Use of Aminophylline to Reverse Acute Kidney Injury in Pediatric Critical Care Patients.

OBJECTIVE: Acute kidney injury (AKI) is a complication encountered in 18% to 51% of pediatric critical care patients admitted for treatment of other primary diagnoses and is an independent risk factor for increased morbidity and mortality. Aminophylline has shown promise as a medication to treat AKI, but published studies have shown conflicting results. Our study seeks to assess the reversal of AKI following the administration of aminophylline in critically ill pediatric patients. METHODS: We performed a single-institution retrospective chart review of pediatric inpatients who were diagnosed with AKI and subsequently treated with non-continuous dose aminophylline between January 2016 and December 2018. Data were collected beginning 2 days prior to the initial dose of aminophylline through completion of the 5-day aminophylline course. RESULTS: Nineteen therapies among 17 patients were included in analysis. Twelve of the therapies resulted in resolution of AKI during the study period. We observed urine output increase of 19% (p = 0.0063) on the day following initiation of aminophylline therapy in the subset of patients whose AKI resolved. Trends toward decreased serum creatinine and lower inotropic support were also noted. CONCLUSIONS: Based on these findings, aminophylline could be considered a potentially effective medication for use as rescue therapy in critically ill children with AKI. Limitations include small study population and retrospective nature. Further research in this area with a larger study population and a randomized control trial would allow for better characterization of the efficacy of aminophylline in reversal of AKI.

Analyzing Relationships Between Economic and Neighborhood-Related Social Determinants of Health and Intensive Care Unit Length of Stay for Critically Ill Children With Medical Complexity Presenting With Severe Sepsis.

Objectives: Of the Social Determinants of Health (SDoH), we evaluated socioeconomic and neighborhood-related factors which may affect children with medical complexity (CMC) admitted to a Pediatric Intensive Care Unit (PICU) in Shelby County, Tennessee with severe sepsis and their association with PICU length of stay (LOS). We hypothesized that census tract-level socioeconomic and neighborhood factors were associated with prolonged PICU LOS in CMC admitted with severe sepsis in the underserved community. Methods: This single-center retrospective observational study included CMC living in Shelby County, Tennessee admitted to the ICU with severe sepsis over an 18-month period. Severe sepsis CMC patients were identified using an existing algorithm incorporated into the electronic medical record at a freestanding children's hospital. SDoH information was collected and analyzed using patient records and publicly available census-tract level data, with ICU length of stay as the primary outcome. Results: 83 encounters representing 73 patients were included in the analysis. The median PICU LOS was 9.04 days (IQR 3.99-20.35). The population was 53% male with a median age of 4.1 years (IQR 1.96-12.02). There were 57 Black/African American patients (68.7%) and 85.5% had public insurance. Based on census tract-level data, about half (49.4%) of the CMC severe sepsis population lived in census tracts classified as suffering from high social vulnerability. There were no statistically significant relationships between any socioeconomic and neighborhood level factors and PICU LOS. Conclusion: Pediatric CMC severe sepsis patients admitted to the PICU do not have prolonged lengths of ICU stay related to socioeconomic and neighborhood-level SDoH at our center. A larger sample with the use of individual-level screening would need to be evaluated for associations between social determinants of health and PICU outcomes of these patients.

SMAD2 and SMAD3 differentially regulate adiposity and the growth of subcutaneous white adipose tissue.

Adipose tissue is the primary site of energy storage, playing important roles in health. While adipose research largely focuses on obesity, fat also has other critical functions, producing adipocytokines and contributing to normal nutrient metabolism, which in turn play important roles in satiety and total energy homeostasis. SMAD2/3 proteins are downstream mediators of activin signaling, which regulate critical preadipocyte and mature adipocyte functions. Smad2 global knockout mice exhibit embryonic lethality, whereas global loss of Smad3 protects mice against diet-induced obesity. The direct contributions of Smad2 and Smad3 in adipose tissues, however, are unknown. Here, we sought to determine the primary effects of adipocyte-selective reduction of Smad2 or Smad3 on diet-induced adiposity using Smad2 or Smad3 "floxed" mice intercrossed with Adiponectin-Cre mice. Additionally, we examined visceral and subcutaneous preadipocyte differentiation efficiency in vitro. Almost all wild type subcutaneous preadipocytes differentiated into mature adipocytes. In contrast, visceral preadipocytes differentiated poorly. Exogenous activin A suppressed differentiation of preadipocytes from both depots. Smad2 conditional knockout (Smad2cKO) mice did not exhibit significant effects on weight gain, irrespective of diet, whereas Smad3 conditional knockout (Smad3cKO) male mice displayed a trend of reduced body weight on high-fat diet. On both diets, Smad3cKO mice displayed an adipose depot-selective phenotype, with a significant reduction in subcutaneous fat mass but not visceral fat mass. Our data suggest that Smad3 is an important contributor to the maintenance of subcutaneous white adipose tissue in a sex-selective fashion. These findings have implications for understanding SMAD-mediated, depot selective regulation of adipocyte growth and differentiation.

The Early STEPS Pilot Study: The Impact of a Brief Consultation Session on Self-reported Parenting Satisfaction.

INTRODUCTION: Evidence-based parenting interventions can augment parental knowledge and skills to reduce parental stress and increase self-efficacy, leading to improved developmental outcomes for children. However, parenting interventions are often multi-session and require considerable time commitments from parents and primary care physicians. We conducted a pilot study to evaluate the effect of a brief consultation session on self-reported parental satisfaction and to assess the feasibility and effectiveness of incorporating occupational therapists (OTs) into a low-income urban pediatric primary care setting to conduct developmental screenings. METHODS: OTs conducted one 45-min consultation on positive parenting practices and promoting child development with parents in a pediatric primary care practice. A one group pretest-posttest design with 6-month follow-up was utilized. Participants included 55 families with 60 children, ages 2 to 65 months 30 days. The primary outcome measure was the change in Parenting Sense of Competence Scale (PSOC) scores from baseline to 6-month follow-up. Additional outcomes were screening results, referral numbers, and follow through in obtaining early intervention services. RESULTS: The paired difference between PSOC scores at baseline and 6 months indicated a significant increase in parenting satisfaction (p < 0.0001). Of 41 children referred, 26 were eligible and obtained services, 12 were lost to follow-up, and 3 did not qualify for services. DISCUSSION: Our preliminary findings suggest one consultation session on positive parenting practices and promoting child development may increase parenting satisfaction. Moreover, OTs can reduce the burden on primary care physicians by providing screenings, consultations, and follow-up. Further research is warranted to evaluate these findings.

Waitlist management in a pediatric weight management clinic: implementing an orientation session.

BACKGROUND: This study evaluates implementation of an orientation session to address a waitlist of more than 2000 referrals to a pediatric weight management clinic in the Mid-South United States. METHODS: An hour-long group-based orientation to the pediatric weight management clinic was implemented to provide information about the structure and expectations of the clinic as well as education on healthy lifestyle recommendations. Families were contacted from the waitlist by telephone and invited to attend an orientation session prior to scheduling a clinic appointment. RESULTS: Of 2251 patients contacted from the waitlist, 768 scheduled an orientation session, of which 264 (34 %) attended. Of the 264 orientation participants, 246 (93 %) scheduled a clinic appointment. Of those, 193 (79 %) completed a clinic visit. Waitlist times decreased from 297.8 ± 219.4 days prior to implementation of orientation sessions to 104.1 ± 219.4 days after. CONCLUSIONS: Orientation has been an effective and efficient way to triage patient referrals while maximizing attendance in limited clinic slots for patients and families demonstrating interest and motivation. Elements of this approach are likely generalizable to other pediatric clinical settings that must strategically manage a large volume of patient referrals.

Physiological Responses to Active Video Games Compared to Treadmill Walking and TV Watching in Obese Children and Adolescents.

The purpose of this study was to examine the physiological responses to playing different active video games (AVG), as well as document the activity level exerted during AVG in relation to treadmill walking (TM) and watching television (TV). 20 youth (age 11-17 yr) with obesity were recruited from the Healthy Lifestyle Clinic and underwent testing under six randomized conditions: 1) TM, 2) TV, 3) Fitnexx, 4) river rush (RRH), 5) reflex ridge (RFR), and 6) space pop (SP). RRH, RFR, and SP are active video games for the Xbox 360. Fitnexx is a prototype AVG. Each test lasted approximately ten minutes each with ten minutes between conditions and participants wore a wireless physiological monitor (Zephyr BioHarness™3) for all tests. Physical activity was assessed via accelerometer, along with heart rate (HR). Rating of Perceived Exertion (RPE) was also gathered for each condition. Repeated-measures ANOVA examined condition differences. Subjects were age 13.3 ± 2.1 years old with BMI 38.7 ± 7.9 (kg·m·s-2). Fitnexx had the highest activity level (0.63 ± 0.19g ~ jog), while activity levels for TM (0.20 ± 0.04g), RRH (0.29 ± 0.05g), RFR (0.31 ± 0.07g), and SP (0.21 ± 0.05g) were moderate (~walk), Ps < 0.05. Fitnexx had the highest HR (157 ± 13 bpm; Ps < 0.001), compared to TM (117 ± 18 bpm), RRH (128 ± 19 bpm), RFR (127 ± 18 bpm), and SP (122 ± 17 bpm), which were statistically similar. Rating of Perceived Exertion (RPE) was highest for Fitnexx (5 ± 4 RPE) compared to TM (2 ± 1 RPE) on 0-10 scale. TV had lowest activity, HR, and RPE (p < 0.04). Given these results, AVG can increase activity levels in youth with obesity and has potential as a therapeutic tool for obese children.

Particulate matter exposure predicts residence in high-risk areas for community acquired pneumonia among hospitalized children.

Particulate matter exposure is a risk factor for lower respiratory tract infection in children. Here, we investigated the geospatial patterns of community-acquired pneumonia and the impact of PM2.5 (particulate matter with an aerodynamic diameter ≤2.5 µm) on geospatial variability of pneumonia in children. We performed a retrospective analysis of prospectively collected population-based surveillance study data of community-acquired pneumonia hospitalizations among children <18 years residing in the Memphis metropolitan area, who were enrolled in the Centers for Disease Control and Prevention sponsored Etiology of Pneumonia in the Community (EPIC) study from January 2010 to June 2012. The outcome measure, residence in high- and low-risk areas for community-acquired pneumonia, was determined by calculating pneumonia incidence rates and performing cluster analysis to identify areas with higher/lower than expected rates of community-acquired pneumonia for the population at risk. High PM2.5 was defined as exposure to PM2.5 concentrations greater than the mean value (>10.75 µg/m3), and low PM2.5 is defined as exposure to PM2.5 concentrations less than or equal to the mean value (≤10.75 µg/m3). We also assessed the effects of age, sex, race/ethnicity, history of wheezing, insurance type, tobacco smoke exposure, bacterial etiology, and viral etiology of infection. Of 810 (96.1%) subjects with radiographic community-acquired pneumonia, who resided in the Memphis metropolitan area and had addresses which were successfully geocoded (Supplementary Figure F2), 220 (27.2%) patients were identified to be from high- (n = 126) or low-risk (n = 94) community-acquired pneumonia areas. Community-acquired pneumonia in Memphis metropolitan area had a non-homogenous geospatial pattern. PM2.5 was associated with residence in high-risk areas for community-acquired pneumonia. In addition, children with private insurance and bacterial, as opposed to viral, etiology of infection had a decreased risk of residence in a high-risk area for community-acquired pneumonia. The results from this paper suggest that environmental exposures as well as social risk factors are associated with childhood pneumonia.

Health-Related Quality of Life of Children with Congenital Adrenal Hyperplasia: A Mixed Methods Study.

PURPOSE: The purpose of this study was to examine the health-related quality of life (HRQOL) of female children with CAH as reported by children and their caregivers. DESIGN AND METHODS: A convergent mixed methods design was selected whereby quantitative and qualitative results were merged to provide a comprehensive understanding of HRQOL of children. Semi-structured interviews were conducted with 20 child-caregiver dyads. The full sample of child-caregiver dyads (N = 25) completed KINDL-R questionnaires, which provided a quantitative measure of children's HRQOL. RESULTS: Children and their caregivers reported good overall HRQOL. Children scored significantly lower on the KINDL-R School subscale compared to their caregivers. Associations were observed between the HRQOL score from one graphic rating scale item and the child's other health issues and child's diagnosis. Themes emerging from the child and caregiver interviews were health-related quality of life, impact of stigma on psychological well-being, information-sharing and disclosure of CAH, and improving the quality of life of children with CAH. CONCLUSION: This mixed methods study provided evidence to understand the health and complex needs of children with CAH. IMPLICATIONS: Clinicians may better support children and caregivers by expanding the focus beyond medication management to include: 1) psychological support and resources (i.e., developmentally appropriate coping and adaptation strategies); 2) continuous education for clinical staff, school nurses, emergency medical transport staff, and providers; and 3) public awareness beyond the clinic and hospital settings.

Predictors of an Extended Length of Stay following an Elective Craniotomy in Children and Young Adults.

BACKGROUND: Length of stay (LOS) is now a generally accepted clinical metric within the USA. An extended LOS following an elective craniotomy can significantly impact overall costs. Few studies have evaluated predictors of an extended LOS in pediatric neurosurgical patients. OBJECTIVE: The aim of the study was to determine predictors of an extended hospital LOS following an elective craniotomy in children and young adults. METHODS: All pediatric patients and young adults undergoing an elective craniotomy between January 1, 2010, and April 1, 2019, were retrospectively identified using a prospectively maintained database. Demographic, clinical, radiological, and surgical data were collected. The primary outcome was extended LOS, defined as a postsurgical stay greater than 7 days. Bivariate and multivariable analyses were performed. RESULTS: A total of 1,498 patients underwent 1,720 elective craniotomies during the study period over the course of 1,698 hospitalizations with a median LOS of 4 days (interquartile range 3-6 days). Of these encounters, 218 (12.8%) had a prolonged LOS. Multivariable analysis demonstrated that non-Caucasian race (OR = 1.9 [African American]; OR = 1.6 [other]), the presence of an existing shunt (OR = 1.8), the type of craniotomy (OR = 0.3 [vascular relative to Chiari]), and the presence of a postoperative complication (OR = 14.7) were associated with an extended LOS. CONCLUSIONS: Inherent and modifiable factors predict a hospital stay of more than a week in children and young adults undergoing an elective craniotomy.

Evaluation of Outcomes Before and After Implementation of a Standardized Postoperative Care Pathway in Pediatric Posterior Spinal Fusion Patients.

BACKGROUND: Standardized pathways decrease variability and improve outcomes and safety. PURPOSE: The article aims to evaluate outcomes of a standardized postoperative care pathway compared with individual surgeon preference. METHODS: A review of patients prestandardization and poststandardization was performed. Patients between the ages of 10-21 years with adolescent idiopathic scoliosis (ICD-9 code 737.30) admitted to the hospital for posterior spinal fusion (CPT code 22630) were included in the study. The prestandardization group (25 patients) was enrolled from April 1, 2010, through March 30, 2011, and the poststandardization group (25 patients) from April 1, 2014, to March 30, 2015. Exclusion criteria were renal disease, epilepsy, neurological disorder, or postoperative complications that led to change in routine care including ileus or fever greater than 102 °F. Data were analyzed using the Wilcoxon signed rank test, with significance set at p < .001. RESULTS: The length of stay (p = .0166), time to ambulation (p < .0001), patient-controlled analgesia use (p < .0001), and postoperative time to resumption of regular diet (p < .0001) were all significantly decreased in the poststandardization group. There were no complications or readmissions in either group. CONCLUSION: The standardized pathway resulted in shorter length of stay, decreased narcotic use, decreased time to regular diet, and decreased time to ambulation with no increase in complication rates.

Concordance Between Transcranial Magnetic Stimulation and Functional Magnetic Resonance Imaging (MRI) Derived Localization of Language in a Clinical Cohort.

Transcranial magnetic stimulation (TMS) is a newer noninvasive language mapping tool that is safe and well-tolerated by children. We examined the accuracy of TMS-derived language maps in a clinical cohort by comparing it against functional magnetic resonance imaging (MRI)-derived language map. The number of TMS-induced speech disruptions and the volume of activation during functional MRI tasks were localized to Brodmann areas for each modality in 40 patients with epilepsy or brain tumor. We examined the concordance between TMS- and functional MRI-derived language maps by deriving statistical performance metrics for TMS including sensitivity, specificity, accuracy, and diagnostic odds ratio. Brodmann areas 6, 44, and 9 in the frontal lobe and 22 and 40 in the temporal lobe were the most commonly identified language areas by both modalities. Overall accuracy of TMS compared to functional MRI in localizing language cortex was 71%, with a diagnostic odds ratio of 1.27 and higher sensitivity when identifying left hemisphere regions. TMS was more accurate in determining the dominant hemisphere for language with a diagnostic odds ratio of 6. This study is the first to examine the accuracy of the whole brain language map derived by TMS in the largest cohort examined to date. While this comparison against functional MRI confirmed that TMS reliably localizes cortical areas that are not essential for speech function, it demonstrated only slight concordance between TMS- and functional MRI-derived language areas. That the localization of specific language cortices by TMS demonstrated low accuracy reveals a potential need to use concordant tasks between the modalities and other avenues for further optimization of TMS parameters.

Factors Associated With Return Visits at 7 Days After Hospital Discharge.

OBJECTIVE: To identify variables associated with return visits to the hospital within 7 days after discharge. METHODS: We performed a retrospective study of 7-day revisits and readmissions between October 2012 and September 2015 using the Pediatric Health Information System database supplemented by electronic medical record data from a tertiary-care children's hospital. We examined factors associated with revisits among the top 10 most frequent indications for hospitalization using generalized estimating equations. RESULTS: There were 736 (4.2%) revisits and 416 (2.3%) readmissions within 7 days. Predictors of 7-day revisits and readmissions included age, length of hospital stay, and presence of a chronic medical condition. In addition, insurance status was associated with risk of revisits and race was associated with risk of readmissions in the bivariate analysis. CONCLUSIONS: In this study, we identified patient characteristics that may be associated with a higher risk of early return to the emergency department and/or readmissions. Early identification of this at-risk group of patients may provide opportunities for intervention and enhanced care coordination at discharge.

A hospital-based analysis of pseudomeningoceles after elective craniotomy in children: what predicts need for intervention?

OBJECTIVE: In pediatric patients, the development of a postoperative pseudomeningocele after an elective craniotomy is not unusual. Most will resolve with time, but some may require intervention. In this study, the authors analyzed patients who required intervention for a postoperative pseudomeningocele following an elective craniotomy or craniectomy and identified factors associated with the need for intervention. METHODS: An institutional operative database of elective craniotomies and craniectomies was queried to identify all surgeries associated with development of a postoperative pseudomeningocele from January 1, 2010, to December 31, 2017. Demographic and surgical data were collected, as were details regarding postoperative events and interventions during either the initial admission or upon readmission. A bivariate analysis was performed to compare patients who underwent observation with those who required intervention. RESULTS: Following 1648 elective craniotomies or craniectomies, 84 (5.1%) clinically significant pseudomeningoceles were identified in 82 unique patients. Of these, 58 (69%) of the pseudomeningoceles were diagnosed during the index admission (8 of which persisted and resulted in readmission), and 26 (31%) were diagnosed upon readmission. Forty-nine patients (59.8% of those with a pseudomeningocele) required one or more interventions, such as lumbar puncture(s), lumbar drain placement, wound exploration, or shunt placement or revision. Only race (p < 0.01) and duraplasty (p = 0.03, OR 3.0) were associated with the need for pseudomeningocele treatment. CONCLUSIONS: Clinically relevant pseudomeningoceles developed in 5% of patients undergoing an elective craniotomy, with 60% of these pseudomeningoceles needing some form of intervention. The need for intervention was associated with race and whether a duraplasty was performed.

Shunt Failure-The First 30 Days.

BACKGROUND: Incontrovertible predictors of shunt malfunction remain elusive. OBJECTIVE: To determine predictors of shunt failure within 30 d of index surgery. METHODS: This was a single-center retrospective cohort study from January 2010 through November 2016. Using a ventricular shunt surgery research database, clinical and procedural variables were procured. An "index surgery" was defined as implantation of a new shunt or revision or augmentation of an existing shunt system. The primary outcome was shunt failure of any kind within the first 30 days of index surgery. Bivariate models were created, followed by a final multivariable logistic regression model using a backward-forward selection procedure. RESULTS: Our dataset contained 655 unique patients with a total of 1206 operations. The median age for the cohort at the time of first shunt surgery was 4.6 yr (range, 0-28; first and third quartile, .37 and 11.8, respectively). The 30-day failure rates were 12.4% when analyzing the first-index operation only (81/655), and 15.7% when analyzing all-index operations (189/1206). Small or slit ventricles at the time of index surgery and prior ventricular shunt operations were found to be significant covariates in both the "first-index" (P < .01 and P = .05, respectively) and "all-index" (P = .02 and P < .01, respectively) multivariable models. Intraventricular hemorrhage at the time of index surgery was an additional predictor in the all-index model (P = .01). CONCLUSION: This study demonstrates that only 3 variables are predictive of 30-day shunt failure when following established variable selection procedures, 2 of which are potentially under direct control of the surgeon.

Psychosocial Functioning After One Year of Interdisciplinary Pediatric Weight Management.

Youth with obesity are more likely than normal-weight peers to experience psychosocial problems. Empirically-based recommendations for addressing pediatric obesity include intensive interdisciplinary weight management comprising medical, behavioral health, nutrition, and exercise components. The present study examined changes in psychosocial functioning associated with frequency of participation in an interdisciplinary pediatric weight management program. Participants were 86 patients (55.8% females; median age = 11.5 years; 67.4% Non-Hispanic Black; median BMI percentile = 99.5) enrolled in an interdisciplinary pediatric weight management program for at least one year. Psychosocial functioning was measured with the Pediatric Symptom Checklist (PSC-17), a caregiver-completed mental health screen that assesses internalizing, externalizing, and attention difficulties as well as global functioning. The PSC-17 was completed at the initial clinic visit (baseline) and repeated one-year later (annual). The Wilcoxon Signed Rank test indicated that annual PSC-17 scores were significantly lower than baseline scores across all domains. Spearman correlation coefficients revealed no significant association between total number of clinic visits and PSC-17 global or subscale scores. However, the number of visits for exercise-only sessions was significantly correlated with caregiver-reported improvement in internalizing behaviors. Findings suggest that participation in interdisciplinary pediatric weight management may improve psychosocial functioning in youth with obesity and that attending supervised exercise sessions may be especially beneficial for improving internalizing behavior symptoms.

Respiratory Syncytial Virus Disease Severity Is Associated with Distinct CD8+ T-Cell Profiles.

Rationale: Respiratory syncytial virus (RSV) causes significant morbidity and mortality in infants worldwide. Although T-helper type 2 (Th2) cell pathology is implicated in severe disease, the mechanisms underlying the development of immunopathology are incompletely understood.Objectives: We aimed to identify local immune responses associated with severe RSV in infants. Our hypothesis was that disease severity would correlate with enhanced Th2 cellular responses.Methods: Nasal aspirates were collected from infants hospitalized with severe (admitted to the pediatric ICU) or moderate (maintained in the general ward) RSV disease at 5 to 9 days after enrollment. The immune response was investigated by evaluating T-lymphocyte cellularity, cytokine concentration, and viral load.Measurements and Main Results: Patients with severe disease had increased proportions of CD8 (cluster of differentiation 8)-positive T cells expressing IL-4 (Tc2) and reduced proportions of CD8+ T cells expressing IFNγ (Tc1). Nasal aspirates from patients with severe disease had reduced concentrations of IL-17. Patients with greater frequencies of Tc1, CD8+ T cells expressing IL-17 (Tc17), and CD4+ T cells expressing IL-17 (Th17) had shorter durations of hospitalization.Conclusions: Severe RSV disease was associated with distinct T-cell profiles. Tc1, Tc17, and Th17 were associated with shorter hospital stay and may play a protective role, whereas Tc2 cells may play a previously underappreciated role in pathology.

Elevated Levels of Type 2 Respiratory Innate Lymphoid Cells in Human Infants with Severe Respiratory Syncytial Virus Bronchiolitis.

Rationale: Studies of the immune responses at the site of respiratory syncytial virus (RSV) infection are sparse despite nearly five decades of research into understanding RSV disease.Objectives: To investigate the role of mucosal innate immune responses to RSV and respiratory viral load in infants hospitalized with the natural disease.Methods: Cytokines, viral load, and type 2 innate lymphoid cell (ILC2) levels in nasal aspirates, collected within 24 hours of enrollment, from infants hospitalized with RSV infection were quantified.Measurements and Main Results: RSV severity in infants was categorized based on admission to the general ward (moderate) or the pediatric ICU (severe). Evaluable subjects included 30 patients with severe and 63 patients with moderate disease (median age, 74 d; range, 9-297 d). ILC2s were found in the nasal aspirates of patients with severe disease (0.051% of total respiratory CD45+ cells) to a significantly greater extent than in patients with moderate disease (0.018%, P = 0.004). Levels of IL-4, IL-13, IL-33, and IL-1ß were significantly higher in nasal aspirates of patients with severe disease compared with those of patients with moderate disease. Factors associated with disease severity were gestational age (odds ratio, 0.49; 95% confidence interval, 0.29-0.82; P = 0.007) and IL-4 (odds ratio, 9.67; 95% confidence interval, 2.45-38.15; P = 0.001).Conclusions: This study shows, for the first time, that elevated levels of ILC2s is associated with infant RSV severity. The findings highlight the dominance of type-2 responses to RSV infection in infants and suggest an important role of ILC2 in shaping the immune response early during RSV infection.

Peripheral venous hypertension in chronic venous disease.

BACKGROUND: Microvascular venous hypertension has emerged as a central feature of chronic venous disease (CVD). Yet, the incidence and severity of peripheral venous hypertension in the clinical setting have not been reported. This is an observational study of venous hypertension in the lower limb of a large cohort of patients with suspected CVD referred to a single referral center during a 16-year period. METHODS: Clinical and venous laboratory test data for 8868 limbs of 5792 patients with CVD symptoms seen from 1999 to 2015 were analyzed. Subset A limbs had a mix of obstruction/reflux or neither (n = 4132). These are limbs in which duplex ultrasound reflux (yes/no) status is known. The incidence and severity of obstruction in these limbs are unknown as tests of obstruction were not routinely performed. Subset B limbs had central obstruction (n = 159). These are limbs with intravascular ultrasound-proven stenosis in the iliac veins that was corrected by stent placement. Reflux was assessed by duplex ultrasound and air plethysmography (venous filling index [VFI90]). Pressure measurements included supine venous pressure, erect venous pressure, and ambulatory venous pressure (AMVP). Pressure measurements are categorized according to Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) clinical class, reflux and obstruction with Venn distributions of prevalence. RESULTS: All pressures (supine, erect, and ambulatory) trended worse in higher CEAP clinical classes. Supine foot venous pressures were elevated in 70% and 76% of subsets A and B, respectively. A positive association between elevated supine pressures and reflux could not be shown in this study. Supine foot venous pressure did not worsen with increasing reflux in the two subsets, but erect foot venous pressure did. Elevated supine pressures were associated with obstruction in subset B. AMVP worsened in most higher reflux categories. Ambulatory venous hypertension was dominantly associated (Venn distribution) with reflux, less commonly with obstruction. CONCLUSIONS: Supine venous hypertension is associated with obstruction and does not worsen with reflux. In contrast, erect foot venous pressure worsens in severe reflux categories. Ambulatory venous hypertension worsens in higher CEAP clinical classes. It worsens with increasing reflux. AMVP is dominantly associated (Venn distribution) with reflux, not obstruction.

Big Data Research in Pediatric Neurosurgery: Content, Statistical Output, and Bibliometric Analysis.

BACKGROUND/AIMS: We sought to describe pediatric "big data" publications since 2000, their statistical output, and clinical implications. METHODS: We searched 4 major North American neurosurgical journals for articles utilizing non-neurosurgery-specific databases for clinical pediatric neurosurgery research. Articles were analyzed for descriptive and statistical information. We analyzed effect sizes (ESs), confidence intervals (CIs), and p values for clinical relevance. A bibliometric analysis was performed using several key citation metrics. RESULTS: We identified 74 articles, which constituted 1.7% of all pediatric articles (n = 4,436) published, with an exponential increase after 2013 (53/74, 72%). The Healthcare Cost and Utilization Project (HCUP) databases were most frequently utilized (n = 33); hydrocephalus (n = 19) was the most common study topic. The statistical output (n = 49 studies with 464 ESs, 456 CIs, and 389 p values) demonstrated that the majority of the ESs (253/464, 55%) were categorized as small; half or more of the CI spread (CIS) values and p values were high (274/456, 60%) and very strong (195/389, 50%), respectively. Associations with a combination of medium-to-large ESs (i.e., magnitude of difference), medium-to-high CISs (i.e., precision), and strong-to-very strong p values comprised only 20% (75/381) of the reported ESs. The total number of citations for the 74 articles was 1,115 (range per article, 0-129), with the median number of citations per article being 8.5. Four studies had > 50 citations, and 2 of them had > 100 citations. The calculated h-index was 16, h-core citations were 718, the e-index was 21.5, and the Google i10-index was 34. CONCLUSIONS: There has been a dramatic increase in the use of "big data" in the pediatric neurosurgical literature. Reported associations that may, as a group, be of greatest interest to practitioners represented only 20% of the total output from these publications. Citations were weighted towards a few highly cited publications.

High acetylsalicylic acid dosing in infants after modified Blalock-Taussig shunt.

OBJECTIVE: Shunt-related adverse events are frequent in infants after modified Blalock-Taussig despite use of acetylsalicylic acid prophylaxis. A higher incidence of acetylsalicylic acid-resistance and sub-therapeutic acetylsalicylic acid levels has been reported in infants. We evaluated whether using high-dose acetylsalicylic acid can decrease shunt-related adverse events in infants after modified Blalock-Taussig. METHODS: In this single-centre retrospective cohort study, we included infants ⩽1-year-old who underwent modified Blalock-Taussig placement and received acetylsalicylic acid in the ICU. We defined acetylsalicylic acid treatment groups as standard dose (⩽7 mg/kg/day) and high dose (⩾8 mg/kg/day) based on the initiating dose. RESULTS: There were 34 infants in each group. Both groups were similar in age, gender, cardiac defect type, ICU length of stay, and time interval to second stage or definitive repair. Shunt interventions (18 versus 32%, p=0.16), shunt thrombosis (14 versus 17%, p=0.74), and mortality (9 versus 12%, p=0.65) were not significantly different between groups. On multiple logistic regression analysis, single-ventricle morphology (odds ratio 5.2, 95% confidence interval of 1.2-23, p=0.03) and post-operative red blood cells transfusion ⩾24 hours [odds ratio 15, confidence interval of (3-71), p<0.01] were associated with shunt-related adverse events. High-dose acetylsalicylic acid treatment [odds ratio 2.6, confidence interval of (0.7-10), p=0.16] was not associated with decrease in these events. CONCLUSIONS: High-dose acetylsalicylic acid may not be sufficient in reducing shunt-related adverse events in infants after modified Blalock-Taussig. Post-operative red blood cells transfusion may be a modifiable risk factor for these events. A randomised trial is needed to determine appropriate acetylsalicylic acid dosing in infants with modified Blalock-Taussig.