Intranasal fentanyl and discharge from the emergency department among children with sickle cell disease and vaso-occlusive pain: A multicenter pediatric emergency medicine perspective.

Children with sickle cell disease (SCD) commonly experience vaso-occlusive pain episodes (VOE) due to sickling of erythrocytes, which often requires care in the emergency department. Our objective was to assess the use and impact of intranasal fentanyl for the treatment of children with SCD-VOE on discharge from the emergency department in a multicenter study. We conducted a cross-sectional study at 20 academic pediatric emergency departments in the United States and Canada. We used logistic regression to test bivariable and multivariable associations between the outcome of discharge from the emergency department and candidate variables theoretically associated with discharge. The study included 400 patients; 215 (54%) were female. The median age was 14.6 (interquartile range 9.8, 17.6) years. Nineteen percent (n = 75) received intranasal fentanyl in the emergency department. Children who received intranasal fentanyl had nearly nine-fold greater adjusted odds of discharge from the emergency department compared to those who did not (adjusted odds ratio 8.99, 95% CI 2.81-30.56, p < .001). The rapid onset of action and ease of delivery without intravenous access offered by intranasal fentanyl make it a feasible initial parenteral analgesic in the treatment of children with SCD presenting with VOE in the acute-care setting. Further study is needed to determine potential causality of the association between intranasal fentanyl and discharge from the emergency department observed in this multicenter study.

Radiographic pneumonia in young febrile infants presenting to the emergency department: secondary analysis of a prospective cohort study.

OBJECTIVE: The lack of evidence-based criteria to guide chest radiograph (CXR) use in young febrile infants results in variation in its use with resultant suboptimal quality of care. We sought to describe the features associated with radiographic pneumonias in young febrile infants. STUDY DESIGN: Secondary analysis of a prospective cohort study in 18 emergency departments (EDs) in the Pediatric Emergency Care Applied Research Network from 2016 to 2019. Febrile (≥38°C) infants aged ≤60 days who received CXRs were included. CXR reports were categorised as 'no', 'possible' or 'definite' pneumonia. We compared demographics, clinical signs and laboratory tests among infants with and without pneumonias. RESULTS: Of 2612 infants, 568 (21.7%) had CXRs performed; 19 (3.3%) had definite and 34 (6%) had possible pneumonias. Patients with definite (4/19, 21.1%) or possible (11/34, 32.4%) pneumonias more frequently presented with respiratory distress compared with those without (77/515, 15.0%) pneumonias (adjusted OR 2.17; 95% CI 1.04 to 4.51). There were no differences in temperature or HR in infants with and without radiographic pneumonias. The median serum procalcitonin (PCT) level was higher in the definite (0.7 ng/mL (IQR 0.1, 1.5)) vs no pneumonia (0.1 ng/mL (IQR 0.1, 0.3)) groups, as was the median absolute neutrophil count (ANC) (definite, 5.8 K/mcL (IQR 3.9, 6.9) vs no pneumonia, 3.1 K/mcL (IQR 1.9, 5.3)). No infants with pneumonia had bacteraemia. Viral detection was frequent (no pneumonia (309/422, 73.2%), definite pneumonia (11/16, 68.8%), possible pneumonia (25/29, 86.2%)). Respiratory syncytial virus was the predominant pathogen in the pneumonia groups and rhinovirus in infants without pneumonias. CONCLUSIONS: Radiographic pneumonias were uncommon in febrile infants. Viral detection was common. Pneumonia was associated with respiratory distress, but few other factors. Although ANC and PCT levels were elevated in infants with definite pneumonias, further work is necessary to evaluate the role of blood biomarkers in infant pneumonias.

Increased Fellow Scholarly Publication Rate After Implementation of a Comprehensive Research Curriculum and Milestone-Based Research Timeline for Pediatric Emergency Medicine Fellows.

OBJECTIVE: Pediatric subspecialty fellows are required to complete a scholarly product during training; however, many do not bring the work to publication. To amplify our fellows' publication success, our pediatric emergency medicine fellowship program implemented a comprehensive research curriculum and established a milestone-based research timeline for each component of a project. Our objective was to assess whether these interventions increased the publication rate and enhanced the graduated fellows' perceived ability to perform independent research. METHODS: Our study was conducted at a tertiary children's hospital affiliated with an academic university, enrolling 3 fellows each year in its pediatric emergency medicine program. A comprehensive research curriculum and a milestone-based research timeline were implemented in 2011. We analyzed the publication rate of our graduating fellows before (2004-2011) and after (2012-2016) our intervention. In addition, in 2017 we surveyed our previous fellows who graduated from 2004 to 2016 and analyzed factors favoring manuscript publication and confidence with various research skills. RESULTS: During the study period, 38 trainees completed the fellowship program. Publication rate increased from 26% ± 17% to 87% ± 30 % ( P < 0.05). When scoring the importance of various factors, fellows most valued mentorship (5 ± 0 vs 4.3 ± 1.0, P < 0.05, postintervention vs preintervention) for the completion of the fellowship study and manuscript. Fellows after the intervention reported greater confidence in performing an analysis of variance (89% vs 36%, odds ratio, 6.3; 95% confidence interval, 1.4-150.1). CONCLUSIONS: Implementation of a comprehensive research curriculum and a milestone-based research timeline was associated with an increase in the publication rate within 3 years of graduation of our pediatric emergency medicine fellows. After implementation, fellows reported an increased importance of mentorship and greater confidence in performing an analysis of variance. We provide a comprehensive curriculum and a research timeline that may serve as a model for other fellowship programs.

Understanding Variation in Rotavirus Vaccine Effectiveness Estimates in the United States: The Role of Rotavirus Activity and Diagnostic Misclassification.

BACKGROUND: Estimates of rotavirus vaccine effectiveness (VE) in the United States appear higher in years with more rotavirus activity. We hypothesized rotavirus VE is constant over time but appears to vary as a function of temporal variation in local rotavirus cases and/or misclassified diagnoses. METHODS: We analyzed 6 years of data from eight US surveillance sites on 8- to 59-month olds with acute gastroenteritis symptoms. Children's stool samples were tested via enzyme immunoassay (EIA); rotavirus-positive results were confirmed with molecular testing at the US Centers for Disease Control and Prevention. We defined rotavirus gastroenteritis cases by either positive on-site EIA results alone or positive EIA with Centers for Disease Control and Prevention confirmation. For each case definition, we estimated VE against any rotavirus gastroenteritis, moderate-to-severe disease, and hospitalization using two mixed-effect regression models: the first including year plus a year-vaccination interaction, and the second including the annual percent of rotavirus-positive tests plus a percent positive-vaccination interaction. We used multiple overimputation to bias-adjust for misclassification of cases defined by positive EIA alone. RESULTS: Estimates of annual rotavirus VE against all outcomes fluctuated temporally, particularly when we defined cases by on-site EIA alone and used a year-vaccination interaction. Use of confirmatory testing to define cases reduced, but did not eliminate, fluctuations. Temporal fluctuations in VE estimates further attenuated when we used a percent positive-vaccination interaction. Fluctuations persisted until bias-adjustment for diagnostic misclassification. CONCLUSIONS: Both controlling for time-varying rotavirus activity and bias-adjusting for diagnostic misclassification are critical for estimating the most valid annual rotavirus VE.

Investigating the morphological transitions in an associative surfactant ternary system.

Associative surfactants systems involving polar oils have recently been shown to stabilize immiscible liquids by forming nanostructures at the liquid interface and have been used to print soft materials. Although these associating surfactant systems show great promise for creating nanostructured soft materials, a fundamental understanding of the self-assembly process is still unknown. In this study, a ternary phase diagram for a system of cationic surfactant cetylpyridinium chloride monohydrate (CPCl), a polar oil (oleic acid), and water is established using experiment and simulation, to study the equilibrium phase behavior. A combination of visual inspection, small-angle X-ray scattering (SAXS), and rheological measurements was employed to establish the phase behavior and properties of the self-assembled materials. Dissipative particle dynamics (DPD) is used to simulate the formation of the morphologies in this system and support the experimental results. The ternary phase diagram obtained from the simulations agrees with the experimental results, indicating the robustness of the computational simulation as a supplement to the mesoscale experimental systems. We observe that morphological transitions (e.g., micelle-to-bilayer and vesicle-to-lamellar) are in agreement between experiments and simulations across the ternary diagram. DPD simulations correctly predict that associative surfactant systems form new nanoscale phases due to the co-assembly of the components. The established ternary phase diagram and the DPD model pave the way towards predicting and controlling the formation of different mesostructures like lamellar or vesicles, opening new avenues to tailor and synthesize desired morphologies for applications related to liquid-in-liquid 3D printing.

Rapid fabrication of precise high-throughput filters from membrane protein nanosheets.

Biological membranes are ideal for separations as they provide high permeability while maintaining high solute selectivity due to the presence of specialized membrane protein (MP) channels. However, successful integration of MPs into manufactured membranes has remained a significant challenge. Here, we demonstrate a two-hour organic solvent method to develop 2D crystals and nanosheets of highly packed pore-forming MPs in block copolymers (BCPs). We then integrate these hybrid materials into scalable MP-BCP biomimetic membranes. These MP-BCP nanosheet membranes maintain the molecular selectivity of the three types of ß-barrel MP channels used, with pore sizes of 0.8 nm, 1.3 nm, and 1.5 nm. These biomimetic membranes demonstrate water permeability that is 20-1,000 times greater than that of commercial membranes and 1.5-45 times greater than that of the latest research membranes with comparable molecular exclusion ratings. This approach could provide high performance alternatives in the challenging sub-nanometre to few-nanometre size range.

Association of Bacteremia with Vaccination Status in Children Aged 2 to 36 Months.

OBJECTIVE: To determine the association between bacteremia and vaccination status in children aged 2-36 months presenting to a pediatric emergency department. STUDY DESIGN: Retrospective cohort study of children aged 2-36 months with blood cultures obtained in the pediatric emergency department between January 2013 and December 2017. The exposure of interest was immunization status, defined as number of Haemophilus influenzae type B (Hib) and Streptococcus pneumoniae vaccinations, and the main outcome positive blood culture. Subjects with high-risk medical conditions were excluded. RESULTS: Of 5534 encounters, 4742 met inclusion criteria. The incidence of bacteremia was 1.5%. The incidence of contaminated blood culture was 5.0%. The relative risk of bacteremia was 0.79 (95% CI 0.39-1.59) for unvaccinated and 1.20 (95% CI 0.52-2.75) for undervaccinated children relative to those who had received age-appropriate vaccines. Five children were found to have S pneumoniae bacteremia and 1 child had Hib bacteremia; all of these subjects had at least 3 sets of vaccinations. No vaccine preventable pathogens were isolated from blood cultures of unvaccinated children. We found no S pneumoniae or Hib in children 2-6 months of age who were not fully vaccinated due to age (95% CI 0-0.13%) and the contamination rate in this group was high compared with children 7-36 months (6.6% vs 3.7%). CONCLUSIONS: Bacteremia in young children is an uncommon event. Contaminated blood cultures were more common than pathogens. Bacteremia from S pneumoniae or Hib is uncommon and, in this cohort, was independent of vaccine status.

Zwitterions Raise the Dielectric Constant of Soft Materials.

Materials exhibiting high dielectric constants (ϵ_{s}) are critical for energy storage and actuators. A successful approach to increase ϵ_{s} is to incorporate polar additives (with high ϵ_{s}) but controlling the resulting dispersion state is difficult. Here, we show that significant ϵ_{s} increases are realized by adding zwitterions, which are small molecules with a cation and an anion separated by covalent bonds. The increase in ϵ_{s} with zwitterion addition is attributed to the large molecular dipole of zwitterions, ranging from 35 to 41 D, as experimentally quantified and confirmed using density functional theory. At elevated zwitterion concentration in an ethylene glycol medium, there is a nonlinear increase of ϵ_{s} that eventually saturates due to the strong Coulombic interactions between zwitterions. The presented work provides a fundamental molecular understanding of why zwitterions are effective additives in boosting ϵ_{s} in soft materials.

Enterovirus D68-Associated Acute Respiratory Illness ─ New Vaccine Surveillance Network, United States, July-November 2018-2020.

Enterovirus D68 (EV-D68) is associated with a broad spectrum of illnesses, including mild to severe acute respiratory illness (ARI) and acute flaccid myelitis (AFM). Enteroviruses, including EV-D68, are typically detected in the United States during late summer through fall, with year-to-year fluctuations. Before 2014, EV-D68 was infrequently reported to CDC (1). However, numbers of EV-D68 detection have increased in recent years, with a biennial pattern observed during 2014-2018 in the United States, after the expansion of surveillance and wider availability of molecular testing. In 2014, a national outbreak of EV-D68 was detected (2). EV-D68 was also reported in 2016 via local (3) and passive national (4) surveillance. EV-D68 detections were limited in 2017, but substantial circulation was observed in 2018 (5). To assess recent levels of circulation, EV-D68 detections in respiratory specimens collected from patients aged <18 years* with ARI evaluated in emergency departments (EDs) or admitted to one of seven U.S. medical centers† within the New Vaccine Surveillance Network (NVSN) were summarized. This report provides a provisional description of EV-D68 detections during July-November in 2018, 2019 and 2020, and describes the demographic and clinical characteristics of these patients. In 2018, a total of 382 EV-D68 detections in respiratory specimens obtained from patients aged <18 years with ARI were reported by NVSN; the number decreased to six detections in 2019 and 30 in 2020. Among patients aged <18 years with EV-D68 in 2020, 22 (73%) were non-Hispanic Black (Black) persons. EV-D68 detections in 2020 were lower than anticipated based on the biennial circulation pattern observed since 2014. The circulation of EV-D68 in 2020 might have been limited by widespread COVID-19 mitigation measures; how these changes in behavior might influence the timing and levels of circulation in future years is unknown. Ongoing monitoring of EV-D68 detections is warranted for preparedness for EV-D68-associated ARI and AFM.

Current status and future directions of self-assembled block copolymer membranes for molecular separations.

One of the most efficient and promising separation alternatives to thermal methods such as distillation is the use of polymeric membranes that separate mixtures based on molecular size or chemical affinity. Self-assembled block copolymer membranes have gained considerable attention within the membrane field due to precise control over nanoscale structure, pore size, and chemical versatility. Despite the rapid progress and excitement, a significant hurdle in using block copolymer membranes for nanometer and sub-nanometer separations such as nanofiltration and reverse osmosis is the lower limit on domain size features. Strategies such as polymer post-functionalization, self-assembly of oligomers, liquid crystals, and random copolymers, or incorporation of artificial/natural channels within block copolymer materials are future directions with the potential to overcome current limitations with respect to separation size.

Controlling nanostructure and mechanical properties in triblock copolymer/monomer blends via reaction-induced phase transitions.

Thermoplastic elastomers based on ABA triblock copolymers are typically limited in modulus and strength due to crack propagation within the brittle regions when the hard end-block composition favors morphologies that exhibit connected domains. Increasing the threshold end-block composition to achieve enhanced mechanical performance is possible by increasing the number of junctions or bridging points per chain, but these copolymer characteristics also tend to increase the complexity of the synthesis. Here, we report an in situ polymerization method to successfully increase the number of effective junctions per chain through grafting of poly(styrene) (PS) to a commercial thermoplastic elastomer, poly(styrene)-poly(butadiene)-poly(styrene) (SBS). The strategy described here transforms a linear SBS triblock copolymer-styrene mixture into a linear-comb-linear architecture in which poly(styrene) (PS) grafts from the mid-poly(butadiene) (PBD) block during the polymerization of styrene. Through systematic variation in the initial SBS/styrene content, nanostructural transitions from disordered spheres to lamellar through reaction-induced phase transitions (RIPT) were identified as the styrene content increased. Surprisingly, maximum mechanical performance (Young's modulus, tensile strength, and elongation at break) was obtained with samples exhibiting lamellar nanostructures, corresponding to overall PS contents of 61-77 wt% PS (including the original PS in SBS). The PS grafting from the PBD block increases the modulus and the strength of the thermoplastic elastomer while preventing brittle fracture due to the greater number of junctions afforded by the PS grafts. The work presented here demonstrates the use of RIPT to transform standard SBS materials into polymer systems with enhanced mechanical properties.

Fabricating Robust Constructs with Internal Phase Nanostructures via Liquid-in-Liquid 3D Printing.

The ability to print soft materials into predefined architectures with programmable nanostructures and mechanical properties is a necessary requirement for creating synthetic biomaterials that mimic living tissues. However, the low viscosity of common materials and lack of required mechanical properties in the final product present an obstacle to the use of traditional additive manufacturing approaches. Here, a new liquid-in-liquid 3D printing approach is used to successfully fabricate constructs with internal nanostructures using in situ self-assembly during the extrusion of an aqueous solution containing surfactant and photocurable polymer into a stabilizing polar oil bath. Subsequent photopolymerization preserves the nanostructures created due to surfactant self-assembly at the immiscible liquid-liquid interface, which is confirmed by small-angle X-ray scattering. Mechanical properties of the photopolymerized prints are shown to be tunable based on constituent components of the aqueous solution. The reported 3D printing approach expands the range of low-viscosity materials that can be used in 3D printing, and enables robust constructs production with internal nanostructures and spatially defined features. The reported approach has broad applications in regenerative medicine by providing a platform to print self-assembling biomaterials into complex tissue mimics where internal supramolecular structures and their functionality control biological processes, similar to natural extracellular matrices.

Effect of chemical substituents attached to the zwitterion cation on dielectric constant.

Materials with high dielectric constant, εs, are desirable in a wide range of applications including energy storage and actuators. Recently, zwitterionic liquids have been reported to have the largest εs of any liquid and, thus, have the potential to replace inorganic fillers to modulate the material εs. Although the large εs for zwitterionic liquids is attributed to their large molecular dipole, the role of chemical substituents attached to the zwitterion cation on εs is not fully understood, which is necessary to enhance the performance of soft energy materials. Here, we report the impact of zwitterionic liquid cation chemical substituents on εs (50 < εs < 300 at room temperature). Dielectric relaxation spectroscopy reveals that molecular reorientation is the main contributor to the high εs. The low Kirkwood factor g calculated for zwitterionic liquids (e.g., 0.1-0.2) suggests the tendency for the antiparallel zwitterion dipole alignment expected from the strong electrostatic intermolecular interactions. With octyl cation substituents, the g is decreased due to the formation of hydrophobic-rich domains that restrict molecular reorientation under applied electric fields. In contrast, when zwitterion cations are functionalized with ethylene oxide (EO) segments, g increases due to the EO segments interacting with the cations, allowing more zwitterion rotation in response to the applied field. The reported results suggest that high εs zwitterionic liquids require a large molecular dipole, compositionally homogeneous liquids (e.g., no aggregation), a maximized zwitterion number density, and a high g, which is achievable by incorporating polar chemical substituents onto the zwitterion cations.

Hypothermia in Young Infants: Frequency and Yield of Sepsis Workup.

OBJECTIVES: Serious bacterial infections (SBIs) in young infants can present with fever or hypothermia. There are substantial data on fever as a presentation for SBI that help to inform the clinical approach. In contrast, data on hypothermia are lacking, thus leaving clinicians without guidance. We aimed to describe the workup and findings, specifically the occurrence, of SBIs in infants younger than 60 days of life with hypothermia. METHODS: We reviewed the medical records of infants younger than 60 days of life with rectal temperature of less than 36.5°C upon arrival to a children's hospital emergency department between January 2013 and December 2014. Comparisons were made between those who were found to have an SBI and those without. Serious bacterial infection was defined as bacteremia, bacterial meningitis, pneumonia, or urinary tract infection (UTI). RESULTS: From the 414 patients identified, 104 (25%) underwent a sepsis evaluation of blood, urine, and/or cerebrospinal fluid culture. Serious bacterial infections were identified in 9 patients: 4 with UTI, 1 with pneumonia, 2 with bacteremia, 1 with pneumonia and UTI, and 1 with meningitis and bacteremia. Compared with patients with negative cultures, patients with SBI were older and had elevated absolute band counts and elevated immature-to-total neutrophil ratio. CONCLUSIONS: Approximately a quarter of infants younger than 60 days with hypothermia were evaluated for SBI. Serious bacterial infection was identified in 9% of evaluated infants (2% of all hypothermic infants). Hypothermia can be a presenting sign of SBI.

Outcomes of Young Infants with Hypothermia Evaluated in the Emergency Department.

OBJECTIVE: To assess the prevalence of serious infections and mortality among infants ≤90 days of age presenting to the emergency department with hypothermia. STUDY DESIGN: We performed a cross-sectional cohort study of infants ≤90 days presenting to any of 40 EDs in the Pediatric Health Information Systems between January 1, 2009, and December 31, 2018. Infants with an International Classification of Diseases, ninth or tenth edition, admission/discharge diagnosis code of hypothermia were included. We determined the prevalence of serious bacterial infection (urinary tract infection, bacteremia, and/or bacterial meningitis), pneumonia, herpes simplex virus (HSV) infection, and emergency department/hospital mortality. RESULTS: We included 3565 infants (1633 male [50.9%] and 3225 ≤30 days of age [90.5%]). Most (65.0%) presented in the first week of life. There were 389 infants (10.8%) with a complex chronic condition. The prevalence of serious bacterial infection was 8.0% (n = 284), including 2.4% (n = 87) with urinary tract infection, 5.6% (n = 199) with bacteremia, and 0.3% (n = 11) with bacterial meningitis. There were 7 patients (0.2%) with neonatal HSV and 9 (0.3%) with pneumonia; 0.2% (n = 6) died. The presence of a complex chronic condition was associated with the presence of serious bacterial infection (P < .001) and was present in 3 of 6 patients who died. In a sensitivity analysis including patients with any diagnosis code of hypothermia (n = 8122), 14.9% had serious bacterial infection, 0.6% had HSV, and 3.3% had pneumonia; 2.0% died. CONCLUSIONS: Of infants with hypothermia ≤90 days of age, 8.3% had serious bacterial infections or HSV. Compared with literature from febrile infants, hypothermia is associated with a high mortality rate. Complex chronic conditions were particularly associated with poor outcomes. Additional research is required to risk stratify young infants with hypothermia.

Biomarkers that differentiate false positive urinalyses from true urinary tract infection.

BACKGROUND: The specificity of the leukocyte esterase test (87%) is suboptimal. The objective of this study was to identify more specific screening tests that could reduce the number of children who unnecessarily receive antimicrobials to treat a presumed urinary tract infection (UTI). METHODS: Prospective cross-sectional study to compare inflammatory proteins in blood and urine samples collected at the time of a presumptive diagnosis of UTI. We also evaluated serum RNA expression in a subset. RESULTS: We enrolled 200 children; of these, 89 were later demonstrated not to have a UTI based on the results of the urine culture obtained. Urinary proteins that best discriminated between children with UTI and no UTI were involved in T cell response proliferation (IL-9, IL-2), chemoattractants (CXCL12, CXCL1, CXCL8), the cytokine/interferon pathway (IL-13, IL-2, INFγ), or involved in innate immunity (NGAL). The predictive power (as measured by the area under the curve) of a combination of four urinary markers (IL-2, IL-9, IL-8, and NGAL) was 0.94. Genes in the pathways related to inflammation were also upregulated in serum of children with UTI. CONCLUSIONS: Urinary proteins involved in the inflammatory response may be useful in identifying children with false positive results with current screening tests for UTI; this may reduce unnecessary treatment.

Corticosteroids to prevent kidney scarring in children with a febrile urinary tract infection: a randomized trial.

BACKGROUND: To evaluate the efficacy of adjuvant systemic corticosteroids in reducing kidney scarring. A previous study suggested that use of adjuvant systemic corticosteroids reduces kidney scarring in children radiologically confirmed to have extensive pyelonephritis. Efficacy of corticosteroids for children with febrile urinary tract infection (UTI) has not been studied. METHODS: Children aged 2 months to 6 years with their first febrile UTI were randomized to corticosteroids or placebo for 3 days (both arms received antimicrobial therapy); kidney scarring was assessed using 99mTc-dimercaptosuccinic acid kidney scan 5-24 months after the initial UTI. RESULTS: We randomized 546 children of which 385 had a UTI and 254 had outcome kidney scans (instead of the 320 planned). Rates of kidney scarring were 9.8% (12/123) and 16.8% (22/131) in the corticosteroid and placebo groups, respectively (p = 0.16), corresponding to an absolute risk reduction of 5.9% (95% confidence interval: - 2.2, 14.1). CONCLUSION: While children randomized to adjuvant corticosteroids tended to develop fewer kidney scars than children who were randomized to receive placebo, a statistically significant difference was not achieved. However, the study was limited by not reaching its intended sample size. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov , NCT01391793, Registered 7/12/2011 Graphical abstract.

Early Hyperoxemia and Outcome Among Critically Ill Children.

OBJECTIVE: To identify whether a high PaO2 (hyperoxemia) at the time of presentation to the PICU is associated with in-hospital mortality. DESIGN: Single-center observational study. SETTING: Quaternary-care PICU. PATIENTS: Encounters admitted between January 1, 2009, and December 31, 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Encounters with a measured PaO2 were included. To account for severity of illness upon presentation, we calculated a modified Pediatric Risk of Mortality IV score excluding PaO2 for each encounter, calibrated for institutional data. Logistic regression was used to determine whether hyperoxemia (PaO2 ≥ 300 torr [39.99 kPa]) in the 12 hours surrounding PICU admission was associated with in-hospital mortality. We reperformed our analysis using a cutoff for hyperoxemia obtained by comparisons of observed versus predicted mortality when encounters were classified by highest PaO2 in 50 torr (6.67 kPa) bins. Results are reported as adjusted odds ratios with 95% CIs. Of 23,719 encounters, 4,093 had a PaO2 recorded in the period -6 to +6 hours after admission. Two hundred seventy-four of 4,093 (6.7%) had in-hospital mortality. The prevalence of hyperoxemia increased with rising modified Pediatric Risk of Mortality IV and was not associated with mortality in multivariable models (adjusted odds ratio, 1.38; 95% CI, 0.98-1.93). When using a higher cutoff of hyperoxemia derived from comparison of observed versus predicted rates of mortality of greater than or equal to 550 torr (73.32 kPa), hyperoxemia was associated with mortality (adjusted odds ratio, 2.78; 95% CI, 2.54-3.05). CONCLUSIONS: A conventional threshold for hyperoxemia at presentation to the PICU was not associated with in-hospital mortality in a model using a calibrated acuity score. Extreme states of hyperoxemia (≥ 73.32 kPa) were significantly associated with in-hospital mortality. Prospective research is required to identify if hyperoxemia before and/or after PICU admission contributes to poor outcomes.

Host and Bacterial Markers that Differ in Children with Cystitis and Pyelonephritis.

OBJECTIVE: To determine whether treatment for urinary tract infections in children could be individualized using biomarkers for acute pyelonephritis. STUDY DESIGN: We enrolled 61 children with febrile urinary tract infections, collected blood and urine samples, and performed a renal scan within 2 weeks of diagnosis to identify those with pyelonephritis. Renal scans were interpreted centrally by 2 experts. We measured inflammatory proteins in blood and urine using LUMINEX or an enzyme-linked immunosorbent assay. We evaluated serum RNA expression using RNA sequencing in a subset of children. Finally, for children with Escherichia coli isolated from urine cultures, we performed a polymerase chain reaction for 4 previously identified virulence genes. RESULTS: Urinary markers that best differentiated pyelonephritis from cystitis included chemokine (C-X-C motif) ligand (CXCL)1, CXCL9, CXCL12, C-C motif chemokine ligand 2, INF γ, and IL-15. Serum procalcitonin was the best serum marker for pyelonephritis. Genes in the interferon-γ pathway were upregulated in serum of children with pyelonephritis. The presence of E coli virulence genes did not correlate with pyelonephritis. CONCLUSIONS: Immune response to pyelonephritis and cystitis differs quantitatively and qualitatively; this may be useful in differentiating these 2 conditions.

Rapid Stabilization of Immiscible Fluids using Nanostructured Interfaces via Surfactant Association.

Surfactant molecules have been extensively used as emulsifying agents to stabilize immiscible fluids. Droplet stability has been shown to be increased when ordered nanoscale phases form at the interface of the two fluids due to surfactant association. Here, we report on using mixtures of a cationic surfactant and long chained alkenes with polar head groups [e.g., cetylpyridinium chloride (CPCl) and oleic acid] to create an ordered nanoscale lamellar morphology at aqueous-oil interfaces. The self-assembled nanostructure at the liquid-liquid interface was characterized using small-angle x-ray scattering, and the mechanical properties were measured using interfacial rheology. We hypothesize that the resulting lamellar morphology at the liquid-liquid interface is driven by the change in critical packing parameter when the CPCl molecules are diluted by the presence of the long chain alkenes with polar head groups, which leads to a spherical micelle-to-lamellar phase transition. The work presented here has larger implications for using nanostructured interfacial material to separate different fluids in flowing conditions for biosystems and in 3D printing technology.