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Objectives Histidine-rich glycoprotein (HRG) and high-mobility group box 1 (HMGB1) regulate the activation of neutrophils and vascular endothelium. The aim of this study was to quantify HRG and HMGB1 levels in patients with Kawasaki disease (KD) and evaluate their use in the clinical management of KD. Methods This study was prospectively performed. Patients were divided into two groups and analysed depending on whether KD symptoms improved by Day 10 of illness. HRG, HMGB1, and other laboratory variables were measured before the first treatment in all cases and, in most cases, afterwards for assessing trends. Results In this prospective study, we enrolled 60 patients with KD and 48 healthy controls. The HRG level in the KD group was significantly lower than that in the healthy control group; HMGB1 levels showed no obvious differences. In the KD group, HRG levels were negatively correlated with white blood cell and neutrophil counts. In the poor responders and responders groups, a tendency for a decrease in HRG and HMGB1 levels, respectively, was observed from pretreatment to post-treatment. Conclusions HRG and HMGB1 are related to the pathogenesis of KD; low HRG and high HMGB1 levels cause resistance against KD treatment.

Objective High mobility group box-1 (HMGB1) has been reported to be involved in influenza A virus-induced acute respiratory distress syndrome (ARDS). We studied the efficacy of an anti-HMGB1 mAb using an in vitro model of TNF-α stimulation or influenza A virus infection in human pulmonary microvascular endothelial cells (HMVECs). Methods Vascular permeability of HMVECs was quantified using the Boyden chamber assay under tumor necrosis factor-α (TNF-α) stimulation or influenza A virus infection in the presence of anti-HMGB1 mAb or control mAb. The intracellular localization of HMGB1 was assessed by immunostaining. Extracellular cytokine concentrations and intracellular viral mRNA expression were quantified by the enzyme-linked immunosorbent assay and quantitative reverse transcription PCR, respectively. Results Vascular permeability was increased by TNF-α stimulation or influenza A infection; HMVECs became elongated and the intercellular gaps were extended. Anti-HMGB1 mAb suppressed both the increase in permeability and the cell morphology changes. Translocation of HMGB1 to the cytoplasm was observed in the non-infected cells. Although anti-HMGB1 mAb did not suppress viral replication, it did suppress cytokine production in HMVECs. Conclusion Anti-HMGB1 mAb might be an effective therapy for severe influenza ARDS.

Staphylococcus aureus infections are known to cause leukocytoclastic vasculitis (LCV). Herein, we describe a case of an 18-month-old with LCV caused by enterotoxin-producing methicillin-sensitive Staphylococcus aureus (MSSA) emanating from an unrecognized pharyngeal abscess. It is critical to consider the possibility of extracutaneous sources of MSSA infection when investigating an infant with vasculitis. Prompt diagnosis and appropriate treatment are vital in preventing potentially life-threatening complications.

Background The relationship between growth hormone (GH)-replacement therapy and the thyroid axis in GH-deficient (GHD) children remains controversial. Furthermore, there have been few reports regarding non-GHD children. We aimed to determine the effect of GH therapy on thyroid function in GHD and non-GHD children and to assess whether thyrotropin-releasing hormone (TRH) stimulation test is helpful for the identification of central hypothyroidism before GH therapy. Methods We retrospectively analyzed data from patients that started GH therapy between 2005 and 2015. The free thyroxine (FT4) and thyroid-stimulating hormone (TSH) concentrations were measured before and during 24 months of GH therapy. The participants were 149 children appropriate for gestational age with GHD (IGHD: isolated GHD) (group 1), 29 small for gestational age (SGA) children with GHD (group 2), and 25 short SGA children (group 3). Results In groups 1 and 2, but not in group 3, serum FT4 concentration transiently decreased. Two IGHD participants exhibited central hypothyroidism during GH therapy, and required levothyroxine (LT4) replacement. They showed either delayed and/or prolonged responses to TRH stimulation tests before start of GH therapy. Conclusions GH therapy had little pharmacological effect on thyroid function, similar changes in serum FT4 concentrations were not observed in participants with SGA but not GHD cases who were administered GH at a pharmacological dose. However, two IGHD participants showed central hypothyroidism and needed LT4 replacement therapy during GH therapy. TRH stimulation test before GH therapy could identify such patients and provoke careful follow-up evaluation of serum FT4 and TSH concentrations.

The purpose of this study is to clarify the relationship between neonatal sepsis and future development of Kawasaki disease (KD). We analyzed data from the National Hospital Organization Neonatal Intensive Care Unit (NHO-NICU) registry study in Japan. Participants in this study were children with a history of hospitalization in the NICU at the participating institutions from 2010 to 2014. A questionnaire was administered at age 3 years to obtain information about the patient's history of KD. There were 8275 infants who were eligible for this study. At 3 years of age, parents of 2161 children responded to the follow-up survey (follow-up rate, 26.1%). Multivariate logistic regression analysis adjusted for preterm birth, sex, use of antibiotics in the NICU, parity, and maternal smoking showed that children with neonatal sepsis were more likely to have a history of KD at 3 years of age (adjusted odds ratio [aOR]: 11.67, 95% confidence interval [CI]: 2.84-47.96).Among infants admitted to the NICU, neonatal sepsis might be associated with development of KD later in life. Further large studies are needed to elucidate the relationship between neonatal infections and KD development.• Preterm birth is known to be a risk factor for Kawasaki disease. •It is not yet known which factors related to preterm birth increase the risk of developing Kawasaki disease.•Neonatal sepsis is associated with an increased risk of subsequent development of Kawasaki disease. •Antibiotic use in the neonatal intensive care unit may also be an independent risk factor for subsequent development of Kawasaki disease.

Background Previous studies showed that preterm birth increased the risk for hospital admissions in infancy and childhood due to some acute diseases. However, the risk of preterm children developing Kawasaki disease remains unknown. In the present study, we investigate whether preterm birth increased the morbidity of Kawasaki disease. Methods We included 36,885 (34,880 term and 2005 preterm) children born in 2010 in Japan. We examined the association between preterm birth and hospitalization due to Kawasaki disease using a large nationwide survey in Japan. Results In log-linear regression models that were adjusted for children's characteristics (sex, singleton birth, and parity), parental characteristics (maternal age, maternal smoking, paternal smoking, maternal education, and paternal income), and residential area, preterm infants were more likely to be hospitalized due to Kawasaki disease (adjusted risk ratio: 1·55, 95% confidence interval: 1.01-2.39). We then examined whether breastfeeding status modified the potential adverse effects of preterm birth on health outcome. Preterm infants with partial breastfeeding or formula feeding had a significantly higher risk of hospitalization due to Kawasaki disease compared with term infants with exclusive breastfeeding. Conclusions Preterm infants were at a high risk for Kawasaki disease, and exclusive breastfeeding might prevent this disease among preterm infants. Impact Previous studies showed that preterm birth increased the risk for hospital admissions in infancy and childhood due to some acute diseases, however, the risk of preterm children developing Kawasaki disease remains unknown. This Japanese large population-based study showed that preterm infants were at a high risk for Kawasaki disease for the first time. Furthermore, this study suggested that exclusively breastfeeding might prevent Kawasaki disease among preterm infants.