Factors affecting guardians' decision-making regarding the SARS-CoV-2 vaccine.

BACKGROUND: In Japan, the vaccination rate against the SARS-CoV-2 vaccine for children was low. Therefore, in this study we investigated the factors influencing guardians' decision-making regarding vaccination of their children. METHODS: From November 1, 2022 to March 31, 2023, pediatric clinics, departments, and midwifery clinics in Saitama Prefecture requested guardians of children under the age of 15 to complete an online questionnaire. RESULTS: Responses were obtained from 894 guardians of children aged 6 months to 15 years; 142 had had one of their children vaccinated at least once and 629 had not had any of their children vaccinated. Among guardians who had not had any of their children vaccinated, "the Age of children" was significantly younger (p < 0.001) and "Prevalence" (p < 0.001), "Free vaccination" (p < 0.001), and "Intentions of national and local governments" (p = 0.005) were selected as reasons significantly less frequently in comparison to guardians who had vaccinated their children. "Japanese adverse reactions" (p < 0.001), "Japanese effectiveness" (p < 0.001), "Adverse reactions" (p < 0.001), "History of adverse reactions" (p < 0.001), and "Reputation of friends" (p = 0.006) were selected significantly more frequently by guardians who had not had any of their children vaccinated. CONCLUSIONS: Guardians who had had one of their children vaccinated at least once emphasized the importance of prevalence and free vaccination. On the other hand, guardians who had not had any of their children vaccinated placed particular importance on adverse reactions and the Japanese data on effectiveness. To guide the decision-making of guardians, it is necessary to quickly collect and publish data on adverse reactions and effectiveness, particularly in Japanese individuals, so that citizens can decide whether to vaccinate themselves and their children.

A registry study of Kawasaki disease patients with coronary artery aneurysms (KIDCAR): a report on a multicenter prospective registry study three years after commencement.

The long-term prognosis of patients with Kawasaki disease (KD) complicated by coronary artery aneurysms (CAA) is still unclear. The present, multicenter registry study aimed to study the factors associated with coronary events (CE) and determine an appropriate management method for patients with KD complicated with CAA. Patients with KD with onset after 2015 and with a medium-sized or large CAA having an actual diameter ≥ 4 mm or a Z-score ≥ 5.0 at 30 days and later after KD onset were included in the annual survey. The primary endpoint was the time-dependent incidence of CE. Associated factors were also examined. In total, 179 patients from 53 centers were enrolled and followed up for a median of 501 days. The median age at KD onset was 2.2 years, 137 patients were male (77%), 47 had incomplete KD (26%), and 36 had large CAA (20%). CE occurred in 13 patients (7%; 95% confidence interval: 4-12%); eight (62%) experienced CE within 1 year, and all the patients experienced a CE within 2 years. All but one patient received antiplatelet drugs and warfarin. Patients with a large CAA had significantly more CAA (2.8 vs. 1.7, p < 0.001), more cases of warfarin use (86% vs. 43%, p < 0.001), and were more likely to have CE (28% vs. 2%, p < 0.001) than those with a medium-sized CAA. On univariate Cox regression analysis, the factors significantly associated with CE were large CAA (hazard ratio (HR): 17.0), three or more CAA (HR: 23.3), and beaded CAA (HR: 15.9). Multivariable Cox regression analysis revealed that the only associated factor was a large CAA. CONCLUSION: Patients with a large CAA were more likely to have a CE within 2 years. Antithrombotic therapy with warfarin did not eliminate the CE risk, and better therapies are desirable. WHAT IS KNOWN: • Coronary artery aneurysms are a serious complication of Kawasaki disease, and coronary events are sometimes fatal. • In previous, retrospective studies in Japan, large aneurysms, male sex, and refractoriness to initial immunoglobulin therapy were considered risk factors for coronary events. WHAT IS NEW: • Of 179 patients with a medium sized or large aneurysm, 13 (7%) experienced coronary events, all of which occurred within 2 years of onset. Factors significantly associated with coronary events were large aneurysms, three or more aneurysms, and beaded aneurysms.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome: Clinical characteristics and treatment outcomes - a single center study in Japan.

BACKGROUND: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is an autoinflammatory disease occurring in children. Although PFAPA is the most common periodic fever syndrome found in children, there are only a few studies defining the clinical characteristics and the efficacy of treatment strategies among Japanese children. This study aimed to clarify the demographic characteristics and clinical features of patients with PFAPA syndrome and to evaluate treatment efficacy. METHODS: We retrospectively reviewed the clinical features of children with PFAPA who visited Saitama Children's Medical Center between January and December 2019. We also evaluated treatment strategies and their efficacy; abortive treatment with corticosteroids, prophylaxis with cimetidine or colchicine, and surgical management with tonsillectomy. RESULTS: A total of 100 Japanese children (61% male) with PFAPA were included. Median age of onset was 3 years, median duration of fever episodes was 5 days, and median interval between episodes was 4 weeks. The symptoms (frequencies) were pharyngitis (89%), exudate on tonsils (71%), cervical adenitis (50%), and aphthous stomatitis (49%). Approximately 37% of patients took prednisolone for aborting fever attacks, showing a 100% response; 93% were treated with cimetidine, showing an 79.6% response, and 18% were treated with colchicine, showing a 66.7% response. Only one patient underwent tonsillectomy. CONCLUSIONS: Among Japanese children with PFAPA, 28% of them were ≥5 years with a male predominance. Pharyngitis is the most frequent symptom associated with fever. Cimetidine is suitable for initial therapy because of its safety and efficacy.

Actinomycosis of the Middle Ear in Children: Case Report and Literature Review.

Actinomycosis of the middle ear is a rare infectious disease, characterized by a slowly progressive clinical course. We report the case of a 9-year-old girl with recurrent otitis media, who presented with clinical signs of a cholesteatoma. She underwent tympanoplasty and ossiculoplasty. After surgery, actinomycosis was diagnosed histologically. We also provide a review of 16 published pediatric cases.

Prospective Study of the Detection of Bacterial Pathogens in Pediatric Clinical Specimens Using the Melting Temperature Mapping Method.

The melting temperature (Tm) mapping method is a novel technique that uses seven primer sets without sequencing to detect dominant bacteria. This method can identify pathogenic bacteria in adults within 3 h of blood collection without using conventional culture methods. However, no studies have examined whether pathogenic bacteria can be detected in clinical specimens from pediatric patients with bacterial infections. Here, we designed a new primer set for commercial use, constructed a database with more bacterial species, and examined the agreement rate of bacterial species in vitro. Moreover, we investigated whether our system could detect pathogenic bacteria from pediatric patients using the Tm mapping method and compared the detection rates of the Tm mapping and culture methods. A total of 256 pediatric clinical specimens from 156 patients (94 males and 62 females; median age, 2 years [<18 years of age]) were used. The observed concordance rates between the Tm mapping method and the culture method for both positive and negative samples were 76.4% (126/165) in blood samples and 79.1% (72/91) in other clinical specimens. The Tm mapping detection rate was higher than that of culture using both blood and other clinical specimens. In addition, using the Tm mapping method, we identified causative bacteria in pediatric clinical specimens quicker than when using blood cultures. Hence, the Tm mapping method could be a useful adjunct for diagnosing bacterial infections in pediatric patients and may be valuable in antimicrobial stewardship for patients with bacterial infections, especially in culture-negative cases. IMPORTANCE This study provides novel insights regarding the use of the melting temperature (Tm) mapping method to identify the dominant bacteria in samples collected from pediatric patients. We designed a new set of primers for commercial use and developed a database of different bacteria that can be identified using these primers. We show that the Tm mapping method could identify bacteria from blood samples and other clinical specimens. Moreover, we provide evidence that the Tm mapping method has a higher detection rate than that of the culture-based methods and can achieve a relatively high agreement rate. We believe that our study makes a significant contribution to this field because rapid identification of the source of bacterial infections can drastically improve patient outcomes and impede the development of antibiotic-resistant bacteria.

Case Reports on Effect of Intratympanic Steroid Injection Therapy on Late-Onset Hearing Loss in Congenital Cytomegalovirus Infection.

BACKGROUND: One of the conditions or symptoms caused by congenital cytomegalovirus (cCMV) infection is late-onset hearing loss. This report examines the cases of two children exhibiting late-onset hearing loss after cCMV infection who showed improvement in hearing after undergoing intratympanic steroid injection therapy (IST). CASES: Case1 is girl aged 8 years and 10 months and case2 is girl aged 5 years and 1 month. Cytomegalovirus (CMV) was not detected in the blood or urine of either child at the time of hearing loss despite them having cCMV infection. FINDINGS: The hearing of both children improved as a result of IST on an outpatient basis. Case1 was given first session of IST in left ear immediately on the day of her visit and second session of IST in left ear 2 days later. Tendency for improvement in threshold on left side was observed (the differences were about 20 to 45 dB). Case2 was given a total of 2 sessions of IST on left ear, 3 days and 5 days after visiting the hospital. The test result of distortion product otoacoustic emissions changed from refer to pass. Tendency for improvement in threshold on left side was observed (the differences were about 5 to 25 dB). CONCLUSIONS: Bearing in mind that late-onset hearing loss in patients with cCMV may be caused by other factors besides CMV, consideration of IST as a possible treatment option is proposed.

Increased Myosin light chain 9 expression during Kawasaki disease vasculitis.

Introduction: Kawasaki disease (KD) is an acute systemic vasculitis that predominantly afflicts children. KD development is known to be associated with an aberrant immune response and abnormal platelet activation, however its etiology is still largely unknown. Myosin light chain 9 (Myl9) is known to regulate cellular contractility of both non-muscle and smooth muscle cells, and can be released from platelets, whereas any relations of Myl9 expression to KD vasculitis have not been examined. Methods: Plasma Myl9 concentrations in KD patients and children with febrile illness were measured and associated with KD clinical course and prognosis. Myl9 release from platelets in KD patients was also evaluated in vitro. Myl9 expression was determined in coronary arteries from Lactobacillus casei cell wall extract (LCWE)-injected mice that develop experimental KD vasculitis, as well as in cardiac tissues obtained at autopsy from KD patients. Results and discussion: Plasma Myl9 levels were significantly higher in KD patients during the acute phase compared with healthy controls or patients with other febrile illnesses, declined following IVIG therapy in IVIG-responders but not in non-responders. In vitro, platelets from KD patients released Myl9 independently of thrombin stimulation. In the LCWE-injected mice, Myl9 was detected in cardiac tissue at an early stage before inflammatory cell infiltration was observed. In tissues obtained at autopsy from KD patients, the highest Myl9 expression was observed in thrombi during the acute phase and in the intima and adventitia of coronary arteries during the chronic phase. Thus, our studies show that Myl9 expression is significantly increased during KD vasculitis and that Myl9 levels may be a useful biomarker to estimate inflammation and IVIG responsiveness to KD.

All trans retinoic acid alleviates coronary stenosis by regulating smooth muscle cell function in a mouse model of Kawasaki disease.

Coronary artery (CA) stenosis is a detrimental and often life-threatening sequela in Kawasaki disease (KD) patients with coronary artery aneurysm (CAA). Therapeutic strategies for these patients have not yet been established. All-trans-retinoic acid (atRA) is a modulator of smooth muscle cell functions. The purpose of this study was to investigate the effect of atRA on CA stenosis in a mouse model of KD. Lactobacillus casei cell wall extract (LCWE) was intraperitoneally injected into 5-week-old male C57BL/6 J mice to induce CA stenosis. Two weeks later, the mice were orally administered atRA (30 mg/kg) 5 days per week for 14 weeks (LCWE + atRA group, n = 7). Mice in the untreated group (LCWE group, n = 6) received corn oil alone. Control mice were injected with phosphate-buffered saline (PBS, n = 5). Treatment with atRA significantly suppressed CA inflammation (19.3 ± 2.8 vs 4.4 ± 2.8, p < 0.0001) and reduced the incidence of CA stenosis (100% vs 18.5%, p < 0.05). In addition, atRA suppressed the migration of human coronary artery smooth muscle cells (HCASMCs) induced by platelet-derived growth factor subunit B homodimer (PDGF-BB). In conclusion, atRA dramatically alleviated CA stenosis by suppressing SMC migration. Therefore, it is expected to have clinical applications preventing CA stenosis in KD patients with CAA.

Retropharyngeal abscess due to Staphylococcus aureus complicated by bilateral neck and intraabdominal abscesses in an immunocompetent infant.

Retropharyngeal abscess is a serious condition, with potentially high morbidity and mortality if not detected early. The patient, a previously healthy 10-month-old girl, was admitted due to retropharyngeal and bilateral cervical lymph node abscesses. The neck abscesses recurred, despite surgical drainage and treatment with intravenous ampicillin-sulbactam. Methicillin-susceptible Staphylococcus aureus was identified from the abscess culture. A mesenteric abscess was also found during treatment. Intravenous ampicillin-sulbactam was switched to intravenous cephazolin and metronidazole, and the patient was successfully treated without further surgical intervention. No recurrence was observed throughout the 1-year follow-up period. Immune function testing, especially neutrophil function, did not reveal any abnormality. Neck abscesses can spread to the deep or shallow neck spaces directly or through the lymph node chains, even in immunocompetent hosts. Clinicians should consider deep neck infection in patients with cervical lymph node abscess, even if they present without the typical signs and symptoms of retropharyngeal abscess.

Infected simple renal cyst due to Streptococcus pneumoniae rapidly diagnosed by the melting temperature mapping method: a case report.

BACKGROUND: Spontaneous infection of preexisting solitary renal cysts has been documented in adults but is extremely rare in children. To date, no cases of simple renal cysts infected with Streptococcus pneumoniae have been described. Recently, reports have described the diagnosis of bacterial infection using the 16 S rRNA gene as well as the accompanying antimicrobial stewardship for microorganisms that are difficult to culture and for culture-negative cases after preceding antibacterial administration. CASE PRESENTATION: A four-year-old Japanese girl who had a pleuroperitoneal shunt inserted to drain a right pleural effusion due to occlusion of the hepatic portion of the inferior vena cava at three years old visited our hospital due to fever and respiratory discomfort. She was incidentally found to have a right simple renal cyst 10 months before admission. The patient was suspected to have pneumonitis or catheter-related blood stream infection on chest X-ray, which showed right-side pleural effusion. She was diagnosed with invasive pneumococcal infection, as Streptococcus pneumoniae was detected from blood culture on admission. Transient improvements in her symptoms and decreases in the white blood cell count and C-reactive protein level were observed after effective antibiotic administration, but her respiratory condition deteriorated. Enhanced CT showed right renal cyst enlargement and enhancement and thickening of the surrounding wall. Using the melting temperature (Tm) mapping method, S. pneumoniae was rapidly detected directly from pus 4.5 hours after drainage. The specimen culture was negative, but the extracted 16 S rDNA sequence revealed 100 % identity for S. pneumoniae from the same specimen the subsequent day. We successfully performed optimal treatment and reduced medical cost based on the positive Tm mapping method result. CONCLUSIONS: We report the first case of a S. pneumoniae-infected simple renal cyst. The drainage culture was negative, but the Tm mapping method rapidly detected S. pneumoniae directly from the drainage. The Tm mapping method may have great impacts on rapid diagnosis and effective antimicrobial stewardship.

Efficacy, safety, and pharmacokinetics of oral valganciclovir in patients with congenital cytomegalovirus infection.

OBJECTIVES: Valganciclovir (VGCV) has been shown to improve sensorineural hearing loss (SNHL) and neurological outcomes in patients with neonatal symptomatic congenital cytomegalovirus (cCMV) infection. However, reports on the pharmacokinetics, efficacy and safety of oral VGCV are limited. The aim of this study is to evaluate the pharmacokinetics of VGCV for use in the treatment of cCMV. METHODS: This was a single-center, retrospective observational study conducted at Saitama Children's Medical Center in Japan between 2012 and 2017. CMV DNA copy number, maximum plasma VGCV concentration (Cmax), and adverse events (ADEs) during treatment were evaluated. RESULTS: A total of 26 patients with cCMV who received VGCV were included in this study. The median age at VGCV initiation was 9.5 months (range 0-46). Twenty-one patients (81%) had SNHL at baseline. Of these, five patients (19%) presented with improved SNHL, and none experienced worsened SNHL during treatment. The mean VGCV Cmax was 3.5 µg/mL (range 2-5.3), with no significant variation among individual values, and the values were maintained during treatment. Furthermore, there were no correlations between the Cmax values and age, sex, SNHL improvement or ADEs. Neutropenia (<1000/mm3) was observed in six patients (23%); however, no serious ADEs occurred. CONCLUSIONS: VGCV prevented the progression of SNHL without serious ADEs due to its stable pharmacokinetics. This study provides safety and tolerability of VGCV for the treatment of cCMV patients.