Time course of peripheral immunophenotypes of multisystem inflammatory syndrome in children.

The etiology of multiple inflammatory syndrome in children (MIS-C) remains poorly understood. As clues to elucidate the pathogenic condition, several characteristic peripheral immunophenotypes have been reported in MIS-C. However, no report has demonstrated the time course of the peripheral immunophenotype along with the clinical course in the same patient. Herein, we clarified the immunological characteristics of a Japanese patient with MIS-C. There was an initial cytokine storm followed by T-cell activation, especially of CD8+ T cells, with the expansion of T-cell receptor Vß 21.3-expressing cells, which suggests superantigen-mediated T-cell activation. In addition, we also found an increase in IgG-producing cells (plasmablasts and switched memory B cells), which were accompanied by elevated serum levels of anti-SARS-CoV-2 spike antigen-specific IgG antibodies. These time course of peripheral immunophenotypes support that immunological activation against SARS-CoV-2 spike protein plays a central role in the etiology of MIS-C.

Kawasaki disease with dilatation of the common bile duct: A case report and review of literature.

BACKGROUND: Kawasaki disease (KD) is a syndrome that results in acute systemic vasculitis and is a major cause of acquired heart disease in developed countries. KD is diagnosed based on certain characteristic symptoms and echocardiogram results. It has been reported that abdominal ultrasound is of value in supporting the diagnosis of KD. Nevertheless, abdominal ultrasound is not a routine procedure in KD. Moreover, dilatation of the common bile duct (CBD) has been rarely reported in previous cases. CASE PRESENTATION: A 4-year-old boy presented with fever and markedly high transaminase level (aspartate aminotransferase, 5323 U/L; alanine aminotransferase, 1554 U/L). The patient was diagnosed as having KD based on characteristic symptoms and echocardiogram findings. Ultrasound revealed dilatation of the CBD as well as cervical lymphadenopathy resembling a cluster of grapes, thickening of the gallbladder wall, and increased periportal echogenicity throughout the liver parenchyma. The patient received initial treatment with intravenous immunoglobulin at day 4 of fever and second-line treatment with intravenous immunoglobulin and prednisolone because of recurrent fever on day 6. Dilatation of the CBD was improved from 6.6 mm on day 4 to 3.1 mm on day 8. Although re-dilatation was observed, it gradually diminished and normalized (4.3 mm on day 28, 4.0 mm on day 63, 3.3 mm on day 105, and 2.8 mm on day 182). CONCLUSION: This case highlights the usefulness of abdominal ultrasound and the importance of considering dilatation of the CBD as one of the complications of KD.

Abdominal aortic thrombus formation in a neonate with an interrupted aortic arch.

We note the risk of paradoxical embolism in patients with congenital heart defects with a right-to-left shunt. These patients should be managed to ensure that abdominal aortic thrombi are not overlooked when their clinical conditions change.

Successful trans-maternal nadolol pharmacotherapy in a fetus presenting with long QT syndrome type 2 complicated by torsade de pointes.

Fetuses with congenital long QT syndrome (LQTS) may experience life-threatening arrhythmias, such as torsade de pointes (TdP), and/or functional atrioventricular block. However, trans-maternal pharmacotherapy for these cases is rarely reported and management practices have yet to be established. The fetus of a mother with genetically-confirmed LQTS type 2 (LQT2) presented with complex arrhythmias, diagnosed via magnetocardiography as ventricular arrhythmias (including TdP), at 28 weeks of gestation. After initiation of trans-maternal nadolol administration at 15 mg/d initial dosage and 30 mg/d subsequent dosage, the frequency of fetal ventricular arrhythmias decreased and almost disappeared within several days. The mother gave birth to the baby at full term without significant complications in either the mother or fetus. This is the first report that demonstrates the efficacy and safety of trans-maternal administration of nadolol for treatment of symptomatic LQT2 fetuses with TdP. .

Prenatal diagnosis of congenital absence of aortic valve associated with restrictive foramen ovale: Hemodynamic features and clinical outcome.

We present the case of a fetus with absent aortic valve (AAV), mitral regurgitation (MR), and restrictive foramen ovale (FO) who survived in utero but died of severe hypoxia after birth. We reported previously two cases of "inverse circulatory shunt" in AAV with MR, that is, blood from the ascending aorta flowing into the left ventricle through aortic regurgitation, to the left atrium due to MR, to the right atrium through FO, to the right ventricle, then to the pulmonary arteries, and to the ascending aorta through the ductus. In the present case, restrictive FO prevented inverse circulatory shunt, but resulted in postnatal death.

Implementation of Point-of-Care Molecular Diagnostics for Mycoplasma pneumoniae Ensures the Correct Antimicrobial Prescription for Pediatric Pneumonia Patients.

Mycoplasma pneumoniae is a leading causative pathogen of pneumonia among pediatric patients, and its accurate diagnosis may aid in the selection of appropriate antimicrobial agents. We established a rapid reporting system of a polymerase chain reaction (PCR) examination for M. pneumoniae that enables physicians to obtain test results approximately 90 minutes after ordering the test. In this study, we evaluated the impact of this system on antimicrobial prescriptions for pediatric pneumonia patients after its implementation from May 2016 to April 2017. In total, we identified 375 pediatric pneumonia patients, and the results of the rapid PCR examinations for Mycoplasma pneumoniae were reported immediately in 90.7% of patients (340/375), with physicians able to use these results to decide on patients' management before the prescription of antimicrobial agents. Of the 375 pediatric pneumoniae patients, M. pneumoniae was detected in 223 (59.5%). Among the 223 M. pneumoniae-positive pneumonia cases, antimicrobial agents for atypical pathogens (macrolides, tetracyclines or quinolones) were prescribed in 97.3% (217/223) at the initial evaluation, and their prescription rates increased to 99.1% (221/223) during management. In contrast, antimicrobial agents for atypical pathogens were prescribed only in 10.5% of 152 M. pneumoniae-negative pneumonia cases at the initial evaluations, and only 1 additional case was prescribed clarithromycin for persistent symptoms during management. In conclusion, we show that molecular technology could be applicable in the field of point-of-care testing in infectious disease, and its implementation will ensure the correct antimicrobial prescription for pediatric pneumonia patients.

Clinical features and seasonal variations in the prevalence of macrolide-resistant Mycoplasma pneumoniae.

BACKGROUND: Mycoplasma pneumoniae is a common pathogen causing pneumonia; macrolide-resistant strains are rapidly spreading across Japan. However, the clinical features of macrolide-resistant M. pneumoniae pneumonia have not been well established. Here, we evaluated the clinical characteristics and seasonal variations in the prevalence of M. pneumoniae with macrolide-resistant mutations (MRM). METHODS: The monthly prevalence of MRM in M. pneumoniae strains isolated from May 2016 to April 2017 was retrospectively analyzed, and the clinical characteristics of pneumonia cases with MRM were compared to those of cases without MRM. The M. pneumoniae isolates and point mutations at site 2063 or 2064 in domain V of 23S rRNA were evaluated by the GENECUBE system and GENECUBE Mycoplasma detection kit. RESULTS: Mycoplasma pneumoniae infection was identified in 383 cases, including 221 cases of MRM (57.7%). The MRM prevalence was 86.3% (44/51) between May and July 2016, demonstrating an apparent decrease in September 2016, subsequently reaching 43.0% (34/79) in November 2016. Mycoplasma pneumoniae pneumonia was diagnosed in 275 cases, including 222 pediatric and 53 adult cases. Macrolide use preceding evaluation was found to be the only feature of MRM pneumonia cases both in children (odds ratio [OR] 3.86, 95% confidence interval [CI]:1.72-8.66) and in adults (OR 7.43, 95% CI: 1.67-33.1). CONCLUSIONS: The determination rate of MRM varied widely throughout the year, and our study demonstrated the challenges in predicting M. pneumoniae with MRM based on clinical features at diagnosis. Therefore, continuous monitoring of the prevalence of MRM is warranted, which may help in selecting an effective treatment.

Prenatal Diagnosis of Congenital Absence of Aortic Valve: A Report of Two Cases with Different Outcomes and a Literature Review.

Congenital absence of aortic valve (AAV) is a rare cardiac anomaly associated with high mortality. We present 2 prenatally diagnosed cases of AAV. In both cases, fetal echocardiography showed no aortic valve tissue and free aortic regurgitation. At 24 weeks' gestation, case 1 showed a hypoplastic hypocontractile left ventricle and mitral atresia, but did not develop hydrops and was born at term. Bilateral pulmonary arterial banding was performed with continuous infusion of prostaglandin E1 at 5 days of age followed by Norwood and bidirectional Glenn procedures at 3 months of age. The hypoplastic non-compliant left ventricle and mitral atresia might have limited aortic regurgitation. Case 2 showed hydrops at 23 weeks' gestation. An enlarged hypocontractile left ventricle and massive mitral insufficiency were noted. The regurgitant flow was directed to the right atrium through a foramen ovale. This peculiar hemodynamic established a malignant circuit which was arbitrarily called 'inverse circulatory shunt'. Intrauterine death occurred at 28 weeks' gestation. An autopsy showed absent aortic valve leaflets but three tiny membranous remnants. Hemodynamic evaluation by fetal echocardiography should include the documentation of the presence of and assessment of the grade of aortic regurgitation, mitral regurgitation and blood flow through a foramen ovale as well as left ventricular function.