investigated using 0.2ml and 0.5ml of DTaP. 176 subjects in DTaP 0.5ml, 178 in DTaP 0.2ml, and 197 in DT 0.1ml groups were enrolled in clinical trial. The relative risk of local reactions in the DTaP 0.2ml group compared to the DT 0.1ml group was 1.13 (95% CI: 0.97–1.30), and that of the DTaP 0.5ml to the DT 0.1ml group was 1.34 (95% CI: 1.18–1.53). The relative risks of local pain and heat were 1.62 (95% CI: 1.33–1.98) and 1.59 (95% CI: 1.19–2.13), respectively, in the DTaP 0.5ml group compared to the DT 0.1ml group. Sero-positive rates against PT and FHA were 54% and 82% before immunization and increased to >95% for both after vaccination with no significant difference in GMT. Instead of the scheduled DT program, 0.2ml of DTaP was acceptable and demonstrated efficient immunogenicity. [ABSTRACT FROM AUTHOR]

The fourth version of the Japanese Pediatric Guidelines for the Treatment and Management of Bronchial Asthma 2008 (JPGL 2008) was published by the Japanese Society of Pediatric Allergy and Clinical Immunology in December 2008. In JPGL 2008, the recommendations were revised on the basis of the JPGL 2005. The JPGL 2008 is different to the Global Initiative for Asthma guideline in that it contains the following items: a classification system of asthma severity; recommendations for long-term management organized by age; a special mention of infantile asthma; and an emphasis on prevention and early intervention. Here we show a summary of the JPGL 2008 revising our previous report concerning JPGL 2005. [ABSTRACT FROM AUTHOR]

Objectives: Synchrotron radiation-based X-ray phase-contrast tomography (XPCT) has proven innovative modality for analyzing 3D morphology and is useful for understanding the pathophysiology of various cardiovascular disease. To elucidate mechanisms of aneurysmal wall enlargement after endovascular aortic repair (TEVAR or EVAR), we evaluated aortic wall samples after TEVAR and EVAR with XPCT. Methods: Human aortic samples of the descending aorta or abdominal aorta were obtained during open aortic repair for aortic aneurysm (Group-A; n=5),and for aneurysm expansion after endovascular repairs (Group-E: n=7). Normal aorta (Group-N: n=10), obtained from autopsy, were also investigated. Effective resolution of XPCT in Japan Synchrotron Radiation Research Institute / SPring-8 is 11.7 μm. Pathological analysis was performed, subsequently. Results: Age of patients was 76.8 ± 5.4 years old in Group-A, 83.4 ± 5.2 in Group-E, and 57.5 ± 9.5 in Group-N. In Group-E, time from endovascular repair to open aortic repair was 64.2 ± 7.2 months, and initial endovascular repair included TEVAR (n=2) and EVAR (n=5). Representative findings of three groups were demonstrated in figures, including XPCT findings (Fig.A), changes of wall density (B), and pathological findings (C). In Group-N, density of the tunica media was not different within tunica media and average of medial density was 1.085 ± 0.003g/cm3. In Group-A, thickness of aortic wall was lower than Group-N, but density of the tunica media was unchanged (1.079 ± 0.022g/cm3). On contrast, in Group-E, density of the tunica media was significantly lower than Group-N (1.063 ± 0.008; p < 0.005), and differences in density within tunica media were well correlated with distribution of elastic fibers and existence of medial necrosis in pathological analysis. Conclusions: X-ray phase-contrast tomography was a cutting-edge modality to understand aortic structures and degeneration of tunica media in aneurysm expansion after endovascular repair was clearly demonstrated. [ABSTRACT FROM AUTHOR]

• In Japan, Prenatal DTaP vaccination lacks required safety information. • Pertussis seroprevalence is approximately 70% among pregnant Japanese women. • Maternal antibody titers in early pregnancy reflect infant antibody titers. • Preconception DTaP vaccination is one way to obtain maternal immunity. • A national survey to evaluate the safety information of prenatal DTaP is necessary. An increasing number of countries have been introducing acellular pertussis vaccination during pregnancy for the prevention of neonatal pertussis. In response to the fact that infantile pertussis cases of 0–5 months age groups remained unchanged despite the universal vaccination program, prenatal pertussis vaccination has been a rising issue in Japan. Hence, we investigated the seroprevalence of pertussis, diphtheria, and tetanus antibodies in Japanese pregnant women and neonates, and evaluated the necessity of diphtheria-tetanus-acellular pertussis (DTaP) vaccination during the preconception or prenatal period. Maternal PT-IgG (EIA) and FHA-IgG (EIA) for the first trimester, within 1 week after delivery, and cord blood were collected, along with colostrum pertussis-IgA (ELISA), diphtheria-IgG (EIA), tetanus-IgG (EIA), and blood samples from the first trimester. The maternal seroprevalence of PT-IgG and FHA-IgG was 69 % and 75 %, respectively. All tested participants were positive for diphtheria-IgG and tetanus-IgG (100 %). First trimester PT-IgG/FHA-IgG antibody titers were significantly associated with cord blood PT-IgG/FHA-IgG titers (P < 0.001). We found that pertussis seroprevalence among pregnant Japanese women was approximately 70 %. The antibody seropositivity rate of pertussis was lower than that of diphtheria and tetanus. Fetal acquired passive immunity against pertussis is higher when the level of maternal antibody in the first trimester is sufficient. At least 30 % of study population did not reach to the threshold value to provide sufficient pertussis immunity for the neonates and themselves. The acellular pertussis vaccine (DTaP) approved in Japan lacks safety information for pregnancy, hence, a solution for prompt administration of prenatal acellular pertussis vaccination might be introducing DTaP in the preconception period. [ABSTRACT FROM AUTHOR]

Background In September 2015, Japan experienced an unusual increase in acute asthma hospitalizations of children that coincided with an enterovirus D68 (EV-D68) epidemic. The objective of this study is to investigate whether EV-D68 had a causal relationship with the spike in asthma hospitalizations. Methods A nation-wide retrospective survey of asthma hospitalizations of children was performed for the period from January 2010 through October 2015. The Japanese Society of Pediatric Allergy and Clinical Immunology asked its affiliated hospitals to report monthly numbers of hospitalizations, ICU admissions and mechanical ventilations due to acute asthma exacerbation. The data were retrieved from medical databases using predefined search criteria: diagnosis of asthma or asthmatic bronchitis, admission, and age <20 years. Monthly numbers of EV-D68 detection were also obtained from the Infectious Disease Surveillance Center of Japan. A Granger causality test was used to analyze the association of EV-D68 detections for asthma exacerbation. Results A total of 157 hospitals reported 87,189 asthma hospitalizations, including 477 ICU admissions and 1193 mechanical ventilations, during the survey period of 5 years and 10 months. The numbers of these events increased drastically in September 2015. The Granger causality test verified the association between EV-D68 and asthma hospitalizations/mechanical ventilations. The most-affected age group was 3–6 years old. Conclusions The spike in pediatric asthma hospitalizations in Japan in September 2015 was found to be associated with the EV-D68 epidemic. Respiratory pathogens can cause “epidemics” of asthma exacerbation. Coordinated surveillance of infectious diseases and asthma may be beneficial for prevention and better control of both illnesses. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Palivizumab effectively prevents severe respiratory syncytial virus (RSV) disease in preterm infants. Our objective was to test whether palivizumab prophylaxis given to preterm infants during the first RSV season reduces the incidence of subsequent recurrent wheezing up to 3 years of life. METHODS: We conducted an observational prospective multicenter (52 registered hospitals in Japan) case-control study in preterm infants with a gestational age between 33 and 35 weeks followed for 3 years. During the 2007-2008 RSV season, the decision to administer palivizumab was made based on standard medical practice. In April 2008, 52 hospitals were recruited. Study participants were pro- spectively followed to the age of 3 years. Parents of study subjects reported the infants' physician's assessment of recurrent wheezing, used a report card and a novel mobile phone-based reporting system by using the Internet. The primary end point was the incidence of physician-diagnosed recurrent wheezing. RESULTS: Of 444 preterm infants enrolled, 349 received palivizumab during the first 6 months of life and 95 infants did not. Physician- diagnosed recurrent wheezing was observed in 6.4% and 18.9% of infants in the treated and untreated groups, respectively (P < .001). This difference remained significant after adjustment for known risk factors of recurrent wheezing (P < .001). CONCLUSIONS: Palivizumab prophylaxis administered to preterm infants 33 to 35 weeks' gestational age is associated with a significantly lower incidence of recurrent wheezing during the first 3 years of life. [ABSTRACT FROM AUTHOR]

Background: Although endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) is widely used worldwide, the fact that it is associated with increased rates of reintervention has been considered a problem. This study aimed to analyze the outcomes of primary open AAA repair and open conversion with explantation of stent grafts after EVAR., Methods: In this retrospective study, we enrolled 1,120 patients (open repair, n = 664; EVAR, n = 456) who underwent AAA repair at Kobe University from 1999 to 2019. Of the 664 patients who underwent open repair, 121 (patients who underwent primary open repair (POR) as a concomitant procedure and patients with ruptured AAA) were excluded from the study. The outcomes of POR were compared with those of open conversion with explantation of stent grafts., Results: Of the 543 patients who underwent open repair, 513 underwent POR and 30 underwent open conversion with explantation of stent grafts. The operation time for POR was significantly less than that for open conversion with explantation. During surgery, patients who underwent open conversion with explantation required significantly more transfusions of red cell concentrate, fresh frozen plasma, and platelet concentrate than those who underwent POR. Overall, 30 patients who underwent open conversion with explantation required a total of 48 reinterventions before surgery. Hospital mortality rates were 0.7% and 0% in the POR and open conversion with explantation groups, respectively (P = 0.62). Although overall survival at 5 years in the POR group was significantly better than that in the open conversion with explantation group (89.3 ± 1.7% vs. 79.5 ± 9.6%; P = 0.01), there were no significant differences between the 2 groups regarding the freedom from aortic event (hospital death, reintervention, and aortic death). According to the multivariate analysis, open conversion with explantation was not an independent risk factor for late death. There were 20 patients who were hesitant to undergo OCE, although we recommended OCE. In a subgroup analysis, the overall mean cost borne by patients who underwent EVAR was approximately 2.3 times higher compared with that borne by patients who underwent POR., Conclusions: Although demanding, both early and long-term outcomes of OCE have been favorable in our present study. OCE is highly recommended in patients with persistent sac enlargement after EVAR., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the effectiveness and safety of pre-emptive transcatheter arterial embolization (P-TAE) for aortic side branches (ASBs) to prevent Type 2 endoleaks (EL2) before endovascular aneurysm repair (EVAR) using the Excluder stent-graft system (Excluder)., Materials and Methods: In this prospective, multicenter study, 80 patients (mean age, 79.1 years [SD ± 6.7]; 85.0% were men; mean aneurysmal sac diameter, 48.4 mm [SD ± 7.4]) meeting the eligibility criteria were prospectively enrolled from 9 hospitals. Before EVAR, P-TAE was performed to embolize the patent ASBs originating from the abdominal aortic aneurysm. Contrast-enhanced computed tomography (CT) was performed at 1 month and 6 months after EVAR. The primary endpoint was EL2 incidence at 6 months, and the secondary endpoints were aneurysmal sac diameter changes at 6 and 12 months, P-TAE outcomes, adverse events related to P-TAE, reintervention, and aneurysm-related mortality., Results: All patients successfully underwent P-TAE without serious. Coil embolization was successful in 81.6% of ASBs. EL2 incidence at 6 months was identified in 18 of 70 (25.7%) patients. Aneurysmal sac diameter shrinkage (≥5 mm) was observed in 30.0% of patients at 6 months and in 40.9% at 12 months. Only 1 patient required reintervention for EL2 within 1 year of EVAR; aneurysm-related deaths were not observed., Conclusions: P-TAE for ASBs before EVAR using Excluder is a safe and effective strategy. It aids in achieving early aneurysmal sac shrinkage and reduces EL2 reintervention at 1 year after EVAR., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

The members of the Japanese Society for Pediatric Infectious Diseases and the Japanese Society of Pediatric Pulmonology have developed Guidelines for the Management of Respiratory Infectious Diseases in Children with the objective of facilitating appropriate diagnosis, treatment and prevention of respiratory infections in children. The first edition was published in 2004 and the fifth edition was published in 2022. The Guideline 2022 consists of 2 parts, clinical questions and commentary, and includes general respiratory infections and specific infections in children with underlying diseases and severe infections. This executive summary outlines the clinical questions in the Guidelines 2022, with reference to the Japanese Medical Information Distribution Service Manual. All recommendations are supported by a systematic search for relevant evidence and are followed by the strength of the recommendation and the quality of the evidence statements., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The clinical features of coronavirus disease 2019 (COVID-19) in children have been changing because of the emergence and rapid spread of variants of concern (VOC). The increase in cases infected with VOC has brought concern with persistent symptoms after COVID-19 in children. This survey aimed to analyze the clinical manifestations and persistent symptoms of pediatric COVID-19 cases in Japan., Methods: We analyzed the clinical manifestations of pediatric COVID-19 cases reported between February 2020 and April 2022 in Japan, using a dedicated database updated voluntarily by the members of the Japan Pediatric Society. Using the same database, we also analyzed persistent symptoms after COVID-19 in children who were diagnosed between February 2020 and November 2021., Results: A total of 5411 and 1697 pediatric COVID-19 cases were included for analyzing clinical manifestations and persistent symptoms, respectively. During the Omicron variant predominant period, the percentage of patients with seizures increased to 13.4% and 7.4% in patient groups 1-4 and 5-11 years of age, respectively, compared with the pre-Delta (1.3%, 0.4%) or Delta period (3.1%, 0.0%). Persistent and present symptoms after 28 days of COVID-19 onset were reported in 55 (3.2%)., Conclusions: Our survey showed that the rate of symptomatic pediatric COVID-19 cases increased gradually, especially during the Omicron variant predominant period, and a certain percentage of pediatric cases had persistent symptoms. Certain percentages of pediatric COVID-19 patients had severe complications or prolonged symptoms. Further studies are needed to follow such patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2021 Japan Pediatric Society.)

Background: Because of the overabundance of vaccination information on the internet, in the media, and on social media, providing clear and correct information on immunization is critical for parental decision-making. In 2018, the Japan Pediatric Society created and distributed a Vaccine Information Statement (VIS) to provide appropriate immunization information to caregivers. The objectives of the present study were to evaluate the effect of the VIS on immunization rates, adherence to schedule, and parental understanding of immunization in Japan., Methods: This cross-sectional study was conducted at 18 centers in 2 prefectures in Japan. Caregivers were assigned to an intervention group, which received the VIS and a questionnaire when their child reached the age of 1 month, and a control group, which received only the questionnaire. Using the self-reported questionnaires, we evaluated vaccination rates and schedule adherence at age 2 months, and parental knowledge, attitudes, and beliefs regarding immunization. Three months later, the questionnaires were returned, and the findings were compared between the 2 groups., Results: We contacted 422 and 428 persons in the intervention and control groups, respectively, and 111/422 (26.3%) and 119/428 (27.8%) returned the surveys. Vaccination rates and adherence rates for the first dose of 4 recommended vaccines did not differ significantly (P > 0.25); however, there were some positive effects on items related to vaccine knowledge (P = 0.03), perceived benefits (P = 0.02), perceived barriers (P < 0.001), and perceived behavioral control (P = 0.01)., Conclusion: The VIS improved parent comprehension of infant immunization. Future studies should examine if the effects of such an intervention persist and affect vaccine uptake throughout childhood., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Background: This study evaluates our 18-year experience of total arch replacement in the octogenarian and nonagenarian population., Methods: Between October 1999 and March 2018, a total of 740 patients underwent total arch replacement at our institution. A total of 139 patients were aged 80 years or more (83.1 ± 2.8 years), and 601 patients were aged less than 80 years (66.9 ± 11.3 years). Early and late outcomes were compared between the groups., Results: In the group aged 80 years or more, operative mortality occurred in 12 patients (8.6%) and significantly improved over time (P = .010). Operative mortality was significantly higher in the group aged 80 years or more (P = .033) when compared with the group aged less than 80 years (4.0%). Regarding postoperative complications, deep sternal wound infection, pneumonia, and tracheostomy occurred in significantly more patients in the group aged 80 years or more. In the group aged 80 years or more, there were 52 late deaths, with 4 aortic-related deaths. Overall survival was 55.4% ± 5.0% at 5 years and 32.2% ± 6.1% at 8 years. Multivariable Cox-hazard regression analysis demonstrated that chronic kidney disease, nonelective surgery, and concurrent procedures were significant risk factors for overall survival in the group aged 80 years or more. Cumulative incidence for reoperation was significantly lower in the group aged 80 years or more (8.7% at 5 years) compared with the group aged less than 80 years (14.2% at 5 years)., Conclusions: Total arch replacement was performed with an acceptable overall survival in octogenarians and nonagenarians, although operative mortality was higher than in younger patients. However, older patients had a lesser burden of reoperation compared with younger patients., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Japanese encephalitis (JE) is the leading cause of viral encephalitis with high mortality and morbidity in Asia. In Japan, however, the active recommendation of JE vaccine was retracted in 2005 because of the potential risk of acute disseminated encephalomyelitis. We aimed to determine the recent incidence of childhood-onset JE after the domestic change of vaccination policy in Japan, and to analyze the clinical features of affected children., Methods: A retrospective nationwide survey was conducted for pediatric patients with JE in Japan from 1995 to 2015. The national surveillance system was used to identify the pediatric patients with JE. Follow-up questionnaires were sent to analyze their clinical and neuroimaging profiles., Results: Among a total of 109 patients registered to the national surveillance, 10 (9%) were less than age 15 years. The annual incidence rate of childhood-onset JE was higher during 2005-15 than that during 1995-2004 (4.3 × 10-3 vs 1.1 × 10-3 per 100000, respectively; P = .04). Endemic regions overlapped with prefectures that farmed pigs harboring antibodies against JE virus with high prevalence. Detailed clinical data were collected from 9 patients. None of them died, but 5 of 9 patients (56%) had neurological sequelae after recovery. One patient who was partially vaccinated with 2 doses of JE vaccine fully recovered from a coma. The age of 3 years or less was associated with unfavorable neurological prognosis., Conclusions: Our data provide evidence for the importance and prophylactic effect of the JE vaccine in young children in the endemic area., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

A follow-up serological study was conducted involving 47 subjects who received 4 doses of diphtheria and tetanus toxoids, combined with the acellular pertussis vaccine (DTaP) together with Salk-type inactivated polio vaccine (DTaP-wIPV), until 6 years of age. All antibody levels declined more rapidly than expected within 3 years after the completion of primary vaccination with the 4th booster dose, and titers persisted until 6 years of age. The positive rate of the IgG antibody against pertussis toxin (PT) was 31.9% (15/47) at 4 years of age, 41.0% (16/39) at 5 years of age, and 40.5% (15/37) at 6 years of age. A significant increase in anti-PT antibodies was observed in 6 subjects, suggesting subclinical infection. Positive rates of antibodies against other targets did not decrease; however, titers of neutralizing antibodies against poliovirus type III decreased in a few subjects. These data suggest the need for an additional preschool booster immunization using DTaP-wIPV.

When using a case-control study design to examine vaccine effectiveness, both the selection of control subjects and the consideration of potential confounders must be the important issues to ensure accurate results. In this report, we described our experience from a case-control study conducted to evaluate the effectiveness of acellular pertussis vaccine combined with diphtheria-tetanus toxoids (DTaP vaccine). Newly diagnosed pertussis cases and age- and sex-matched friend-controls were enrolled, and the history of DTaP vaccination was compared between groups. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for development of pertussis. After adjustment for potential confounders, four doses of DTaP vaccination showed a lower OR for pediatrician-diagnosed pertussis (OR=0.11, 95% CI, 0.01-0.99). In addition, the decreasing OR of four doses vaccination was more pronounced for laboratory-confirmed pertussis (OR=0.07, 95%CI, 0.01-0.82). Besides, positive association with pertussis was observed in subjects with a history of steroid treatment (OR=5.67) and those with a recent contact with a lasting cough (OR=4.12). When using a case-control study to evaluate the effectiveness of vaccines, particularly those for uncommon infectious diseases such as pertussis, the use of friend-controls may be optimal due to the fact that they shared a similar experience for exposure to the pathogen as the cases. In addition, to assess vaccine effectiveness as accurately as possible, the effects of confounding should be adequately controlled with a matching or analysis technique., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Seroepidemiological studies on pertussis, diphtheria and tetanus were performed on 1,540 nursing students enrolled in S-university between 1994 and 2011. Antibody titers against pertussis toxin (PT) and filamentous hemagglutinin (FHA), diphtheria antitoxin titer, and tetanus antitoxin titer were measured using sera taken during enrollment. The antibody-seropositive rates and geometric mean titers (GMTs) were calculated by according to birth year (1975-1993). The pertussis anti-PT and anti-FHA antibody-seropositive rates (seropositive levels were both defined as ≥10 EU/mL) were 12%-53% and 47%-84%, respectively. The anti-PT antibody-seropositive rate was lower than the anti-FHA rate. The anti-PT antibody GMTs were 2.0-11 EU/mL, whereas the anti-FHA antibody GMTs were 10 EU/mL or more (8.8-31 EU/mL) in almost every group. The diphtheria antitoxin-seropositive rate (≥0.1 IU/mL) was 49%-79%, and the GMT was nearly 0.1 IU/mL. The tetanus antitoxin-seropositive rate (≥0.01 IU/mL) was 91%-100%, and the GMT was 0.3 IU/mL or more for all the groups. While the nursing students' diphtheria and tetanus antitoxin levels were sufficient to prevent both diseases, the anti-PT antibody-seropositive rate and the GMT were both lower than the level required to prevent pertussis, suggesting that many of the nursing students were pertussis-susceptible. These findings suggest a need for pertussis vaccination in young adults or early adolescents.

Aim: To retrospectively analyze factors affecting the long-term survival of patients with pancreatic cancer who underwent pancreatic resection., Methods: From January 2000 to December 2011, 195 patients underwent pancreatic resection in our hospital. The prognostic factors after pancreatic resection were analyzed in all 195 patients. After excluding the censored cases within an observational period, the clinicopathological characteristics of 20 patients who survived ≥ 5 (n = 20) and < 5 (n = 76) years were compared. For this comparison, we analyzed the patients who underwent surgery before June 2008 and were observed for more than 5 years. For statistical analyses, the log-rank test was used to compare the cumulative survival rates, and the χ (2) and Mann-Whitney tests were used to compare the two groups. The Cox-Hazard model was used for a multivariate analysis, and P values less than 0.05 were considered significant. A multivariate analysis was conducted on the factors that were significant in the univariate analysis., Results: The median survival for all patients was 27.1 months, and the 5-year actuarial survival rate was 34.5%. The median observational period was 595 d. With the univariate analysis, the UICC stage was significantly associated with survival time, and the CA19-9 ≤ 200 U/mL, DUPAN-2 ≤ 180 U/mL, tumor size ≤ 20 mm, R0 resection, absence of lymph node metastasis, absence of extrapancreatic neural invasion, and absence of portal invasion were favorable prognostic factors. The multivariate analysis showed that tumor size ≤ 20 mm (HR = 0.40; 95%CI: 0.17-0.83, P = 0.012) and negative surgical margins (R0 resection) (HR = 0.48; 95%CI: 0.30-0.77, P = 0.003) were independent favorable prognostic factors. Among the 96 patients, 20 patients survived for 5 years or more, and 76 patients died within 5 years after operation. Comparison of the 20 5-year survivors with the 76 non-survivors showed that lower concentrations of DUPAN-2 (79.5 vs 312.5 U/mL, P = 0.032), tumor size ≤ 20 mm (35% vs 8%, P = 0.008), R0 resection (95% vs 61%, P = 0.004), and absence of lymph node metastases (60% vs 18%, P = 0.036) were significantly associated with the 5-year survival., Conclusion: Negative surgical margins and a tumor size ≤ 20 mm were independent favorable prognostic factors. Histologically curative resection and early tumor detection are important factors in achieving long-term survival.

Background and Aim of the Study: Recent brain complications (e.g., bleeding or infarction) in patients with active infective endocarditis (AIE) are recognized as a contraindication for early surgery. Nafamostat mesilate (NM) is a synthetic protease-inhibiting agent that has not only potent inhibitory activity against coagulation factors (Xlla, Xa) but also an anti-inflammatory action. Herein is reported the authors' successful surgical experience using NM with low-dose heparinization in patients with AIE complicated by recent cerebral complications., Methods: Twenty-eight patients (mean age 54.9 +/- 18.7 years) who had undergone surgery for AIE of the native valve (n = 21) or prosthetic valve (n = 7) were reviewed retrospectively. AIE was present in the aortic (n = 8), mitral (n = 16), aortic/mitral (n = 4) and tricuspid (n = 1) valves. Twenty-two of 28 patients had preoperative stroke, and six had active brain bleeding. Surgery was performed at a mean of 2.4 +/- 2.1 days after the onset of stroke. NM (209 +/- 152 mg) with low-dose heparin (3796 +/- 1218 IU; 67.4 +/- 20.3 IU/kg) was used for anticoagulation during cardiopulmonary bypass (CPB). The activated clotting time (ACT) was maintained at 350-450 s by the precise administration of NM into a cardiotomy reservoir (0.5 mg/kg/h) and a venous reservoir (sliding controlled dose at 1.5 mg/kg/h)., Results: The CPB time was 181.3 +/- 92.6 min. Five patients (17.8%) died during hospitalization due to persistent sepsis (n = 3), brain death caused by massive brain embolism before CPB establishment (n = 1), and pneumonia (n = 1). There was no further aggravation of intracranial bleeding, and no new hemorrhagic stroke., Conclusion: Nafamostat mesilate, administered in conjunction with low-dose heparinization, served as an effective anticoagulant for early surgery in patients with AIE complicated by stroke, and caused no further deterioration of the cerebral lesions.

Objectives: The present study analyzes the early patency of intercostal artery reconstruction, using graft interposition and aortic patch anastomosis, and determines the fate of reattached intercostal arteries after repair of thoracoabdominal aortic aneurysms., Methods: We selected 115 patients (mean age, 63 ± 15 years; range, 19-83 years; male, n = 83) treated by thoracoabdominal aortic aneurysm repair with 1 or more reconstructed intercostal arteries at the Kobe University Graduate School of Medicine between October 1999 and December 2012. The intercostal arteries were reconstructed using graft interposition (n = 66), aortic patch anastomosis (n = 42), or both (n = 7)., Results: The hospital mortality rate was 7.8% (n = 9). Eleven patients (9.6%) developed spinal cord ischemic injury (permanent, n = 6, transient, n = 5). The average number of reconstructed intercostal arteries per patient was 3.0 ± 1.5 (1-7), and 345 intercostal arteries were reattached. The overall patency rate was 74.2% (256/345) and that of aortic patch anastomosis was significantly better than that of graft interposition (90.8% [109/120] vs 65.3% [147/225], P < .01), but significantly worse for patients with than without spinal cord ischemic injury (51.9% [14/27] vs 76.1% [242/318], P = .01). There was no patch aneurysm in graft interposition during a mean of 49 ± 38 (range, 2-147) postoperative months, but aortic patch anastomosis including 4 intercostal arteries became dilated in 2 patients., Conclusions: Aortic patch anastomosis might offer better patency rates and prevent spinal cord ischemic injury compared with graft interposition. Although aneurysmal changes in intercostal artery reconstructions are rare, large blocks of aortic wall reconstruction should be closely monitored., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Group B Streptococcus (GBS) is one of the leading causes of neonatal bacterial infections. Population-based surveillance of GBS-related invasive diseases among newborns and infants from 10 prefectures in Japan was performed between 2007 and 2012. The characteristics of cases and isolated GBS are described in this study. The incidence rate of GBS-related invasive diseases was 0.13 per 1,000 live births. Analysis of GBS samples obtained from 60 invasive cases showed that the most frequent serotypes were III (48.3%), Ia (30.0%), and Ib (10.0%). All isolates were susceptible to penicillin G, ampicillin, cefotaxime, imipenem, and panipenem. However, 14, 2, and 7 isolates were resistant to erythromycin, clindamycin, and both erythromycin and clindamycin, respectively. Multilocus sequence typing revealed that GBS sequence type (ST) 23, ST17, and ST335 caused higher incidences of meningitis. These data show that serotypes III, Ia, and Ib together caused more than 80% of invasive infections in Japanese infants, and that GBS strains are still susceptible to β-lactam antibiotics.

The recent increase of pertussis in young adults in Japan is hypothesized to be due in part to waning protection from the acellular pertussis vaccine. While a booster immunization may prevent an epidemic of pertussis among these young adults, little is known about the safety and immunogenicity of such a booster with the diphtheria, tetanus, and acellular pertussis vaccine (DTaP), which is currently available in Japan. One hundred and eleven medical students with a mean age of 19.4 years were randomly divided into 2 groups of 55 and 56 subjects and received, respectively, 0.2 or 0.5 ml of DTaP. Immunogenicity was assessed by performing the immunoassay using serum, and the geometric mean concentration (GMC), GMC ratio (GMCR), seropositive rate, and booster response rate were calculated. Adverse reactions and adverse events were monitored for 7 days after vaccination. After booster vaccination in the two groups, significant increases were found in the antibodies against pertussis toxin, filamentous hemagglutinin, diphtheria toxoid, and tetanus toxoid, and the booster response rates for all subjects reached 100%. The GMCs and GMCRs against all antigens were significantly higher in the 0.5-ml group than in the 0.2-ml group. No serious adverse events were observed. Frequencies of local reactions were similar in the 2 groups, although the frequency of severe local swelling was significantly higher in the 0.5-ml group. These data support the acceptability of booster immunization using both 0.2 and 0.5 ml of DTaP for young adults for controlling pertussis. (This study was registered at UMIN-CTR under registration number UMIN000010672.).

Freeze dried, cell culture-derived Japanese encephalitis vaccine (Inactivated) (JEBIK(®)V) is approved for a three-dose primary immunization followed by a one-dose booster immunization in Japan. We conducted a multicenter, double-blinded, randomized controlled trial of the safety and immunogenicity of the vaccine in 370 healthy children who received three doses of 5, 2.5 or 1.25 μg of virus protein per 0.5 mL formulation subcutaneously. Children received two doses of test vaccine 7-28 days apart followed by a dose 6-12 months after the second vaccination. The three-dose regimen showed a good safety profile with no serious vaccine-related adverse events. Fever and reactions at the injection site were common adverse reactions at each dose of vaccine. The seroconversion rates were 100%, 99.2% and 95.0% after two doses in the 5, 2.5 and 1.25 μg groups, respectively, and 100.0% after three doses in all groups. The geometric mean titers were high for all three formulations after the second and third doses, with a very clear dose-response relationship. These results indicate that JEBIK(®)V is likely to be a useful vaccine., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: To study the effect of treatment of latent tuberculosis infection (LTBI) on QuantiFERON TB-2G (QFT-2G) test results., Subjects and Methods: QFT-2G was used for a contact investigation in a junior high school and those positive or doubtful positive (TB Antigen-Nil response > or = 0.1 and < 0.35 IU/ml) were indicated for treatment of LTBI with INH. All subjects who completed treatment of LTBI were re-tested with QFT-2G approximately 1 month after completion of treatment and a subset were again re-tested 8 to 11 months after the completion of treatment. The levels of IFN-gamma response in each QFT-2G test were compared., Results: Initially, 43 subjects (28 QFT-2G positive and 15 doubtful positive) were indicated treatment of LTBI, and 41 (95%) completed 6-months treatment. These 41 subjects were re-tested with QFT-2G approximately 1 month after the completion of treatment. Among 28 pre-treatment positives, 19 remained positive, 6 became doubtful positive, and 3 reverted to negative. Among 13 pre-treatment doubtful positives, 1 converted to positive, 5 remained doubtful positive, and 7 reverted to negative. The QFT-2G responses after the completion of treatment significantly declined compared with the pre-treatment level (geometric means; before treatment ESAT-6: 0.30 IU/ml, CFP-10: 0.09 IU/ml, after treatment ESAT-6:0.18 IU/ml, CFP-10: 0.05 IU/ml, dependent t-test; ESAT-6: p = 0.020, CFP-10: p = 0.005). At 8 to 11 months after the completion of treatment, 30 randomly selected subjects received the third QFT-2G test. Among 19 positives at the completion of treatment, 14 remained positive, 4 become doubtful positive, and 1 reverted to negative. Among 8 doubtful positives at completion of treatment, 4 converted to positive, 3 remained doubtful positive, and 1 reverted to negative. A further decline of QFT-2G responses was not observed. Three subjects negative at the completion of treatment were re-tested and remained negative at the third test., Conclusion: QFT-2G responses significantly declined after the treatment of LTBI, despite the rate of reversion in QFT-2G being low. This low reversion rate suggests QFT-2G would not be useful as a marker to evaluate the success of treatment for LTBI. However, the finding that QFT-2G responses significantly decline after the treatment of LTBI suggests the possibility that this decline could be used as a marker of the susceptibility of the infective M. tuberculosis strain to the prophylactic drug used. The outbreak investigation has been carried out for over two years, and none of 229 students who were TST positive, but QFT-2G negative and because of this result not indicated treatment of LTBI, have developed TB, suggesting that QFT-2G reflects TB infection more accurately than the TST, even in school children.

Recently, the incidence of reported pertussis cases of adults has dramatically increased in Japan. In the present study, we analyzed seven Bordetella pertussis isolates recovered from adults in Japan using pulsed-field gel electrophoresis (PFGE) and sequencing of their antigenic and virulence-associated proteins, compared with those from children. PFGE analysis demonstrated that the adult strains were closely related to the child strains (78-100% genetic similarity). On the other hand, the genotyping revealed that 71% (5/7) of the adult strains and 47% (25/53) of the child strains had the same combination of antigenic/virulence-associated allelic variants (ptxS1B/prn1/fim2-1/fim3A/fhaB1/tcfA2) as the Japanese vaccine strain Tohama, respectively. In comparison to the child strains, there was no apparent antigenic and genetic shift in the adult strains. Our result suggests that (i) there is no B. pertussis circulating strain specific to adults and (ii) the antigenic/virulence-associated proteins are unrelated to the rise in adult pertussis incidence in Japan.

The objectives of this study were to develop a population pharmacokinetic model and to determine the covariates affecting the pharmacokinetics of busulfan in Japanese pediatric patients who received high-dose oral busulfan as a conditioning regimen before hematopoietic stem cell transplantation. Population analysis was performed using retrospective therapeutic drug monitoring data (including test dose data) from 103 children. Their ages ranged from 2 months to 11 years old (mean age, 30 months; median age, 18 months). The plasma concentration of busulfan in all 1028 samples was measured with the same high-performance liquid chromatography method. Maximum likelihood estimates were sought for pharmacokinetic parameters with the NONMEM program. The best structural covariate-free model for busulfan was a one-compartment model with an exponential error model to account for intersubject variability and a proportional error model to account for intrasubject variability. The apparent oral clearance was found to be correlated with age, aspartate transaminase, and type of disease (malignant disease or other). The apparent volume of distribution was related to body weight. The busulfan formulation (1% powder form or crystal form) and dose (milligrams per kilogram) influenced the absorption rate constant. It was estimated that oral clearance expressed per kilogram of body weight is low at early infancy, then increases to a maximum at approximately 2 years of age and, thereafter, decreases. In conclusion, we have developed a population pharmacokinetic model of oral busulfan in children, particularly for those younger than 4 years old, that takes into consideration not only body size, but also several other covariates.

In Japan, mass vaccination for diphtheria, pertussis, and/or tetanus has been mandated by the Vaccination Law since 1948. In order to evaluate the efficacy of this vaccination policy, we conducted seroepidemiological studies on pertussis, diphtheria, and tetanus among individuals aged 0 - 80 years. The pertussis toxin seropositive rates of the vaccine-eligible groups and vaccine-ineligible groups were 55.0 and 57.9%, respectively. The seropositive rate of each group for diphtheria antitoxin was 76.3 and 75.7%, respectively. The tetanus antitoxin seropositive rates were 91.7 and 10.5%, respectively, showing a significant difference between the two groups (P < 0.001). For the three diseases, variations were seen between age groups in the geometric mean antibody titers due to changes of the vaccination program. The results of this study show that natural Bordetella pertussis infection has occurred more frequently than expected. In order to establish the most appropriate vaccination program for the control of pertussis, diphtheria, and tetanus in Japan, further evaluation is necessary.

Haemophilus influenza carriage was examined in unvaccinated nursery contacts of a patient with H. influenzae type b (Hib) meningitis and isolates were typed by pulsed-field gel electrophoresis (PFGE). Nasopharyngeal isolates were classified into eight PFGE patterns. Seven Hib carriers were found among 15 nursery contacts. The isolates from the carriers showed a PFGE pattern identical to that of the meningitis strain. The carrier rate of non-disease-associated strains was also high (47%, 7 of 15). This study suggests that the clonal spread of invasive (serotype b) H. influenzae strains is accompanied by a high carriage rate of non-disease-associated strains.