Invasive fungal infections in the Paediatric Intensive Care Unit: A Hong Kong Study.

INTRODUCTION: Invasive fungal infections (IFI) cause significant mortality and morbidity in the Paediatric Intensive Care Unit (PICU). Early recognition and prompt treatment of invasive fungal infections are important. This article reviewed the mortality and morbidity of IFIs in the PICU of Hong Kong Children's Hospital.

Methods: Retrospective review of all PICU admissions from April 2019 to May 2021. The following data were retrieved: age, gender, diagnosis, comorbidity, clinical manifestation, type of fungus, duration of stay at PICU, absolute neutrophil count, use of immunosuppressive therapy, presence of central venous catheter and use of total parental nutrition. The primary outcomes were the incidence and mortality of IFIs among PICU patients. The secondary outcomes were risk factors for developing IFI in PICU and clinical course of IFIs. Numerical variables were compared between groups by Mann-Whitney U test and categorical variables by Fisher's exact test.

Results: There were 692 PICU admissions over the study period from April 2019 to May 2021. There were 24 death cases during this period of time. The crude mortality was 3%. Fourteen patients (2%) fulfilling the criteria for IFIs were identified using hospital electronic record system and according to PICU documentation. Eight of these 14 patients (57%) had hematological malignancy, 2 (17%) had solid tumours and 4 had non-oncological conditions. There were 4 (29%) patients who had received hematopoietic stem cells transplant because of oncological problems. Six patients (43%) were neutropenic with absolute neutrophil count less than 1x 109 at diagnosis of IFI. Six (43%) had received immunosuppressive therapy including steroid, cyclosporin A, Mycophenolate mofetil (MMF), Sirolimus or tacrolimus. 12 (86%) had had central venous catheter. Eight (57%) were on parenteral nutrition. Rhizopus or Aspergillus infection (5/14) were associated with nonsurvival (p = 0.031).

Conclusion: All patients with IFIs managed in the PICU have haemato-oncology diseases or are recipients of stem cell transplantation. IFIs with Rhizopus or Aspergillus as a group are associated with high mortality in the PICU. Awareness of this pathology with prompt diagnosis and treatment may improve the outcome of these infections and reduce the mortality.

A case series of appendicitis and pseudo-appendicitis in a paediatric intensive care unit.

INTRODUCTION: Appendicitis is a common childhood condition that can be diagnostically challenging. Severe cases may necessitate support in the critical or intensive care unit. These "critical appendicitis diagnoses" have rarely been described. CASE DESCRIPTION: We retrospective reviewed the PICU database of the Hong Kong Children's Hospital and identified cases of suspected and confirmed appendicitis. Clinical features, radiologic findings and final diagnosis of each case were summarized and reported in this case series. We review six anonymized cases of appendicitis managed in a paediatric intensive care unit (PICU) to illustrate the different age spectrum and clinical manifestations of the condition. Rupture of the inflamed appendix, peritonitis and pancreatitis were some of the complications encountered. Crohn disease was found in one case as an underlying diagnosis. Also, one girl clinically diagnosed with appendicitis was found to be a case of ruptured hepatoblastoma with no appendicitis (i.e., pseudoappendicitis). CONCLUSION: Prompt diagnosis, surgical removal of the inflamed appendix, and use of appropriate antimicrobials when indicated are essential in reducing mortality and morbidity associated with severe appendicitis. Significant premorbid conditions such as acute myeloid leukemia, mitochondrial encephalopathy lactic acidosis syndrome (MELAS), inflammatory bowel disease and complications may be present in patients needing intensive care as is illustrated in the present cases. Pseudoappendicitis is an important differential diagnosis. Imaging is crucial and useful in establishing and confirming the diagnosis of appendicitis and pseudo-appendicitis in these PICU cases.

The Sequential Use of Extracorporeal Cytokine Removal Devices in an Adolescent With COVID-19 Receiving Continuous Renal Replacement Therapy.

A 14-year-old male developed multisystem inflammatory syndrome in children (MIS-C) after acquiring the SARS-CoV-2 infection. He deteriorated rapidly requiring inotropic and ventilatory support as well as continuous renal replacement therapy (CRRT) due to rhabdomyolysis-associated acute kidney injury. A hemoadsoprtion column Cytosorb® was first incorporated into the CRRT circuit for myoglobin and cytokines removal, which was followed by sequential use of another type of cytokine-removing hemofilter (Oxiris®) (altogether 100 hours of extracorporeal blood purification [EBP] therapy). There was no major complication related to the EBP therapy. Cytokine profile revealed a marked reduction of levels of several cytokines including tumor necrosis factor-α, interleukin (IL)-6, IL-8, and IL-10 after the EBP therapy. It was noted that both pro-inflammatory and anti-inflammatory cytokines were removed, and the removal efficacy varied between different devices. His condition improved and the serum ferritin, C-reactive protein, and procalcitonin levels also dropped gradually, which correlated well with his clinical progress and the trend of cytokine levels. Our case demonstrated that extracorporeal cytokine removal can be safely applied in children with MIS-C and can be considered as adjunctive therapy in selected patients with critically ill conditions.

The successful application of hemoadsorption for extracorporeal liver support in a child with acute liver failure.

A 6-year-old boy developed acute liver failure with hepatic coma due to drug rash with eosinophilia and systemic symptoms (DRESS) after multiple antibiotics exposure. He had hyperbilirubinemia, elevated serum bile acids and hyperammonemia with peak serum levels of total bilirubin, direct bilirubin, bile acids and ammonia measuring 418, 328, 174, and 172 µmol/L respectively. In addition to the use of systemic steroid and other supportive therapy, he also received three sessions of hemoadsorption using the Cytosorb® column incorporated into the continuous renal replacement therapy circuit as extracorporeal liver support for a total duration of 75 h, which brought down his serum levels of total bilirubin to 119 µmol/L, bile acids to 58 µmol/L, and ammonia to 55 µmol/L. His conscious level gradually regained coupling an improvement of liver function. Except for mild thrombocytopenia and electrolyte disturbances, the therapy was well tolerated with no major complication encountered. Our case demonstrated that hemoadsorption can be safely employed as an adjunctive extracorporeal liver support modality in children with acute liver failure. The potential role and technical concerns of applying such technique in pediatric patients requires further evaluation in future studies.

Drugs for paediatric hyperinflammatory syndromes.

Background: Many syndromes are associated with exaggerated inflammation. Children with hyperinflammatory syndromes often present with vague and non-specific symptoms that pose diagnostic and management challenges. The recent literature seems biased towards referring these syndromes only to the multisystem inflammatory syndrome in children (MIS-C) that is associated with COVID-19. The purpose of this paper is to provide an updated narrative review on the pathophysiology, manifestations and management approaches for common hyperinflammatory syndromes. Methods: An extensive PubMed search of all publications in the English literature was performed with Clinical Queries for various hyperinflammatory syndromes and conditions using the undermentioned Medical Subject Headings: "hyperinflammation", "hyperinflammatory syndromes", "sepsis syndrome", "severe inflammatory response syndrome" and "acute respiratory distress syndrome". Categories were limited to reviews and clinical trials for the age range from birth to 18 years. Results: The criteria, presentation and management of these hyperinflammatory syndromes are described. Hyperinflammatory syndromes refer to a basket of inflammatory syndromes often associated with multisystem involvement and aberrant cytokine release and should be differentiated from autoinflammatory, autoimmune and hyperimmune syndromes. The major subtypes of hyperinflammatory syndromes, including macrophage activation syndrome, haemophagocytic lymphohistiocytosis, cytokine release syndrome and cytokine storm syndrome, are described. MIS-C associated with SARS-CoV-2 represents the latest addition. It must be understood that the syndrome is not exclusive to COVID-19 but could be caused by various viral infections. Early recognition, prompt and proactive treatment can reduce potential complications and improve outcomes and survival rates in paediatric patients. Anti-inflammatory medications for the management of these syndromes are described. Conclusion: The incidence of these hyperinflammatory conditions is generally low in comparison to other disease conditions. Except for paediatric inflammatory multisystem syndrome/MIS-C, the mortality is high and the hospital stay is prolonged in affected patients. Acute and critical care physicians must be aware of these conditions and their initial management. Corticosteroids are often used in the initial phrase but various disease-specific drugs and biologics are needed in subsequent management and expert management of these often-difficult conditions is crucial.

Clinical Characteristics and Outcomes of Acute Childhood Encephalopathy in a Tertiary Pediatric Intensive Care Unit.

AIM: Childhood encephalopathy comprises a wide range of etiologies with distinctive distribution in different age groups. We reviewed the pattern of encephalopathy admitted to the pediatric intensive care unit (PICU) of a tertiary children's hospital. METHODS: We reviewed the medical records and reported the etiologies, clinical features, and outcomes of children with encephalopathy. RESULTS: Twenty-four admissions to the PICU between April 2019 and May 2020 were reviewed. The median (interquartile range) age was 10.0 (14.7) years and 62.5% were boys. Confusion (66.7%) was the most common presentation. Adverse effects related to medications (33.3%) and metabolic disease (20.8%) were predominant causes of encephalopathies in our study cohort. Methotrexate was responsible for most of the medication-associated encephalopathy (37.5%), whereas Leigh syndrome, pyruvate dehydrogenase deficiency and Wernicke's encephalopathy accounted for those with metabolic disease. The median Glasgow Coma Scale (GCS) on admission was 12.5 (9.0). Antimicrobials (95.8%) and antiepileptic drugs (60.9%) were the most frequently given treatment. Children aged 2 years or younger were all boys (P = 0.022) and had a higher proportion of primary metabolic disease (P = 0.04). Intoxication or drug reaction only occurred in older children. The mortality was 8.3%, and over half of the survivors had residual neurological disability upon PICU discharge. Primary metabolic disease (P = 0.002), mechanical ventilation (P = 0.019), failure to regain GCS back to baseline level (P = 0.009), and abnormal cognitive function on admission (P = 0.03) were associated with cerebral function impairment on PICU discharge. CONCLUSIONS: Primary metabolic encephalopathy was prevalent in younger children, whereas drug-induced toxic encephalopathy was common among older oncology patients. Survivors have significant neurologic morbidity. Failure to regain baseline GCS was a poor prognostic factor for neurological outcomes.

Childhood pertussis is still here: An Asian city's perspectives.

INTRODUCTION: Pertussis, or whooping cough, is a highly contagious respiratory infection that is caused by the bacterium Bordetella pertussis. It is one of the most common causes of death in childhood. It is also a frequent cause of chronic cough in children, adolescents, and adults. METHODS: Global and Hong Kong perspectives of childhood pertussis were described. RESULTS: Hong Kong has prided herself in the city's childhood immunization program. There appear to be no major outbreaks of pertussis since the 1960s. Nevertheless, pediatricians may see isolated cases of pertussis or pertussis-like cases from time to time. Occasionally, infants are severely affected with apneas and managed with ventilator supports in the PICU. Outbreaks of the notifiable disease continue to occur despite a reasonable surveillance system and vaccination program in Hong Kong. Vaccination of mothers, adolescents, and adults are efficacious methods to further reduce the risks of pertussis. Macrolides remain efficacious antibiotics especially used early during the infectious phase. Infants with pertussis may require intensive care support and morbidity is high. CONCLUSIONS: Physicians should be reminded from time to time that outbreaks of pertussis still exist in Hong Kong and in many cities globally.

Recommendations on the Management of Interhospital Transport of Pediatric Patients With Mediastinal Mass.

PURPOSE: Children with mediastinal masses often present with insidious symptoms to nonspecialist centers and require interhospital transport to oncology centers for definitive care. We evaluated clinical characteristics and patient outcomes and proposed a management protocol. MATERIALS AND METHODS: This is a retrospective review of all children with mediastinal mass at the pediatric intensive care unit of the Hong Kong Children's Hospital between April 2019 and March 2020. RESULTS: Ten children with a median age of 14.5 years (interquartile range, 9.3-17.0 years) were included. Leukemia and lymphoma accounted for the majority of cases (n = 6, 60%). Nearly all patients (n = 9, 90%) required interhospital transport before definitive treatment could be instituted. There were no deaths, but 2 patients were transported with significant respiratory compromise. Among patients requiring more than 1 interhospital transport, there was a higher incidence of shortness of breath (100% vs 40%; odds ratio, 33; P = 0.048) and orthopnea (80% vs 0%; odds ratio, 33; P = 0.048), whereas none had a neck mass (0% vs 80%; odds ratio, 0.03; P = 0.048). CONCLUSIONS: Children with mediastinal mass are at risk of life-threatening cardiorespiratory compromise. Pretransport assessment, planning, and stabilization along with clear management plans for deterioration during transport are crucial especially for patients who are symptomatic at time of presentation, to reduce risks associated with delays in arriving at the specialist point of care for definitive treatment.

Self-perceived disease control in childhood eczema.

BACKGROUND: Atopic eczema (AE) is a common relapsing inflammatory skin disease in children which is often associated with chronicity and poor quality of life. Unlike atopic asthma, control of AE is seldom assessed in therapeutics. AIM: To investigate the utility of a Traffic Light Control (TLC) system as a measurement/assessment of self-perceived eczema control. METHODS: This is a prospectively study of all Chinese children (aged 6-18 years old) with eczema attending the pediatric dermatology clinic of a tertiary hospital from January to June 2020. Eczema control, eczema severity, quality of life and biophysical skin condition of consecutive patients at the pediatric dermatology clinic of a teaching hospital were evaluated with the validated Chinese versions of Depressive, Anxiety, Stress Scales (DASS-21), Patient Oriented Eczema Measure (POEM), transepidermal water loss (TEWL), and stratum corneum skin hydration (SH), respectively. With a visual TLC analogy, patients were asked if their eczema is under control (green light), worsening (yellow) or in flare-up (red light). RESULTS: Among AE patients (n = 36), self-perceived TLC as green (under control), amber (worsening) and red (flare up) reflected acute and chronic severity (SCORAD, NESS, POEM) and quality of life (CDLQI) (p < .0001), but not SH, TEWL or Depression, anxiety and stress. CONCLUSIONS: Eczema control can be semi-quantified with a child-friendly TLC self-assessment system. AE patients reporting worse eczema control have worse acute and chronic eczema severity, more impairment of quality of life; but not the psychologic symptoms of depression, anxiety and stress or skin hydration or transepidermal water loss. TLC can be linked to an eczema action plan to guide patient management.

Pediatric Extracorporeal Life Support Transport in Western Canada: Experience over 14 years.

This retrospective cohort study describes all children transported on extracorporeal life support (ECLS) by the Stollery Children's Hospital Pediatric Transport team (SCH-PTT) between 2004 and 2018. We compared outcomes and complications between primary (SCH-PTT performed ECLS cannulation) vs. secondary (cannulation performed by referring facility) transports, as well as secondary transports from referring centers with and without an established ECLS cannulation program. SCH-PTT performed 68 ECLS transports during the study period. Median (IQR) transport distance was 298 (298-1,068) kilometers. Mean (SD) times from referral call to ECLS-initiation were: primary transports 7.8 (2.9) vs. 2.5(3.5) hours for secondary transports, p value < 0.001. Complications were common (n = 65, 95%) but solved without leading to adverse outcomes. There were no significant differences in the number of complications between primary and secondary transports. There was no significant difference in survival to ECLS decannulation between primary 9 (90%) and secondary transports 43 (74%), p value = 0.275. ECLS survival was higher for children cannulated by the SCH-PTT or a center with an ECLS cannulation program: 42 (82%) vs. 10 (59%), p value = 0.048. Critically ill children on ECLS can be safely transported by a specialized pediatric ECLS transport team. Secondary transports from a center with an ECLS cannulation program are also safe and have similar results as primary transports.

Successful Treatment of Rhabdomyolysis-Associated Acute Kidney Injury with Haemoadsorption and Continuous Renal Replacement Therapy.

We report two children with rhabdomyolysis-associated acute kidney injury who were successfully treated with a haemoadsorption column CytoSorb® in addition to continuous renal replacement therapy (CRRT). A 14-year-old girl with multiorgan failure requiring extracorporeal membrane oxygenation developed rhabdomyolysis due to reperfusion injury. Her creatine kinase (CK) and lactate levels continued to escalate despite high-dose CRRT. A haemoadsorption column was therefore added post-CRRT filter, which brought down the CK level from 264,500 IU/L to 97,436 IU/L after 8 hours of therapy. Another 4-year-old boy with epilepsy and cerebral palsy who was admitted for gastroenteritis with dehydration developed acute kidney injury and rhabdomyolysis with a peak CK level of 946,060 IU/L. He was initially treated with CRRT for 40 hours, which reduced his CK level to 147,580 IU/L. Two sessions of haemoadsorption were then performed in addition to the CRRT, which further lowered his CK level to 32,306 IU/L in 48 hours. Both patients demonstrated enhanced reduction of CK levels when the haemoadsorption column was used in addition to the CRRT, and no specific complication related to the haemoadsorption therapy was reported. Our cases showed that haemoadsorption can be considered as an adjunctive therapy for children with severe rhabdomyolysis-associated acute kidney injury.