Kobe Children's Hospital

Differences of sex development (DSD) are congenital conditions in which chromosomal, gonadal, and anatomical sex characteristics are discordant with typical male or female development. These clinical practice guidelines provide evidence-based recommendations for the diagnosis and management of individuals with DSD across the lifespan. The guidelines were developed by a multidisciplinary committee of specialists representing pediatric endocrinology, adult endocrinology, urology, gynecology, psychiatry, and psychology. The committee employed a systematic review of the literature and used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to assess the strength of recommendations and the quality of evidence. Key areas addressed include the initial management of infants with atypical genitalia, diagnostic approaches, hormonal treatment, surgical interventions, gonadal tumor risk assessment, fertility preservation, and the transition from pediatric to adult care. The guidelines integrate international best practices with Japan's unique sociocultural, healthcare, and legal contexts for optimal DSD management and aim to improve clinical care for individuals with DSD while acknowledging the limited high-quality evidence in many aspects of DSD management.

ABSTRACTEvidence for the use of prophylactic anti‐seizure medication (ASM) in traumatic brain injury (TBI) in reducing the occurrence of early post‐traumatic seizure (EPTS) remains equivocal. This study aimed to analyze the prevalence of EPTS in children with TBI, compare clinical characteristics of those with and without EPTS, and explore the association between prophylactic ASM and EPTS. We performed an observational study among 28 pediatric intensive care units in 15 countries from January 2014 to October 2022. The rate of EPTS was compared between individuals prescribed prophylactic ASM and those who were not. Logistic regression was used to examine the association between ASM and EPTS. Among 697 children with TBI, 161 (23.1%) developed EPTS and 280 (40.2%) received prophylactic ASM treatment. Use of prophylactic ASM was associated with a lower likelihood of developing EPTS (27/280 (9.6%) vs. 134/417 (32.1%), p < 0.001). The most frequently used prophylactic ASMs were phenytoin, levetiracetam, and phenobarbital. Age ≤ 4 years and GCS ≤ 8 were associated with increased odds of developing EPTS (aOR 2.29, 95% CI 1.54–3.40, p < 0.001 and aOR 1.80, 95% CI 1.18–2.74, p = 0.01). Our data provide evidence supporting the potential protective role of prophylactic ASM against EPTS.

In western countries, adult and pediatric patients requiring mechanical ventilation are treated in ICUs. However, in Japan, there is concern that many children on mechanical ventilation are being treated in general wards. This study aimed to compare patient characteristics and treatment outcomes between mechanically ventilated children in general wards and ICUs using a national inpatient database in Japan. A retrospective cohort study using a national inpatient database. The study was carried out using a national inpatient database in Japan between July 2010 and March 2022, which includes data from multiple hospitals across the country. Patient characteristics were compared between patients in general wards and ICUs. We performed a 1:1 propensity score matching to compare in-hospital mortality between the groups. A total of 129,375 mechanically ventilated children 14 years old or younger who were hospitalized in general wards or ICUs were included in the study. None. During the study period, we identified 129,375 eligible patients. Of these, 63% of all patients, 78% of nonoperative patients, and 17% of postoperative patients were treated in general wards. Overall, 56% of the 48,137 ICU patients were postoperative and 70% of them underwent cardiac surgery. The one-to-one propensity score matching created 15,760 pairs, and in-hospital mortality was significantly higher in general ward patients than in ICU patients (6.4% vs. 4.1%; odds ratio, 1.49; 95% CI, 1.35-1.65; p < 0.001). Most of the children on mechanical ventilation in Japan were treated in general wards. The treatment of patients in general wards was associated with higher mortality than in ICUs, suggesting the need to centralize the care for mechanically ventilated pediatric patients in ICUs.

The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.

Cytokine storm syndrome (CSS), commonly associated with hemophagocytic lymphohistiocytosis (HLH), is a fatal hyperinflammatory syndrome. Differentiating the underlying diseases responsible for CSS is essential for timely therapeutic decisions. This study explored the clinical usefulness of serum cytokine profiling in distinguishing underlying diseases in patients with CSS. Serum samples were collected from 143 adult and pediatric patients with CSS and 22 healthy controls. The cohort included patients with various diagnoses of primary and secondary HLH and Kawasaki disease (KD)-like hyperinflammatory syndromes. Serum levels of 48 cytokines were analyzed in 97 patients using a bead-based multiplex immunoassay (Luminex assay). Serum levels of interferon alpha (IFN-α), interleukin-18 (IL-18), IL-6, CXCL9, and soluble tumor necrosis factor receptor II (sTNF-RII) were measured in 165 participants using enzyme-linked immunosorbent assay (ELISA). Luminex assay categorized patients with CSS into five clusters based on serum cytokine patterns. ELISA revealed distinct cytokine patterns, wherein patients with histiocytic necrotizing lymphadenitis-associated HLH and systemic lupus erythematosus-associated macrophage activation syndrome (MAS) showed elevated IFN-α; systemic juvenile idiopathic arthritis-associated and adult-onset Still's disease-associated MAS, X-linked inhibitor of apoptosis protein deficiency with HLH, and NLRC4-associated autoinflammatory disorder exhibited higher IL-18 levels. Additionally, KD shock syndrome had higher IL-6 levels than the other groups. CXCL9 was significantly elevated in patients with virus-associated HLH, familial HLH, malignant lymphoma-associated HLH, and KD-MAS. Multisystem inflammatory syndrome in children and toxic shock syndrome also showed moderate elevations of CXCL9 and IL-6 levels. Serum cytokine profiling effectively differentiates CSS subtypes, facilitating better diagnosis and personalized treatment strategies based on specific disease backgrounds.

We aimed to assess the association between base excess (BE) levels and neurological outcomes in patients with out-of-hospital cardiac arrest (OHCA), accounting for the time from cardiac arrest onset to blood sampling. This multicentre study was conducted in Osaka, Japan, and enrolled consecutive patients with OHCA who were transported to 16 medical centres between 2012 and 2021. Patients aged≥18years with witnessed OHCA and available BE measurements upon hospital arrival were examined. Patients were stratified into Q1 (BE≤-21.1mmol/L), Q2 (-21.1<BE≤-15.7mmol/L), Q3 (-15.7<BE≤-10.4mmol/L) and Q4 (BE>-10.4mmol/L) groups based on BE levels. The primary outcome was 1-month survival with a favourable neurological outcome (Cerebral Performance Category scale score: 1 or 2). Among the 23,854 patients with OHCA, only 6066 were included in the final analysis. Approximately 3.2%, 4.7%, 9.9% and 23.7% of patients in the Q1, Q2, Q3 and Q4 groups, respectively, achieved favourable neurological outcomes at 1month. Compared with Q4, the adjusted odds ratio for a favourable neurological outcome in Q1 was 0.13. Subgroup analysis revealed a significant interaction between prehospital return of spontaneous circulation (ROSC) and neurological outcomes; neurological outcomes worsened as BE decreased in patients with ROSC but not in those without ROSC. Lower BE levels upon hospital arrival are associated with poorer neurological outcomes and may serve as prognostic indicators in patients with OHCA who achieved prehospital ROSC.