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OBJECTIVES Healthcare utilization after bronchiolitis hospitalization is incompletely understood. We aimed to characterize readmissions and outpatient visits within 1 year after hospital discharge. METHODS Retrospective multicenter observational cohort study of children under 24-months old admitted with bronchiolitis between January 1, 2010 and December 12, 2019 to the Pediatric Health Information Systems database. A single-center nested subset using linked electronic health records allowed analysis of outpatient visits. RESULTS There were 308 306 admissions for bronchiolitis among 271 115 patients across 47 hospitals between 2010–2019. The percent of patients readmitted within 30 days after discharge was 6.0% (16 167 of 271 115), and 17.8% (48 332 of 271 115) of patients were readmitted within 1 year. 22.9% (16 919 of 74 001) of patients admitted to an ICU and 26.8% (7865 of 29 378) of patients undergoing mechanical ventilation were readmitted within 1 year. There were 1438 patients with outpatient healthcare data available. There were a median (interquartile range) of 9 (6–13) outpatient visits per patient within 1 year after discharge. Outpatient healthcare use increased for 4 months following bronchiolitis hospitalization compared with previously reported age-matched controls. Higher income, white race, commercial insurance, complex chronic conditions, ICU admission, and mechanical ventilation were associated with higher outpatient utilization. Higher quartiles of outpatient use were associated with readmission for bronchiolitis and all-cause readmissions. CONCLUSIONS Readmissions in the year after bronchiolitis hospitalization are common, and outpatient healthcare use is increased for 4 months following discharge. Prospective study is needed to track long-term outcomes of infants with bronchiolitis.

BACKGROUND During the coronavirus disease 2019 pandemic, many women physicians experienced increased caregiver responsibilities, potentially leading to worsened gender inequities. METHODS We surveyed faculty and trainees at a quaternary-care children’s hospital regarding work environment, household obligations, and academic productivity to examine differential effects on productivity by gender and parenting status. We used descriptive statistics for demographics and analyzed Likert-scale responses with χ2 or Fisher’s exact tests. We performed multivariable logistic regression to determine factors associated with self-reported academic productivity. We analyzed free-response comments using thematic analysis. RESULTS The August 2021 survey was completed by 366 respondents (65% women; 46% response rate). Women were significantly more likely to report decreased academic productivity than men (66% [146/222] vs 30% [38/129], P CONCLUSIONS The coronavirus disease 2019 pandemic has differentially impacted men and women physicians, with women physician parents more likely to report decreased academic productivity than men with children. Unreliable childcare was a significant contributor to this disparity. Institutions must prioritize initiatives to improve gender equity in medicine.

The objective of this study was to evaluate patient-specific factors associated with dexmedetomidine dose requirements during continuous infusion. A retrospective cross-sectional analysis of electronic health record-derived data spanning 10 years for patients admitted with a primary respiratory diagnosis at a quaternary children's hospital and who received a dexmedetomidine continuous infusion (n = 346 patients) was conducted. Penalized regression was used to select demographic, clinical, and medication characteristics associated with a median daily dexmedetomidine dose. Identified characteristics were included in multivariable linear regression models and sensitivity analyses. Critically ill children had a median hourly dexmedetomidine dose of 0.5 mcg/kg/h (range: 0.1–1.8), median daily dose of 6.7 mcg/kg/d (range: 0.9–38.4), and median infusion duration of 1.6 days (range: 0.25–5.0). Of 26 variables tested, 15 were selected in the final model with days of dexmedetomidine infusion (β: 1.9; 95% confidence interval [CI]: 1.6, 2.3), median daily morphine milligram equivalents dosing (mg/kg/d) (β: 0.3; 95% CI: 0.1, 0.5), median daily ketamine dosing (mg/kg/d) (β: 0.2; 95% CI: 0.1, 0.3), male sex (β: −1.1; 95% CI: −2.0, −0.2), and non-Black reported race (β: −1.2; 95% CI: −2.3, −0.08) significantly associated with median daily dexmedetomidine dose. Approximately 56% of dose variability was explained by the model. Readily obtainable information such as demographics, concomitant medications, and duration of infusion accounts for over half the variability in dexmedetomidine dosing. Identified factors, as well as additional environmental and genetic factors, warrant investigation in future studies to inform precision dosing strategies.

Key Points Question What factors are associated with increasing hospital costs for patients with bronchiolitis? Findings In this cross-sectional study of 385 883 bronchiolitis hospitalizations, children hospitalized in later years received more costly and intensive care without objective evidence of increasing severity of illness. Substantial changes in coding practices were observed, with an increasing proportion of patients diagnosed with respiratory failure between 2010 and 2019. Meaning This study suggests that future research on trends in bronchiolitis should account for changes in the patterns of diagnostic coding., Importance Increasing hospital costs for bronchiolitis have been associated with increasing patient complexity and mechanical ventilation. However, the associations of illness severity and diagnostic coding practices with bronchiolitis hospitalization costs have not been examined. Objective To investigate the association of patient complexity, illness severity, and diagnostic coding practices with bronchiolitis hospitalization costs. Design, Setting, and Participants This retrospective cross-sectional study included 385 883 infants aged 24 months or younger who were hospitalized with bronchiolitis at 39 hospitals in the Pediatric Health Information System database from January 1, 2010, to December 31, 2019. Exposure Hospitalization for bronchiolitis. Main Outcomes and Measures Inflation-adjusted standardized unit cost (expressed in dollar units) per hospitalization over time. A nested subgroup analysis was performed to further examine factors associated with changes in cost. Results A total of 385 883 bronchiolitis hospitalizations were studied; the patients had a mean (SD) age of 7.5 (6.4) months and included 227 309 of 385 883 boys (58.9%) and 253 870 of 385 883 publicly insured patients (65.8%). Among patients hospitalized with bronchiolitis, the median standardized unit cost per hospitalization increased significantly during the study period (from $5636 [95% CI, $5558-$5714] in 2010 to $6973 [95% CI, $6915-$7030] in 2019; P, This cross-sectional study of more than 385 000 children hospitalized with bronchiolitis investigates the association of the complexity of a patient’s condition, illness severity, and diagnostic coding practices with bronchiolitis hospitalization costs.

The COVID-19 pandemic has pushed medical educators and learners to adapt to virtual learning (VL) in an expedited manner. The effect of VL for critical care education has not yet been evaluated. In a quantitative analysis of survey data and attendance records, we sought to determine the association of VL with conference attendance and work-life balance. Attending physicians, fellows, and advanced practice providers (APP) at a pediatric critical care department at a quaternary children's hospital participated in the study. Attendance records were obtained before and after the adaption of a VL platform. In addition, an electronic, anonymous survey to evaluate current satisfaction and the strengths and weaknesses of VL as well as its impact on work-life balance was administered. In total, 31 learners (17 attending physicians, 13 fellows, and 1 APP) completed the survey. A total of 83.9% (26/31) of participants were satisfied, and 77.4% (24/31) found VL to be similar or more engaging than non-VL. However, 6.5% (2/31) of learners reported difficulty in using the new platform, 87% (27/31) of participants supported VL as an effective learning tool, and 83.3% (25/30) reported a positive impact on work-life balance. Additionally, median monthly conference attendance increased significantly from 85 to 114 attendees per month (p

OBJECTIVES: To determine the changes in ICU admissions, ventilatory support, length of stay, and cost for patients with bronchiolitis in the United States. METHODS: Retrospective cross-sectional study of the Pediatric Health Information Systems database. All patients age RESULTS: Of 203 859 admissions for bronchiolitis, 39 442 (19.3%) were admitted to an ICU, 6751 (3.3%) received IMV, and 9983 (4.9%) received NIV. ICU admissions for bronchiolitis doubled from 11.7% in 2010 to 24.5% in 2019 (P < .001 for trend), whereas ICU admissions for all children in Pediatric Health Information Systems CONCLUSIONS: The proportions of children with bronchiolitis admitted to an ICU and receiving NIV have substantially increased, whereas the proportion receiving IMV is unchanged over the past decade. Further study is needed to better understand the factors underlying these temporal patterns.

Introduction: Continuous renal replacement therapy (CRRT) has become a primary treatment of severe acute kidney injury in children admitted to the intensive care unit. CRRT “downtime” (when the circuit is not active) can represent a significant portion of the prescribed treatment time and adversely affects clearance. The objective of this study was to evaluate factors associated with CRRT “downtime” and to determine whether instituting a tandem therapeutic plasma exchange (TPE) protocol could significantly and robustly decrease circuit downtime in patients receiving both therapies. Methods: This is a retrospective cohort study of 116 patients undergoing CRRT in the pediatric, neonatal, or cardiac ICU at UPMC Children’s Hospital of Pittsburgh from January 2014 to July 2020. We performed multivariable logistic regression to determine factors associated with CRRT downtime. We instituted a tandem TPE protocol whereby TPE and CRRT could run in parallel without pausing CRRT in April 2018. We analyzed the effect of the protocol change by plotting downtime for patients undergoing CRRT and TPE on a run chart. The effect of initiating tandem TPE on downtime was assessed by special cause variation. Results: For 108/139 (77.7%) sessions with downtime data available, the median (IQR) percentage of downtime was 6.2% (1.7–12.7%). Multivariable logistic regression showed that TPE was significantly associated with CRRT downtime (p = 0.003), and that age, sex, race, catheter size, and anticoagulation were not. For patients undergoing TPE, the median (IQR) percentage of downtime was 14.7% (10.5–26%) and 3.4% (1.3–4.9%) before and after initiation of tandem TPE, respectively (p < 0.001). The difference in downtime percentage met criteria for special cause variation. Conclusions: Interruptions for TPE increase CRRT downtime. Tandem TPE significantly reduces CRRT downtime in patients undergoing both procedures concomitantly.

Renal damage is a progressive complication of sickle cell disease (SCD). Microalbuminuria is common in children with SCD, while a smaller number of children have more severe renal manifestations necessitating kidney biopsy. There is limited information on renal biopsy findings in children with SCD and subsequent management and outcome. This is a multicenter retrospective analysis of renal biopsy findings and clinical outcomes in children and adolescents with SCD. We included children and adolescents (age ≤ 20 years) with SCD who had a kidney biopsy performed at a pediatric nephrology unit. The clinical indication for biopsy, biopsy findings, subsequent treatments, and outcomes were analyzed. Thirty-six SCD patients (ages 4–19 years) were identified from 14 centers with a median follow-up of 2.6 years (0.4–10.4 years). The indications for biopsy were proteinuria (92%) and elevated creatinine (30%). All biopsies had abnormal findings, including mesangial hypercellularity (75%), focal segmental glomerulosclerosis (30%), membranoproliferative glomerulonephritis (16%), and thrombotic microangiopathy (2%). There was increased use of hydroxyurea, angiotensin-converting-enzyme inhibitors, and angiotensin receptor blockers following renal biopsy. At last follow-up, 3 patients were deceased, 2 developed insulin-dependent diabetes mellitus, 6 initiated chronic hemodialysis, 1 received a bone marrow transplant, and 1 received a kidney transplant. Renal biopsies, while not commonly performed in children with SCD, were universally abnormal. Outcomes were poor in this cohort of patients despite a variety of post-biopsy interventions. Effective early intervention to prevent chronic kidney disease (CKD) is needed to reduce morbidity and mortality in children with SCD.

Objective To identify trends in pediatric emergency department (ED) utilization following the COVID-19 pandemic. Methods We performed a cross-sectional study from 37 geographically diverse US children's hospitals. We included ED encounters between January 1, 2010 and December 31, 2020, transformed into time-series data. We constructed ensemble forecasting models of the most common presenting diagnoses and the most common diagnoses leading to admission, using data from 2010 through 2019. We then compared the most common presenting diagnoses and the most common diagnoses leading to admission in 2020 to the forecasts. Results 29,787,815 encounters were included, of which 1,913,085 (6.4%) occurred during 2020. ED encounters during 2020 were lower compared to prior years, with a 65.1% decrease in April relative to 2010–2019. In forecasting models, encounters for depression and diabetic ketoacidosis remained within the 95% confidence interval [CI]; fever, bronchiolitis, hyperbilirubinemia, skin/subcutaneous infections and seizures occurred within the 80–95% CI during the portions of 2020, and all other diagnoses (abdominal pain, otitis media, asthma, pneumonia, trauma, upper respiratory tract infections, and urinary tract infections) occurred below the predicted 95% CI. Conclusion Pediatric ED utilization has remained low following the COVID-19 pandemic, and below forecasted utilization for most diagnoses. Nearly all conditions demonstrated substantial declines below forecasted rates from the prior decade and which persisted through the end of the year. Some declines in non-communicable diseases may represent unmet healthcare needs among children. Further study is warranted to understand the impact of policies aimed at curbing pandemic disease on children.

Importance In early 2020, the United States declared a public health emergency in response to coronavirus disease 2019 (COVID-19) and implemented a variety of social distancing measures. The association between the COVID-19 pandemic and the number of pediatric admissions is unclear. Objective To determine the changes in patterns of pediatric admissions in 2020 compared with the prior decade. Design, Setting, and Participants This cross-sectional study included 49 US hospitals contributing to the Pediatric Health Information Systems database. Inpatient admissions were transformed into time-series data, and ensemble forecasting models were generated to analyze admissions across a range of diagnoses in 2020 compared with previous years. The setting was inpatient admissions. All patients discharged between January 1, 2010, and June 30, 2020, from an inpatient hospital encounter were included. Main Outcomes and Measures Number of hospital admissions by primary diagnosis for each encounter. Results Of 5 424 688 inpatient encounters among 3 372 839 patients (median [interquartile range] age, 5.1 [0.7-13.3] years; 2 823 748 [52.1%] boys; 3 171 224 [58.5%] White individuals) at 49 hospitals, 213 571 (3.9%) were between January 1, 2020, and June 30, 2020. There was a decrease in the number of admissions beginning in March 2020 compared with the period from 2010 to 2019. At the nadir, admissions in April 2020 were reduced 45.4% compared with prior years (23 798 in April 2020 compared with a median [interquartile range] of 43 550 [42 110-43 946] in April 2010-2019). Inflation-adjusted hospital charges decreased 27.7% in the second quarter of 2020 compared with prior years ($4 327 580 511 in 2020 compared with a median [interquartile range] of $5 983 142 102 [$5 762 690 022-$6 324 978 456] in 2010-2019). Seasonal patterns were evident between 2010 and 2019 for a variety of common pediatric conditions, including asthma, atrial septal defects, bronchiolitis, diabetic ketoacidosis, Kawasaki syndrome, mental health admissions, and trauma. Ensemble models were able to discern seasonal patterns in admission diagnoses and accurately predicted admission rates from July 2019 until December 2019 but not from January 2020 to June 2020. All diagnoses except for birth decreased below the model 95% CIs between January 2020 and June 2020. Conclusions and Relevance In this cross-sectional study, pediatric admissions to US hospitals decreased in 2020 across an array of pediatric conditions. Although some conditions may have decreased in incidence, others may represent unmet needs in pediatric care during the COVID-19 pandemic.

A relationship between Pao2 and mortality has previously been observed in single-center studies. We performed a retrospective cohort study of the Pediatric Health Information System plus database including patients less than or equal to 21 years old admitted to a medical or cardiac ICU who received invasive ventilation within 72 hours of admission. We trained and validated a multivariable logistic regression mortality prediction model with very good discrimination (C-statistic, 0.86; 95% CI, 0.79-0.92; area under the precision-recall curve, 0.39) and acceptable calibration (standardized mortality ratio, 0.96; 95% CI, 0.75-1.23; calibration belt p = 0.07). Maximum Pao2 measurements demonstrated a parabolic ("U-shaped") relationship with PICU mortality (Box-Tidwell p < 0.01). Maximum Pao2 was a statistically significant predictor of risk-adjusted mortality (standardized odds ratio, 1.27; 95% CI, 1.23-1.32; p < 0.001). This analysis is the first multicenter pediatric study to identify a relationship between the extremes in Pao2 values and PICU mortality. Clinicians should remain judicious in the use of oxygen when caring for children.

Context: While uncommon, spinal cord injuries most frequently occur in adolescent and young adult males. Established treatment options are limited and focused on supportive care. Therapeutic systemic hypothermia is an emerging experimental treatment currently undergoing clinical trials in adults. Findings: Here we report a case of a 13-year-old male with an American Spinal Injury Association Impairment Scale grade C traumatic cervical spinal cord injury treated with 48 hours of therapeutic systemic hypothermia who made a complete neurological recovery. To our knowledge, this is the youngest such case report. Clinical relevance: This case suggests that consideration should be given to including pediatric patients in future clinical trials of therapeutic hypothermia for spinal cord injury.

BACKGROUND AND OBJECTIVES: Steroid resistant nephrotic syndrome (SRNS) due to focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is a leading cause of end stage kidney disease in children. Recurrence of primary disease following transplantation is a major cause of allograft loss. The clinical determinants of disease recurrence are not completely known. Our objectives were to determine risk factors for recurrence of FSGS/MCD following kidney transplantation, and factors that predict response to immunosuppression following recurrence. STUDY DESIGN: Multicenter study of pediatric patients with kidney transplants performed for ESKD due to SRNS between 1/2006–12/2015. Demographics, clinical course, and biopsy data were collected. Patients with primary-SRNS (PSRNS) were defined as those initially resistant to corticosteroid therapy at diagnosis, and patients with late-SRNS (LSRNS) as those initially responsive to steroids who subsequently developed steroid resistance. We performed logistic regression to determine risk factors associated with nephrotic syndrome (NS) recurrence. RESULTS: We analyzed 158 patients; 64 (41%) had recurrence of NS in their renal allograft. Disease recurrence occurred in 78% of patients with LSRNS compared to 39% of those with PSRNS. Patients with MCD on initial native kidney biopsy had a 76% recurrence rate compared with a 40% recurrence rate in those with FSGS. Multivariable analysis showed that MCD histology (OR; 95% CI: 5.6; 1.3–23.7) compared to FSGS predicted disease recurrence. CONCLUSIONS: Pediatric patients with MCD and LSRNS are at higher risk of disease recurrence following kidney transplantation. These findings may be useful for designing studies to test strategies for preventing recurrence.

Supplemental Digital Content is available in the text., Introduction: The Centers for Disease Control and Prevention recommends tracking risk-adjusted antimicrobial prescribing. Prior studies have used prescribing variation to drive quality improvement initiatives without adjusting for severity of illness. The present study aimed to determine the relationship between antimicrobial prescribing and risk-adjusted ICU mortality in the Pediatric Health Information Systems (PHIS) database, assessed by IBM-Watson risk of mortality. A nested analysis sought to assess an alternative risk model incorporating laboratory data from federated electronic health records. Methods: Retrospective cohort study of pediatric ICU patients in PHIS between 1/1/2010 and 12/31/2019, excluding patients admitted to a neonatal ICU, and a nested study of PHIS+ from 1/1/2010 to 12/31/2012. Hospital antimicrobial prescription volumes were assessed for association with risk-adjusted mortality. Results: The cohort included 953,821 ICU encounters (23,851 [2.7%] nonsurvivors). There was 4-fold center-level variability in antimicrobial use. ICU antimicrobial use was not correlated with risk-adjusted mortality assessed using IBM-Watson. A risk model incorporating laboratory data available in PHIS+ significantly outperformed IBM-Watson (c-statistic 0.940 [95% confidence interval 0.933–0.947] versus 0.891 [0.881–0.901]; P < 0.001, area under the precision recall curve 0.561 versus 0.297). Risk-adjusted mortality was inversely associated with antimicrobial prescribing in this smaller cohort using both the PHIS+ and Watson models (P = 0.05 and P < 0.01, respectively). Conclusions: Antimicrobial prescribing among pediatric ICUs in the PHIS database is variable and not associated with risk-adjusted mortality as assessed by IBM-Watson. Expanding existing administrative databases to include laboratory data can achieve more meaningful insights when assessing multicenter antibiotic prescribing practices.

Objectives To assess the frequency, yield, and cost of echocardiograms meeting “rarely appropriate” criteria. Study design Retrospective, single-center study of pediatric patients presenting with syncope. Patients were categorized according to the appropriate use criteria and based upon location of care (emergency department only, primary care setting only, or referred to a pediatric cardiologist). Multivariable regression was used to determine factors associated with performance of a “rarely appropriate” echocardiogram. Costs were calculated using fair market values from the Healthcare Bluebook. Results The cohort included 637 patients presenting with syncope during the 1-year study. Echocardiograms were ordered for 127 of 637 (20.1%) including 0 of 328 emergency department patients, 1 of 66 (1.5%) primary care setting patients, and 127 of 243 (52.3%) patients evaluated by a pediatric cardiologist. Use of echocardiography by pediatric cardiologists was categorized as “appropriate” in 92 of 127 (72.4%), “maybe appropriate” in 6 of 127 (4.7%), and “rarely appropriate” in 29 of 127 (22.8%). Abnormal findings were seen in 6 of 127 (4.7%) echocardiograms but in none of the “rarely appropriate” studies. In multivariable analysis, female sex and younger age were the only factors associated with performance of a “rarely appropriate” echocardiogram. “Rarely appropriate” echocardiograms cost an estimated $16 704.00 ($576.00 per patient) in the 1-year study. Conclusions “Rarely appropriate” echocardiograms performed for syncope do not contribute management changing diagnostic information. However, they burden patients with additional cost and perhaps contribute to increased need for follow-up.

OBJECTIVE: Mechanical ventilation of patients with ARDS should balance lung and diaphragm protective principles, which may be difficult to achieve in routine clinical practice. Through a Phase I clinical trial, we sought to determine whether a computerized decision support (CDS) based protocol (Real-time Effort Driven ventilator management (REDvent)) is feasible to implement, results in improved acceptance for lung and diaphragm protective ventilation and improves clinical outcomes over historical controls. DESIGN: Interventional non-blinded pilot study SETTING: Pediatric Intensive Care Unit PATIENTS: Mechanically ventilated children with ARDS INTERVENTIONS: A CDS tool was tested which prioritized lung protective management of ΔP (PIP-PEEP), PEEP/FiO(2), and ventilator rate. Esophageal manometry was used to maintain patient effort in a physiologic range. Protocol acceptance was reported, and enrolled patients were matched 4:1 with respect to age, initial OI, and percentage of immune compromise to historical control patients for outcome analysis. MEASUREMENTS AND MAIN RESULTS: Thirty-two patients were included. Acceptance of protocol recommendations was over 75%. 128 matched historical controls were used for analysis. Compared to historical controls, patients treated with REDvent received lower ΔP and V(T), and higher PEEP when FiO(2) was > 0.60. REDvent was associated with 6 more ventilator free days, shorter duration until the first spontaneous breathing trial and 3 fewer days on MV amongst survivors (all p = < 0.05) in comparison to historical controls, while maintaining no difference in the rate of reintubation. CONCLUSIONS: A CDS based protocol prioritizing lung protective ventilation balanced with reduction of controlled ventilation to maintain physiologic levels of patient effort can be implemented and may be associated with shorter duration of ventilation.

Background The Accreditation Council for Graduate Medical Education (ACGME) Clinical Learning Environment Review (CLER) program focuses on aspects of the graduate medical education learning environment, such as patient safety. Data from CLER site visits reveal that many resident physicians do not receive adequate training on patient safety. Objective We evaluated a pediatric resident-led safety council as a method to meet CLER Pathways to Excellence patient safety objectives. Methods The Duke Pediatric Residency Safety Council (PRSC) created an infrastructure for residents to participate in department safety efforts, review safety events, and act as leaders for safety initiatives. Annual surveys were distributed to graduate medical education trainees through the institution's patient safety center and the PRSC. Survey results of safety attitudes were compared over time within the pediatrics program and between pediatrics and nonpediatrics trainees at the institution. Resident-submitted safety reports were tracked through an institutional safety event repository. Results From 2013 to 2017, the percentage of residents who strongly agreed that they could submit a safety report doubled (from 35% [6 of 17] to 73% [22 of 30], P = .011). The average number of safety reports submitted by a pediatrics resident per year did not significantly change during this period (from 3.0 to 3.8, P = .11). In 2017, 90% of pediatrics residents (27 of 30) agreed or strongly agreed that their concerns would be addressed if they entered a safety report. Conclusions The council addressed 5 of the 7 CLER Pathways to Excellence in patient safety.

Adolescence is a time of exploration, biochemical and immunological transformation, emotional lability, and transition from childhood to adulthood. During this time, adolescent transplant recipients are vulnerable to poor kidney outcomes including the development of acute and chronic transplant rejection. This chapter will focus on the unique challenges that clinicians face when treating adolescent transplant recipients with particular attention to mechanism, diagnosis, and treatment of acute and chronic kidney transplant rejection.

Exposure to arsenic is a global health concern. We previously documented an inhibitory effect of inorganic Arsenite on IgE-mediated degranulation of RBL-2H3 mast cells (Hutchinson et al., 2011; J. Appl. Toxicol. 31: 231-241). Mast cells are tissue-resident cells that are positioned at the host-environment interface, thereby serving vital roles in many physiological processes and disease states, in addition to their well-known roles in allergy and asthma. Upon activation, mast cells secrete several mediators from cytoplasmic granules, in degranulation. The present study is an investigation of Arsenite's molecular target(s) in the degranulation pathway. Here, we report that arsenic does not affect degranulation stimulated by either the Ca(2) (+) ionophore A23187 or thapsigargin, which both bypass early signaling events. Arsenic also does not alter degranulation initiated by another non-IgE-mediated mast cell stimulant, the G-protein activator compound 48/80. However, arsenic inhibits Ca(2) (+) influx into antigen-activated mast cells. These results indicate that the target of arsenic in the degranulation pathway is upstream of the Ca(2) (+) influx. Phospho-Syk and phospho-p85 phosphoinositide 3-kinase enzyme-linked immunosorbent assays data show that arsenic inhibits early phosphorylation events. Taken together, this evidence indicates that the mechanism underlying arsenic inhibition of mast cell degranulation occurs at the early tyrosine phosphorylation steps in the degranulation pathway. Copyright © 2016 John Wiley & Sons, Ltd.

1. Jonathan Pelletier, MD* 2. Rasheed Gbadegesin, MD, MBBS† 3. Betty Staples, MD* 1. *Department of Pediatrics and 2. †Department of Pediatric Nephrology, Duke Children's Hospital and Health Center, Durham, NC 1. 1. Reddy P Clinical Approach to Renal Tubular Acidosis in Adult Patients. Reddy P Int J Clin Pract. 2011;65(3):350–360 [OpenUrl][1][CrossRef][2][PubMed][3] 2. 1. Batlle D, 2. Haque SK Genetic Causes and Mechanisms of Distal Renal Tubular Acidosis. Batlle D, Haque SK. Nephrol Dial Transplant. 2012;27(10):3691–3704 [OpenUrl][4][CrossRef][5][PubMed][6][Web of Science][7] 3. 1. Karet FE Mechanisms in Hyperkalemic Renal Tubular Acidosis. Karet FE. J Am Soc Nephrol. 2009;20(2):251–254 [OpenUrl][8][Abstract/FREE Full Text][9] 4. 1. Haque SK, 2. Ariceta G, 3. Batlle D Proximal Renal Tubular Acidosis: A Not So Rare Disorder of Multiple Etiologies. Haque SK, Ariceta G, Batlle D Nephrol Dial Transplant. 2012;27(12):4273–4287 [OpenUrl][10][CrossRef][11][PubMed][12][Web of Science][13] 5. 1. Gbadegesin R, 2. Foreman W 1. Chand DH, 2. Valentini RP Renal Tubular Acidosis. Gbadegesin R, Foreman W In: Chand DH, Valentini RP, eds. Clinician's Manual of Pediatric Nephrology. 1st ed. Singapore: World Scientific Publishing Co; 2011 The body temporarily buffers hydrogen ions (H+) with plasma proteins, hemoglobin, and bicarbonate (HCO3−), but H+ must be excreted to prevent acidosis. The major functions of the kidneys in acid-base homeostasis are to excrete H+ and reabsorb HCO3−. Failure to perform these functions results in HCO3− wasting, leading to renal tubular acidosis (RTA), which is categorized into 3 major groups: distal (type I), proximal (type II), and hyperkalemic (type IV) RTA. Excretion of H+ to balance acid production is primarily the function of the distal convoluted tubule and collecting duct (DCT/CD), where α-intercalated cells actively transport H+ into the tubule. Secreted H+ combines with ammonia to form ammonium in the DCT/CD lumen. Because of its positive charge, ammonium cannot diffuse out of the tubular lumen, and it is passed in the urine. In distal RTA, α-intercalated cells cannot secrete sufficient H+ into the tubular lumen, resulting in decreased … [1]: {openurl}?query=rft.jtitle%253DInternational%2Bjournal%2Bof%2Bclinical%2Bpractice%26rft.stitle%253DInt%2BJ%2BClin%2BPract%26rft.aulast%253DReddy%26rft.auinit1%253DP.%26rft.volume%253D65%26rft.issue%253D3%26rft.spage%253D350%26rft.epage%253D360%26rft.atitle%253DClinical%2Bapproach%2Bto%2Brenal%2Btubular%2Bacidosis%2Bin%2Badult%2Bpatients.%26rft_id%253Dinfo%253Adoi%252F10.1111%252Fj.1742-1241.2009.02311.x%26rft_id%253Dinfo%253Apmid%252F21314872%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1111/j.1742-1241.2009.02311.x&link_type=DOI [3]: /lookup/external-ref?access_num=21314872&link_type=MED&atom=%2Fpedsinreview%2F38%2F11%2F537.atom [4]: {openurl}?query=rft.jtitle%253DNephrol%2BDial%2BTransplant%26rft_id%253Dinfo%253Adoi%252F10.1093%252Fndt%252Fgfs442%26rft_id%253Dinfo%253Apmid%252F23114896%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [5]: /lookup/external-ref?access_num=10.1093/ndt/gfs442&link_type=DOI [6]: /lookup/external-ref?access_num=23114896&link_type=MED&atom=%2Fpedsinreview%2F38%2F11%2F537.atom [7]: /lookup/external-ref?access_num=000310631500007&link_type=ISI [8]: {openurl}?query=rft.jtitle%253DJ%2BAm%2BSoc%2BNephrol%26rft_id%253Dinfo%253Adoi%252F10.1681%252FASN.2008020166%26rft_id%253Dinfo%253Apmid%252F19193780%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [9]: /lookup/ijlink?linkType=ABST&journalCode=jnephrol&resid=20/2/251&atom=%2Fpedsinreview%2F38%2F11%2F537.atom [10]: {openurl}?query=rft.jtitle%253DNephrol%2BDial%2BTransplant%26rft_id%253Dinfo%253Adoi%252F10.1093%252Fndt%252Fgfs493%26rft_id%253Dinfo%253Apmid%252F23235953%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [11]: /lookup/external-ref?access_num=10.1093/ndt/gfs493&link_type=DOI [12]: /lookup/external-ref?access_num=23235953&link_type=MED&atom=%2Fpedsinreview%2F38%2F11%2F537.atom [13]: /lookup/external-ref?access_num=000312645800008&link_type=ISI

Study objective Cigarette smoking remains the leading cause of preventable death in the United States, and tobacco use rates are known to be higher among emergency department (ED) patients than in the general population. Despite recommendations from the Society for Academic Emergency Medicine and the American College of Emergency Physicians, many emergency clinicians remain uncertain about the benefits of providing ED-based smoking cessation interventions. To address this gap in knowledge, we performed a systematic review of cessation interventions initiated in the adult or pediatric ED setting. Methods We conducted an electronic search of the MEDLINE and CINAHL databases through February 2014 and hand searched references from potentially relevant articles. We identified eligible studies, evaluated bias and validity, and extracted data and synthesized findings. Results Seventeen studies underwent critical appraisal, with 13 included in qualitative synthesis. The majority (11/13, 85%) of investigations did not report significant differences in tobacco abstinence between cessation intervention groups. The 2 studies reporting significant differences in cessation both used motivational interviewing-based interventions. Two studies evaluated patient satisfaction with ED-based tobacco cessation interventions, and both reported greater than 90% satisfaction. Conclusions Findings indicate that ED visits in combination with ED-initiated tobacco cessation interventions are correlated with higher cessation rates than those reported in the National Health Interview Survey. Clear data supporting the superiority of one intervention type were not identified. Lack of a standardized control group prevented quantitative evaluation of pooled data, and future research is indicated to definitively evaluate intervention efficacy.

The original version of this article unfortunately contained a mistake. The subtitle “A Midwest Pediatric Nephrology Consortium (MWPNC) study” was missing. The correct title including subtitle is given above.

Triclosan is a broad-spectrum antibacterial agent, which has been shown previously to alleviate human allergic skin disease. The purpose of this study was to investigate the hypothesis that the mechanism of this action of triclosan is, in part, due to effects on mast cell function. Mast cells play important roles in allergy, asthma, parasite defense, and carcinogenesis. In response to various stimuli, mast cells degranulate, releasing allergic mediators such as histamine. In order to investigate the potential anti-inflammatory effect of triclosan on mast cells, we monitored the level of degranulation in a mast cell model, rat basophilic leukemia cells, clone 2H3. Having functional homology to human mast cells, as well as a very well defined signaling pathway leading to degranulation, this cell line has been widely used to gain insight into mast-cell driven allergic disorders in humans. Using a fluorescent microplate assay, we determined that triclosan strongly dampened the release of granules from activated rat mast cells starting at 2 μM treatment, with dose-responsive suppression through 30 μM. These concentrations were found to be non-cytotoxic. The inhibition was found to persist when early signaling events (such as IgE receptor aggregation and tyrosine phosphorylation) were bypassed by using calcium ionophore stimulation, indicating that the target for triclosan in this pathway is likely downstream of the calcium signaling event. Triclosan also strongly suppressed F-actin remodeling and cell membrane ruffling, a physiological process that accompanies degranulation. Our finding that triclosan inhibits mast cell function may explain the clinical data mentioned above and supports the use of triclosan or a mechanistically similar compound as a topical treatment for allergic skin disease, such as eczema.

1. Jonathan Pelletier, MD* 2. Kathleen Bartlett, MD* 1. *Duke Children's Hospital and Health Center, Durham NC A 17-year-old boy with a history of restrictive eating disorder and orthostatic hypotension presents via emergency medical services from an eating disorder facility with 1 week of dizziness and confusion and 1 day of fever. He also reports months of daily first-morning, nonbloody, and nonbilious vomiting. On presentation to the emergency department he is febrile (temperature, 102.9°F [39.4°C]), tachycardic (heart rate, 112 beats/min), and hypotensive (blood pressure, 91/46 mm Hg) and requires oxygen via nasal cannula. His weight is 114.2 lb (51.8 kg) (3rd percentile), height is 64.6 in (164 cm) (5th percentile), and BMI is 19.3 (15th percentile). General physical examination findings are normal. Shortly after arrival, the patient develops a brief episode of upper extremity tonic extension, unresponsiveness, and desaturation. He recovers spontaneously without an apparent postictal period. Repeated neurologic examination reveals slowed but appropriate responses to questioning. Cranial nerves, strength, sensation, and reflexes are normal. Upper extremity coordination is normal, but he has right greater than left ataxia with heel-to-shin testing. The patient is unable to stand for gait and Romberg testing due to dizziness. Laboratory tests before fluid therapy are remarkable for a serum sodium concentration of 149 mEq/L (149 mmol/L) (reference range, 135–145 mEq/L [135–145 mmol/L]), a serum chloride concentration of 118 mEq/L (118 mmol/L) (reference range, 96–108 mEq/L [96–108 mmol/L]), leukocytosis, and normocytic anemia. Urinalysis results are normal, …

NE (typhlitis) is a potentially life-threatening disease process characterized by bowel wall edema, ulceration, and hemorrhage in an immunosuppressed patient. We report a 15-year-old boy status post deceased donor renal transplantation who presented with fever, abdominal pain, and diarrhea. Laboratory studies revealed neutropenia 5 days prior to admission, and abdominal computed tomography revealed bowel wall thickening in the cecum consistent with NE. He was treated with piperacillin-tazobactam and gentamicin and recovered. To our knowledge, this is the first report of a case of NE in a pediatric kidney transplant recipient.

Allergic diseases such as asthma have been on the rise in recent decades. Environmental or occupational exposure to estrogenic synthetic chemicals is suspected to be a contributing factor, and previous experimental studies indicated that estradiol and some xenoestrogens increase allergic signaling responses, such as degranulation, in immune cells. In the current study, data showed that the estrogen mimetic 4-tert-octylphenol (4tOP) enhances immunoglobulin (Ig) E-mediated degranulation of mammalian mast cell line RBL-2H3 (RBL). At the noncytotoxic concentrations 10-20 μM, 4tOP significantly increased degranulation in antigen (Ag)-activated RBLs but exerted no marked effect on spontaneous levels. Our data suggest that the industrial chemical 4tOP has the potential to enhance allergic disease in individuals who are exposed.

Millions of people worldwide are exposed to arsenic (As), a toxicant which increases the risk of various cancers, cardiovascular disease and several other health problems. Arsenic is a potent endocrine disruptor, including of the estrogen receptor. It was recently shown that environmental estrogen-receptor disruptors can affect the signaling of mast cells, which are important players in parasite defense, asthma and allergy. Antigen (Ag) or allergen crosslinking of IgE-bound receptors on mast cells leads to signaling, culminating in degranulation, the release of histamine and other mediators. Because As is an endocrine disruptor and because endocrine disruptors have been found to affect degranulation, here we have tested whether sodium arsenite affects degranulation. Using the rat basophilic leukemia (RBL) mast cell model, we have measured degranulation in a fluorescence assay. Arsenic alone had no effect on basal levels of degranulation. However, As strongly inhibited Ag-stimulated degranulation at environmentally relevant concentrations, in a manner that is very dependent on concentrations of both As and Ag. The concentrations of As effective at inhibiting degranulation were not cytotoxic. This inhibition may be a mechanism underlying the traditional Chinese medicinal use of As to treat asthma. These data indicate that As may inhibit the ability of humans to fight off parasitic disease.