Givosiran for the Treatment of Pediatric Acute Intermittent Porphyria.

Acute intermittent porphyria (AIP) causes neurovisceral symptoms and organ toxicity resulting in acute and chronic health conditions. Treatment has traditionally involved avoiding triggers and utilizing carbohydrates and hemin infusions for acute attacks. Givosiran, an FDA-approved small interfering RNA, has shown benefit in adults in reducing attacks. However, its usage in pediatrics is extremely limited. We present a pediatric patient with AIP, requiring frequent hemin infusions for severe attacks, which have a resolution of her disease state and symptoms with the initiation of givosiran therapy.

Trends in Disease Severity Among Critically Ill Children With Severe Acute Respiratory Syndrome Coronavirus 2: A Retrospective Multicenter Cohort Study in the United States.

OBJECTIVES: To describe trends in critical illness from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children over the course of the COVID-19 pandemic. We hypothesized that PICU admission rates were higher in the Omicron period compared with the original outbreak but that fewer patients needed endotracheal intubation. DESIGN: Retrospective cohort study. SETTING: This study took place in nine U.S. PICUs over 3 weeks in January 2022 (Omicron period) compared with 3 weeks in March 2020 (original period). PATIENTS: Patients less than or equal to 21 years old who screened positive for SARS-CoV-2 infection by polymerase chain reaction or hospital-based rapid antigen test and were admitted to a PICU or intermediate care unit were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 267 patients (239 Omicron and 28 original) were reviewed. Forty-five patients in the Omicron cohort had incidental SARS-CoV-2 and were excluded from analysis. The Omicron cohort patients were younger compared with the original cohort patients (median [interquartile range], 6 yr [1.3-13.3 yr] vs 14 yr [8.3-17.3 yr]; p = 0.001). The Omicron period, compared with the original period, was associated with an average increase in COVID-19-related PICU admissions of 13 patients per institution (95% CI, 6-36; p = 0.008), which represents a seven-fold increase in the absolute number admissions. We failed to identify an association between cohort period (Omicron vs original) and odds of intubation (odds ratio, 0.7; 95% CI, 0.3-1.7). However, we cannot exclude the possibility of up to 70% reduction in intubation. CONCLUSIONS: COVID-19-related PICU admissions were seven times higher in the Omicron wave compared with the original outbreak. We could not exclude the possibility of up to 70% reduction in use of intubation in the Omicron versus original epoch, which may represent differences in PICU/hospital admission policy in the later period, or pattern of disease, or possibly the impact of vaccination.

Concomitant thrombotic thrombocytopenic purpura and ANCA-associated vasculitis in an adolescent.

Thrombotic thrombocytopenic purpura (TTP) rarely occurs with systemic vasculitis. A 17-year-old girl presented with non-bloody diarrhea, menorrhagia, and syncope. She had severe anemia (hemoglobin = 3.8 g/dl), thrombocytopenia (platelet = 7,000/mm(3)), and acute kidney injury (serum creatinine, Cr = 2.3 mg%). Peripheral smear examination confirmed the presence of microangiopathic hemolytic anemia. Additionally, she had a positive anti-nuclear antibody (1:1600) and normal complement levels. We considered the diagnosis of TTP, possibly associated with systemic lupus erythematosus, and promptly initiated pulse methylprednisolone and daily 3-4 l of plasma exchange therapy. Following resolution of her thrombocytopenia in 48 h, we performed a kidney biopsy that revealed diffuse proliferative, focal crescentic, and necrotizing glomerulonephritis with mild IgG immunofluorescence staining. Concomitantly, autoimmune work-up was significant for positive perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA = 1:640) and decreased von Willebrand factor cleaving protease activity (<5%). A final diagnosis of TTP with microscopic polyangiitis (p-ANCA-mediated) was made and treatment with daily oral cyclophosphamide and prednisone resolved her renal injury over 2 months (follow-up Cr = 1.0 mg%). Our case highlights the importance of identifying systemic disorders such as ANCA-associated vasculitis with TTP.

Unintentional Window Falls in Children and Adolescents.

OBJECTIVE: Unintentional window falls represent a preventable source of injury and death in children. Despite major campaigns in some larger cities, there continue to be unintentional falls from windows throughout the United States. We aimed to identify risk factors and trends in unintentional window falls in the pediatric population in a national and regional sample. METHODS: A retrospective analysis of annual emergency department (ED) visits from the National Electronic Injury Surveillance System using product codes specific to windows, as well as patient encounters for unintentional window falls from January 2007 to August 2017 using site-specific trauma registries from 10 tertiary care children's hospitals in New England. National and state-specific census population estimates were used to compute rates per 100,000 population. RESULTS: There were 38,840 ED visits and 496 regional patients who unintentionally fell from a window across the study period between 0 and 17 years old. The majority of falls occurred in children under the age of 6 and were related to falls from a second story or below. A decreased trend in national ED visits was seen, but no change in rates over time for regional trauma center encounters. A high number of falls was found to occur in smaller cities surrounding metropolitan areas and from single family residences. CONCLUSIONS: Falls from windows represent a low proportion of overall types of unintentional sources of injury in children but are a high risk for severe disability. These results provide updated epidemiologic data for targeted intervention programs, as well as raise awareness for continued education and advocacy.

High flow nasal cannulae therapy in infants with bronchiolitis.

OBJECTIVES: To determine whether the introduction of heated humidified high-flow nasal cannulae (HFNC) therapy was associated with decreased rates of intubation for infants <24 months old with bronchiolitis admitted to a pediatric intensive care unit (PICU). STUDY DESIGN: A retrospective chart review of infants with bronchiolitis admitted before and in the season after introduction of HFNC. RESULTS: In the season after the introduction of HFNC, only 9% of infants admitted to the PICU with bronchiolitis required intubation, compared with 23% in the prior season (P=.043). This 68% decrease in need for intubation persisted in a logistic regression model controlling for age, weight, and RSV status. HFNC therapy resulted in a greater decrease in respiratory rate compared with other forms of respiratory support, and those infants with the greatest decrease in respiratory rate were least likely to be intubated. In addition, median PICU length of stay for children with bronchiolitis decreased from 6 to 4 days after the introduction of HFNC. DISCUSSION: We hypothesize that HFNC decreases rates of intubation in infants with bronchiolitis by decreasing the respiratory rate and work of breathing by providing a comfortable and well-tolerated means of noninvasive ventilatory support.

Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units.

IMPORTANCE: The recent and ongoing coronavirus disease 2019 (COVID-19) pandemic has taken an unprecedented toll on adults critically ill with COVID-19 infection. While there is evidence that the burden of COVID-19 infection in hospitalized children is lesser than in their adult counterparts, to date, there are only limited reports describing COVID-19 in pediatric intensive care units (PICUs). OBJECTIVE: To provide an early description and characterization of COVID-19 infection in North American PICUs, focusing on mode of presentation, presence of comorbidities, severity of disease, therapeutic interventions, clinical trajectory, and early outcomes. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included children positive for COVID-19 admitted to 46 North American PICUs between March 14 and April 3, 2020. with follow-up to April 10, 2020. MAIN OUTCOMES AND MEASURES: Prehospital characteristics, clinical trajectory, and hospital outcomes of children admitted to PICUs with confirmed COVID-19 infection. RESULTS: Of the 48 children with COVID-19 admitted to participating PICUs, 25 (52%) were male, and the median (range) age was 13 (4.2-16.6) years. Forty patients (83%) had significant preexisting comorbidities; 35 (73%) presented with respiratory symptoms and 18 (38%) required invasive ventilation. Eleven patients (23%) had failure of 2 or more organ systems. Extracorporeal membrane oxygenation was required for 1 patient (2%). Targeted therapies were used in 28 patients (61%), with hydroxychloroquine being the most commonly used agent either alone (11 patients) or in combination (10 patients). At the completion of the follow-up period, 2 patients (4%) had died and 15 (31%) were still hospitalized, with 3 still requiring ventilatory support and 1 receiving extracorporeal membrane oxygenation. The median (range) PICU and hospital lengths of stay for those who had been discharged were 5 (3-9) days and 7 (4-13) days, respectively. CONCLUSIONS AND RELEVANCE: This early report describes the burden of COVID-19 infection in North American PICUs and confirms that severe illness in children is significant but far less frequent than in adults. Prehospital comorbidities appear to be an important factor in children. These preliminary observations provide an important platform for larger and more extensive studies of children with COVID-19 infection.

Prospective detection of hyperglycemia in critically ill children using continuous glucose monitoring.

OBJECTIVE: To evaluate the extent of hyperglycemia in nondiabetic children admitted to a pediatric intensive care unit using an interstitial continuous glucose monitor, and to compare the ability of this interstitial continuous glucose monitoring system to detect hyperglycemia with that of intermittent laboratory monitoring. DESIGN: Prospective observational study. SETTING: Ten-bed pediatric intensive care unit in an academic referral medical center in western Massachusetts. PATIENTS: A convenience sample of 20 nondiabetic children, aged 1-18, anticipated to require intensive care >2 days. INTERVENTIONS: Placement of a subcutaneous continuous glucose monitor for 72 hrs with a subsequent second sensor placed if the patient and family agreed. Glucose levels were compared with laboratory glucose values. MEASUREMENTS AND MAIN RESULTS: Elevated glucose levels were revealed by 16,337 sensor glucose readings over a mean of 68 +/- 5.2 hrs per patient. Forty-three percent of readings were >125 mg/dL (6.9 mmol/L), 27.2% were >140 mg/dL (7.8 mmol/L), and 4.0% were >200 mg/dL (11.1 mmol/L). Laboratory glucose measurements demonstrated hyperglycemia less frequently and missed significant periods of hyperglycemia. CONCLUSIONS: Significant hyperglycemia is present in pediatric intensive care patients and may be underestimated by intermittent laboratory monitoring.