ABSTRACT
BACKGROUND: Biomarkers for early detection of anthracycline (AC)-induced cardiotoxicity may allow cardioprotective intervention before irreversible damage. Circulating microRNAs (miRNAs) are promising biomarkers of cardiovascular disease, however, have not been studied in the setting of AC-induced cardiotoxicity. This study aimed to identify AC-induced alterations in plasma miRNA expression in children and correlate expression with markers of cardiac injury. METHODS AND RESULTS: Candidate plasma profiling of 24 miRNAs was performed in 33 children before and after a cycle of AC (n=24) or noncardiotoxic chemotherapy (n=9). Relative miRNA changes between the pre- and postcycle time points (6, 12, and 24 hours) were determined within each treatment group and compared across groups. Plasma miRNA expression patterns were further explored with respect to AC dose and high-sensitivity troponin T. Greater chemotherapy-induced dysregulation was observed in this panel of candidate, cardiac-related plasma miRNAs in patients receiving anthracyclines compared with those receiving noncardiotoxic chemotherapy (24-hour MANOVA; P=0.024). Specifically, plasma miRs-29b and -499 were upregulated 6 to 24 hours post-AC, and their postchemotherapy expression significantly correlated with AC dose. Patients with acute cardiomyocyte injury (high-sensitivity troponin T increase ≥5 ng/L from baseline) demonstrated higher expression of miR-29b and miR-499 post-AC compared with those without. CONCLUSIONS: In this pilot study, cardiac-related plasma miRNAs are dysregulated following ACs. Plasma miR-29b and -499 are acutely elevated post-AC, with dose response relationships observed with anthracycline dose and markers of cardiac injury. Further evaluation of miRNAs may provide mechanistic insight into AC-induced cardiotoxicity and yield biomarkers to facilitate earlier intervention to mitigate cardiotoxicity.
Subject(s)
Anthracyclines/adverse effects , Antibiotics, Antineoplastic/adverse effects , Heart Diseases/blood , MicroRNAs/blood , Myocytes, Cardiac/metabolism , Adolescent , Age Factors , Cardiotoxicity , Case-Control Studies , Child , Child, Preschool , Dose-Response Relationship, Drug , Early Diagnosis , Female , Genetic Markers , Heart Diseases/chemically induced , Heart Diseases/diagnosis , Heart Diseases/genetics , Humans , Infant , Male , MicroRNAs/genetics , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/pathology , Pilot Projects , Predictive Value of Tests , Prospective Studies , Time Factors , Troponin T/bloodABSTRACT
Therapy combining dinutuximab with granulocyte macrophage colony stimulating factor, interleukin 2, and isotretinoin has significant side effects; however, these complications are generally predictable and can be managed proactively.
ABSTRACT
BACKGROUND: This retrospective review provides preliminary data regarding the safety and efficacy of olanzapine for chemotherapy-induced vomiting (CIV) control in children. PROCEDURE: Children <18 years old who received olanzapine for acute chemotherapy-induced nausea and vomiting (CINV) control from December 2010 to August 2013 at four institutions were identified. Patient characteristics, chemotherapy, antiemetic prophylaxis, olanzapine dosing, CIV control, liver function test results and adverse events were abstracted from the health record. Toxicity was graded using CTCAEv4.03. RESULTS: Sixty children (median age 13.2 years; range: 3.10-17.96) received olanzapine during 158 chemotherapy blocks. Olanzapine was most often (59%) initiated due to a history of poorly controlled CINV. The mean initial olanzapine dose was 0.1 mg/kg/dose (range: 0.026-0.256). Most children who received olanzapine beginning on the first day of the chemotherapy block experienced complete CIV control throughout the acute phase (83/128; 65%). There was no association between the olanzapine dose/kg and complete CIV control (OR 1.01; 95% CI: 0.999-1.020; P = 0.091). Sedation was reported in 7% of chemotherapy blocks and was significantly associated with increasing olanzapine dose (OR: 1.17; 95% CI: 1.08-1.27; P = 0.0001). Of the 25 chemotherapy blocks where ALT and/or AST were reported more than once, grade 1-3 elevations were observed in five. The mean weight change in 31 children who received olanzapine during more than one chemotherapy block was 0% (range: -22 to +18). CONCLUSION: Olanzapine may be an important option to improve CIV control in children. Prospective controlled evaluation of olanzapine for CINV prophylaxis in children is warranted.
Subject(s)
Antiemetics/administration & dosage , Antineoplastic Agents , Benzodiazepines/administration & dosage , Neoplasms/drug therapy , Vomiting , Acute Disease , Adolescent , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Child , Child, Preschool , Female , Humans , Male , Olanzapine , Retrospective Studies , Vomiting/chemically induced , Vomiting/drug therapyABSTRACT
Communicating about end-of-life issues with a pediatric patient and their families can be difficult and uncomfortable for many nurses. The purposes of this article are to provide nurses a foundational overview of the child's understanding of death through the lens of awareness, development, and experience and to provide effective ways for nurses to implement this knowledge as they approach the topic of death with patients and their families.