BackgroundThe late cardiotoxic effects of anthracycline chemotherapy influence morbidity and mortality in the growing population of childhood cancer survivors. Even with lower anthracycline doses, evidence of adverse cardiac remodeling and reduced exercise capacity exist. We aim to examine the relationship between cardiac structure, function and cardiovascular magnetic resonance (CMR) tissue characteristics with chemotherapy dose and exercise capacity in childhood cancer survivors.MethodsThirty patients (15 ± 3 years), at least 2 years following anthracycline treatment, underwent CMR, echocardiography, and cardiopulmonary exercise testing (peak VO2). CMR measured ventricular function, mass, T1 and T2 values, and myocardial extracellular volume fraction, ECV, a measure of diffuse fibrosis based on changes in myocardial T1 values pre- and post-gadolinium. Cardiac function was also assessed with conventional and speckle tracking echocardiography.ResultsPatients had normal LVEF (59 ± 7%) but peak VO2 was 17% lower than age-predicted normal values and were correlated with anthracycline dose (r = −0.49). Increased ECV correlated with decreased mass/volume ratio (r = −0.64), decreased LV wall thickness/height ratio (r = −0.72), lower peak VO2(r = −0.52), and higher cumulative dose (r = 0.40). Echocardiographic measures of systolic and diastolic function were reduced compared to normal values (p < 0.01), but had no relation to ECV, peak VO2 or cumulative dose.ConclusionsMyocardial T1 and ECV were found to be early tissue markers of ventricular remodeling that may represent diffuse fibrosis in children with normal ejection fraction post anthracycline therapy, and are related to cumulative dose, exercise capacity and myocardial wall thinning.

LG. Prevalence of post-thrombotic syndrome following asymptomatic thrombosis in survivors of acute lymphoblastic leukemia. J Thromb Haemost 2008; 6: 589-94.Summary. Background: Deep vein thrombosis (DVT) is a complication of treatment of acute lymphoblastic leukemia (ALL) in children but little is known about the long-term outcomes of these DVT. Objective: To determine the incidence of post-thrombotic syndrome (PTS) in (i) children with ALL diagnosed with asymptomatic DVT using radiographic testing and (ii) an unselected group of ALL survivors. Methods: Cross-sectional study in two populations. Group I comprised children in the Prophylactic Antithrombin Replacement in Kids with ALL treated with L-Asparaginase (PARKAA) study diagnosed with DVT by radiographic tests. Group II consisted of non-selected childhood ALL survivors <21 years. PTS was assessed using a standardized scoring sheet. Results: Group I: 13 PARKAA patients (median age 12 years) were assessed, and 7 had PTS (54%; 95% CI, 25-81). All patients had collaterals, three also had increased arm circumference. Group II: 41 patients (median age 13 years) with a history of ALL were enrolled, and 10 had PTS (24%; 95% CI, 11-38). All patients had collaterals; five also had increased arm circumference. Conclusion: There is a high incidence of PTS in survivors of childhood ALL with radiographically diagnosed asymptomatic DVT. A significant proportion of ALL survivors develop PTS, indicating previously undiagnosed DVT.

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Background: The prevalence and severity of pain, nausea/vomiting, and anxiety (PNVA) among hospitalized children is not well established. We describe the prevalence and severity of PNVA among hospitalized patients from oncology, general pediatrics, and cardiology services in a tertiary care center. Methods: Patients were recruited on admission and enrolled if their caregiver consented, spoke English, and were anticipated to stay 2–30 days. Symptoms were measured weekdays using age-validated tools. PNVA symptoms were described and compared. Results: We enrolled 496 (49.4%) patients of 1005 admitted. Patients were predominantly Caucasian (57.9%) on their first admission (53.6%). The average (SD) age was 8.6 years (5.9) in oncology, 4.2 (5.3) in general pediatrics and 2.6 (4.0) in cardiology. 325 (65.6%) patients reported anxiety, 275 (55.4%) reported nausea and 256 (52.0%) reported pain. Mean (SD) severity out of 10 was 3.7 (2.5) for anxiety, 3.2 (2.1) for nausea and 3.0 (1.5) for pain. Prevalence of PNVA was no different between clinical programs, but pain (p = 0.008) and nausea (p = 0.006) severity were. PNVA symptom co-occurrence was positively correlated (p < 0.001). Conclusions: Anxiety was the most common and severe symptom for hospitalized children. Patients in oncology demonstrated the least severe pain and nausea with no difference in anxiety between services.

Our findings suggest that impaired LV contractility and functional reserve play a role in the reduced exercise capacity in anthracycline cardiotoxicity rather than LV distensibility.

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BackgroundSome pediatric tertiary care centres in North America supplement conventional care with complementary therapies, together known as pediatric integrative medicine (PIM). Evidence to support the safety and efficacy of PIM is emerging, but the cost-effectiveness of an inpatient PIM service has yet to be assessed.Methods/DesignThis study is a pragmatic cluster controlled clinical trial. Usual care will be compared to usual care augmented with PIM in three pediatric divisions; oncology, general medicine, and cardiology at one large urban tertiary care Canadian Children's Hospital. The primary outcome of the feasibility study is enrolment; the primary outcome of the main study is cost-effectiveness. Other secondary outcomes include the prevalence and severity of key symptoms (i.e. pain, nausea/vomiting and anxiety), efficacy of PIM interventions, patient safety, and parent satisfaction.DiscussionThis trial will be the first to evaluate the comparative effectiveness, both clinical and cost, of a PIM inpatient service. The evidence from this study will be useful to families, clinicians and decision makers, and will describe the clinical and economic value of PIM services for pediatric patients admitted to hospital.