A regional multidisciplinary network enhances child abuse case management.

BACKGROUND: We previously reported an inadequate response to intracranial hemorrhage (ICH) cases under 24 months of age in Yokohama from 2011 to 2013. Hence, it is very important to evaluate how the establishment of a regional multidisciplinary network for child abuse affects the response to ICH cases in medical institutions. METHODS: We conducted a questionnaire survey of ICH cases under 24 months of age from 2014 to 2016 using a regional multidisciplinary network for child abuse established in Yokohama in September 2013. We investigated the patients' characteristics, examinations to identify inflicted injury, and reports made to the hospital-based child protection team (CPT) or regional child protective service (CPS), and compared the results of a previous study and the current study, which corresponds to before and after the establishment of the regional network, respectively. RESULTS: The total number of ICH cases was 50 in 3 years. The number of cases surveyed for covert fracture and fundus hemorrhage increased significantly after the establishment of the regional network (P = 0.0001 and P = 0.0182, respectively). The number of cases reported as suspected child abuse was 41 (82%) to the hospital-based CPTs and 27 (54%) to the regional CPSs. There were significant differences between before and after the establishment of the regional network regarding CPT (P = 0.0062) and CPS (P = 0.0215) reports. CONCLUSIONS: A regional multidisciplinary network can enhance response and cooperation to address child abuse. It deepens our understanding of such care and improves awareness by hospital personnel of child abuse.

Fulminant type 1 diabetes mellitus in Japanese children and adolescents: multi-institutional joint research of the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes.

Fulminant type 1 diabetes mellitus (FT1DM) is a subtype of type 1 diabetes mellitus characterized by a remarkably abrupt onset. In Japan, FT1DM accounts for approximately 20% of acute-onset adult type 1 diabetes mellitus cases; however, reports of pediatric-onset FT1DM are rare. We aimed to determine the frequency and clinical characteristics of FT1DM in Japanese children and adolescents by conducting a 2-phase questionnaire survey among the members of the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT) regarding their clinical experience with FT1DM. Responses were obtained from 54 of the 79 participating hospitals (68.4%). Of these, 8 hospitals managed a total of 15 pediatric patients with FT1DM (4 patients in each of 2 hospitals, 2 patients in 1 hospital, and 1 patient in each of 5 hospitals). The distribution of patient age was biphasic, with peaks in children younger than 5 years and older than 8 years of age. The clinical characteristics of FT1DM in this population (such as the duration from onset of symptoms to diagnosis, severity of symptoms, preceding flu-like episodes, and abnormal laboratory data) did not differ from those of patients with adult-onset FT1DM. The frequency of pediatric-onset FT1DM is low compared with that of adult-onset FT1DM. The genetic background and susceptibility patterns of pediatric patients with FT1DM may differ from those typical of adults with FT1DM, but both age groups share similar clinical characteristics.

Neurological prognostic factors for human herpes virus 6/7-associated acute encephalopathy in children: A single-center study.

AIM: To identify prognostic factors for severe neurological sequelae and epileptic seizures in children with human herpes virus (HHV) 6/7-associated acute encephalopathy (AE). METHODS: We retrospectively studied pediatric cases of HHV6/7-associated AE between April 2011 and March 2021. Neurological sequelae were assessed using the Pediatric Cerebral Performance Category scale (PCPC) and the presence of epileptic seizures 1 year after onset. We investigated the prognostic factors between the non-severe sequelae group (PCPC scores ≤ 2) and severe sequelae group (PCPC scores ≥ 3) in patients without severe neurological complications before onset. RESULTS: Forty patients, ranging from 4 to 95 months old, were included. AE with biphasic seizures and late reduced diffusion were the most common types of encephalopathy (n = 28). Among the 36 patients evaluated neurological sequelae, 17, nine, eight, and two were categorized as PCPC 1, 2, 3 and 4, respectively. Epileptic seizures were observed in nine patients. In the severe sequelae group, significantly more cases with coma in the acute phase and thalamic lesions on MRI and higher serum aspartate aminotransferase, alanine aminotransferase (ALT), and lactate dehydrogenase levels were observed. Multivariate analysis showed a significant between-group difference in the rate of coma (p = 0.0405). Patients with epileptic seizures had a higher rate of coma and thalamic lesions and higher serum ALT and urinary beta 2-microglobulin levels, but there was no significant difference in the multivariate analysis. CONCLUSIONS: In HHV6/7-associated AE, coma was a significant prognostic factor for severe neurological sequelae.

New-onset pediatric nephrotic syndrome following Pfizer-BioNTech SARS-CoV-2 vaccination: a case report and literature review.

Various new vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been rapidly developed. The new onset and recurrence of nephrotic syndrome triggered by some vaccines have been documented and several adult cases of minimal change nephrotic syndrome newly developing after SARS-CoV-2 vaccination have been reported. However, no reports of pediatric cases have been published. Indications for SARS-CoV-2 vaccines have been expanded to those as young as 12 years old and vaccination of children has just started in Japan. We encountered a 15-year-old boy without underlying disease who newly developed nephrotic syndrome after SARS-CoV-2 vaccination with BNT162b2 (Pfizer-BioNTech). He developed eyelid edema 4 days after vaccination and peripheral edema of the lower extremities a further 4 days later. Twenty-one days after vaccination, 60 mg of oral daily prednisolone was started. He achieved complete remission in 12 days without complications such as hypertension or acute kidney injury. We clinicians should be aware of the possibility of nephrotic syndrome developing after SARS-CoV-2 vaccination, not only in adults, but also in children.

Children with type 2 diabetes mellitus are at greater risk of macrovascular complications.

BACKGROUND: Type 2 diabetes mellitus (DM) is a risk factor for macrovascular complications in adults. Recently young-onset type 2 DM has increased worldwide and the increase of macrovascular complications in the young is worrisome. METHODS: Plasma values for plasminogen activator inhibitor-1 (PAI-1) as a marker for promotion, and adiponectin as a marker for inhibition of atherosclerosis, were compared in 33 patients with type 1 DM (16 boys, 17 girls; age 14.9 +/- 3.7 years, mean +/- standard deviation) with those of 43 patients with type 2 DM (15 boys, 28 girls; age 16.5 +/- 3.5 years). RESULTS: The PAI-1 level was significantly higher (19.3 +/- 8.1 vs 32.9 +/- 17.2 ng/ml; P < 0.001) and the adiponectin level was significantly lower (10.1 +/- 3.8 vs 7.4 +/- 3.7 microg/ml; P < 0.005) in the type 2 DM group. In obese patients, the PAI-1 level was significantly higher (P < 0.005) and the adiponectin level was lower (P= 0.15) in the type 2 DM group. Also, in the non-obese subjects, the PAI-1 level was significantly higher (P < 0.05) and the adiponectin level was lower (P= 0.11) in the type 2 DM group. CONCLUSIONS: Even in young patients, type 2 DM is a risk factor for macrovascular complications compared with type 1 DM.

Genetics of Congenital Isolated TSH Deficiency: Mutation Screening of the Known Causative Genes and a Literature Review.

CONTEXT: Congenital isolated TSH deficiency (i-TSHD) is a rare form of congenital hypothyroidism. Five genes (IGSF1, IRS4, TBL1X, TRHR, and TSHB) responsible for the disease have been identified, although their relative frequencies and hypothalamic/pituitary unit phenotypes have remained to be clarified. OBJECTIVES: To define the relative frequencies and hypothalamic/pituitary unit phenotypes of congenital i-TSHD resulting from single gene mutations. PATIENTS AND METHODS: Thirteen Japanese patients (11 boys and 2 girls) with congenital i-TSHD were enrolled. IGSF1, IRS4, TBL1X, TRHR, and TSHB were sequenced. For a TBL1X mutation (p.Asn382del), its pathogenicity was verified in vitro. For a literature review, published clinical data derived from 74 patients with congenital i-TSHD resulting from single-gene mutations were retrieved and analyzed. RESULTS: Genetic screening of the 13 study subjects revealed six mutation-carrying patients (46%), including five hemizygous IGSF1 mutation carriers and one hemizygous TBL1X mutation carrier. Among the six mutation carriers, one had intellectual disability and the other one had obesity, but the remaining four did not show nonendocrine phenotypes. Loss of function of the TBL1X mutation (p.Asn382del) was confirmed in vitro. The literature review demonstrated etiology-specific relationship between serum prolactin (PRL) levels and TRH-stimulated TSH levels with some degree of overlap. CONCLUSIONS: The mutation screening study covering the five causative genes of congenital i-TSHD was performed, showing that the IGSF1 defect was the leading genetic cause of the disease. Assessing relationships between serum PRL levels and TRH-stimulated TSH levels would contribute to predict the etiologies of congenital i-TSHD.

Safety and efficacy of DTaP-IPV vaccine use in healthcare workers for prevention of pertussis.

Pertussis can be fatal for infants. The best way to prevent infant pertussis is to promote adult immunization. However, Tdap has not been licensed in Japan, so we investigated the effect and safety of the DTaP-IPV vaccine instead. The study examined 154 pediatric healthcare workers. Participants without effective levels of antibodies against pertussis toxin were given DTaP-IPV, reduced to 0.2 mL. In total, 48 of the 154 participants (31.2%) were seronegative for pertussis toxin. After vaccination of the seronegative participants, 40 of the 41 measured (97.5%) had acquired an effective response, and all 35 of those tested maintained a protective antibody level ten months after vaccination. Redness was observed in 14 of the 41 (34.1%) and soreness in 19 (46.3%). This study demonstrated that vaccination with reduced 0.2 mL DTaP-IPV successfully provided effective immunity. At least ten months after vaccination, all subjects maintained an adequate level of antibodies.

SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7.

Adrenal hypoplasia is a rare, life-threatening congenital disorder. Here we define a new form of syndromic adrenal hypoplasia, which we propose to term MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) syndrome. By exome sequencing and follow-up studies, we identified 11 patients with adrenal hypoplasia and common extra-adrenal features harboring mutations in SAMD9. Expression of the wild-type SAMD9 protein, a facilitator of endosome fusion, caused mild growth restriction in cultured cells, whereas expression of mutants caused profound growth inhibition. Patient-derived fibroblasts had restricted growth, decreased plasma membrane EGFR expression, increased size of early endosomes, and intracellular accumulation of giant vesicles carrying a late endosome marker. Of interest, two patients developed myelodysplasitc syndrome (MDS) that was accompanied by loss of the chromosome 7 carrying the SAMD9 mutation. Considering the potent growth-restricting activity of the SAMD9 mutants, the loss of chromosome 7 presumably occurred as an adaptation to the growth-restricting condition.

Comparison of brachial artery flow-mediated dilation in youth with type 1 and type 2 diabetes mellitus.

AIMS/INTRODUCTION: Brachial artery flow-mediated dilation (FMD) is a method of evaluating the function of vascular endothelial cells and is utilized for early diagnosis of atherosclerotic diseases. Only a few studies evaluated the risks for major vascular complications in youth with type 1 and 2 diabetes mellitus from the aspect of the early development of atherosclerosis. We studied whether there is a difference in vascular endothelial cell function between youth with type 1 and 2 diabetes mellitus. MATERIALS AND METHODS: We assessed %FMD of 24 patients with type 1 diabetes mellitus and 27 patients with type 2 diabetes mellitus aged 12-20 years along with glycated hemoglobin, lipid metabolism markers such as triglycerides, and inflammatory biomarkers such as total adiponectin levels in adolescent patients with type 1 or 2 diabetes mellitus. The significance of the difference in each factor between the type 1 and type 2 diabetes groups was assessed using Student's t-test. RESULTS: The %FMD was significantly lower in patients with type 2 diabetes. The body mass index and blood pressure were significantly higher, and total and high-molecular-weight adiponectin levels were significantly lower in patients with type 2 diabetes. %FMD significantly correlated with systolic blood pressure. CONCLUSIONS: The results suggest that youth with type 2 diabetes have more advanced damage of the vascular endothelium and therefore are at higher risk for major vascular complications. Therefore, monitoring the progression of atherosclerosis would also be beneficial in youth with diabetes mellitus, and measurement of FMD could be further warranted.

Acute encephalopathy of Bacillus cereus mimicking Reye syndrome.

We present an 11-year-old boy diagnosed as having acute encephalopathy and liver failure with the underlying condition of a metabolic dysfunction. He developed convulsions and severe consciousness disturbance following gastroenteritis after the ingestion of some fried rice. He showed excessive elevation of transaminases, non-ketotic hypoglycemia and hyperammonemia, which were presumed to reflect a metabolic dysfunction of the mitochondrial beta-oxidation, and he exhibited severe brain edema throughout the 5th hospital day. He was subjected to mild hypothermia therapy for encephalopathy, and treated with high-dose methylprednisolone, cyclosporine and continuous hemodiafiltration for liver failure, systemic organ damage and hyperammonemia. The patient recovered with the sequela of just mild intelligence impairment. In this case, Bacillus cereus, producing emetic toxin cereulide, was detected in a gastric fluid specimen, a stool specimen and the fried rice. It was suggested that the cereulide had toxicity to mitochondria and induced a dysfunction of the beta-oxidation process. The patient was considered as having an acute encephalopathy mimicking Reye syndrome due to food poisoning caused by cereulide produced by B. cereus.

A report of two cases of Kawasaki disease treated with plasma exchange.

Kawasaki disease is a generalized vasculitis of unknown etiology that occurs predominantly in infants and young children. It is very important to prevent its cardiovascular manifestations, especially coronary artery lesions. Early treatment with intravenous immunoglobulin reduces cardiovascular sequelae, but some patients do not respond to this treatment, and they have a high incidence of coronary artery lesions. On the other hand, acute heart failure is rare in Kawasaki disease. We report on the cases of two patients with persistent fever and shock even after intravenous immunoglobulin therapy. In both cases, plasma exchange may have reduced the risk of coronary artery lesions and proved effective against acute heart failure with catecholamine-refractory shock; yet the mechanism of this improvement remains unclear.