Publications by authors named "Robert W Hickey"

86 Publications

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

J Pediatr 2021 Jan 13. Epub 2021 Jan 13.

Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH; Division of Emergency Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

Objective: To determine the association between bacteremia and vaccination status in children aged 2-36 months presenting to a pediatric emergency department.

Study Design: Retrospective cohort study of children aged 2-36 months with blood cultures obtained in the pediatric emergency department between January 2013 and December 2017. The exposure of interest was immunization status, defined as number of Haemophilus influenzae type B (Hib) and Streptococcus pneumoniae vaccinations, and the main outcome positive blood culture. Subjects with high-risk medical conditions were excluded.

Results: Of 5534 encounters, 4742 met inclusion criteria. The incidence of bacteremia was 1.5%. The incidence of contaminated blood culture was 5.0%. The relative risk of bacteremia was 0.79 (95% CI 0.39-1.59) for unvaccinated and 1.20 (95% CI 0.52-2.75) for undervaccinated children relative to those who had received age-appropriate vaccines. Five children were found to have S pneumoniae bacteremia and 1 child had Hib bacteremia; all of these subjects had at least 3 sets of vaccinations. No vaccine preventable pathogens were isolated from blood cultures of unvaccinated children. We found no S pneumoniae or Hib in children 2-6 months of age who were not fully vaccinated due to age (95% CI 0-0.13%) and the contamination rate in this group was high compared with children 7-36 months (6.6% vs 3.7%).

Conclusions: Bacteremia in young children is an uncommon event. Contaminated blood cultures were more common than pathogens. Bacteremia from S pneumoniae or Hib is uncommon and, in this cohort, was independent of vaccine status.
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http://dx.doi.org/10.1016/j.jpeds.2021.01.005DOI Listing
January 2021

Rates of Presentation, Treatments and Serious Neurologic Disorders Among Children and Young Adults Presenting to US Emergency Departments With Headache.

J Child Neurol 2020 Dec 24:883073820979137. Epub 2020 Dec 24.

Division of Pediatric Emergency Medicine, Department of Pediatrics, 6619UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Objective: To evaluate rates of presentation, neuroimaging, therapies, and serious neurologic disorders (SNDs) among children and young adults presenting to the emergency department with headache.

Methods: We performed a cross-sectional study of a nationally representative sample survey of visits to US emergency departments between 2002 and 2017. We identified encounters of patients ≤25 years old with chief complaint of headache. We report the rates of presentation, imaging, and treatments and report proportions having concomitant diagnoses of serious neurologic disorders.

Results: Among encounters ≤25 years, 2.0% had a chief complaint of headache, with no change in the yearly rates of encounters ( = .98). Overall, 20.8% had a head computed tomography (CT), with a reduction in performance between 2007 and 2016 ( < .01). One-quarter (25.2%, 95% confidence interval [CI] 22.2%-28.3%) were given narcotics and 2.5% (95% CI 1.7%-3.2%) had serious neurologic disorders.

Conclusion: Overall, 2.0% of emergency department encounters among patients ≤25 years were for headache, with low rates of serious neurologic disorders. CT use appeared to be declining.
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http://dx.doi.org/10.1177/0883073820979137DOI Listing
December 2020

Vaccine Effectiveness Against Pediatric Influenza Hospitalizations and Emergency Visits.

Pediatrics 2020 11 5;146(5). Epub 2020 Oct 5.

Influenza Division and.

Background: Influenza A(H1N1)pdm09 viruses initially predominated during the US 2018-2019 season, with antigenically drifted influenza A(H3N2) viruses peaking later. We estimated vaccine effectiveness (VE) against laboratory-confirmed influenza-associated hospitalizations and emergency department (ED) visits among children in the New Vaccine Surveillance Network.

Methods: We tested children 6 months to 17 years with acute respiratory illness for influenza using molecular assays at 7 pediatric hospitals (ED patients <5 years at 3 sites). Vaccination status sources were parental report, state immunization information systems and/or provider records for inpatients, and parental report alone for ED patients. We estimated VE using a test-negative design, comparing odds of vaccination among children testing positive versus negative for influenza using multivariable logistic regression.

Results: Of 1792 inpatients, 226 (13%) were influenza-positive: 47% for influenza A(H3N2), 36% for A(H1N1)pdm09, 9% for A (not subtyped), and 7% for B viruses. Among 1944 ED children, 420 (22%) were influenza-positive: 48% for A(H3N2), 35% for A(H1N1)pdm09, 11% for A (not subtyped), and 5% for B viruses. VE was 41% (95% confidence interval [CI], 20% to 56%) against any influenza-related hospitalizations, 41% (95% CI, 11% to 61%) for A(H3N2), and 47% (95% CI, 16% to 67%) for A(H1N1)pdm09. VE was 51% (95% CI, 38% to 62%) against any influenza-related ED visits, 39% (95% CI, 15% to 56%) against A(H3N2), and 61% (95% CI, 44% to 73%) against A(H1N1)pdm09.

Conclusions: The 2018-2019 influenza vaccine reduced pediatric influenza A-associated hospitalizations and ED visits by 40% to 60%, despite circulation of a drifted A(H3N2) clade.
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http://dx.doi.org/10.1542/peds.2020-1368DOI Listing
November 2020

Serious Diagnoses for Headaches After ED Discharge.

Pediatrics 2020 11 2;146(5). Epub 2020 Oct 2.

Division of Emergency Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago and Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

Background: Headache is a common complaint among children presenting to the emergency department (ED) and can be due to serious neurologic and nonneurologic diagnoses (SNNDs). We sought to characterize the children discharged from the ED with headache found to have SNNDs at revisits.

Methods: We performed a multicenter retrospective cohort study using data from 45 pediatric hospitals from October 1, 2015, to March 31, 2019. We included pediatric patients (≤18 years) discharged from the ED with a principal diagnosis of headache, excluding patients with concurrent or previous SNNDs or neurosurgeries. We identified rates and types of SNNDs diagnosed within 30 days of initial visit and compared these rates with those of control groups defined as patients with discharge diagnoses of cough, chest pain, abdominal pain, and soft tissue complaints.

Results: Of 121 621 included patients (57% female, median age 12.4 years, interquartile range: 8.8-15.4), 608 (0.5%, 95% confidence interval: 0.5%-0.5%) were diagnosed with SNNDs within 30 days. Most were diagnosed at the first revisit (80.8%); 37.5% were diagnosed within 7 days. The most common SNNDs were benign intracranial hypertension, cerebral edema and compression, and seizures. A greater proportion of patients with SNNDs underwent neuroimaging, blood, and cerebrospinal fluid testing compared with those without SNNDs ( < .001 for each). The proportion of SNNDs among patients diagnosed with headache (0.5%) was higher than for control cohorts (0.0%-0.1%) ( < .001 for each).

Conclusions: A total 0.5% of pediatric patients discharged from the ED with headache were diagnosed with an SNND within 30 days. Further efforts to identify at-risk patients remain a challenge.
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http://dx.doi.org/10.1542/peds.2020-1647DOI Listing
November 2020

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

Pediatr Nephrol 2020 11 15;35(11):2113-2120. Epub 2020 Jun 15.

University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Background: To evaluate the efficacy of adjuvant systemic corticosteroids in reducing kidney scarring. A previous study suggested that use of adjuvant systemic corticosteroids reduces kidney scarring in children radiologically confirmed to have extensive pyelonephritis. Efficacy of corticosteroids for children with febrile urinary tract infection (UTI) has not been studied.

Methods: Children aged 2 months to 6 years with their first febrile UTI were randomized to corticosteroids or placebo for 3 days (both arms received antimicrobial therapy); kidney scarring was assessed using Tc-dimercaptosuccinic acid kidney scan 5-24 months after the initial UTI.

Results: We randomized 546 children of which 385 had a UTI and 254 had outcome kidney scans (instead of the 320 planned). Rates of kidney scarring were 9.8% (12/123) and 16.8% (22/131) in the corticosteroid and placebo groups, respectively (p = 0.16), corresponding to an absolute risk reduction of 5.9% (95% confidence interval: - 2.2, 14.1).

Conclusion: While children randomized to adjuvant corticosteroids tended to develop fewer kidney scars than children who were randomized to receive placebo, a statistically significant difference was not achieved. However, the study was limited by not reaching its intended sample size.

Clinical Trial Registration: Clinicaltrials.gov , NCT01391793, Registered 7/12/2011 Graphical abstract.
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http://dx.doi.org/10.1007/s00467-020-04622-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529851PMC
November 2020

Severe Acute Respiratory Syndrome Coronavirus 2 Infections in Children: Multicenter Surveillance, United States, January-March 2020.

J Pediatric Infect Dis Soc 2020 Nov;9(5):609-612

COVID-19 Response Team, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Previous reports of coronavirus disease 2019 among children in the United States have been based on health jurisdiction reporting. We performed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing on children enrolled in active, prospective, multicenter surveillance during January-March 2020. Among 3187 children, only 4 (0.1%) SARS-CoV-2-positive cases were identified March 20-31 despite evidence of rising community circulation.
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http://dx.doi.org/10.1093/jpids/piaa075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337823PMC
November 2020

Diagnostic Accuracy of Non-Invasive Thermal Evaluation of Ventriculoperitoneal Shunt Flow in Shunt Malfunction: A Prospective, Multi-Site, Operator-Blinded Study.

Neurosurgery 2020 10;87(5):939-948

Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

Background: Thermal flow evaluation (TFE) is a non-invasive method to assess ventriculoperitoneal shunt function. Flow detected by TFE is a negative predictor of the need for revision surgery. Further optimization of testing protocols, evaluation in multiple centers, and integration with clinical and imaging impressions prompted the current study.

Objective: To compare the diagnostic accuracy of 2 TFE protocols, with micropumper (TFE+MP) or without (TFE-only), to neuro-imaging in patients emergently presenting with symptoms concerning for shunt malfunction.

Methods: We performed a prospective multicenter operator-blinded trial of a consecutive series of patients who underwent evaluation for shunt malfunction. TFE was performed, and preimaging clinician impressions and imaging results were recorded. The primary outcome was shunt obstruction requiring neurosurgical revision within 7 d. Non-inferiority of the sensitivity of TFE vs neuro-imaging for detecting shunt obstruction was tested using a prospectively determined a priori margin of -2.5%.

Results: We enrolled 406 patients at 10 centers. Of these, 68/348 (20%) evaluated with TFE+MP and 30/215 (14%) with TFE-only had shunt obstruction. The sensitivity for detecting obstruction was 100% (95% CI: 88%-100%) for TFE-only, 90% (95% CI: 80%-96%) for TFE+MP, 76% (95% CI: 65%-86%) for imaging in TFE+MP cohort, and 77% (95% CI: 58%-90%) for imaging in the TFE-only cohort. Difference in sensitivities between TFE methods and imaging did not exceed the non-inferiority margin.

Conclusion: TFE is non-inferior to imaging in ruling out shunt malfunction and may help avoid imaging and other steps. For this purpose, TFE only is favored over TFE+MP.
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http://dx.doi.org/10.1093/neuros/nyaa128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566379PMC
October 2020

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

J Pediatr 2020 06;221:132-137.e2

Division of Pediatric Emergency Medicine, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Objective: To assess the prevalence of serious infections and mortality among infants ≤90 days of age presenting to the emergency department with hypothermia.

Study Design: We performed a cross-sectional cohort study of infants ≤90 days presenting to any of 40 EDs in the Pediatric Health Information Systems between January 1, 2009, and December 31, 2018. Infants with an International Classification of Diseases, ninth or tenth edition, admission/discharge diagnosis code of hypothermia were included. We determined the prevalence of serious bacterial infection (urinary tract infection, bacteremia, and/or bacterial meningitis), pneumonia, herpes simplex virus (HSV) infection, and emergency department/hospital mortality.

Results: We included 3565 infants (1633 male [50.9%] and 3225 ≤30 days of age [90.5%]). Most (65.0%) presented in the first week of life. There were 389 infants (10.8%) with a complex chronic condition. The prevalence of serious bacterial infection was 8.0% (n = 284), including 2.4% (n = 87) with urinary tract infection, 5.6% (n = 199) with bacteremia, and 0.3% (n = 11) with bacterial meningitis. There were 7 patients (0.2%) with neonatal HSV and 9 (0.3%) with pneumonia; 0.2% (n = 6) died. The presence of a complex chronic condition was associated with the presence of serious bacterial infection (P < .001) and was present in 3 of 6 patients who died. In a sensitivity analysis including patients with any diagnosis code of hypothermia (n = 8122), 14.9% had serious bacterial infection, 0.6% had HSV, and 3.3% had pneumonia; 2.0% died.

Conclusions: Of infants with hypothermia ≤90 days of age, 8.3% had serious bacterial infections or HSV. Compared with literature from febrile infants, hypothermia is associated with a high mortality rate. Complex chronic conditions were particularly associated with poor outcomes. Additional research is required to risk stratify young infants with hypothermia.
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http://dx.doi.org/10.1016/j.jpeds.2020.03.002DOI Listing
June 2020

Patterns of Influenza Vaccination and Vaccine Effectiveness Among Young US Children Who Receive Outpatient Care for Acute Respiratory Tract Illness.

JAMA Pediatr 2020 Jul;174(7):705-713

Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia.

Importance: The burden of influenza among young children is high, and influenza vaccination is the primary strategy to prevent the virus and its complications. Less is known about differences in clinical protection following 1 vs 2 doses of initial influenza vaccination.

Objectives: To describe patterns of influenza vaccination among young children who receive outpatient care for acute respiratory tract illness in the US and compare vaccine effectiveness (VE) against medically attended laboratory-confirmed influenza by number of influenza vaccine doses received.

Design: This test-negative case-control study was conducted in outpatient clinics, including emergency departments, at 5 sites of the US Influenza Vaccine Effectiveness Network during the 2014-2015 through 2017-2018 influenza seasons. The present study was performed from November 5, 2014, to April 12, 2018, during periods of local influenza circulation. Children aged 6 months to 8 years with an acute respiratory tract illness with cough who presented for outpatient care within 7 days of illness onset were included. All children were tested using real-time, reverse-transcriptase polymerase chain reaction for influenza for research purposes.

Exposures: Vaccination in the enrollment season with either 1 or 2 doses of inactivated influenza vaccine as documented from electronic medical records, including state immunization information systems.

Main Outcomes And Measures: Medically attended acute respiratory tract infection with real-time, reverse-transcriptase polymerase chain reaction testing for influenza.

Results: Of 7533 children, 3480 children (46%) were girls, 4687 children (62%) were non-Hispanic white, and 4871 children (65%) were younger than 5 years. A total of 3912 children (52%) were unvaccinated in the enrollment season, 2924 children (39%) were fully vaccinated, and 697 children (9%) were partially vaccinated. Adjusted VE against any influenza was 51% (95% CI, 44%-57%) among fully vaccinated children and 41% (95% CI, 25%-54%) among partially vaccinated children. Among 1519 vaccine-naive children aged 6 months to 2 years, the VE of 2 doses in the enrollment season was 53% (95% CI, 28%-70%), and the VE of 1 dose was 23% (95% CI, -11% to 47%); those who received 2 doses were less likely to test positive for influenza compared with children who received only 1 dose (adjusted odds ratio, 0.57; 95% CI, 0.35-0.93).

Conclusions And Relevance: Consistent with US influenza vaccine policy, receipt of the recommended number of doses resulted in higher VE than partial vaccination in 4 influenza seasons. Efforts to improve 2-dose coverage for previously unvaccinated children may reduce the burden of influenza in this population.
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http://dx.doi.org/10.1001/jamapediatrics.2020.0372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199168PMC
July 2020

Early Hyperoxemia and Outcome Among Critically Ill Children.

Pediatr Crit Care Med 2020 02;21(2):e129-e132

Department of Pediatrics, University of Pittsburgh School of Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA.

Objective: To identify whether a high PaO2 (hyperoxemia) at the time of presentation to the PICU is associated with in-hospital mortality.

Design: Single-center observational study.

Setting: Quaternary-care PICU.

Patients: Encounters admitted between January 1, 2009, and December 31, 2018.

Interventions: None.

Measurements And Main Results: Encounters with a measured PaO2 were included. To account for severity of illness upon presentation, we calculated a modified Pediatric Risk of Mortality IV score excluding PaO2 for each encounter, calibrated for institutional data. Logistic regression was used to determine whether hyperoxemia (PaO2 ≥ 300 torr [39.99 kPa]) in the 12 hours surrounding PICU admission was associated with in-hospital mortality. We reperformed our analysis using a cutoff for hyperoxemia obtained by comparisons of observed versus predicted mortality when encounters were classified by highest PaO2 in 50 torr (6.67 kPa) bins. Results are reported as adjusted odds ratios with 95% CIs. Of 23,719 encounters, 4,093 had a PaO2 recorded in the period -6 to +6 hours after admission. Two hundred seventy-four of 4,093 (6.7%) had in-hospital mortality. The prevalence of hyperoxemia increased with rising modified Pediatric Risk of Mortality IV and was not associated with mortality in multivariable models (adjusted odds ratio, 1.38; 95% CI, 0.98-1.93). When using a higher cutoff of hyperoxemia derived from comparison of observed versus predicted rates of mortality of greater than or equal to 550 torr (73.32 kPa), hyperoxemia was associated with mortality (adjusted odds ratio, 2.78; 95% CI, 2.54-3.05).

Conclusions: A conventional threshold for hyperoxemia at presentation to the PICU was not associated with in-hospital mortality in a model using a calibrated acuity score. Extreme states of hyperoxemia (≥ 73.32 kPa) were significantly associated with in-hospital mortality. Prospective research is required to identify if hyperoxemia before and/or after PICU admission contributes to poor outcomes.
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http://dx.doi.org/10.1097/PCC.0000000000002203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304556PMC
February 2020

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

Pediatr Nephrol 2020 02 22;35(2):321-329. Epub 2019 Nov 22.

Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, USA.

Background: The specificity of the leukocyte esterase test (87%) is suboptimal. The objective of this study was to identify more specific screening tests that could reduce the number of children who unnecessarily receive antimicrobials to treat a presumed urinary tract infection (UTI).

Methods: Prospective cross-sectional study to compare inflammatory proteins in blood and urine samples collected at the time of a presumptive diagnosis of UTI. We also evaluated serum RNA expression in a subset.

Results: We enrolled 200 children; of these, 89 were later demonstrated not to have a UTI based on the results of the urine culture obtained. Urinary proteins that best discriminated between children with UTI and no UTI were involved in T cell response proliferation (IL-9, IL-2), chemoattractants (CXCL12, CXCL1, CXCL8), the cytokine/interferon pathway (IL-13, IL-2, INFγ), or involved in innate immunity (NGAL). The predictive power (as measured by the area under the curve) of a combination of four urinary markers (IL-2, IL-9, IL-8, and NGAL) was 0.94. Genes in the pathways related to inflammation were also upregulated in serum of children with UTI.

Conclusions: Urinary proteins involved in the inflammatory response may be useful in identifying children with false positive results with current screening tests for UTI; this may reduce unnecessary treatment.
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http://dx.doi.org/10.1007/s00467-019-04403-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942213PMC
February 2020

Association of Severe Hyperoxemia Events and Mortality Among Patients Admitted to a Pediatric Intensive Care Unit.

JAMA Netw Open 2019 08 2;2(8):e199812. Epub 2019 Aug 2.

Department of Pediatrics, University of Pittsburgh School of Medicine; UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.

Importance: A high Pao2, termed hyperoxemia, is postulated to have deleterious health outcomes. To date, the association between hyperoxemia during the ongoing management of critical illness and mortality has been incompletely evaluated in children.

Objective: To examine whether severe hyperoxemia events are associated with mortality among patients admitted to a pediatric intensive care unit (PICU).

Design, Setting, And Participants: A retrospective cohort study was conducted over a 10-year period (January 1, 2009, to December 31, 2018); all 23 719 PICU encounters at a quaternary children's hospital with a documented arterial blood gas measurement were evaluated.

Exposures: Severe hyperoxemia, defined as Pao2 level greater than or equal to 300 mm Hg (40 kPa).

Main Outcomes And Measures: The highest Pao2 values during hospitalization were dichotomized according to the definition of severe hyperoxemia and assessed for association with in-hospital mortality using logistic regression models incorporating a calibrated measure of multiple organ dysfunction, extracorporeal life support, and the total number of arterial blood gas measurements obtained during an encounter.

Results: Of 23 719 PICU encounters during the inclusion period, 6250 patients (13 422 [56.6%] boys; mean [SD] age, 7.5 [6.6] years) had at least 1 measured Pao2 value. Severe hyperoxemia was independently associated with in-hospital mortality (adjusted odds ratio [aOR], 1.78; 95% CI, 1.36-2.33; P < .001). Increasing odds of in-hospital mortality were observed with 1 (aOR, 1.47; 95% CI, 1.05-2.08; P = .03), 2 (aOR, 2.01; 95% CI, 1.27-3.18; P = .002), and 3 or more (aOR, 2.53; 95% CI, 1.62-3.94; P < .001) severely hyperoxemic Pao2 values obtained greater than or equal to 3 hours apart from one another compared with encounters without hyperoxemia. A sensitivity analysis examining the hypothetical outcomes of residual confounding indicated that an unmeasured binary confounder with an aOR of 2 would have to be present in 37% of the encounters with severe hyperoxemia and 0% of the remaining cohort to fail to reject the null hypothesis (aOR of severe hyperoxemia, 1.31; 95% CI, 0.99-1.72).

Conclusions And Relevance: Greater numbers of severe hyperoxemia events appeared to be associated with increased mortality in this large, diverse cohort of critically ill children, supporting a possible exposure-response association between severe hyperoxemia and outcome in this population. Although further prospective evaluation appears to be warranted, this study's findings suggest that guidelines for ongoing management of critically ill children should take into consideration the possible detrimental effects of severe hyperoxemia.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.9812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707098PMC
August 2019

Normal saline bolus use in pediatric emergency departments is associated with poorer pain control in children with sickle cell anemia and vaso-occlusive pain.

Am J Hematol 2019 06 29;94(6):689-696. Epub 2019 Apr 29.

Department of Pediatrics, Division of Pediatric Emergency Medicine, Emory University School of Medicine, Atlanta, Georgia.

Vaso-occlusive pain events (VOE) are the leading cause of emergency department (ED) visits in sickle cell anemia (SCA). This study assessed the variability in use of intravenous fluids (IVFs), and the association of normal saline bolus (NSB), on pain and other clinical outcomes in children with SCA, presenting to pediatric emergency departments (PED) with VOE. Four-hundred charts of children age 3-21 years with SCA/VOE receiving parenteral opioids at 20 high-volume PEDs were evaluated in a retrospective study. Data on type and amount of IVFs used were collected. Patients were divided into two groups: those who received NSB and those who did not. The association of NSB use on change in pain scores and admission rates was evaluated. Among 400 children studied, 261 (65%) received a NSB. Mean age was 13.8 ± 4.9 years; 46% were male; 92% had hemoglobin-SS. The IVFs (bolus and/or maintenance) were used in 84% of patients. Eight different types of IVFs were utilized and IVF volume administered varied widely. Mean triage pain scores were similar between groups, but improvement in pain scores from presentation-to-ED-disposition was smaller in the NSB group (2.2 vs 3.0, P = .03), while admission rates were higher (71% vs 59%, P = .01). Use of NSB remained associated with poorer final pain scores and worse change in pain scores in our multivariable model. In conclusion, wide variations in practice utilizing IVFs are common. NSB is given to >50% of children with SCA/VOE, but is associated with poorer pain control; a controlled prospective trial is needed to determine causality.
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http://dx.doi.org/10.1002/ajh.25471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6510594PMC
June 2019

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

J Pediatr 2019 06 21;209:146-153.e1. Epub 2019 Mar 21.

Department of Pediatrics, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA; Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA.

Objective: To determine whether treatment for urinary tract infections in children could be individualized using biomarkers for acute pyelonephritis.

Study Design: We enrolled 61 children with febrile urinary tract infections, collected blood and urine samples, and performed a renal scan within 2 weeks of diagnosis to identify those with pyelonephritis. Renal scans were interpreted centrally by 2 experts. We measured inflammatory proteins in blood and urine using LUMINEX or an enzyme-linked immunosorbent assay. We evaluated serum RNA expression using RNA sequencing in a subset of children. Finally, for children with Escherichia coli isolated from urine cultures, we performed a polymerase chain reaction for 4 previously identified virulence genes.

Results: Urinary markers that best differentiated pyelonephritis from cystitis included chemokine (C-X-C motif) ligand (CXCL)1, CXCL9, CXCL12, C-C motif chemokine ligand 2, INF γ, and IL-15. Serum procalcitonin was the best serum marker for pyelonephritis. Genes in the interferon-γ pathway were upregulated in serum of children with pyelonephritis. The presence of E coli virulence genes did not correlate with pyelonephritis.

Conclusions: Immune response to pyelonephritis and cystitis differs quantitatively and qualitatively; this may be useful in differentiating these 2 conditions.
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http://dx.doi.org/10.1016/j.jpeds.2019.01.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535366PMC
June 2019

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

Pediatr Emerg Care 2018 Nov 12. Epub 2018 Nov 12.

Department of Pediatrics, Baylor College of Medicine, Houston, TX.

Objectives: Serious bacterial infections (SBIs) in young infants can present with fever or hypothermia. There are substantial data on fever as a presentation for SBI that help to inform the clinical approach. In contrast, data on hypothermia are lacking, thus leaving clinicians without guidance. We aimed to describe the workup and findings, specifically the occurrence, of SBIs in infants younger than 60 days of life with hypothermia.

Methods: We reviewed the medical records of infants younger than 60 days of life with rectal temperature of less than 36.5°C upon arrival to a children's hospital emergency department between January 2013 and December 2014. Comparisons were made between those who were found to have an SBI and those without. Serious bacterial infection was defined as bacteremia, bacterial meningitis, pneumonia, or urinary tract infection (UTI).

Results: From the 414 patients identified, 104 (25%) underwent a sepsis evaluation of blood, urine, and/or cerebrospinal fluid culture. Serious bacterial infections were identified in 9 patients: 4 with UTI, 1 with pneumonia, 2 with bacteremia, 1 with pneumonia and UTI, and 1 with meningitis and bacteremia. Compared with patients with negative cultures, patients with SBI were older and had elevated absolute band counts and elevated immature-to-total neutrophil ratio.

Conclusions: Approximately a quarter of infants younger than 60 days with hypothermia were evaluated for SBI. Serious bacterial infection was identified in 9% of evaluated infants (2% of all hypothermic infants). Hypothermia can be a presenting sign of SBI.
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http://dx.doi.org/10.1097/PEC.0000000000001674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511495PMC
November 2018

A Modern Epidemic: Increasing Pediatric Emergency Department Visits and Admissions for Headache.

Pediatr Neurol 2018 12 4;89:19-25. Epub 2018 Aug 4.

A Children's Hospital of Pittsburgh of UPMC, Department of Pediatrics, Pittsburgh, Pennsylvania.

Objective: Headaches represent 0.9% to 2.6% of visits to a pediatric emergency department (PED). We noted a trend of increasing visits for headache in our tertiary care PED and sought to further characterize this trend.

Methods: We identified PED visits with International Classification of Disease, Ninth Revision, Clinical Modification diagnoses for headache at 25 hospitals in Pediatric Health Information System between 2003 and 2013. To further characterize demographics and treatment trends over time we used the electronic health record in our emergency department to identify children ages four to 18 between January 2007 and December 2014 with International Classification of Disease, Ninth Revision codes for headache: a random sample of 50 visits per year were chosen for chart review.

Results: Pediatric Health Information System visits for headache increased by 166% (18,041 in 2003 and 48,020 in 2013); by comparison, total PED visits increased by 57.6%. The percent admission increased by 300% (2020 admissions in 2003 and 8087 admissions in 2013). At our hospital, headache visits increased 111% from 896 visits in 2007 to 1887 visits in 2014; total PED visits increased 30.2%. The admission percentage for headache increased 187% with 156 admissions in 2007 and 448 in 2014. Management over time differed in the frequency of head computed tomography which decreased 3.7% per year (r = -0.93, 95% CI -0.99, -0.64) from 34% in 2007 to 18% in 2014.

Conclusion: Pediatric emergency department visits for headache are increasing and a growing proportion of these patients are admitted. This finding identifies a potential patient population to target for interventions to improve outpatient management and reduce pediatric emergency department utilization.
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http://dx.doi.org/10.1016/j.pediatrneurol.2018.07.015DOI Listing
December 2018

Laxative-Induced Contact Dermatitis.

Pediatr Emerg Care 2019 Jul;35(7):e127

From the Department of Pediatrics, Division of Pediatric Emergency Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA.

A 5-year-old female with Charcot-Marie-Tooth neuropathy and a history of constipation presented to the emergency department with a new blistering buttocks rash, which was initially concerning for nonaccidental burn. Upon further investigation, it was found that Ex-Lax had been given to the patient for constipation. This had resulted in a bowel movement, which led to an irritant dermatitis. The patient was eventually diagnosed with senna-induced erosive diaper dermatitis. This case report highlights the importance of a thorough history and physical examination to prevent an unnecessary child abuse work-up.
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http://dx.doi.org/10.1097/PEC.0000000000001498DOI Listing
July 2019

Dog bites in a U.S. county: age, body part and breed in paediatric dog bites.

Acta Paediatr 2018 05 5;107(5):893-899. Epub 2018 Feb 5.

Division of Pediatric Emergency Medicine, Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

Aim: To compare characteristics of gender, age, body part and breed in dog bites.

Methods: We reviewed 14 956 dog bites (4195 paediatric) reported to the Allegheny County Health Department, USA, between 2007 and 2015. Using predefined age groups, we performed linear regression to assess for subject age and bite frequency and used binary logistic regression to evaluate for differences in gender and body part. We used chi-squared test with Bonferroni correction to evaluate for differences in reported breeds with age.

Results: There was a negative correlation (-0.80, r = 0.64) between age and bite frequency. Children 0-3 years had a higher odds ratio (OR) of bites to the face [21.12, 95% confidence interval (CI): 17.61-25.33] and a lower OR of bites to the upper (OR: 0.14, 95% CI: 0.12-0.18) and lower (OR: 0.19, 95% CI: 0.14-0.27) extremities. 'Pit bulls' accounted for 27.2% of dog bites and were more common in children 13-18 years (p < 0.01). Shih-Tzu bites were more common in children three years of age and younger (p < 0.01).

Conclusion: Dog bites occur with higher frequency at younger ages, and head and neck injuries are more common in younger children. Pit bull bites are more common in adolescents and Shih-Tzu bites more common in younger children.
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http://dx.doi.org/10.1111/apa.14218DOI Listing
May 2018

In reply.

Ann Emerg Med 2017 12;70(6):927-928

Division of Pediatric Emergency Medicine, Department of Pediatrics, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA.

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http://dx.doi.org/10.1016/j.annemergmed.2017.07.475DOI Listing
December 2017

Practice Variation and Effects of E-mail-only Performance Feedback on Resource Use in the Emergency Department.

Acad Emerg Med 2017 08 6;24(8):948-956. Epub 2017 Jun 6.

The Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA.

Objectives: Higher resource utilization in the management of pediatric patients with undifferentiated vomiting and/or diarrhea does not correlate consistently with improved outcomes or quality of care. Performance feedback has been shown to change physician practice behavior and may be a mechanism to minimize practice variation. We aimed to evaluate the effects of e-mail-only, provider-level performance feedback on the ordering and admission practice variation of pediatric emergency physicians for patients presenting with undifferentiated vomiting and/or diarrhea.

Methods: We conducted a prospective, quality improvement intervention and collected data over 3 consecutive fiscal years. The setting was a single, tertiary care pediatric emergency department. We collected admission and ordering practices data on 19 physicians during baseline, intervention, and postintervention periods. We provided physicians with quarterly e-mail-based performance reports during the intervention phase. We measured admission rate and created four categories for ordering practices: no orders, laboratory orders, pharmacy orders, and radiology orders.

Results: There was wide (two- to threefold) practice variation among physicians. Admission rates ranged from 15% to 30%, laboratory orders from 19% to 43%, pharmacy orders from 29% to 57%, and radiology orders from 11% to 30%. There was no statistically significant difference in the proportion of patients admitted or with radiology or pharmacy orders placed between preintervention, intervention, or postintervention periods (p = 0.58, p = 0.19, and p = 0.75, respectively). There was a significant but very small decrease in laboratory orders between the preintervention and postintervention periods.

Conclusions: Performance feedback provided only via e-mail to pediatric emergency physicians on a quarterly basis does not seem to significantly impact management practices for patients with undifferentiated vomiting and/or diarrhea.
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http://dx.doi.org/10.1111/acem.13211DOI Listing
August 2017

Ropivacaine Intramuscular Paracervical Injections for Pediatric Headache: A Randomized Placebo-Controlled Trial.

Ann Emerg Med 2017 Sep 29;70(3):323-330. Epub 2017 Apr 29.

Division of Pediatric Emergency Medicine, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA. Electronic address:

Study Objective: We seek to determine whether ropivacaine cervical paraspinal injections compared with normal saline solution injections provide headache relief to pediatric patients that is sufficient for emergency department (ED) discharge.

Methods: We enrolled children aged 7 to 17 years in a double-blinded, randomized, controlled trial of patients presenting to a pediatric ED with headache. Subjects were randomized into 1 of 3 groups: bilateral cervical paraspinal injections of either (1) 0.5% ropivacaine or (2) normal saline solution, or (3) a natural history group (not blinded) receiving no headache therapy for the first 30 minutes. Pain scores were assessed at enrollment and at 10-, 20-, and 30-minute intervals after the administration of the injections. After the intervention period of 30 minutes, additional therapy was provided as needed. Primary outcome was the proportion of children discharged with adequate pain relief at 30 minutes without additional therapy. Secondary outcomes included reduction in pain scores, reoccurrence of headache, and re-presentation to health care with headache.

Results: One hundred fifty-three children were enrolled. The proportion discharged with adequate pain relief 30 minutes after the injections did not differ between the 2 intervention groups (32% in the ropivacaine group versus 28% in the saline solution group; effect difference 4%; 95% confidence interval -14% to 21%). In contrast, only 4% percent of patients in the natural history group were discharged without additional therapy after the 30-minute assessment. Reduction of pain scores (2.0 and 2.2 in ropivacaine versus saline solution), headache reoccurrence, and return to care was similar between the 2 treatment groups.

Conclusion: Cervical paraspinal injections of either ropivacaine or saline solution were effective for approximately one third of patients.
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http://dx.doi.org/10.1016/j.annemergmed.2017.03.011DOI Listing
September 2017

The Effectiveness of Prescribed Rest Depends on Initial Presentation After Concussion.

J Pediatr 2017 06 29;185:167-172. Epub 2017 Mar 29.

Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI. Electronic address:

Objective: To evaluate if patients with signs of injury respond differently to prescribed rest after concussion compared with patients with symptoms only.

Study Design: Secondary analysis was completed of a prospective randomized controlled trial (NCT01101724) of pediatric concussion patients aged 11-18 years. Patients completed computerized neurocognitive testing and standardized balance assessment at the emergency department within 24 hours of injury and on follow-up (3 and 10 days). Patients were randomized to rest or usual care and completed activity and symptom diaries for 10 days after injury. A series of 2?×?2 ANOVAs with grouping factors of patient group (symptoms, signs) and treatment arm (prescribed rest, standard of care) were used to examine differences on clinical measures. Univariate nonparametric test (ie, ? with ORs and 95% CIs) was used to examine the association between treatment arm and symptom status 1-9 days after injury.

Results: A 2?×?2 factorial ANOVA revealed a significant patient group × treatment arm interaction for symptom score at 3 days after injury (F?=?6.31, P?=?.01, ??=?0.07). Prescribed rest increased the likelihood of still being symptomatic at days 1-6 and 8 (P?
Conclusion: Compared with patients with signs of injury, patients with predominantly symptoms were more likely to remain symptomatic after injury if prescribed rest, whereas patients with signs of injury benefited from rest after a concussion. Individualized treatment planning after concussion should start in the emergency department.

Trial Registration: ClinicalTrials.gov: NCT01101724.
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http://dx.doi.org/10.1016/j.jpeds.2017.02.072DOI Listing
June 2017

Acute Management of Refractory and Unstable Pediatric Supraventricular Tachycardia.

J Pediatr 2017 02 29;181:177-182.e2. Epub 2016 Nov 29.

Department of Pediatrics, Division of Pediatric Emergency Medicine, University of Pittsburgh, Pittsburgh, PA. Electronic address:

Objective: To characterize the management of acute pediatric supraventricular tachycardia (SVT), placing special emphasis on infants, patients refractory to adenosine (refractory SVT), and patients with hypotension, poor perfusion, or altered mental status (unstable SVT).

Study Design: Retrospective cohort study of patients 0-18 years of age without congenital heart disease who presented to our pediatric hospital from January 2003 to December 2012 for the treatment of acute SVT. Multiple logistic regression was applied to identify whether age was a risk factor for different SVT therapies. Model fit and residuals also were examined.

Results: We identified 179 episodes for SVT. First dose of adenosine was effective in 72 (56%) episodes, and a second dose was effective in 27 of 54 (50%) episodes, leaving 27 (15%) episodes with refractory SVT. The response to the first dose of adenosine increased proportionally with age (OR 1.13, 95% CI 1.05-1.2). Only 1 of 17 episodes in infants responded to the first dose of adenosine. Refractory SVT was more frequent in infants vs older children (χ = 5.9 [1 df], P = .01). Unstable SVT was present in 13 episodes and was treated with adenosine and antiarrhythmics. Synchronized cardioversion was performed on 3 patients, 2 patients with unstable SVT, and 1 with refractory SVT.

Conclusion: In children with SVT, young age is associated with decreased response to the first dose of adenosine and increased odds of adenosine-refractory SVT. In the treatment of unstable SVT, medical management with various antiarrhythmics before cardioversion may have a role in a subset of patients. Synchronized cardioversion rarely is performed for acute SVT.
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http://dx.doi.org/10.1016/j.jpeds.2016.10.051DOI Listing
February 2017

Comparison of Physician Implicit Racial Bias Toward Adults Versus Children.

Acad Pediatr 2017 03 13;17(2):120-126. Epub 2016 Sep 13.

Division of General Internal Medicine, University of Pittsburgh, and Veterans Affairs Pittsburgh Healthcare System, Center for Health Equity Research and Promotion, Pittsburgh, Pa.

Background And Objectives: The general population and most physicians have implicit racial bias against black adults. Pediatricians also have implicit bias against black adults, albeit less than other specialties. There is no published research on the implicit racial attitudes of pediatricians or other physicians toward children. Our objectives were to compare implicit racial bias toward adults versus children among resident physicians working in a pediatric emergency department, and to assess whether bias varied by specialty (pediatrics, emergency medicine, or other), gender, race, age, and year of training.

Methods: We measured implicit racial bias of residents before a pediatric emergency department shift using the Adult and Child Race Implicit Association Tests (IATs). Generalized linear models compared Adult and Child IAT scores and determined the association of participant demographics with Adult and Child IAT scores.

Results: Among 91 residents, we found moderate pro-white/anti-black bias on both the Adult (mean = 0.49, standard deviation = 0.34) and Child Race IAT (mean = 0.55, standard deviation = 0.37). There was no significant difference between Adult and Child Race IAT scores (difference = 0.06, P = .15). Implicit bias was not associated with resident demographic characteristics, including specialty.

Conclusions: This is the first study demonstrating that resident physicians have implicit racial bias against black children, similar to levels of bias against black adults. Bias in our study did not vary by resident demographic characteristics, including specialty, suggesting that pediatric residents are as susceptible as other physicians to implicit bias. Future studies are needed to explore how physicians' implicit attitudes toward parents and children may impact inequities in pediatric health care.
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http://dx.doi.org/10.1016/j.acap.2016.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5337439PMC
March 2017

History of Somatization Is Associated with Prolonged Recovery from Concussion.

J Pediatr 2016 Jul 5;174:39-44.e1. Epub 2016 Apr 5.

Department of Pediatrics, Division of Pediatric Emergency Medicine, Children's Hospital of Pittsburgh, Pittsburgh, PA.

Objective: To determine the association between a history of somatization and prolonged concussion symptoms, including sex differences in recovery.

Study Design: A prospective cohort study of 10- to 18-year-olds with an acute concussion was conducted from July 2014 to April 2015 at a tertiary care pediatric emergency department. One hundred twenty subjects completed the validated Children's Somatization Inventory (CSI) for pre-injury somatization assessment and Postconcussion Symptoms Scale (PCSS) at diagnosis. PCSS was re-assessed by phone at 2 and 4 weeks. CSI was assessed in quartiles with a generalized estimating equation model to determine relationship of CSI to PCSS over time.

Results: The median age of our study participants was 13.8 years (IQR 11.5, 15.8), 60% male, with separate analyses for each sex. Our model showed a positive interaction between total CSI score, PCSS and time from concussion for females P < .01, and a statistical trend for males, P = .058. Females in the highest quartile of somatization had higher PCSS than the other 3 CSI quartiles at each time point (B -26.7 to -41.1, P values <.015).

Conclusions: Patients with higher pre-injury somatization had higher concussion symptom scores over time. Females in the highest somatization quartile had prolonged concussion recovery with persistently high symptom scores at 4 weeks. Somatization may contribute to sex differences in recovery, and assessment at the time of concussion may help guide management and target therapy.
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http://dx.doi.org/10.1016/j.jpeds.2016.03.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4925238PMC
July 2016

The Impact of Cognitive Stressors in the Emergency Department on Physician Implicit Racial Bias.

Acad Emerg Med 2016 Mar 22;23(3):297-305. Epub 2016 Feb 22.

Division of General Internal Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA.

Objectives: The emergency department (ED) is characterized by stressors (e.g., fatigue, stress, time pressure, and complex decision-making) that can pose challenges to delivering high-quality, equitable care. Although it has been suggested that characteristics of the ED may exacerbate reliance on cognitive heuristics, no research has directly investigated whether stressors in the ED impact physician racial bias, a common heuristic. We seek to determine if physicians have different levels of implicit racial bias post-ED shift versus preshift and to examine associations between demographics and cognitive stressors with bias.

Methods: This repeated-measures study of resident physicians in a pediatric ED used electronic pre- and postshift assessments of implicit racial bias, demographics, and cognitive stressors. Implicit bias was measured using the Race Implicit Association Test (IAT). Linear regression models compared differences in IAT scores pre- to postshift and determined associations between participant demographics and cognitive stressors with postshift IAT and pre- to postshift difference scores.

Results: Participants (n = 91) displayed moderate prowhite/antiblack bias on preshift (mean ± SD = 0.50 ± 0.34, d = 1.48) and postshift (mean ± SD = 0.55 ± 0.39, d = 1.40) IAT scores. Overall, IAT scores did not differ preshift to postshift (mean increase = 0.05, 95% CI = -0.02 to 0.14, d = 0.13). Subanalyses revealed increased pre- to postshift bias among participants working when the ED was more overcrowded (mean increase = 0.09, 95% CI = 0.01 to 0.17, d = 0.24) and among those caring for >10 patients (mean increase = 0.17, 95% CI = 0.05 to 0.27, d = 0.47). Residents' demographics (including specialty), fatigue, busyness, stressfulness, and number of shifts were not associated with postshift IAT or difference scores. In multivariable models, ED overcrowding was associated with greater postshift bias (coefficient = 0.11 per 1 unit of NEDOCS score, SE = 0.05, 95% CI = 0.00 to 0.21).

Conclusions: While resident implicit bias remained stable overall preshift to postshift, cognitive stressors (overcrowding and patient load) were associated with increased implicit bias. Physicians in the ED should be aware of how cognitive stressors may exacerbate implicit racial bias.
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http://dx.doi.org/10.1111/acem.12901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5020698PMC
March 2016

Protein disulfide isomerase as a novel target for cyclopentenone prostaglandins: implications for hypoxic ischemic injury.

FEBS J 2015 May 27;282(10):2045-59. Epub 2015 Mar 27.

Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, PA, USA.

Cyclooxygenase-2 (COX-2) is an important contributor to ischemic brain injury. Identification of the downstream mediators of COX-2 toxicity may allow the development of targeted therapies. Of particular interest is the cyclopentenone family of prostaglandin metabolites. Cyclopentenone prostaglandins (CyPGs) are highly reactive molecules that form covalent bonds with cellular thiols. Protein disulfide isomerase (PDI) is an important molecule for the restoration of denatured proteins following ischemia. Because PDI has several thiols, including thiols within the active thioredoxin-like domain, we hypothesized that PDI is a target of CyPGs and that CyPG binding of PDI is detrimental. CyPG-PDI binding was detected in vitro via immunoprecipitation and MS. CyPG-PDI binding decreased PDI enzymatic activity in recombinant PDI treated with CyPG, and PDI immunoprecipitated from neuronal culture treated with CyPG or anoxia. Toxic effects of binding were demonstrated in experiments showing that: (a) pharmacologic inhibition of PDI increased cell death in anoxic neurons, (b) PDI overexpression protected neurons exposed to anoxia and SH-SY5Y cells exposed to CyPG, and (c) PDI overexpression in SH-SY5Y cells attenuated ubiquitination of proteins and decreased activation of pro-apoptotic caspases. In conclusion, CyPG production and subsequent binding of PDI is a novel and potentially important mechanism of ischemic brain injury. We show that CyPGs bind to PDI, cyclopentenones inhibit PDI activity, and CyPG-PDI binding is associated with increased neuronal susceptibility to anoxia. Additional studies are necessary to determine the relative role of CyPG-dependent inhibition of PDI activity in ischemia and other neurodegenerative disorders.
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http://dx.doi.org/10.1111/febs.13259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972022PMC
May 2015