Olga A. Taylor

Stigmasterol, a soy lipid-derived phytosterol, is an antagonist of the bile acid nuclear receptor FXR.

Phytosterols, components of soy-derived lipids, are among the proposed exacerbants of parenteral nutrition–associated cholestasis (PNAC). We investigated whether phytosterols contribute to bile acid (BA)–induced hepatocyte damage by antagonizing a nuclear receptor (NR) critically involved in hepatoprotection from cholestasis, FXR (farnesoid X receptor, NR1H4). In HepG2 cells, stigmasterol acetate (StigAc), a water-soluble Stig derivative, suppressed ligand-activated expression of FXR target genes involved in adaptation to cholestasis (i.e. BSEP, FGF-19, OSTα/β). Furthermore, StigAc antagonized BA-activated, FXR target genes SHP and BSEP in FXR+/+, but not in FXR−/− mouse hepatocytes. Both Stig and StigAc inhibited BA-activated, FXR-dependent reporter gene expression in transfected HepG2 cells, whereas the most prevalent phytosterol in lipids, β-sitosterol, had no inhibitory effect. Finally, among six ligand-activated NR-ligand binding domains (LBDs) tested, antagonism by StigAc was specific to only two (FXR and PXR, pregnane X receptor, NR1I2). We demonstrate that Stig, a phytosterol prevalent in soy-derived PN lipid solutions, is a potent in vitro antagonist of the NR for bile acids FXR.

Managing painful procedures in children with cancer.

Children with cancer experience repeated invasive and painful medical procedures. Pain and distress does not decrease with repeated procedures and may worsen if pain is not adequately managed. In 1990, the first recommendations on the management of pain and anxiety associated with procedures for children with cancer were published. Guiding principles described in the recommendations continue to hold true today: maximize comfort and minimize pain, use nonpharmacologic and pharmacologic interventions, prepare the child and family, consider the developmental age of the child, support family and child involvement, assure provider competency in performing procedures and sedation, and use appropriate monitoring to assure safety. This article reviews these key components for managing painful procedures in children and reviews the latest pharmacological and nonpharmacological interventions most effective in minimizing pain and discomfort.

Children's Coping Strategies for Chemotherapy-Induced Nausea and Vomiting

PURPOSE/OBJECTIVES To identify anticipatory, acute, and delayed chemotherapy-induced nausea and vomiting (CINV) frequency and coping strategies used among pediatric patients with cancer. DESIGN Prospective, cohort design. SETTING A pediatric teaching hospital in the southern United States. SAMPLE A convenience sample of 40 children aged 7-12 years scheduled to receive either moderately emetic chemotherapy or highly emetic chemotherapy for cancer treatment. METHODS Children completed the Adapted Rhodes Index of Nausea and Vomiting for Pediatrics and the Kidcope-Younger Version. MAIN RESEARCH VARIABLES CINV and coping strategies. FINDINGS CINV occurred during the anticipatory, acute, and delayed times, with the highest frequency occurring during the delayed time. The most frequently used coping strategies were distraction and wishful thinking, whereas the most effective strategies were social support and distraction. No statistically significant differences were observed in the frequency or efficacy of coping strategies over time. CONCLUSIONS CINV occurs throughout chemotherapy treatment. The most efficacious coping strategies included active and passive coping, with active coping strategies being more effective. IMPLICATIONS FOR NURSING Nurses should recognize that CINV occurs at all points of chemotherapy treatment. Nurses can assist children in developing active coping strategies to manage their CINV.

Nausea and vomiting perspectives among children receiving moderate to highly emetogenic chemotherapy treatment.

Background: Chemotherapy-induced nausea and vomiting (CINV) are common adverse effects, but occurrences among pediatric oncology patients are not well documented. Objective: The primary aim was to describe anticipatory, acute, and delayed CINV among children with cancer from the child’s, caregiver’s, and nurse’s perspective. A secondary aim evaluates the correlation of CINV among the child’s, caregiver’s, and nurse’s perspectives. Methods: CINV perspectives were evaluated before, during, and after a single course of highly or moderately emetogenic chemotherapy. CINV were evaluated among 40 pediatric cancer patients using the Adapted Rhodes Index of Nausea and Vomiting for Pediatrics, among their caregivers using the Adapted Rhodes Index of Nausea and Vomiting for Parents, and among their nurses using the National Cancer Institute Nausea and Vomiting Grading Criteria. Results: CINV were reported by the patient, caregiver, and nurse at all times, with the most frequent reports occurring in the delayed period. Patient’s mean total nausea and vomiting scores increased significantly over time. Patient reports of anticipatory, acute, and delayed CINV correlated with caregiver and nurse reports except for anticipatory nausea between the nurse and patient. Conclusions: CINV occurred throughout the chemotherapy course, with delayed CINV occurring most frequently and with greater severity and distress. Caregiver CINV reports correlated closely with patient reports. Implications for Practice: Nurses need to be aware of the frequency, severity, and distress of CINV throughout the chemotherapy regimen. CINV can occur before and after chemotherapy treatment and should be assessed so that appropriate interventions can be implemented.

Neurocognitive predictors of academic outcomes among childhood leukemia survivors

Background: Acute lymphoblastic leukemia is the most common pediatric cancer, and survival approaches 90%. Acute lymphoblastic leukemia survivors are more likely than healthy peers or siblings to experience academic underachievement, yet little is known about neurocognitive predictors of academic outcomes. Objectives: Objectives were to compare neurocognitive abilities to age-adjusted standardized norms, examine change over time in neurocognitive abilities, and establish neurocognitive predictors of academic outcomes. Methods: Seventy-one children were followed over the course of therapy. Cognitive abilities were assessed during induction when the child was in remission (baseline) and annually for 3 years (years 1, 2, and 3). Reading and mathematics abilities were assessed at year 3. Results: Fine motor dexterity was significantly below age-adjusted norms at all data points but showed improvement over time. Baseline visual-motor integration was within the reference range but significantly declined by year 3, and mean scores at years 2 and 3 were significantly below age-adjusted norms. Verbal short-term memory was significantly below age-adjusted norms at all assessments. Visual-motor integration predicted reading and mathematics abilities. Verbal short-term memory predicted reading abilities, and visual short-term memory predicted mathematics abilities. Conclusions: Central nervous system–directed therapy is associated with specific neurocognitive problems. Visual-spatial skills and verbal and visual short-term memory predict academic outcomes. Implications for Practice: Early assessment of visual-spatial perception and short-term memory can identify children at risk of academic problems. Children who are at risk of academic problems could benefit from a school-based individual educational program and/or educational intervention.

F2-Isoprostanes A Measure of Oxidative Stress in Children Receiving Treatment for Leukemia

Acute lymphoblastic leukemia (ALL) is the most prevalent and curable cancer among children and adolescents less than 15 years of age in the United States. Essential for cure of childhood ALL is prophylactic treatment of the central nervous system (CNS), with methotrexate (MTX) being the most widely used drug in this treatment. While CNS treatment has contributed to long-term disease-free survival, resulting declines in academic abilities have been reported. There is growing evidence that CNS treatment with MTX increases oxidative stress, a potential mechanism of CNS injury. This article reports changes in oxidative stress, measured by the biomarker F2-isoprostane (F2-IsoP), in the cerebrospinal fluid (CSF) in 47 children with ALL during the first 18 months of treatment. The number of CSF samples ranged from 5 to 14 during postinduction and from 1 to 9 during continuation. Total doses of intrathecal MTX during postinduction were significantly correlated with the mean and highest concentrations of F2-IsoP during postinduction and the mean concentration of F2-IsoP during continuation. F2-IsoP concentrations during postinduction and continuation were higher in children who received more than six doses of intrathecal MTX. New therapies for a highly curable disease such as childhood leukemia have the potential to be individualized in the future, requiring reliable molecular and biochemical markers, such as oxidative stress indicators. Innovative use of biomarkers has the potential to increase our understanding of treatment-related toxicities and associated symptoms and to inform future therapeutic approaches for optimizing cure and quality of life among children with leukemia.

The influence of oxidative stress on symptom occurrence, severity, and distress during childhood leukemia treatment.

PURPOSE/OBJECTIVES To explore the symptom trajectory during the first 16 months of childhood leukemia treatment and any associations with the oxidative stress pathway measured by cerebrospinal fluid (CSF) concentration of oxidized phosphatidylcholine (PC), the predominant glycerophospholipid in the brain and cell membranes. DESIGN Prospective, longitudinal design. SETTING Two cancer centers in the southwestern United States. SAMPLE 36 children (aged 3-14 years) newly diagnosed with acute lymphoblastic leukemia. METHODS Symptoms were measured using the Memorial Symptom Assessment Scale at six specific time points during treatment. Biochemical changes in oxidative stress were measured by oxidized PC in the CSF. MAIN RESEARCH VARIABLES Childhood cancer symptoms, oxidized PC. FINDINGS Significant differences were found in the number of symptoms experienced during the three phases of treatment. Symptom trajectory changes and influence of the oxidative stress pathway on symptom experiences were identified. CONCLUSIONS Symptoms experienced during treatment for childhood leukemia are associated with increased oxidative stress. IMPLICATIONS FOR NURSING Children with leukemia experience symptoms throughout treatment. Physiologic measures indicate the influence of oxidative stress on symptoms.

Fatigue and Oxidative Stress in Children Undergoing Leukemia Treatment

Fatigue is a frequent and distressing symptom in children undergoing leukemia treatment; however, little is known about factors influencing this symptom. Antioxidants such as glutathione can decrease symptom severity in adult oncology patients, but no study has evaluated antioxidants’ effects on symptoms in pediatric oncology patients. This study describes fatigue patterns and associations of fatigue with antioxidants represented by reduced glutathione (GSH) and the reduced/oxidized glutathione (GSH/GSSG) ratio among children receiving leukemia treatment. A repeated measures design assessed fatigue and antioxidants among 38 children from two large U.S. cancer centers. Fatigue was assessed among school-age children and by parent proxy among young children. Antioxidants (GSH and GSH/GSSG ratio) were assessed from cerebrospinal fluid at four phases during leukemia treatment. Young children had a steady decline of fatigue from the end of induction treatment through the continuation phase of treatment, but no significant changes were noted among the school-age children. Mean antioxidant scores varied slightly over time; however, the GSH/GSSG ratios in these children were significantly lower than the normal ratio. Mean GSH/GSSG ratios significantly correlated to fatigue scores of the school-age children during early phases of treatment. Children with low mean GSH/GSSG ratios demonstrated oxidative stress. The low ratios noted early in therapy were significantly correlated with higher fatigue scores during induction and postinduction treatment phases. This finding suggests that increased oxidative stress during the more intensive phases of therapy may explain the experience of fatigue children report.

Evaluation of Biomarkers of Oxidative Stress and Apoptosis in Patients With Severe Methotrexate Neurotoxicity: A Case Series

Central nervous system (CNS) treatment is an essential part of acute lymphocytic leukemia (ALL) therapy, and the most common CNS treatment is intrathecal (IT) and high-dose intravenous (IV) methotrexate (MTX). Treatment with MTX may cause neurotoxicity, which is often accompanied by neurologic changes, delays in treatment, and prolonged hospital stays. This article reports clinical presentations of 3 patients with severe MTX toxicity as well as levels of oxidative stress and apoptosis biomarkers in cerebrospinal fluid (CSF). Oxidative stress was measured by oxidized phosphatidylcholine (PC), oxidized phosphatidylinositol (PI), and F2 isoprostanes; apoptosis was measured by caspase 3/7 activity. Most consistent biomarker changes in all 3 cases were increases in caspase 3/7 and F2 isoprostanes prior to acute toxicity while increases in oxidized phospholipids occurred slightly later. Progressive increases in F2 isoprostanes and caspase 3/7 activity prior to and/or during acute toxicity suggests MTX induces oxidative stress and an associated increase in apoptosis. These findings support the role of oxidative stress in MTX-related neurotoxicity.

Using Improvement Science to Promote Evidence-Based Practice in a Childhood Cancer and Hematology Center

A major children’s cancer and hematology center established a Quality Transformation (QT) Core to develop and monitor empirical outcomes that demonstrate excellence in clinical care. The QT Core, based on the Institute of Medicine’s domains of quality health care, aims to ensure that care is safe, effective, patient centered, timely, efficient, and equitable. Specific goals for the first year of the QT Core were to develop a team of improvement science experts, engage faculty and staff in QT initiatives, promote accountability for excellence in clinical care, and establish specific metrics to evaluate process, structure, and outcomes for QT Core projects. The purpose of this article is to discuss the successful development of a quality transformation core within a pediatric subspecialty and demonstrate the principles of improvement science through an actual quality transformation project designed to implement an evidence-based guideline for procedural sedation for children with cancer. The QT Core within this subspecialty was founded on principles of successful transformation of patient care that includes motivation to change, leaders committed to quality, active engagement of staff in meaningful problem-solving initiatives, alignment with organization goals with resource allocation, and integration to bridge boundaries throughout an organization. These key principles are demonstrated through the discussion of the development of the QT Core and implementation of an evidence-based procedure sedation guideline. Pediatric and pediatric subspecialty groups can be on the forefront of national initiatives that promote quality health care, exemplified by the QT Core developed within the cancer and hematology center.