Clinical characteristics of unvaccinated or incompletely vaccinated children with neurological manifestations due to SARS-CoV-2 Omicron infection.

Omicron generally causes milder disease than previous strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially in fully vaccinated individuals. However, incompletely vaccinated children may develop Omicron-related complications such as those affecting the central nervous system. To characterize the spectrum of clinical manifestations of neuro-COVID and to identify potential biomarkers associated with clinical outcomes, we recruited 15 children hospitalized for Omicron-related neurological manifestations in three hospitals in Hong Kong (9 boys and 6 girls aged 1-13 years). All were unvaccinated or incompletely vaccinated. Fourteen (93.3%) were admitted for convulsion, including benign febrile seizure (n = 7), complex febrile seizure (n = 2), seizure with fever (n = 3), and recurrent breakthrough seizure (n = 2), and the remaining nonconvulsive patient developed encephalopathic state with impaired consciousness. None of the seven children with benign febrile seizure and six of eight children with other neurological manifestations had residual deficits at 9-month follow-up. SARS-CoV-2 RNA was undetectable in the cerebrospinal fluid (CSF) specimens of seven patients who underwent lumbar puncture. Spike-and-wave/sharp waves affecting the frontal lobes were detected in four of seven (57.1%) patients who underwent electroencephalogram. Children with Omicron-related neurological manifestations had significantly higher blood levels of IL-6 (p < 0.001) and CHI3L1 (p = 0.022) than healthy controls, and higher CSF levels of IL-6 (p = 0.002) than children with non-COVID-19-related febrile illnesses. Higher CSF-to-blood ratios of IL-8 and CHI3L1 were associated with longer length of stay, whereas higher ratios of IL-6 and IL-8 were associated with higher blood tau level. The role of CSF:blood ratio of IL-6, IL-8, and CHI3L1 as prognostic markers for neuro-COVID should be further evaluated.

Diazoxide-unresponsive Hyperinsulinemic Hypoglycaemia in a Preterm Infant with Heterozygous Insulin Receptor Gene Mutation.

Homozygous or compound heterozygous mutations in insulin receptor gene (INSR) lead to marked insulin resistance and hyperglycaemia in Donohue syndrome and Rabson-Mendenhall syndrome, conditions which are associated with significant morbidity early in life. On the other hand, heterozygous INSR gene mutations result in milder phenotype known as type A insulin resistance syndrome. While presentation in adults with this condition is well reported, phenotypes in infant are less well-characterized. We herein report an infant presenting with hyperinsulinemic hypoglycaemia who did not respond to diazoxide therapy. She was subsequently found to carry heterozygous INSR gene mutation. Our patient was a female infant born at 29 weeks of gestation who developed recurrent hypoglycaemia in early infancy. Workup showed hyperinsulinism and she was started on first-line therapy with diazoxide and high-calorie feeds. However, continuous blood glucose monitoring showed post-prandial hyperglycaemia followed by rapid fall to hypogylcaemia. Whole exome sequencing was performed to investigate for diazoxide-unresponsive hyperinsulinism, which revealed a likely pathogenic mutation in the INSR gene c.1246C>T p. (R416X). This nonsense mutation was inherited from the father. With the molecular diagnosis, diazoxide was stopped and she followed a diet with low glycaemic-index food. Subsequent monitoring showed stable glucose profile. Our case highlights the importance to consider type A insulin resistance syndrome when no mutation could be identified in the ABCC8/KCNJ11 genes in diazoxide-unresponsive hyperinsulinism. With autosomal dominant inheritance, cascade screening should be performed in family members to identify those harbouring the mutation as they are at risk of early onset diabetes.

Air dispersal of respiratory viruses other than severe acute respiratory coronavirus virus 2 (SARS-CoV-2) and the implication on hospital infection control.

BACKGROUND: Air dispersal of respiratory viruses other than SARS-CoV-2 has not been systematically reported. The incidence and factors associated with air dispersal of respiratory viruses are largely unknown. METHODS: We performed air sampling by collecting 72,000 L of air over 6 hours for pediatric and adolescent patients infected with parainfluenza virus 3 (PIF3), respiratory syncytial virus (RSV), rhinovirus, and adenovirus. The patients were singly or 2-patient cohort isolated in airborne infection isolation rooms (AIIRs) from December 3, 2021, to January 26, 2022. The viral load in nasopharyngeal aspirates (NPA) and air samples were measured. Factors associated with air dispersal were investigated and analyzed. RESULTS: Of 20 singly isolated patients with median age of 30 months (range, 3 months-15 years), 7 (35%) had air dispersal of the viruses compatible with their NPA results. These included 4 (40%) of 10 PIF3-infected patients, 2 (66%) of 3 RSV-infected patients, and 1 (50%) of 2 adenovirus-infected patients. The mean viral load in their room air sample was 1.58×103 copies/mL. Compared with 13 patients (65%) without air dispersal, these 7 patients had a significantly higher mean viral load in their NPA specimens (6.15×107 copies/mL vs 1.61×105 copies/mL; P < .001). Another 14 patients were placed in cohorts as 7 pairs infected with the same virus (PIF3, 2 pairs; RSV, 3 pairs; rhinovirus, 1 pair; and adenovirus, 1 pair) in double-bed AIIRs, all of which had air dispersal. The mean room air viral load in 2-patient cohorts was significantly higher than in rooms of singly isolated patients (1.02×104 copies/mL vs 1.58×103 copies/mL; P = .020). CONCLUSION: Air dispersal of common respiratory viruses may have infection prevention and public health implications.

Who should return for an oral glucose tolerance test? A proposed clinical pathway based on retrospective analysis of 332 children.

OBJECTIVES: Fasting plasma glucose or oral glucose tolerance test (OGTT) is the traditional diagnostic tool for type 2 diabetes (T2DM). However, fasting is required and implementation in all overweight/obese subjects is not practical. This study aimed to formulate a clinical pathway to stratify subjects according to their risk of abnormal OGTT. METHODS: This retrospective study included patients with overweight or obesity who had undergone OGTT in a tertiary paediatric unit from 2012 to 2018. The optimal haemoglobin A1c (HbA1c) cutoff that predicts abnormal OGTT was evaluated. Other non-fasting parameters, in combination with this HbA1c cutoff, were also explored as predictors of abnormal OGTT. RESULTS: Three hundred and thirty-two patients (boys: 54.2%, Chinese: 97.3%) were included for analysis, of which, 272 (81.9%) patients had normal OGTT while 60 (18.0%) patients had abnormal OGTT (prediabetes or T2DM). Optimal HbA1c predicting abnormal OGTT was 5.5% (AUC 0.71; sensitivity of 66.7% and specificity of 71%). When HbA1c≥5.5% was combined with positive family history and abnormal alanine transaminase (ALT) level, the positive predictive value for abnormal OGTT was increased from 33.6 to 61.6%. CONCLUSIONS: HbA1c, family history of T2DM and ALT level could be used to derive a clinical pathway to stratify children who have high risk of abnormal OGTT.

Primary varicella zoster infection compared to varicella vaccine reactivation associated meningitis in immunocompetent children.

We diagnosed varicella zoster virus (VZV) meningitis in a healthy adolescent boy who presented without a rash or fever. We aim to compare VZV reactivation meningitis in children after primary VZV infection and VZV vaccination. We reviewed the literature up until June 2020 using Pubmed/MEDLINE and EMBASE databases using 'varicella zoster', 'meningitis' and 'children' as keywords. Only English articles were included. Twenty-five cases were included in this review. Children who had VZV reactivation meningitis after vaccination were younger (7 ± 3.4 years vs. 11.9 ± 3.6 years, P = 0.0038), had a shorter interval between first exposure to reactivation (5.6 ± 2.9 years vs. 8.8 ± 3.2 years, P = 0.018) and more likely to have a rash (100% vs. 55%, P = 0.04). VZV reactivation meningitis occurs after both primary VZV infection and VZV vaccination. The absence of exanthem, fever or meningism does not rule out VZV meningitis.

Headache in a Child with Pseudohypoparathyroidism: An Alarming Symptom Not to Miss.

BACKGROUND: While the endocrine manifestations of pseudohypoparathyroidism are well known, less is known about the associated brain and spine abnormalities. These abnormalities may present with nonspecific symptoms in the paediatric population, and lack of awareness to these uncommon manifestations of the disease may result in a delay in necessary intervention. Case Presentation. We herein present a case of known pseudohypoparathyroidism type 1a who presented initially with minor head injury. She later developed progressive worsening headache, increased irritability, and vomiting. Repeated imaging showed hydrocephalus and Chiari malformation type 1 necessitating emergency craniectomy. CONCLUSION: Growth hormone deficiency, a common manifestation of pseudohypoparathyroidism type 1a, results in underdevelopment of the posterior cranial fossa and may account for the higher incidence of Chiari malformation in this group of patients. Other associated neurological features reported in pseudohypoparathyroidism type 1a include spinal stenosis, syringomyelia, and craniosynostosis. While less commonly seen, awareness to these associations is important in order to optimize the multidisciplinary care to this group of patients.

Isoniazid-induced gynaecomastia: report of a paediatric case and review of literature.

BACKGROUND: Gynaecomastia is a fairly common condition in puberty but is rare in prepubertal boys. While it is necessary to exclude possible endocrinopathay in prepubertal gynaecomastia, medication is an important and potentially reversible cause to consider in new onset gynaecomastia. Isoniazid-induced gynaecomastia has been reported in adult males, but none was reported in the paediatric population and general paediatricians may not be aware of this uncommon side effect. CASE PRESENTATION: We hereby report a 11-year-old prepubertal boy who developed gynaecomastia while taking anti-tuberculosis drugs. Investigations excluded endocrinopathies. Gynaecomastia subsided 8 weeks after stopping isoniazid. CONCLUSION: This case is the first paediatric case report describing the association of gynaecomastia with isoniazid use. It is important for general paediatricians to recognize this entity, as prompt diagnosis and cessation of the offending drug can lead to resolution of the problem.

Linking Healthcare and Social Service Databases to Study the Epidemiology of Child Maltreatment and Associated Health Problems: Hong Kong's Experience.

OBJECTIVE: To examine the incidence and trend of child maltreatment and its associated health problems in Hong Kong by linking healthcare and social service databases. STUDY DESIGN: Data on 4816 children under the age of 18 years registered with the Child Protection Registry and matching health records in public hospitals in Hong Kong from 2003 to 2010 were extracted. Associations were examined between different types of child maltreatment and child's medical diagnosis according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes including suicidal attempt (X60-X84), nonchild maltreatment related injuries (S00-S99; T00-T98, excluding T74 and T76 that are maltreatment related injuries), mental health problems (F00-F99), and congenital malformations/chromosomal abnormalities (Q00-Q99). RESULTS: Significant rising trends were found for child physical abuse, neglect, and sexual abuse during the period from 2003 to 2010. Psychological abuse remained stable. Risk of suicide attempt was higher among children suffering from sexual abuse, psychological abuse, and children experiencing multiple abuses; mental health diagnoses were more common in victims of psychological and multiple abuses. Congenital malformations and chromosomal abnormalities were more commonly found among neglected children. CONCLUSIONS: In contrast to the decreasing trend observed in the West during the study period, there has been an escalating trend in child maltreatment in Hong Kong and child maltreatment is strongly associated with major health problems. This is one of the first studies to demonstrate the power of linking healthcare and social service databases, which allows for both a better understanding of the impact of child maltreatment and as a guide future policy and service planning.