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Summary Background Vietnam has emerged as one of the world's leading success stories in responding to COVID-19. After a prolonged period of little to no transmission, there was an outbreak of unknown source in July, 2020, in the Da Nang region, but the outbreak was quickly suppressed. We aimed to use epidemiological, behavioural, demographic, and policy data from the COVID-19 outbreak in Da Nang to calibrate an agent-based model of COVID-19 transmission for Vietnam, and to estimate the risk of future outbreaks associated with reopening of international borders in the country. Methods For this modelling study, we used comprehensive data from June 15 to Oct 15, 2020, on testing, COVID-19 cases, and quarantine breaches within an agent-based model of SARS-CoV-2 transmission to model a COVID-19 outbreak in Da Nang in July, 2020. We applied this model to quantify the risk of future outbreaks in Vietnam in the 3 months after the reopening of international borders, under different behavioural scenarios, policy responses (ie, closure of workplaces and schools), and ongoing testing. Findings We estimated that the outbreak in Da Nang between July and August, 2020, resulted in substantial community transmission, and that higher levels of symptomatic testing could have mitigated this transmission. We estimated that the outbreak peaked on Aug 2, 2020, with an estimated 1060 active infections (95% projection interval 890–1280). If the population of Vietnam remains highly compliant with mask-wearing policies, our projections indicate that the epidemic would remain under control even if a small but steady flow of imported infections escaped quarantine into the community. However, if complacency increases and testing rates are relatively low (10% of symptomatic individuals are tested), the epidemic could rebound again, resulting in an estimated 2100 infections (95% projected interval 1050–3610) in 3 months. These outcomes could be mitigated if the behaviour of the general population responds dynamically to increases in locally acquired cases that exceed specific thresholds, but only if testing of symptomatic individuals is also increased. Interpretation The successful response to COVID-19 in Vietnam could be improved even further with higher levels of symptomatic testing. If the previous approaches are used in response to new COVID-19 outbreaks, epidemic control is possible even in the presence of low levels of imported cases. Funding Ministry of Science and Technology (Vietnam). Translation For the Vietnamese translation of the abstract see Supplementary Materials section.

Objectives To determine the feasibility of having caregivers assist in recognition of clinical deterioration in children hospitalized with febrile illness in a resource-limited setting. Design Single-center, prospective, interventional pilot study. Setting General pediatric wards at Kenyatta National Hospital, Nairobi, Kenya's largest public tertiary-care hospital. Patients Children hospitalized with acute febrile illness, accompanied by caregivers available at the bedside for 24 hours soon after hospital admission. Interventions Caregivers were trained to recognize signs of critical illness using the Family-Assisted Severe Febrile Illness Therapy tool, which quantifies patients' work of breathing, mental status, and perfusion, producing color-coded flags to signal illness severity. Caregivers' Family-Assisted Severe Febrile Illness Therapy assessments were compared with healthcare professional assessments and to established Pediatric Early Warning Scores (PEWS). An initial study stage was followed by refinement of training and a larger second stage with intervention/control arms. Measurements and main results A total of 107 patient/caregiver pairs were enrolled in the interventional arm; 106 caregivers underwent Family-Assisted Severe Febrile Illness Therapy training and were included in the analysis. Patient characteristics included median age 1.1 years (0.2-10 yr), 55 (52%) female, and diagnoses: pneumonia (64 [60%]), meningitis (38 [36%]), gastroenteritis (24 [23%]), and malaria (21 [20%]). Most caregivers had primary (34 [32%]) or secondary (53 [50%]) school education. Fourteen of 106 patients (13%) died during their stay, six within 2 days. Across all severity levels, caregiver Family-Assisted Severe Febrile Illness Therapy assessments matched professionals in 87% and 94% for stages 1 and 2, respectively. Caregiver Family-Assisted Severe Febrile Illness Therapy assessments had a moderate to strong correlation with coinciding Pediatric Early Warning Scores and were sensitive to life-threatening deterioration: for all six patients who died within 2 days of admission, caregiver assessment reached the highest alert level. Conclusions Caregiver involvement in recognition of critical illness in hospitalized children in low-resource settings may be feasible. This may facilitate earlier detection of clinical deterioration where staffing is severely limited by constrained resources. Further validation of the Family-Assisted Severe Febrile Illness Therapy tool is warranted, followed by its application in a larger multisite patient population to assess provider response and associated clinical outcomes.

BACKGROUND: In newborns with gastroschisis, both primary repair and delayed fascial closure with initial silo placement are considered safe with similar outcomes although cost differences have not been explored. METHODS: A retrospective review was performed of newborns admitted with gastroschisis at a single center from 2011–2016. Demographic, clinical, and cost data during the initial hospitalization were collected. Differences between procedure costs and clinical endpoints were analyzed using multivariable linear regression adjusting for prematurity, complicated gastroschisis, and performance of additional operations. RESULTS: 80 patients with gastroschisis met inclusion criteria. Rates of primary fascial, primary umbilical cord closure, and delayed closure were 14%, 65%, and 21%, respectively. Delayed closure was associated with an increase in total hospital costs by 57% compared to primary repair (p

Background Half of global child deaths occur in sub-Saharan Africa. Understanding child mortality patterns and risk factors will help inform interventions to reduce this heavy toll. The Nanoro Health and Demographic Surveillance System (HDSS), Burkina Faso was described previously, but patterns and potential drivers of heterogeneity in child mortality in the district had not been studied. Similar studies in other districts indicated proximity to health facilities as a risk factor, usually without distinction between facility types. Methods Using Nanoro HDSS data from 2009 to 2013, we estimated the association between under-5 mortality and proximity to inpatient and outpatient health facilities, seasonality of death, age group, and standard demographic risk factors. Results Living in homes 40–60 min and > 60 min travel time from an inpatient facility was associated with 1.52 (95% CI: 1.13–2.06) and 1.74 (95% CI: 1.27–2.40) greater hazard of under-5 mortality, respectively, than living in homes Conclusions Our results emphasize the importance of geographical proximity to health care, distinguish between inpatient and outpatient facilities, and also show a seasonal effect, probably driven by malaria.

Previous studies from low-resource countries have highlighted concerns surrounding non-specific effects of whole-cell pertussis vaccination, particularly in females. We sought to examine the effects of sex and birth weight on health services utilization following first exposure to whole-cell pertussis vaccine. Using a self-controlled case series design and by calculating relative incidence ratios (RIRs), we compared the relative incidence of emergency department visits and/or hospital admissions between sexes and between birth weight quintiles. Females had a higher relative incidence of events following vaccination compared to males (RIR = 1.13, 95% CI: 0.99, 1.30), which persisted after adjustment for birth weight (RIR = 1.12, 95% CI: 0.97, 1.28). We also observed a trend of increasing relative incidence of events over decreasing quintiles of birth weight; infants in the lowest quintile had a 26% higher relative event rate compared to the highest quintile, which was robust to adjustment for sex (Unadjusted RIR = 1.26, 95% CI: 1.01, 1.56; Adjusted RIR = 1.23, 95% CI: 0.99, 1.53). The risk of all-cause health services utilization immediately following vaccination, was elevated in female infants and infants having lower birth weight. Further study is warranted to determine if vaccine dosing should take infant weight into account.

Prader-Willi syndrome (PWS, OMIM # 176270) and Down syndrome (DS, OMIM #190685) are neurodevelopmental genetic disorders with higher rates of autism spectrum disorder (ASD). The Aberrant Behavior Checklist (ABC) is a caregiver rating scale that assesses maladaptive behaviors. Overlapping symptoms exist between PWS, DS, and ASD, including maladaptive behaviors. We aimed to evaluate ABC profiles between PWS, DS, and ASD alone (without known genetic syndrome). In addition, we hypothesized PWS and DS with a comorbid ASD positive screen or diagnosis would have similar ABC profiles to ASD alone. ABC data from the following cohorts were analyzed: PWS (Seattle Children's Hospital, n = 28, mean age = 12.8 ± 4.9 years; University of Florida, n = 35, mean age = 9.3 ± 7.1 years), DS (Johns Hopkins, n = 406, mean age = 8.1 ± 2.4 years), and ASD (University of Florida, n = 102, mean age = 10.8 ± 3.5 years). ASD alone had significantly higher ABC scores. Subgroups of PWS and DS with a comorbid ASD positive screen or diagnosis had similarities in scores with the ASD only group, with subscale patterns unique to each syndrome. The ABC indicated worse maladaptive behaviors in children with ASD, including those with genetic syndromes. Although more studies are needed to evaluate the utility and the accuracy of the ABC as a tool to screen for ASD in special populations, it may be a useful adjunct in screening those children with PWS or DS who need more in depth ASD evaluation.

BACKGROUND: The advent of regional multidisciplinary intestinal rehabilitation programs has been associated with improved survival in pediatric intestinal failure. Yet, the optimal timing of referral for intestinal rehabilitation remains unknown. We hypothesized that the degree of intestinal failure-associated liver disease (IFALD) at initiation of intestinal rehabilitation would be associated with overall outcome. METHODS: The multicenter, retrospective Pediatric Intestinal Failure Consortium (PIFCon) database was used to identify all subjects with baseline bilirubin data. Conjugated bilirubin (CBili) was used as a marker for IFALD, and we stratified baseline bilirubin values as CBili4 mg/dL. The association between baseline CBili and mortality was examined using Cox proportional hazards regression. RESULTS: Of 272 subjects in the database, 191 (70%) children had baseline bilirubin data collected. 38% and 28% of patients had CBili>4 mg/dL and CBili4 mg/dL, prematurity, race, and small bowel atresia. On regression analysis controlling for age, prematurity, and diagnosis, the risk of mortality was increased by 3-fold for baseline CBili 2–4 mg/dL (HR 3.25 [1.07 – 9.92], p=0.04) and 4-fold for baseline CBili>4 mg/dL (HR 4.24 [1.51–11.92], p=0.006). On secondary analysis, CBili>4 mg/dL at baseline was associated with a lower chance of attaining enteral autonomy. CONCLUSION: In children with intestinal failure treated at intestinal rehabilitation programs, more advanced IFALD at referral is associated with increased mortality and decreased prospect of attaining enteral autonomy. Early referral of children with intestinal failure to intestinal rehabilitation programs should be strongly encouraged.

OBJECTIVES Ventricular assist devices have gained popularity in the management of refractory heart failure in children listed for heart transplantation. Our primary aim was to compare the composite endpoint of all-cause pretransplant mortality and loss of transplant eligibility in children who were treated with a ventricular assist device versus a medically managed cohort. DESIGN This was a retrospective cohort analysis. SETTINGS Data were obtained from the Scientific Registry of Transplant Recipients. PATIENTS The at-risk population (n = 1,380) was less than 18 years old, either on a ventricular assist device (605 cases) or an equivalent-severity, intensively medically treated group (referred to as MED, 775 cases). INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The impact of ventricular assist devices was estimated via Cox proportional hazards regression (hazard ratio), dichotomizing 1-year outcomes to "poor" (22%: 193 deaths, 114 too sick) versus all others (940 successful transplants, 41 too healthy, 90 censored), while adjusting for conventional risk factors. Among children 0-12 months old, ventricular assist device was associated with a higher risk of poor outcomes (hazard ratio, 2.1; 95% CI, 1.5-3.0; p < 0.001). By contrast, ventricular assist device was associated with improved outcomes for ages 12-18 (hazard ratio, 0.3; 95% CI, 0.1-0.7; p = 0.003). For candidates 1-5 and 6-11 years old, there were no differences in outcomes between the ventricular assist device and MED groups (hazard ratio, 0.8 and 1.0, p = 0.43 and 0.9). The interaction between ventricular assist devices and age group was strongly significant (p < 0.001). CONCLUSIONS This is a comparative study of ventricular assist devices versus medical therapy in children. Age is a significant modulator of waitlist outcomes for children with end-stage heart failure supported by ventricular assist device, with the impact of ventricular assist devices being more beneficial in adolescents.

BACKGROUND: Erythropoietin stimulating agent hyporesponsiveness (ESAH) is associated with increased cardiovascular mortality in patients with end-stage renal disease (ESRD) on hemodialysis. Dynamic treatment Regimes (DTR), a type of clinical decision support (CDS) tool that guide the prescription of specific therapies in response to variations in patient states, have been used to guide treatment for chronic clinical problems that require frequent monitoring and therapy changes. Our objective is to explore the role of utilizing a DTR to reduce ESAH in pediatric hemodialysis patients. METHODS: Retrospective analysis of ESRD patients on hemodialysis who received ESAs. Dosing was adjusted using a locally developed protocol designed to target a hemoglobin between 10–12 g/dl. Analyzing this protocol as a DTR, we assessed adherence to the protocol over time measuring how the hypo-response index (ESA dose/hemoglobin value) changed due to varying levels of adherence. RESULTS: 18 patients met study criteria. Median hemoglobin was 11.4 g/dl (range: 6.1–15.4), and median weekly ESA dose (darbepoetin-equivalent) was 0.4 mcg/kg/dose (range: 0–2.1). Full adherence to the DTR was identified in 266 (71%) of the 4 week periods, with a median average adherence score of 0.80 (range: 0.63–0.91). As adherence to the DTR improved, ESAH decreased. During the last 12 weeks, 13 out of 18 patients had lower average ESA/hemoglobin ratio than the first 12 weeks. CONCLUSION: A DTR appears to be well-suited to the treatment of anemia in ESRD and reduces ESAH. Our work shows the potential of DTRs to drive the development and evaluation of clinical practice guidelines.

Background Image quality of high resolution chest computed tomographies (HRCTs) depends on adequate breath holds at end inspiration and end expiration. We hypothesized that implementation of spirometry-assisted breath holds in children undergoing HRCTs would improve image quality over that obtained with voluntary breath holds by decreasing motion artifact and atelectasis. Methods This is a retrospective case-control study of HRCTs obtained at a tertiary care children’s hospital before and after implementation of a spirometry-assisted CT protocol, in which children ≥8 years of age are first trained in supine slow vital capacity maneuvers and then repeat the maneuvers in the CT scanner, coached by a respiratory therapist. Spirometry-assisted CT scans (cases) were matched by age, gender and diagnosis (cystic fibrosis vs other) to CT scans obtained with voluntary breath holds in the 6 years before implementation of the spirometry assistance protocol (controls), and evaluated by 2 blinded pediatric radiologists. Results Among both cases and controls ( N = 50 each), 10 carried the diagnosis of cystic fibrosis and 40 had other diagnoses. Mean age was 12.9 years (range: 7.5-20.1) among cases and 13.0 (7.1-19.7) among controls. Mean (SD) inspiratory image density among cases was −852 (37) Hounsfield units (HU) and −828 (43) among controls ( p = 0.006). Mean (SD) expiratory image density was −629 (95) HU among cases and −688 (83) HU among controls ( p = 0.002). Mean (SD) change in image density between inspiratory and expiratory images was +222 (85) HU among cases and +140 (76) HU among controls ( p p = 0.39 by Fisher’s exact test), and on expiratory images in 20 cases and 18 controls ( p > 0.80). Atelectasis was present on inspiratory images in 8 cases and 9 controls and on expiratory images in 9 cases and 10 controls ( p > 0.80). Conclusions Spirometry-assisted CTs had a significantly greater difference in lung density between inspiratory and expiratory scans than those performed with voluntary breath holds, likely improving the ability to detect air trapping. No appreciable difference in image quality was detected for the presence of motion artifact or atelectasis.

Limited data exist on drug resistance and antiretroviral treatment (ART) outcomes in HIV-1-infected children in West Africa. We determined the prevalence of baseline resistance and correlates of virologic failure (VF) in a cohort of ART-naive HIV-1-infected children10 years of age initiating ART in Mali.Reverse transcriptase and protease genes were sequenced at baseline (before ART) and at 6 months. Resistance was defined according to the Stanford HIV Genotypic Resistance database. VF was defined as viral load ≥1000 copies/mL after 6 months of ART. Logistic regression was used to evaluate factors associated with VF or death1 month after enrollment. Post hoc, antiretroviral concentrations were assayed on baseline samples of participants with baseline resistance.One-hundred twenty children with a median age 2.6 years (interquartile range: 1.6-5.0) were included. Eighty-eight percent reported no prevention of mother-to-child transmission exposure. At baseline, 27 (23%), 4 (3%) and none had non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor or protease inhibitor resistance, respectively. Thirty-nine (33%) developed VF and 4 died1 month post-ART initiation. In multivariable analyses, poor adherence [odds ratio (OR): 6.1, P = 0.001], baseline NNRTI resistance among children receiving NNRTI-based ART (OR: 22.9, P0.001) and protease inhibitor-based ART initiation among children without baseline NNRTI resistance (OR: 5.8, P = 0.018) were significantly associated with VF/death. Ten (38%) with baseline resistance had detectable levels of nevirapine or efavirenz at baseline; 7 were currently breastfeeding, but only 2 reported maternal antiretroviral use.Baseline NNRTI resistance was common in children without reported NNRTI exposure and was associated with increased risk of treatment failure. Detectable NNRTI concentrations were present despite few reports of maternal/infant antiretroviral use.

The purpose of the project was to compare the temporal artery thermometer (TAT) to the digital probe thermometer readings at axillary or oral sites, to determine the relative precision and sensitivity of the three methods of thermometry, to compare their readings to core temperature when feasible, and to survey patient and family thermometer preferences.A randomized crossover design in a 70-bed surgical unit over eight months. Two sets of temperature measurements were obtained for each patient: TAT, axillary, oral (depending on patient ability) and a bladder temperature representing core body temperature (when available). Each method was used twice on each patient, to examine within-method precision. Following measurement, patients or caregivers provided their thermometer preference. For younger/nonverbal patients, a professional observer recorded a disruption score. N=298 patients were enrolled RESULTS: TAT was more precise than oral and axillary thermometers (p0.001 vs. axillary, p=0.001 vs. oral). TAT measurements were higher on average than axillary and oral, by 0.7°C and 0.6°C respectively (p0.001). TAT's disruption score for younger patients was 0.6 points lower on average than axillary (p0.001). 84% of patients and families who indicated a clear thermometry preference chose TAT. Only 3 patients had bladder-temperature devices, and therefore accuracy could not be analyzed.TAT is more precise, more fever sensitive, less disruptive to younger children, and more preferred by patients and families.TAT is an acceptable temperature measure that could be substituted for oral or axillary temperature in acute care pediatric settings.

Transitioning CD19-directed chimeric antigen receptor (CAR) T cells from early-phase trials in relapsed patients to a viable therapeutic approach with predictable efficacy and low toxicity for broad application among patients with high unmet need is currently complicated by product heterogeneity resulting from transduction of undefined T-cell mixtures, variability of transgene expression, and terminal differentiation of cells at the end of culture. A phase 1 trial of 45 children and young adults with relapsed or refractory B-lineage acute lymphoblastic leukemia was conducted using a CD19 CAR product of defined CD4/CD8 composition, uniform CAR expression, and limited effector differentiation. Products meeting all defined specifications occurred in 93% of enrolled patients. The maximum tolerated dose was 106 CAR T cells per kg, and there were no deaths or instances of cerebral edema attributable to product toxicity. The overall intent-to-treat minimal residual disease–negative (MRD−) remission rate for this phase 1 study was 89%. The MRD− remission rate was 93% in patients who received a CAR T-cell product and 100% in the subset of patients who received fludarabine and cyclophosphamide lymphodepletion. Twenty-three percent of patients developed reversible severe cytokine release syndrome and/or reversible severe neurotoxicity. These data demonstrate that manufacturing a defined-composition CD19 CAR T cell identifies an optimal cell dose with highly potent antitumor activity and a tolerable adverse effect profile in a cohort of patients with an otherwise poor prognosis. This trial was registered at www.clinicaltrials.gov as #NCT02028455.

Background Just-in-time (JIT) training refers to education occurring immediately prior to clinical encounters. An in situ JIT room in a pediatric emergency department (ED) was created for procedural education. Objective We examined trainee self-reported JIT room use, its impact on trainee self-perception of procedural competence/confidence, and the effect its usage has on the need for intervention by supervising physicians during procedures. Methods Cross-sectional survey study of a convenience sample of residents rotating through the ED and supervising pediatric emergency medicine physicians. Outcomes included JIT room use, trainee procedural confidence, and frequency of supervisor intervention during procedures. Results Thirty-one of 32 supervising physicians (97%) and 122 of 186 residents (66%) completed the survey, with 71% of trainees reporting improved confidence, and 68% reporting improved procedural skills (P Conclusions Use of the JIT room led to improved trainee confidence and supervisor reports of less procedural intervention. Although it carries financial and time costs, an in situ JIT room may be important for convenient JIT training.

OBJECTIVES Recent advances in medical and surgical management have led to improved long-term survival in children with intestinal failure. Yet, limited data exist on their neurodevelopmental and cognitive outcomes. The aim of the present study was to measure neurodevelopmental outcomes in children with intestinal failure. METHODS Children enrolled in a regional intestinal failure program underwent prospective neurodevelopmental and psychometric evaluation using a validated scoring tool. Cognitive impairment was defined as a mental developmental index

Objective To evaluate whether quantitative metrics of white matter fractional anisotropy (FA) and mean diffusivity (MD) were different in patients presenting to our clinic with persistent symptoms after a concussion. Design Matched control retrospective study. Setting Primary not-for-profit Institution. Patients Consecutive patients seen at a primary care institution's Sports Concussion Clinic for sport-related concussion that underwent diffusion tensor imaging. Interventions (Independent variables): Type of sports, days from Injury, number of symptoms, weeks out when Magnetic Resonance Imaging (MRI) ordered, history of psychological issues, length of symptoms, age, sex, MRI imaging data. Main outcome measure Difference in white matter FA and MD. Results Seventeen concussion patients, ages 9 and 17 (average = 12.5 years; median = 13 years, 11 males and 6 females), were matched with age and gender controls who had an MRI following a complaint of headache. Patients reported an average of 11.5 concussion symptoms, out of a total possible 22 and were seen at an average of 30 days post injury. No region met tract based spatial statistics criteria for significant differences between concussed and healthy control groups (all p > 0.05). Similarly, when comparing group averages from the atlas based regional summaries, no region met the 0.2 false discovery rate (FDR) threshold for significant differences (the smallest unadjusted p-values were 0.02 for MD and 0.14 for FA). Conclusions Our results did not show measurable diffusion tensor imaging (DTI) changes with standard clinical data acquisition and quantitative processing for the individual patient. At this time DTI should not be considered a technique that can diagnose concussion within an individual subject.

OBJECTIVES: To assess providers’ recommendations as to comfort care versus medical and surgical management in clinical scenarios of newborns with severe bowel loss and to assess how a variety of factors influence providers’ decision making. STUDY DESIGN: We conducted a survey of pediatric surgeons and neonatologists via the American Pediatric Surgical Association and American Academy of Pediatrics Section of Neonatal-Perinatal Medicine. We examined how respondents’ recommendations were affected by a variety of patient and provider factors. RESULTS: 288 neonatologists and 316 pediatric surgeons responded. Irrespective of remaining bowel length, comfort care was recommended by 73% of providers for a premature infant with necrotizing enterocolitis and 54% for a full-term infant with midgut volvulus. Presence of comorbidities and earlier gestational age increased the proportion of providers recommending comfort care. Neonatologists were more likely to recommend comfort care than surgeons across all scenarios (odds ratio 1.45–2.00, P < .05), and this difference was more pronounced with infants born closer to term. In making these recommendations, neonatologists placed more importance on neurodevelopmental outcomes (p90% in infants with intestinal failure, a majority of providers still recommend comfort care in infants with massive bowel loss. Significant differences were identified in clinical decision-making between surgeons and neonatologists. These data reinforce the need for targeted education on long-term outcomes in intestinal failure to neonatal and surgical providers.

Deposition of the complement split product C4d is a phenomenon studied extensively as a marker for complement activation in antibody-mediated transplant rejection. C4d also is observed in placental disease processes including spontaneous abortion, infarct, and villitis of unknown origins. Massive chronic intervillositis is a rare placental abnormality associated with increased risk of growth restriction, fetal death, and recurrent fetal loss. In this study, we evaluated C4d immunostaining in placentas with accumulation of intervillous monocytes with and without villitis. Archived placentas from Kosair Children's Hospital (Louisville, KY) and Seattle Children's Hospital (Seattle, WA) were selected and divided into 4 groups, 16 cases of intervillositis with complicated pregnancy, 15 cases of uncomplicated intervillositis, 20 cases of complicated villitis, and 13 cases of uncomplicated villitis, all with varying degrees of monocytic cells in the intervillous space. Representative specimen blocks were immunohistochemically stained for C4d. The percentage of positive staining of the microvillous surface of the syncytiotrophoblast was scored by five pathologists, and the following consensus score was determined: 0 = 0% to 5%; 1 = 5% to 25%; 2 = 25% to 75%; and 3 ≥ 75%. C4d immunostain localized to the microvillous border of syncytiotrophoblast in many of the placentas. C4d staining was more strongly associated with intervillositis than with villitis (odds ratio: 6.3; confidence interval: 2.1–18.7; P = 0.001).

Background: Air pollution is linked to low lung function and to respiratory events, yet little is known of associations with lung structure. Objectives: We examined associations of particulate matter (PM2.5, PM10) and nitrogen oxides (NOx) with percent emphysema-like lung on computed tomography (CT). Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) recruited participants (45–84 years of age) in six U.S. states. Percent emphysema was defined as lung regions < –910 Hounsfield Units on cardiac CT scans acquired following a highly standardized protocol. Spirometry was also conducted on a subset. Individual-level 1- and 20-year average air pollution exposures were estimated using spatiotemporal models that included cohort-specific measurements. Multivariable regression was conducted to adjust for traditional risk factors and study location. Results: Among 6,515 participants, we found evidence of an association between percent emphysema and long-term pollution concentrations in an analysis leveraging between-city exposure contrasts. Higher concentrations of PM2.5 (5 μg/m3) and NOx (25 ppb) over the previous year were associated with 0.6 (95% CI: 0.1, 1.2%) and 0.5 (95% CI: 0.1, 0.9%) higher average percent emphysema, respectively. However, after adjustment for study site the associations were –0.6% (95% CI: –1.5, 0.3%) for PM2.5 and –0.5% (95% CI: –1.1, 0.02%) for NOx. Lower lung function measures (FEV1 and FVC) were associated with higher PM2.5 and NOx levels in 3,791 participants before and after adjustment for study site, though most associations were not statistically significant. Conclusions: Associations between ambient air pollution and percentage of emphysema-like lung were inconclusive in this cross-sectional study, thus longitudinal analyses may better clarify these associations with percent emphysema. Citation: Adar SD, Kaufman JD, Diez-Roux AV, Hoffman EA, D’Souza J, Stukovsky KH, Rich SS, Rotter JI, Guo X, Raffel LJ, Sampson PD, Oron AP, Raghunathan T, Barr RG. 2015. Air pollution and percent emphysema identified by computed tomography in the Multi-Ethnic Study of Atherosclerosis. Environ Health Perspect 123:144–151; http://dx.doi.org/10.1289/ehp.1307951

Objective.The validity of our current definitions for clinically inactive disease (CID) in juvenile idiopathic arthritis (JIA) based on physical examination is challenged by the development of advanced musculoskeletal imaging tools. We aimed to prospectively determine the prevalence of abnormal ultrasound (US) findings in children with CID in JIA and their clinical significance.Methods.Children aged ≥ 4 years with CID and a history of arthritis from a single tertiary center were approached over 1 year. Standard US of knees, tibiotalar joints, subtalar joints, and wrists were performed at baseline and at a followup visit. US images were scored by 2 pediatric musculoskeletal radiologists.Results.Forty children with CID were enrolled and followed clinically. The median duration of inactive disease was 1 year. The most common International League of Associations for Rheumatology JIA categories were extended oligoarticular JIA (30%) and rheumatoid factor–negative polyarthritis (38%). At baseline, among a total of 289 joints scanned, 24 joints (8%) had at least 1 abnormal finding in 18 (45%) of 40 subjects. When evaluated at the individual joint level against flares identified during followup exams, these baseline US findings had a sensitivity of 15% and a positive predictive value of 12%. The predictive performance of the second US was even less.Conclusion.Our study demonstrates that nearly half of children with CID had abnormal US findings in 1 of 8 commonly affected joints. These findings did not correlate with subsequent clinical flares in up to 2 years of followup.

BACKGROUND Post-traumatic hydrocephalus (PTH) is a potentially treatable cause of poor recovery from traumatic brain injury (TBI) that remains poorly understood, particularly among children. OBJECTIVE To better understand the risk factors for pediatric PTH using a large, multi-institutional database. METHODS We conducted a retrospective cohort study using administrative data from 42 pediatric hospitals participating in the Pediatric Health Information System. All patients ≤21 yr surviving a hospitalization with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for TBI were identified. The primary outcome was PTH, defined by an ICD-9-CM procedure code for surgical management of hydrocephalus within 6 mo. Data were analyzed using multivariable logistic regression. RESULTS We identified 91 583 patients ≤21 yr with TBI, 846 of whom developed PTH. Odds of PTH were significantly higher in children

Background Pediatrics and pediatric nephrology lag behind adult medicine in producing randomized controlled trials (RCTs). Physician attitudes have been shown to play a significant role in RCT enrollment. Methods We surveyed members of the American Society of Pediatric Nephrology regarding beliefs about RCTs and factors influencing decisions to recommend RCT enrollment. Regression analyses were used to identify the effects of variables on an aggregate score summarizing attitudes toward RCTs. Results One hundred thirty replies were received. Sixty-six percent had enrolled patients in RCTs. Respondents in practice for more than 15 years were more likely to have recruited a patient to an RCT than those in practice for less than 5 years. Respondents were more willing to recommend RCT enrollment if the study was multicenter, patients were sicker or had a poorer prognosis, or if the parent or participant received a financial incentive versus the provider. In multiple regression analysis, history of enrolling patients in an RCT was the only significant predictor of higher aggregate RCT-friendly attitude. Conclusions Many pediatric nephrologists have never enrolled a patient in an RCT, particularly those in practice for less than 5 years. Respondents who have not enrolled patients in RCTs have a less RCT-friendly attitude. Provision of improved training and resources might increase participation of junior providers in RCTs.

BACKGROUND AND OBJECTIVES:Appendicitis guidelines recommend either narrower- or extended-spectrum antibiotics for treatment of complicated appendicitis. The goal of this study was to compare the effectiveness of extended-spectrum versus narrower-spectrum antibiotics for children with appendicitis.METHODS:We performed a retrospective cohort study of children aged 3 to 18 years discharged between 2011 and 2013 from 23 freestanding children’s hospitals with an appendicitis diagnosis and appendectomy performed. Subjects were classified as having complicated appendicitis if they had a postoperative length of stay ≥3 days, a central venous catheter placed, major or severe illness classification, or ICU admission. The exposure of interest was receipt of systemic extended-spectrum antibiotics (piperacillin ± tazobactam, ticarcillin ± clavulanate, ceftazidime, cefepime, or a carbapenem) on the day of appendectomy or the day after. The primary outcome was 30-day readmission for wound infection or repeat abdominal surgery. Multivariable logistic regression, propensity score weighting, and subgroup analyses were used to control for confounding by indication.RESULTS:Of 24 984 patients, 17 654 (70.7%) had uncomplicated appendicitis and 7330 (29.3%) had complicated appendicitis. Overall, 664 (2.7%) patients experienced the primary outcome, 1.1% among uncomplicated cases and 6.4% among complicated cases (P < .001). Extended-spectrum antibiotic exposure was significantly associated with the primary outcome in complicated (adjusted odds ratio, 1.43 [95% confidence interval, 1.06 to 1.93]), but not uncomplicated, (adjusted odds ratio, 1.32 [95% confidence interval, 0.88 to 1.98]) appendicitis. These odds ratios remained consistent across additional analyses.CONCLUSIONS:Extended-spectrum antibiotics seem to offer no advantage over narrower-spectrum agents for children with surgically managed acute uncomplicated or complicated appendicitis.

Importance Airway management in infants with Robin sequence is challenging. Objective upper airway measures associated with severe airway compromise requiring tracheotomy are needed to guide decision making. Objectives To define objective upper airway measures in infants with Robin sequence from craniofacial computed tomography (CT) and to identify those measures in Robin sequence associated with tracheotomy. Design, Setting, and Participants A cohort study (2003 to 2014, over 1-year follow-up) of 37 infants with Robin sequence evaluated for surgical management and 37 selected age- and sex-matched controls without a craniofacial condition conducted in a pediatric institution’s craniofacial center. Main Outcomes and Measures Define and compare CT-generated upper airway measures in these groups: infants with Robin sequence vs controls, and infants with Robin sequence with vs without tracheotomy. A negative difference signifies lower values for the Robin sequence and tracheotomy groups. Clinical data collected included age and height at time of CT scan, sex, tracheotomy presence, associated syndrome, and laboratory indicators of hypoventilation and hypoxemia. To evaluate interrater reliability, 2 raters performed each measurement in the Robin sequence group. Results In 74 infants, 17 of 28 measures were different between infants with Robin sequence and those in the control group. Tracheotomy was performed in 14 of 37 (38%) infants with Robin sequence. Infants with tracheotomy more commonly had associated syndromes (12 of 14 [86%] vs 11 of 23 [48%]) and a history of hypoventilation and hypoxemia (13 of 14 [93%] vs 15 of 23 [65%]). Five of the 11 measures associated with tracheotomy were reliable and simpler to measure with the following mean differences (95% CIs) between groups: tongue length, 0.87 (0.26 to 1.48); tongue position relative to palate, 0.83 (0.22 to 1.45); mandibular total length, −0.8 (−1.42 to −0.19); gonial angle, 0.71 (0.08 to 1.34); and inferior pogonial angle, 0.66 (0.02 to 1.29). Using a receiver operating characteristic analysis, a composite score of these 5 measures for predicting tracheotomy risk yielded an area under the curve of 0.83 and achieved 86% sensitivity and 74% specificity. Conclusions and Relevance Computed tomography measures quantifying tongue position and mandibular configuration can identify infants with Robin sequence, and importantly, differentiate those who have severe upper airway compromise requiring tracheotomy. Following validation, these measures can be used for objective upper airway assessment and for expediting clinical decision-making in these challenging cases for which no such tools currently exist.

OBJECTIVES:Among patients with food-related anaphylaxis, to describe trends in emergency and hospital care and determine the revisit rate.METHODS:This retrospective cohort study included children 6 months to 18 years of age with food-related anaphylaxis from 37 children’s hospitals between 2007 and 2012. Summary statistics and trends for patient characteristics were evaluated. Multivariable regression was used to identify predictors for hospital admission. Revisit rates to either the emergency department (ED) and/or inpatient unit were calculated.RESULTS:7303 patients were evaluated in the ED; 3652 (50%) were admitted to the hospital. Hospital admission rates varied widely (range, 20%–98%). Food-related anaphylaxis increased from 41 per 100 000 ED visits to 72 per 100 000 while hospital admission rates did not change. Males (odds ratio [OR], 1.2 [95% confidence interval (CI), 1.0–1.4]), patients CONCLUSIONS:The incidence of food-related anaphylaxis in pediatric EDs is increasing, but rates of hospital admission are stable. Hospital admission is common but widely variable. Further research is needed to identify optimal management practices for this potentially life-threatening problem.

Intestinal neuronal dysplasia type B (IND) denotes an increased proportion of hyperplastic submucosal ganglia, as resolved histochemically in 15-μm-thick frozen sections. IND has been reported proximal to the aganglionic segment in patients with Hirschsprung disease (HSCR) and is putatively associated with a higher rate of postsurgical dysmotility. We developed and validated histological criteria to diagnose IND-like submucosal ganglion cell hyperplasia (IND-SH) in paraffin sections and used the approach to study the incidence and clinical and/or genetic associations of IND-SH at the proximal margins of HSCR pull-through resection specimens. Full-circumference paraffin sections from the proximal margins of 64 HSCR colonic pull-through specimens and 24 autopsy controls were immunostained for neuron-specific Hu antigen, and nucleated ganglion cells in each submucosal ganglion were counted. In controls, an age-related decline in the relative abundance of “giant” ganglia (≥7 nucleated Hu-positive [Hu+] ganglion cells) was observed. A conservative diagnostic threshold for IND-SH (control mean ± 3× standard deviation) was derived from 15 controls less than 25 weeks of age. No control exceeded this threshold, whereas in the same age range, IND-SH was observed at the proximal margins in 15% (7 of 46) of HSCR resections, up to 15 cm proximal to the aganglionic segment. No significant correlation was observed between IND-SH and length of or distance from the aganglionic segment, sex, trisomy 21, RET or SEMA3C/D polymorphisms, or clinical outcome, but analysis of more patients, with better long-term follow-up will be required to clarify the significance of this histological phenotype.

Background. More than 80% of surgical inpatients at US children’s hospitals receive antibiotics, accounting for >40% of all inpatient pediatric antibiotic use. We aimed to examine the collective pool of all systemic antibiotics prescribed to children hospitalized for surgical conditions and identify common surgical conditions with highly variable and potentially unnecessary antibiotic use, because these conditions may represent antimicrobial stewardship priorities. Methods. We conducted a retrospective cross-sectional study of surgical inpatients discharged in 2012 at 37 freestanding children’s hospitals. We captured all systemic antibiotic use as days of therapy (DOT), and we reported surgical conditions by frequency and contribution to overall antibiotic use. We used multivariable logistic and Poisson regression with marginal standardization to estimate (1) the standardized proportion and (2) DOT of condition-specific targeted antibiotic use among top surgical condition patients. Results. Among 151 345 surgical inpatients, 82.9% received antimicrobials for a median 2 DOT per subject (interquartile range, 1–5; range, 1–958). The most commonly received antibiotics were cefazolin (16.7% of all DOT), vancomycin (12.5%), and piperacillin/tazobactam (6.9%). The top 10 conditions contributing most to antibiotic use accounted for 51.3% of all antibiotic use. Among these, adjusted use of postoperative and perioperative vancomycin varied across hospitals among craniotomy and cardiothoracic surgery subjects (all P < .001); adjusted use of broad-spectrum antipseudomonal agents varied across hospitals among gastrointestinal surgery subjects (all P< .001). Conclusions. Use of (1) vancomycin for pediatric cardiothoracic and neurosurgical patients and (2) broadspectrum antipseudomonal agents for gastrointestinal surgery patients represent potentially high-yield targets for stewardship efforts to reduce unnecessary antimicrobial use.

Gastroschisis is a newborn anomaly requiring emergent surgical intervention. We review our experience with gastroschisis to examine trends in contemporary surgical management.Infants who underwent initial surgical management of gastroschisis from 1996 to 2014 at a pediatric hospital were reviewed. Closure techniques included primary fascial repair using suture or sutureless umbilical closure, and staged repair using sutured or spring-loaded silo (SLS). Data were separated into 3 clinical eras: pre-SLS (1996 to 2004), SLS (2005 to 2008), and umbilical closure (2009 to 2014).In the pre-SLS era, 60% (34/57) of infants with gastroschisis underwent primary repair. With the advent of SLS, there was a decrease in primary repair (15%, 10/68, P.0001). Following introduction of sutureless umbilical closure, 61% (47/77) of infants have undergone primary repair. On multivariate regression, primary repair was associated with shorter intensive care unit stays (P .001) and time to initiate enteral nutrition (P.01).Following introduction of a less invasive technique for gastroschisis repair, most infants with gastroschisis were able to be repaired primarily. Primary repair should be considered in all babies with gastroschisis and favorable anatomy.

To examine the effects of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients.This was a double-blind, randomized controlled study of children undergoing dental procedures. Participants were randomly assigned to receive either Reiki therapy or the control therapy (sham Reiki) preoperatively. Postoperative pain scores, opioid requirements, and side effects were assessed. Family members were also asked about perioperative care satisfaction. Multiple linear regressions were used for analysis.Thirty-eight children participated. The blinding procedure was successful. No statistically significant difference was observed between groups on all outcome measures.Our study provides a successful example of a blinding procedure for Reiki therapy among children in the perioperative period. This study does not support the effectiveness of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients.

Traffic related air pollution (TRAP) has been associated with increased atherosclerosis, left ventricular mass, myocardial infarction; endothelial dysfunction may mediate these effects. In the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air), an interquartile (25th to 75th

Introduction: Multiply recurrent pre-B-cell ALL, and particularly relapse following allo-HSCT, has dismal outcomes due in large part to ineffectual therapies. The primary objectives of the Phase 1 portion of the PLAT-02 study (NCT02028455) were to determine the feasibility of manufacturing products of defined composition and transgene expression, the safety of the cryopreserved T cell product infusion, and to describe the full toxicity profile, including development of clinically significant GVHD in the post-allo-HSCT cohort. Methods: Subjects on the PLAT-02 study undergo apheresis, with their CD4 and CD8 T cell subsets prepared immunomagnetically. Following anti-CD3xCD28 bead stimulation, T cell lines are transduced with a SIN lentiviral vector that directs the co-expression of the FMC63scFv:IgG4hinge:CD28tm:4-1BB:ζ CAR and the selection/tracking/suicide construct EGFRt. Transduced cells are propagated using recombinant human cytokine cocktails to numbers suitable for clinical use over 10-22 days, during which time they are subjected to EGFRt immunomagnetic positive selection. Shortly following lymphodepleting chemotherapy, cryopreserved CD4/EGFRt+ and CD8/EGFRt+ T cell products are thawed and infused at the bedside such that patients receive a 1:1 ratio of EGFRt+ CD4 and CD8 T cells at the protocol-prescribed dose level. Results: 45 subjects have been enrolled and 43 have been treated from dose level 1 (5 x 105 CAR-T cells/kg) through 4 (10 x 106 CAR-T cells/kg). Therapeutic T cell products were released on all 45 enrolled subjects, with 1 subject requiring a second apheresis. Two subjects died of disease prior to their infusion. All 43 infused subjects received lymphodepletion chemotherapy prior to T cell infusion (cyclophosphamide, n=27; fludarabine/cyclophosphamide; n=14 cyclophosphamide/etoposide n=1; fludarabine n=1,). 91% (39/43) of subjects received infusions at the desired 1:1 CD4:CD8 ratio and their infusions were well tolerated with only 1 related AE >grade 2. 93% (40/43) of subjects had a documented MRD-negative CR within 21 days following CAR-T cell therapy. The 12 month event-free survival (EFS) is 50.8% (95% CI 36.6, 69.9) and 12 month OS is 69.5% (95% CI 55.8, 86.5). All responding subjects exhibited in vivo expansion of CAR-T cells. The % of CAR T cell expansion over time is not impacted by dose level or lymphodepletion but is impacted by disease burden (p=0.004) and total CD19 antigen burden (p=0.001) at the time of lymphodepletion. The median duration of functional CAR-T cell persistence as measured by ongoing B-cell aplasia (BCA) is impacted by the total CD19 antigen burden in the bone marrow at time of lymphodepletion (>15% vs Conclusions: Infusions of defined composition CD4:CD8 CD19 CAR/EGFRt+ T cells/kg produce high rates of MRD-negative CR in pediatric and young adult B-cell ALL patients. Based on intent to treat analyses without a proliferation screen, we have found it is feasible to generate CAR products from each of the enrolled subjects. Despite the high rates of MRD-negative CR, the durability of remission is highly influenced by the functional persistence of CAR-T cells. Strategies to enhance persistence are currently being investigated, including episodic antigen stimulation through subject derived tAPC engineered to express truncated CD19. Disclosures Gardner: Amgen: Honoraria. Li:Juno Therapeutics: Employment, Equity Ownership. Jensen:Juno Therapeutics, Inc: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Exposure to traffic-related air pollution is associated with risk of cardiovascular disease and mortality. We examined whether exposure to diesel exhaust increased blood pressure (BP) in human subjects. We analyzed data from 45 nonsmoking subjects, 18 to 49 years of age in double-blinded, crossover exposure studies, randomized to order. Each subject was exposed to diesel exhaust, maintained at 200 μg/m 3 of fine particulate matter, and filtered air for 120 minutes on days separated by ≥2 weeks. We measured BP pre-exposure, at 30-minute intervals during exposure, and 3, 5, 7, and 24 hours from exposure initiation and analyzed changes from pre-exposure values. Compared with filtered air, systolic BP increased at all of the points measured during and after diesel exhaust exposure; the mean effect peaked between 30 and 60 minutes after exposure initiation (3.8 mm Hg [95% CI: −0.4 to 8.0 mm Hg] and 5.1 mm Hg [95% CI: 0.7–9.5 mm Hg], respectively). Sex and metabolic syndrome did not modify this effect. Combining readings between 30 and 90 minutes, diesel exhaust exposure resulted in a 4.4-mm Hg increase in systolic BP, adjusted for participant characteristics and exposure perception (95% CI: 1.1–7.7 mm Hg; P =0.0009). There was no significant effect on heart rate or diastolic pressure. Diesel exhaust inhalation was associated with a rapid, measurable increase in systolic but not diastolic BP in young nonsmokers, independent of perception of exposure. This controlled trial in humans confirms findings from observational studies. The effect may be important on a population basis given the worldwide prevalence of exposure to traffic-related air pollution.

Introduction. ALL relapse following allogeneic HSCT has dismal outcomes due in large part to ineffective therapies. The primary objectives of the Phase 1 portion of this study, which is restricted to the subset of pediatric and young adult patients who relapse following HSCT, is to determine the feasibility of manufacturing products of defined composition and transgene expression, the safety of the cryopreserved T cell product infusion, and to describe the full toxicity profile, including development of clinically significant GVHD. Therapeutic responses are also tracked based on multiparameter flow and IgH deep sequencing. Methods. CD4 and CD8 T cell subsets are immunomagnetically isolated from apheresis products obtained from the research participant. Following anti-CD3xCD28 bead stimulation, T cell lines are transduced with a SIN lentiviral vector that directs the co-expression of the FMC63scFv:IgG4hinge: CD28tm:4-1BB:ζ CAR and the selection/tracking/suicide construct EGFRt. Transduced cells are propagated using recombinant human cytokines to numbers suitable for clinical use over 10-20 days during which time they are subjected to EGFRt immunomagnetic positive selection. Shortly following lymphodepleting chemotherapy, cryopreserved CD4/EGFRt+ and CD8/EGFRt+T cell products are thawed and infused at the bedside such that patients receive a 1:1 ratio of EGFRt+CD4 and CD8 T cells at the protocol prescribed dose level. Results. Six subjects (4m – 3 yr s/p HSCT) have been treated at dose level 1 (5 X 105 CAR T cells/kg); four were treated with active disease, and two were treated while MRD negative. All patients received lymphodepleting chemotherapy prior to T cell infusion. The infusions were well tolerated with only 1 AE > grade 2 (grade 3 anaphylaxis related to the DMSO). All five responding subjects exhibited in vivo expansion of CAR T cells (peak engraftment 13.4 - 93.6 % CAR+ T cells/circulating T cells occurring 8-14 days post infusion) that were predominantly CD8+. Subjects with higher disease burden had higher peak PB CAR T cell levels compared to those with MRD negative marrows (62.7% v 19.6%). Accumulation of CAR T cells in bone marrow and CSF was observed. Five of the six subjects obtained or maintained an MRD negative CR following CAR T cell therapy, while the subject who did not have a therapeutic response failed to have detectable cell product engraftment. Four of the five subjects who had engraftment of CAR T cells have ongoing persistence with accompanying B cell aplasia and leukemia control (35 days-5 months as of August 1, 2014). Only one subject required immunomodulatory treatment for sCRS (tocilizumab and dexamethasone), and that subject lost persistence at day +42. Of the 2 subjects with identified malignant IgH rearrangement, deep sequencing of bone marrow (BM) showed no evidence of the clone by day +21 and day +63, respectively. Each of the five responding subjects developed some degree of CRS with fever and hypotension as the hallmark symptoms (2/6 admitted to ICU). Three of these patients developed encephalopathy (2 grade 1 and 1 grade 4) that was fully reversible. One subject developed de novo grade 2 acute skin GVHD shortly following CAR T cell engraftment and CRS. Skin biopsy revealed that only 9% of skin localized T cells marked EGFRt+ while 79% of circulating T cells marked EGFRt+. This subject was treated with a 2 week course of 1 mg/kg of prednisone, followed by a rapid taper over a six week period and resolution of the GVHD, and has ongoing persistent CAR+T cells. Conclusions. Infusions of 5x105 defined composition CD4:CD8 CD19CAR/EGFRt+ T cells/kg have produced encouraging rates of MRD negative CRs in pediatric and young adults ALL patients who have suffered a postHSCT relapse. Based on intent to treat, we have found it is feasible to generate donor-derived products from each of the six enrolled patients. Expected toxicities include CRS with ~30% ICU admission rate and encephalopathy with severity ranging from mild to severe, but fully reversible. Although one patient developed acute GVHD post T cell therapy, our preliminary assessment suggests that CAR T cells were not mediators of this response. This study continues to accrue at increasing dose levels and updated results will be reported at the meeting. Disclosures Off Label Use: tociluzimab for treatment of cytokine release syndrome cetuximab for the ablation of T cells CAR T cells for the treatment of leukemia. Jensen:Juno: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.

Background Diesel exhaust (DE) exposures are very common, yet exposure-related symptoms haven’t been rigorously examined. Objective Describe symptomatic responses to freshly generated and diluted DE and filtered air (FA) in a controlled human exposure setting; assess whether such responses are altered by perception of exposure. Methods 43 subjects participated within three double-blind crossover experiments to order-randomized DE exposure levels (FA and DE calibrated at 100 and/or 200 micrograms/m3 particulate matter of diameter less than 2.5 microns), and completed questionnaires regarding symptoms and dose perception. Results For a given symptom cluster, the majority of those exposed to moderate concentrations of diesel exhaust do not report such symptoms. The most commonly reported symptom cluster was of the nose (29%). Blinding to exposure is generally effective. Perceived exposure, rather than true exposure, is the dominant modifier of symptom reporting. Conclusion Controlled human exposure to moderate-dose diesel exhaust is associated with a range of mild symptoms, though the majority of individuals will not experience any given symptom. Blinding to DE exposure is generally effective. Perceived DE exposure, rather than true DE exposure, is the dominant modifier of symptom reporting.

Post-hemorrhagic hydrocephalus (PHH) is a common complication of intraventricular hemorrhage (IVH) of prematurity, but the risk factors that predispose infants with IVH to PHH have not been fully elucidated.