Continuous renal replacement therapy for two neonates with hyperammonemia

Objectives: This study aims to assess the feasibility of using hemofiltration for ammonia clearance in low body weight infants with an inborn error of metabolism. Design: A study of two cases. Setting: Quaternary pediatric hospital (Saint Louis Children's Hospital) NICU and PICU. Patients: Infants <6 months of age with an ICD-9 diagnosis of 270.6 (hyperammonemia). Interventions: Continuous renal replacement therapy (CRRT). Measurements and Main Results: We measure serum ammonia levels over time and the rate of ammonia clearance over time. Continuous renal replacement therapy was more effective than scavenger therapy alone (Ammonul™) for rapid removal of ammonia in low weight infants (as low as 2.5 kg). Conclusions: Continuous renal replacement therapy is technically feasible in low weight infants with severe hyperammonemia secondary to an inborn error of metabolism

Global PARITY: Study design for a multi-centered, international point prevalence study to estimate the burden of pediatric acute critical illness in resource-limited settings

Background: The burden of pediatric critical illness and resource utilization by children with critical illness in resource limited settings (RLS) are largely unknown. Without specific data that captures key aspects of critical illness, disease presentation, and resource utilization for pediatric populations in RLS, development of a contextual framework for appropriate, evidence-based interventions to guide allocation of limited but available resources is challenging. We present this methods paper which describes our efforts to determine the prevalence, etiology, hospital outcomes, and resource utilization associated with pediatric acute, critical illness in RLS globally. Methods: We will conduct a prospective, observational, multicenter, multinational point prevalence study in sixty-one participating RLS hospitals from North, Central and South America, Africa, Middle East and South Asia with four sampling time points over a 12-month period. Children aged 29 days to 14 years evaluated for acute illness or injury in an emergency department) or directly admitted to an inpatient unit will be enrolled and followed for hospital outcomes and resource utilization for the first seven days of hospitalization. The primary outcome will be prevalence of acute critical illness, which Global PARITY has defined as death within 48 hours of presentation to the hospital, including ED mortality; or admission/transfer to an HDU or ICU; or transfer to another institution for a higher level-of-care; or receiving critical care-level interventions (vasopressor infusion, invasive mechanical ventilation, non-invasive mechanical ventilation) regardless of location in the hospital, among children presenting to the hospital. Secondary outcomes include etiology of critical illness, in-hospital mortality, cause of death, resource utilization, length of hospital stay, and change in neurocognitive status. Data will be managed via REDCap, aggregated, and analyzed across sites. Discussion: This study is expected to address the current gap in understanding of the burden, etiology, resource utilization and outcomes associated with pediatric acute and critical illness in RLS. These data are crucial to inform future research and clinical management decisions and to improve global pediatric hospital outcomes

The burden of critical illness in hospitalized children in low- and middle-income countries: Protocol for a systematic review and meta-analysis

BACKGROUND: The majority of childhood deaths occur in low- and middle-income countries (LMICs). Many of these deaths are avoidable with basic critical care interventions. Quantifying the burden of pediatric critical illness in LMICs is essential for targeting interventions to reduce childhood mortality. OBJECTIVE: To determine the burden of hospitalization and mortality associated with acute pediatric critical illness in LMICs through a systematic review and meta-analysis of the literature. DATA SOURCES AND SEARCH STRATEGY: We will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, and LILACS using MeSH terms and keywords. Results will be limited to infants or children (ages \u3e28 days to 12 years) hospitalized in LMICs and publications in English, Spanish, or French. Publications with non-original data (e.g., comments, editorials, letters, notes, conference materials) will be excluded. STUDY SELECTION: We will include observational studies published since January 1, 2005, that meet all eligibility criteria and for which a full text can be located. DATA EXTRACTION: Data extraction will include information related to study characteristics, hospital characteristics, underlying population characteristics, patient population characteristics, and outcomes. DATA SYNTHESIS: We will extract and report data on study, hospital, and patient characteristics; outcomes; and risk of bias. We will report the causes of admission and mortality by region, country income level, and age. We will report or calculate the case fatality rate (CFR) for each diagnosis when data allow. CONCLUSIONS: By understanding the burden of pediatric critical illness in LMICs, we can advocate for resources and inform resource allocation and investment decisions to improve the management and outcomes of children with acute pediatric critical illness in LMICs

2-D and 3-D Radiation Transfer Models of High-Mass Star Formation

2-D and 3-D radiation transfer models of forming stars generally produce bluer 1-10 micron colors than 1-D models of the same evolutionary state and envelope mass. Therefore, 1-D models of the shortwave radiation will generally estimate a lower envelope mass and later evolutionary state than multidimensional models. 1-D models are probably reasonable for very young sources, or longwave analysis (wavelengths > 100 microns). In our 3-D models of high-mass stars in clumpy molecular clouds, we find no correlation between the depth of the 10 micron silicate feature and the longwave (> 100 micron) SED (which sets the envelope mass), even when the average optical extinction of the envelope is >100 magnitudes. This is in agreement with the observations of Faison et al. (1998) of several UltraCompact HII (UCHII) regions, suggesting that many of these sources are more evolved than embedded protostars. We have calculated a large grid of 2-D models and find substantial overlap between different evolutionary states in the mid-IR color-color diagrams. We have developed a model fitter to work in conjunction with the grid to analyze large datasets. This grid and fitter will be expanded and tested in 2005 and released to the public in 2006.Comment: 10 pages, 8 figures, to appear in the proceedings of IAU Symp 227, Massive Star Birth: A Crossroads of Astrophysics, (Cesaroni R., Churchwell E., Felli M., Walmsley C. editors

Association of interleukin 7 immunotherapy with lymphocyte counts among patients with severe coronavirus disease 2019 (COVID-19)

This case series examines whether interleukin 7 (IL-7) is associated with restored host protective immunity in patients with severe coronavirus disease 2019 (COVID-19) and immunosuppression

The temporal relationship between local school closure and increased incidence of pediatric diabetic ketoacidosis

IMPORTANCE: The incidence of pediatric diabetic ketoacidosis (DKA) increased early in the COVID-19 pandemic, but the relative contribution of behavioral changes and viral-related pathophysiology are unknown. OBJECTIVE: To evaluate the relationship between school closure date and onset of increased DKA to help clarify the etiology of the increased incidence. DESIGN: A multi-center, quality-controlled Pediatric Intensive Care Unit (PICU) database was used to identify the number of admissions to a participating PICU with DKA on each calendar day from 60 days before local school closure to 90 days after, and compared to baseline data from the same periods in 2018-2019. Interrupted time series and multiple linear regression analyses were used to identify admission rates that differed significantly between 2020 and baseline. SETTING: Eighty-one PICUs in the United StatesParticipants: Children ages 29 days to 17 years admitted to a PICU with DKAExposures: Statewide school closureMain outcome/measure: Rate of admission to the PICU for DKA. RESULTS: There were 1936 admissions for children with DKA in 2020 and 1795 admissions/year to those same PICUs in 2018-2019. Demographics and clinical outcomes did not differ before school closure, but pandemic-era patients were less often white and had longer hospital length of stay in the post-school closure period. The difference between 2020 admissions and 2018-2019 admissions was not different than zero before school closure, and significantly higher than zero after school closure, but was significantly increased in 2020 at \u3e30 days after school closure ( CONCLUSIONS/RELEVANCE: An increase in pediatric DKA admissions began one month after school closures. Given that behavioral changes started near school closure dates and viral activity peaked weeks after, this suggests that behavioral factors may not be the primary etiology and it is possible that SARS-CoV-2 infection may have direct effects on pediatric DKA

Overlapping but disparate inflammatory and immunosuppressive responses to SARS-CoV-2 and bacterial sepsis: An immunological time course analysis

Both severe SARS-CoV-2 infections and bacterial sepsis exhibit an immunological dyscrasia and propensity for secondary infections. The nature of the immunological dyscrasias for these differing etiologies and their time course remain unclear. In this study, thirty hospitalized patients with SARS-CoV-2 infection were compared with ten critically ill patients with bacterial sepsis over 21 days, as well as ten healthy control subjects. Blood was sampled between days 1 and 21 after admission for targeted plasma biomarker analysis, cellular phenotyping, and leukocyte functional analysi

Dysregulation of the leukocyte signaling landscape during acute COVID-19

The global COVID-19 pandemic has claimed the lives of more than 750,000 US citizens. Dysregulation of the immune system underlies the pathogenesis of COVID-19, with inflammation mediated tissue injury to the lung in the setting of suppressed systemic immune function. To define the molecular mechanisms of immune dysfunction in COVID-19 we utilized a systems immunology approach centered on the circulating leukocyte phosphoproteome measured by mass cytometry. We find that although COVID-19 is associated with wholesale activation of a broad set of signaling pathways across myeloid and lymphoid cell populations, STAT3 phosphorylation predominated in both monocytes and T cells. STAT3 phosphorylation was tightly correlated with circulating IL-6 levels and high levels of phospho-STAT3 was associated with decreased markers of myeloid cell maturation/activation and decreased ex-vivo T cell IFN-γ production, demonstrating that during COVID-19 dysregulated cellular activation is associated with suppression of immune effector cell function. Collectively, these data reconcile the systemic inflammatory response and functional immunosuppression induced by COVID-19 and suggest STAT3 signaling may be the central pathophysiologic mechanism driving immune dysfunction in COVID-19