A Narrative Review on Diabetic Ketoacidosis in Children.

BACKGROUND: Diabetic ketoacidosis (DKA) is a life-threatening complication in children with diabetes mellitus. There are considerable differences in the management approaches for DKA between different countries. One of the main areas of differences between guidelines is the administration of fluid, with most guidelines adopting a restrictive approach. This is based on the concern over cerebral oedema, a lethal sequela allegedly to be caused by excessive fluid administration. However, in recent years, new clinical studies suggest that there is no causal relationship between intravenous fluid therapy and DKA-related cerebral injury. The British Society of Paediatric Endocrinology updated its guideline in 2020 to adopt a more permissive approach to fluid administration, which has sparked controversy among some paediatricians. OBJECTIVES: The purpose of this article is to provide a narrative review on the management of DKA. METHODS: A PubMed search was performed with clinical queries using the key term "diabetic ketoacidosis". The search strategy included randomized controlled trials, clinical trials, meta-analyses, observational studies, guidelines, and reviews. The search was restricted to English literature and the age range of 18 years and younger. Moreover, we reviewed and compared major guidelines. CONCLUSION: The management of DKA involves early recognition, accurate diagnosis, meticulous fluid and insulin treatment with close monitoring of blood glucose, ketones, electrolytes, renal function, and neurological status. There is still limited clinical evidence to support either a restrictive or permissive approach in the fluid management of paediatric DKA patients. Clinicians should exercise caution when applying different guidelines in their clinical practice, considering the specific circumstances of individual paediatric patients.

Prevalence and Outcomes of Infections in Critically-ill Paediatric Oncology Patients: A Retrospective Observation Study.

PURPOSE: The survival of paediatric oncology patients has improved substantially in the past decades due to advances in the field of oncology. Modern cancer treatments often come with life-threatening complications, of which infection is one of the most common causes in this patient population. This study aims to investigate the prevalence and outcomes of common infections in haemato-oncology patients during their stay in paediatric intensive care unit (PICU) and to identify any factors associated with these infections. METHODS: A retrospective observational study was conducted on all children with a haemato-oncology diagnosis or who underwent haematopoietic stem cell transplantation (HSCT) and who were admitted to the Hong Kong Children's Hospital PICU over a one-year period. Infection characteristics and patient outcomes were evaluated and compared between different sub-groups. Univariable and multi-variable analyses were employed to identify risk factors associated with the development of active infection. RESULTS: Forty-five (36.3%) of 124 critically ill haemato-oncology admissions to PICU were associated with infections, of which 31 (25%) admissions involved bacterial infections, 26 (20.9%) involved viral infections and 6 (4.8%) involved fungal infections. Bloodstream infection was the most common type of infection. More than half (61.3%) of the bacterial infections were due to an antibiotic-resistant strain. After adjusting for confounding variables, post-HSCT status and neutropenia were significantly associated with active infections. CONCLUSION: Infections in critically-ill haemato-oncological patients are associated with post haematopoietic stem cell transplant status and neutropenia. Further study is warranted to review effective strategies that may mitigate the likelihood of infection in this patient population.

SARS-CoV-2 Encephalitis versus Influenza Encephalitis: More Similarities than Differences.

BACKGROUND: From time to time, physicians face challenging diagnostic and therapeutic issues concerning the acute management of children with viral encephalitis. OBJECTIVE: The aim of this article is to provide an updated narrative review on the similarities and differences between SARS-CoV-2 and influenza encephalitis. METHODS: A PubMed search was performed with the function "Clinical Queries" using the key terms "SARS-CoV-2" OR "Influenza" AND "Encephalitis". The search strategy included meta-analyses, clinical trials, randomized controlled trials, reviews and observational studies. The search was restricted to the English literature and pediatric population. This article compares similarities and contrasts between SARS-CoV-2 and influenza-associated encephalitis. RESULTS: Encephalitis is an uncommon manifestation of both influenza and SARS-CoV-2. Both vi-ruses are associated with fever and respiratory symptoms. However, SARS-CoV-2 patients may on-ly have mild symptoms or be asymptomatic as silent carriers, rendering the disease spread difficult to control. Influenza patients usually have more severe symptomatology and are often bed bound for several days limiting its spread. Influenza is associated with seasonal and annual outbreaks, whereas SARS-CoV-2 has become endemic. Complications of encephalitis are rare in both viral infections but, when present, may carry serious morbidity and mortality. Many long-term sequelae of COVID-19 infections (long COVID-19) have been described but not with influenza infections. Mortality as-sociated with encephalitis appears higher with influenza than with SARS-CoV-2. Prophylaxis by immunization is available for both influenza and SARS-CoV-2. Specific efficacious antivirals are also available with oseltamivir for influenza and nirmatrelvir/ritonavir for SARS-CoV-2. Steroids are indicated with more severe SARS-CoV-2 but their role is not distinct in influenza disease. CONCLUSION: Encephalitis is a rare complication of influenza and SARS-CoV-2 infections. Both car-ry significant morbidity and mortality. Efficacious vaccines for prophylaxis and antivirals for treat-ment are available for both viruses.

Hypertonic glucose pleurodesis for preterm neonates with chylothorax.

Chylothorax is a known complication of postcardiac surgery and the most common cause of pleural effusion in neonates. Conservative management is usually adopted, including Nil-per-Oral (NPO), treatment of underlying etiology of infection, and use of octreotide. Chylothorax resistant to medical therapy and drainage is often treated by chemical pleurodesis. Previously used pleurodesis agents have included talc, minocycline, OK-432, bleomycin, and povidone-iodine. 50% Dextrose (D50) has been reported to be useful for pleurodesis in adults. We successfully managed two cases of prematurely born infants with D50 as an alternative chemical sclerosant for chemical pleurodesis in a resistant chylothorax and discussed evidence of its use in the literature.

Elimination, Containment, and Mitigation of COVID-19: A Personal Story about International Travels.

BACKGROUND: The author and his wife report their unique experience of international travels during the COVID-19 pandemic, and discuss issues encountered in various countries. METHODS: Narrated discussion of issues encountered during the COVID-19 pandemic. DISCUSSION: "Zero-COVID" versus "Living with COVID-19" strategies are compared. Children have unique issues with COVID-19 pandemic. Evaluation of efficacy of the approaches in pandemic with time should consider the main types of interventions (e.g., border management/quarantine; physical distancing; mask use; case isolation, testing and contact tracing; vaccination). The key metrics that can be used to compare the impacts of different strategies between the cities (e.g., cumulative case rate, cumulative mortality rate, case fatality risk, stringency index, economic performance) should be identified. Research in these approaches can help manage future pandemics in coronaviruses and emerging infections. The UK started with very loose mitigation ('herd immunity') and then switched to a suppression approach in 2021, followed by "living with the virus" approach. Whereas HK has been targeting towards elimination throughout. In between, countries like Singapore, Australia and New Zealand have shifted from zero-COVID strategy to living with the virus. It is easier to have effective social control measures in Hong Kong because it has clear borders and an authoritarian government, but it did not have a clear exit policy when Omicron spread.

Respiratory Syncytial Virus is the Most Common Causative Agent of Viral Bronchiolitis in Young Children: An Updated Review.

BACKGROUND: Viral bronchiolitis is a common condition and a leading cause of hospitalization in young children. OBJECTIVE: This article provides readers with an update on the evaluation, diagnosis, and treatment of viral bronchiolitis, primarily due to RSV. METHODS: A PubMed search was conducted in December 2021 in Clinical Queries using the key terms "acute bronchiolitis" OR "respiratory syncytial virus infection". The search included clinical trials, randomized controlled trials, case control studies, cohort studies, meta-analyses, observational studies, clinical guidelines, case reports, case series, and reviews. The search was restricted to children and English literature. The information retrieved from the above search was used in the compilation of this article. RESULTS: Respiratory syncytial virus (RSV) is the most common viral bronchiolitis in young children. Other viruses such as human rhinovirus and coronavirus could be etiological agents. Diagnosis is based on clinical manifestation. Viral testing is useful only for cohort and quarantine purposes. Cochrane evidence-based reviews have been performed on most treatment modalities for RSV and viral bronchiolitis. Treatment for viral bronchiolitis is mainly symptomatic support. Beta-agonists are frequently used despite the lack of evidence that they reduce hospital admissions or length of stay. Nebulized racemic epinephrine, hypertonic saline and corticosteroids are generally not effective. Passive immunoprophylaxis with a monoclonal antibody against RSV, when given intramuscularly and monthly during winter, is effective in preventing severe RSV bronchiolitis in high-risk children who are born prematurely and in children under 2 years with chronic lung disease or hemodynamically significant congenital heart disease. Vaccines for RSV bronchiolitis are being developed. Children with viral bronchiolitis in early life are at increased risk of developing asthma later in childhood. CONCLUSION: Viral bronchiolitis is common. No current pharmacologic treatment or novel therapy has been proven to improve outcomes compared to supportive treatment. Viral bronchiolitis in early life predisposes asthma development later in childhood.

Functional outcomes at PICU discharge in hemato-oncology children at a tertiary oncology center in Hong Kong.

BACKGROUND: Advancements in cancer treatment have resulted in longer survival but often at the expense of new therapy-associated morbidities. The aim of this study is to evaluate functional outcomes of hemato-oncology patients at PICU discharge, and to identify associated risk factors. METHODS: A single-center retrospective observational study. All children (< 19 years) with a hemato-oncology diagnosis admitted to the Hong Kong Children's Hospital PICU over a 2-year period were included. Functional status upon admission and discharge were compared. Univariable and multi-variable analyses were employed to identify risk factors associated with new morbidities. RESULTS: Out of 288 PICU admissions, there were 277 live discharges (mortality 4%), of which 52 (18.8%) developed new morbidities. Emergency admission, severity of illness at admission, organ dysfunction and support were associated with new morbidities (OR 1.08-11.96; p < 0.05). Adjusting for confounding factors, higher Pediatric Logistic Organ Dysfunction 2 score at admission was significantly associated with development of new morbidities (OR 1.34; 95% CI 1.18-1.54; p < 0.001). CONCLUSION: Critically ill children with hemato-oncological diseases had a higher rate of developing new morbidities (18.8%) compared with the general PICU population (4-8%). This was associated with severity of illness at admission. Further work is warranted to understand the lasting effects of these new morbidities and mitigating interventions.

Case Report: Primary Thoracic Low-Grade Fibromyxoid Sarcoma in a Young Girl Presenting With Mediastinal Mass Syndrome.

Low-grade fibromyxoid sarcomas (LGFMSs) are typically adult-onset tumors that arise from the extremities. Here, we report an exceptional case of primary thoracic LGFMS in an 8-year-old girl that resulted in mediastinal syndrome. In reporting this case, we discuss the clinical challenges, role of molecular profiling and review reported cases of pediatric thoracic LGFMSs.

Spinal muscular atrophy: Surviving respiratory failure, intensive care and pursuing creatively fulfilled life.

INTRODUCTION: Spinal muscular atrophy is a congenital condition associated with mutations in the SMN1 gene. Patients have normal intellectual development, but the natural history is progressive respiratory failure resulting in premature death. CASE: Diagnosed with spinal muscular atrophy type 2 in early primary school, the wheelchair-bound girl developed severe pneumonia on one occasion, when she became critically ill and was admitted to the paediatric intensive care unit with multiorgan dysfunction, requiring mechanical ventilation and high inotropic support. Parents and the patient expressed strong desire for full respiratory and intensive care support to be given. Survived the episode, she is wheelchair ambulatory and continues to pursue a creative artistic career. DISCUSSION: Children with SMA and their families need to be supported by a comprehensive multi-disciplinary team to manage this illness. Pediatricians and healthcare givers must provide up-to-date health advice on COVID-19 prophylaxis and management to special groups of patients with respiratory and neurological risks.

Lessons from Animal Culling during Human Pandemics: Is Vaccination a Viable Option for Animals?

Animal reservoirs for respiratory and coronavirus have been major health concerns. Zoonosis due to coronavirus involves bats, civet cat, camels, pangolins and now the minks. In the same vein, influenza pandemics occur when a new strain of the influenza virus is transmitted to humans from another animal species. Species thought to be of particular importance in the emergence of new human influenza strains are swine and poultry and these hosts are often culled during epidemics or pandemics. It is often too easy for humans to forget that millions of animals can die or be slaughtered in human pandemics, including the recent cull of minks in Europe and chickens in Asia. To co-exist with nature in a sustainable way, we must respect our animals by ensuring their welfare and immunizing them against pathogens where possible. Zoonotic diseases are here to stay and will continue to cause major epidemics and pandemics. The other side of the coin is that reverse zoonosis can also have devastating effects on animal populations if pandemics are not effectively prevented and controlled. Unfortunately, none of the COVID-19 vaccines in production are set aside to save the minks. We advocate that animals be immunized to save human lives.

Staphylococcus aureus Infections in the Paediatric Intensive Care Unit: Illustrated Cases.

Staphylococcus aureus is known to be one of the most common gram-positive microorganisms and an important pathogen associated with sepsis and toxic shock. We present four anonymized consecutive cases in a paediatric intensive care unit (PICU) to illustrate the different clinical manifestations of staphylococcal infections, including local infection versus systemic infection, toxic shock versus septic shock, and osteomyelitis. Eczema, short gut syndrome, and scald injury may be associated. Haematologic and coagulopathic abnormalities may be present. Prompt diagnosis and use of appropriate antimicrobial treatments is essential to reducing mortality and morbidity associated with staphylococcal infections.

Analysis of compound heterozygotes reveals that the mouse floxed Pax6 (tm1Ued) allele produces abnormal eye phenotypes.

Analysis of abnormal phenotypes produced by different types of mutations has been crucial for our understanding of gene function. Some floxed alleles that retain a neomycin-resistance selection cassette (neo cassette) are not equivalent to wild-type alleles and provide useful experimental resources. Pax6 is an important developmental gene and the aim of this study was to determine whether the floxed Pax6 (tm1Ued) (Pax6 (fl) ) allele, which has a retained neo cassette, produced any abnormal eye phenotypes that would imply that it differs from the wild-type allele. Homozygous Pax6 (fl/fl) and heterozygous Pax6 (fl/+) mice had no overt qualitative eye abnormalities but morphometric analysis showed that Pax6 (fl/fl) corneas tended be thicker and smaller in diameter. To aid identification of weak effects, we produced compound heterozygotes with the Pax6 (Sey-Neu) (Pax6 (-)) null allele. Pax6 (fl/-) compound heterozygotes had more severe eye abnormalities than Pax6 (+/-) heterozygotes, implying that Pax6 (fl) differs from the wild-type Pax6 (+) allele. Immunohistochemistry showed that the Pax6 (fl/-) corneal epithelium was positive for keratin 19 and negative for keratin 12, indicating that it was abnormally differentiated. This Pax6 (fl) allele provides a useful addition to the existing Pax6 allelic series and this study demonstrates the utility of using compound heterozygotes with null alleles to unmask cryptic effects of floxed alleles.