Randall Childrens Hospital at Legacy Emanuel

Portland, United States

Randall Childrens Hospital at Legacy Emanuel

Portland, United States
SEARCH FILTERS
Time filter
Source Type

Huston R.K.,PC and Pediatrix Medical Group | Heisel C.F.,Randall Childrens Hospital at Legacy Emanuel | Vermillion B.R.,Randall Childrens Hospital at Legacy Emanuel | Christensen J.M.,Oregon State University | Minc L.,Oregon State University
Nutrition in Clinical Practice | Year: 2017

Introduction: Calcium chloride (CaCl2) has been the only calcium additive available in the United States that has a low aluminum (Al) content. Calcium gluconate in glass vials (CaGluc-Gl) has a high Al content while calcium gluconate in plastic vials (CaGluc-Pl) has a low Al content. The purpose of this study was to measure Al concentrations in neonatal parenteral nutrition (PN) solutions prepared using various calcium additives. Methods: Samples of solutions compounded with CaCl2 or CaGluc-Gl and sodium phosphate (NaPhos) as well as CaGluc-Pl and sodium glycerophosphate (NaGP) with and without cysteine were analyzed for Al content. Samples of the cysteine and calcium gluconate additives were also sent for analysis. Results: Solutions containing CaCl2 and CaGlu-Pl had mean Al concentrations of 1.2-2.3 mcg/dL, while those with CaGlu-Gl had mean concentrations of 14.6-15.1 mcg/dL. Solutions made with NaGP were low in Al content. The measured Al content of 2 lots of the cysteine additive were 168 ± 23 mcg/L and 126 ± 5 mcg/L. The Al concentration equalled 2730 ± 20 mcg/L for the CaGlu-Gl additive and 310 ± 80 mcg/L for the CaGlu-Pl additive. Conclusion: The study indicates that solutions containing CaCl2 or CaGluc-Pl and NaPhos or NaGP are low in Al content. Using these options for calcium and phosphate additives can limit aluminum intake from neonatal PN to levels within the Food and Drug Administration guideline of ≤5 mcg/kg/d. © The American Society for Parenteral and Enteral Nutrition.


Kingsbury D.J.,Randall Childrens Hospital at Legacy Emanuel | Bader-Meunier B.,Hopital Necker Enfants Malades | Patel G.,AbbVie | Arora V.,AbbVie | And 2 more authors.
Clinical Rheumatology | Year: 2014

The objective of this study was to assess the safety of adalimumab in patients aged 2 to <4 years old or ≥4 years old weighing <15 kg with moderately to severely active polyarticular juvenile idiopathic arthritis (JIA). Clinical effectiveness and pharmacokinetics (PK) of adalimumab were also evaluated. This was an international, multicenter, open-label, phase 3b study in 32 patients with active JIA that were treated with adalimumab 24 mg/m2 (maximum = 20 mg/dose) every other week up to 120 weeks, with or without concomitant methotrexate. Adverse events (AEs) were summarized for completed visits. Efficacy endpoints included American College of Rheumatology pediatric (PedACR) 30/50/70/90 responses and JIA core components. Adalimumab serum trough concentrations were measured in a subset of patients. Among the patients, 88 % were female. Baseline mean age, weight, and JIA duration were 3 years, 13 kg, and 12 months, respectively; 39 % had elevated C-reactive protein. AE incidence rates included any AEs (29/32, 91 %), serious AEs (5/32, 16 %), infectious AEs (25/32, 78 %), and serious infections (3/32, 9 %). No deaths, malignancies, or opportunistic infections were reported. Growth was not adversely impacted. At week 96, 92 % of patients achieved PedACR30, and 77 % achieved PedACR70. Improvements in JIA core components were observed. Mean steady-state serum adalimumab trough concentrations were 7-8 μg/mL at weeks 12 and 24. Adalimumab was well tolerated in JIA patients aged 2 to <4 years old or ≥4 years old weighing <15 kg. The efficacy and PK of adalimumab were comparable to those seen in older JIA patients. © 2014 The Author(s).


Karageorgiadis A.S.,U.S. National Institutes of Health | Papadakis G.Z.,U.S. National Institutes of Health | Biro J.,U.S. National Institutes of Health | Keil M.F.,U.S. National Institutes of Health | And 12 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2015

Context: Ectopic ACTH/CRH syndrome is a rare cause of Cushing syndrome (CS), especially in children. The localization, work-up, and management of ACTH/CRH-secreting tumors are discussed. Setting: A retrospective study was conducted of patients under 21 years of age evaluated at the National Institutes of Health (NIH) for CS and diagnosed with ectopic ACTH/CRH-secreting tumors during the period 2009-2014. Patients: Seven patients with ectopicACTH/CRHCS are included in this study with amedianage 13.6 years (range 1-21), and 3 are female. Measurements: Clinical, biochemical, radiological features, treatment, and histological findings are described. Results: Seven patients were found to have ACTH/CRH-secreting tumors, all with neuroendocrine features. The site of the primary lesion varied: pancreas (3), thymus (2), liver (1), right lower pulmonary lobe (1). Patients underwent biochemical evaluation for CS, including diurnal serum cortisol and ACTH levels, urinary free cortisol levels (UFC), and CRH stimulation tests. All patients underwent radiological investigations including MRI, CT, and PET scan; imaging with octreotide and 68 gallium DOTATATE scans were performed in individual cases. Five patients underwent inferior petrosal sinus sampling; 4 patients had sampling for ACTH and CRH levels from additional sites. Three patients underwent trans-sphenoidal surgery (TSS), and 3 patients required bilateral adrenalectomy. Three patients (43%) died due to metastatic disease, demonstrating the high mortality rate. One of the unique findings in these seven patients is that in each case, their neuroendocrine tumors were ultimately proven to be co-secreting ACTH and CRH. This explains the enigmatic presentation, in which 3 patients initially thought to have Cushing's disease (CD) with corresponding pituitary hyperplasia underwent TSS prior to the correct localization of the causative tumor. Conclusions: EctopicACTH/CRHco-secreting tumors are extremely rare in children and adolescents. The diagnosis of this condition is frequently missed and is sometimes confused with CD due to the effect of CRH on the pituitary. © 2015 by the Endocrine Society.


Bath S.,University of Portland | Lines J.,Randall Childrens Hospital at Legacy Emanuel | Loeffler A.M.,Randall Childrens Hospital at Legacy Emanuel | Malhotra A.,University of the Pacific at Stockton | Turner R.B.,University of Portland
Journal of Thoracic and Cardiovascular Surgery | Year: 2016

Objectives: The optimal duration of antimicrobial prophylaxis following pediatric cardiac surgery is still debated. Adult studies suggest that shorter durations are adequate, but there is a paucity of data on pediatric patients. Methods: This quasi-experimental study reviewed the charts of patients 18 years and younger who underwent cardiac surgery from April 2011 to November 2014 at a single institution. Starting in April 2013, a protocol was implemented to limit antimicrobial prophylaxis to 48 hours following sternal closure. Two analyses were performed: (1) identification of risk factors for surgical site infections from the entire cohort, and (2) comparison of surgical site infection incidence in the pre- and postprotocol groups. Results: In the entire cohort, delayed sternal closure (adjusted odds ratio [OR], 5.7; 95% confidence interval [CI], 1.8-17.9) and younger age (adjusted OR, 2.1; 95% CI, 1.1-3.8) were associated with incidence of surgical site infection. Following the protocol change, duration of antimicrobial prophylaxis decreased from 4.2 ± 2.7 to 1.9 ± 1.3 days (P < .0001). After adjusting for age and delayed sternal closure, the postprotocol group had an adjusted OR of 0.98 (95% CI, 0.32-3.00) for occurrence of surgical site infection. Other outcomes were not altered following the protocol change. Conclusions: Restricting antimicrobial prophylaxis to 48 hours following pediatric cardiac surgery did not increase the incidence of surgical site infection at our institution. Further study is needed to validate this finding and to identify practices that reduce surgical site infections in those with delayed sternal closure. © 2016 The American Association for Thoracic Surgery.


Henderson L.A.,Harvard University | Zurakowski D.,Harvard University | Angeles-Han S.T.,Emory University | Lasky A.,Randall Childrens Hospital at Legacy Emanuel | And 2 more authors.
Pediatric Rheumatology | Year: 2016

Background: There is not yet a commonly accepted, standardized approach in the treatment of juvenile idiopathic uveitis when initial steroid therapy is insufficient. We sought to assess current practice patterns within a large cohort of children with juvenile uveitis. Methods: This is a cross-sectional cohort study of patients with uveitis enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRAnet) registry. Clinical information including, demographic information, presenting features, disease complications, and medications were collected. Chi-square and Fisher's exact tests were used to assess for associations between medications and clinical characteristics. Results: Ninety-two children with idiopathic and 656 with juvenile idiopathic arthritis (JIA)-associated uveitis were identified. Indication (arthritis or uveitis) for medication use was not available for JIA patients; therefore, detailed analysis was limited to children with idiopathic uveitis. In this group, 94 % had received systemic steroids. Methotrexate (MTX) was used in 76 % of patients, with oral and subcutaneous forms given at similar rates. In multivariable analysis, non-Caucasians were more likely to be treated initially with subcutaneous MTX (P = 0.003). Of the 53 % of patients treated with a biologic DMARD, all received a tumor necrosis factor (TNF) inhibitor. TNF inhibitor use was associated with a higher frequency of cataracts (52 % vs 21 %; P = 0.001) and antinuclear antibody positivity (49 % vs 29 %; P = 0.04), although overall complication rates were not higher in these patients. Conclusion: Among idiopathic uveitis patients enrolled in the CARRAnet registry, MTX was the most commonly used DMARD, with subcutaneous and oral forms equally favored. Patients who received a TNF inhibitor were more likely to be ANA positive and have cataracts. © 2016 Henderson et al.


PubMed | Randall Childrens Hospital at Legacy Emanuel, Emory University, Harvard University and Duke Childrens
Type: Journal Article | Journal: Pediatric rheumatology online journal | Year: 2016

There is not yet a commonly accepted, standardized approach in the treatment of juvenile idiopathic uveitis when initial steroid therapy is insufficient. We sought to assess current practice patterns within a large cohort of children with juvenile uveitis.This is a cross-sectional cohort study of patients with uveitis enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRAnet) registry. Clinical information including, demographic information, presenting features, disease complications, and medications were collected. Chi-square and Fishers exact tests were used to assess for associations between medications and clinical characteristics.Ninety-two children with idiopathic and 656 with juvenile idiopathic arthritis (JIA)-associated uveitis were identified. Indication (arthritis or uveitis) for medication use was not available for JIA patients; therefore, detailed analysis was limited to children with idiopathic uveitis. In this group, 94% had received systemic steroids. Methotrexate (MTX) was used in 76% of patients, with oral and subcutaneous forms given at similar rates. In multivariable analysis, non-Caucasians were more likely to be treated initially with subcutaneous MTX (P=0.003). Of the 53% of patients treated with a biologic DMARD, all received a tumor necrosis factor (TNF) inhibitor. TNF inhibitor use was associated with a higher frequency of cataracts (52% vs 21%; P=0.001) and antinuclear antibody positivity (49% vs 29%; P=0.04), although overall complication rates were not higher in these patients.Among idiopathic uveitis patients enrolled in the CARRAnet registry, MTX was the most commonly used DMARD, with subcutaneous and oral forms equally favored. Patients who received a TNF inhibitor were more likely to be ANA positive and have cataracts.


PubMed | Oregon Health And Science University, Randall Childrens Hospital at Legacy Emanuel, Oncotide Pharmaceuticals, Inc., Dana-Farber Cancer Institute and University of Navarra
Type: Journal Article | Journal: Oncotarget | Year: 2016

Recent evidence suggests that inhibition of protein phosphatase 2A (PP2A) tumor suppressor activity via the SET oncoprotein contributes to the pathogenesis of various cancers. Here we demonstrate that both SET and c-MYC expression are frequently elevated in T-ALL cell lines and primary samples compared to healthy T cells. Treatment of T-ALL cells with the SET antagonist OP449 restored the activity of PP2A and reduced SET interaction with the PP2A catalytic subunit, resulting in a decrease in cell viability and c-MYC expression in a dose-dependent manner. Since a tight balance between phosphatases and kinases is required for the growth of both normal and malignant cells, we sought to identify a kinase inhibitor that would synergize with SET antagonism. We tested various T-ALL cell lines against a small-molecule inhibitor screen of 66 compounds targeting two-thirds of the tyrosine kinome and found that combined treatment of T-ALL cells with dovitinib, an orally active multi-targeted small-molecule receptor tyrosine kinase inhibitor, and OP449 synergistically reduced the viability of all tested T-ALL cell lines. Mechanistically, combined treatment with OP449 and dovitinib decreased total and phospho c-MYC levels and reduced ERK1/2, AKT, and p70S6 kinase activity in both NOTCH-dependent and independent T-ALL cell lines. Overall, these results suggest that combined targeting of tyrosine kinases and activation of serine/threonine phosphatases may offer novel therapeutic strategies for the treatment of T-ALL.


PubMed | Cincinnati Childrens Hospital Medical Center, University of Genoa, Randall Childrens Hospital at Legacy Emanuel, Hospital for Sick Children and 14 more.
Type: Journal Article | Journal: Arthritis research & therapy | Year: 2017

Canakinumab is a human anti-interleukin-1 (IL-1) monoclonal antibody neutralizing IL-1-mediated pathways. We sought to characterize the molecular response to canakinumab and evaluate potential markers of response using samples from two pivotal trials in systemic juvenile idiopathic arthritis (SJIA).Gene expression was measured in patients with febrile SJIA and in matched healthy controls by Affymetrix DNA microarrays. Transcriptional response was assessed by gene expression changes from baseline to day 3 using adapted JIA American College of Rheumatology (aACR) response criteria (50 aACR JIA). Changes in pro-inflammatory cytokines IL-6 and IL-18 were assessed up to day 197.Microarray analysis identified 984 probe sets differentially expressed (2-fold difference; P<0.05) in patients versus controls. Over 50% of patients with 50 aACR JIA were recognizable by baseline expression values. Analysis of gene expression profiles from patients achieving 50 aACR JIA response at day 15 identified 102 probe sets differentially expressed upon treatment (2-fold difference; P<0.05) on day 3 versus baseline, including IL-1, IL-1 receptors (IL1-R1 and IL1-R2), IL-1 receptor accessory protein (IL1-RAP), and IL-6. The strongest clinical response was observed in patients with higher baseline expression of dysregulated genes and a strong transcriptional response on day 3. IL-6 declined by day 3 (8-fold decline; P<0.0001) and remained suppressed. IL-18 declined on day 57 (1.5-fold decline, P0.002).Treatment with canakinumab in SJIA patients resulted in downregulation of innate immune response genes and reductions in IL-6 and clinical symptoms. Additional research is needed to investigate potential differences in the disease mechanisms in patients with heterogeneous gene transcription profiles.Clinicaltrials.gov: NCT00886769 (trial 1). Registered on 22 April 2009; NCT00889863 (trial 2). Registered on 21 April 2009.


PubMed | University of the Pacific at Stockton, Randall Childrens Hospital at Legacy Emanuel and University of Portland
Type: Journal Article | Journal: The Journal of thoracic and cardiovascular surgery | Year: 2016

The optimal duration of antimicrobial prophylaxis following pediatric cardiac surgery is still debated. Adult studies suggest that shorter durations are adequate, but there is a paucity of data on pediatric patients.This quasi-experimental study reviewed the charts of patients 18years and younger who underwent cardiac surgery from April 2011 to November 2014 at a single institution. Starting in April 2013, a protocol was implemented to limit antimicrobial prophylaxis to 48hours following sternal closure. Two analyses were performed: (1) identification of risk factors for surgical site infections from the entire cohort, and (2) comparison of surgical site infection incidence in the pre- and postprotocol groups.In the entire cohort, delayed sternal closure (adjusted odds ratio [OR], 5.7; 95% confidence interval [CI], 1.8-17.9) and younger age (adjusted OR, 2.1; 95% CI, 1.1-3.8) were associated with incidence of surgical site infection. Following the protocol change, duration of antimicrobial prophylaxis decreased from 4.22.7 to 1.91.3days (P<.0001). After adjusting for age and delayed sternal closure, the postprotocol group had an adjusted OR of 0.98 (95% CI, 0.32-3.00) for occurrence of surgical site infection. Other outcomes were not altered following the protocol change.Restricting antimicrobial prophylaxis to 48hours following pediatric cardiac surgery did not increase the incidence of surgical site infection at our institution. Further study is needed to validate this finding and to identify practices that reduce surgical site infections in those with delayed sternal closure.


PubMed | PC and Pediatrix Medical Group, Randall Childrens Hospital at Legacy Emanuel and Oregon State University
Type: | Journal: Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition | Year: 2016

Calcium chloride (CaClSamples of solutions compounded with CaClSolutions containing CaClThe study indicates that solutions containing CaCl

Loading Randall Childrens Hospital at Legacy Emanuel collaborators
Loading Randall Childrens Hospital at Legacy Emanuel collaborators