A multicenter study of diet quality on birth weight and gestational age in infants of HIV-infected women.

We determined factors associated with diet quality and assessed the relationship between diet quality, birth weight, and gestational age in a prospective national multicenter cohort study. We evaluated diet quality with the Healthy Eating Index (HEI, scale 0-100) in the third trimester of pregnancy with three 24-hr multiple-pass dietary recalls in 266 HIV+ women enrolled in the Pediatric HIV/AIDS Cohort Study. Covariates included demographics, food security, pre-pregnancy body mass index, HIV disease severity, substance use, and antiretroviral exposures. A two-stage multivariate process using classification and regression trees (CART) followed by multiple regression described HEI tendencies, controlled possible confounding effects, and examined the association of HEI with birth weight and gestational age. To assess the stability of the CART solution, both the HEI 2005 and 2010 were evaluated. The mean HEI scores were 56.1 and 47.5 for the 2005 and 2010 HEI, respectively. The first-stage CART analysis examined the relationship between HEI and covariates. Non-US born versus US-born mothers had higher HEI scores (15-point difference, R2  = 0.28). There was a secondary partition due to alcohol/cigarette/illicit drug usage (3.5-point difference, R2  = 0.03) among US-born women. For the second-stage CART adjusted multiple regression, birth weight z-score was positively related to HEI 2005 and 2010 (partial r's > 0.13, P's ≤ 0.0398), but not gestational age (r = 0.00). We conclude that diet quality among HIV+ women is associated with higher birth weight. Despite the influence of a large cultural effect and poor prenatal behaviors, interventions to improve diet in HIV+ women may help to increase birth weight.

HIV Infection and Carotid Artery Intima-media Thickness: Pooled Analyses Across 5 Cohorts of the NHLBI HIV-CVD Collaborative.

BACKGROUND: Age and human immunodeficiency virus (HIV) treatment may affect the association of HIV infection with atherosclerosis. METHODS: We used identical carotid artery B-mode ultrasonographic methods in 5 cohorts participating in the National Heart, Lung, and Blood Institute HIV-CVD Collaborative to measure intima-media thickness of the right far wall of the common carotid artery (CCA-IMT) and carotid artery bifurcation (BIF-IMT) between 2010 and 2013. Participants aged 6-75 years were either HIV infected or uninfected. Linear regression assessed associations of CCA-IMT and BIF-IMT with HIV infection and cardiovascular disease risk factors, within age and HIV treatment groups. Adjustment variables included sex, race/ethnicity, smoking, height, weight, and use of antihypertensive and lipid-lowering drugs. RESULTS: We studied 867 HIV-infected and 338 HIV-uninfected male and 696 HIV-infected and 246 HIV-uninfected female participants. Among both middle-aged (30-49 years) and older adults (50-75 years), HIV-infected participants had CCA-IMT and BIF-IMT values that were similar to or lower than those in HIV-uninfected participants. In contrast, among those aged 6-29 years, HIV infection was associated with higher CCA-IMT and BIF-IMT values. Among HIV-infected participants, associations of higher systolic blood pressure and lower high-density lipoprotein cholesterol with Carotid artery intima-media thickness strengthened with age. CONCLUSIONS: The effects of HIV on carotid artery structure may differ across the lifespan, with traditional determinants of cardiovascular disease burden playing a larger role and HIV playing a lesser role in older adults than in young adults and children.

Impaired mitochondrial function is abrogated by dexrazoxane in doxorubicin-treated childhood acute lymphoblastic leukemia survivors.

BACKGROUND: Impaired cardiac function in doxorubicin-treated childhood cancer survivors is partly mediated by the disruption of mitochondrial energy production. Doxorubicin intercalates into mitochondrial DNA (mtDNA) and disrupts genes encoding for polypeptides that make adenosine triphosphate. METHODS: This cross-sectional study examined mtDNA copy numbers per cell and oxidative phosphorylation (OXPHOS) in peripheral blood mononuclear cells (PBMCs) in 64 childhood survivors of high-risk acute lymphoblastic leukemia (ALL) who had been treated on Dana-Farber Cancer Institute childhood ALL protocols and had received doxorubicin alone (42%) or doxorubicin with the cardioprotectant dexrazoxane (58%). The number of mtDNA copies per cell and the OXPHOS enzyme activity of nicotinamide adenine dinucleotide dehydrogenase (complex I [CI]) and cytochrome c oxidase (complex IV [CIV]) were measured with quantitative real-time polymerase chain reaction immunoassays and thin-layer chromatography, respectively. RESULTS: At a median follow-up of 7.8 years after treatment, the median number of mtDNA copies per cell for patients treated with doxorubicin alone (1106.3) was significantly higher than the median number for those who had also received dexrazoxane (310.5; P = .001). No significant differences were detected between the groups for CI or CIV activity. CONCLUSIONS: Doxorubicin-treated survivors had an increased number of PBMC mtDNA copies per cell, and concomitant use of dexrazoxane was associated with a lower number of mtDNA copies per cell. Because of a possible compensatory increase in mtDNA copies per cell to maintain mitochondrial function in the setting of mitochondrial dysfunction, overall OXPHOS activity was not different between the groups. The long-term sustainability of this compensatory response in these survivors at risk for cardiac dysfunction over their lifespan is concerning.

Cardiovascular disease in adult survivors of childhood cancer.

Treatment advances have increased survival in children with cancer, but subclinical, progressive, irreversible, and sometimes fatal treatment-related cardiovascular effects may appear years later. Cardio-oncologists have identified promising preventive and treatment strategies. Dexrazoxane provides long-term cardioprotection from doxorubicin-associated cardiotoxicity without compromising the efficacy of anticancer treatment. Continuous infusion of doxorubicin is as effective as bolus administration in leukemia treatment, but no evidence has indicated that it provides long-term cardioprotection; continuous infusions should be eliminated from pediatric cancer treatment. Angiotensin-converting enzyme inhibitors can delay the progression of subclinical and clinical cardiotoxicity. All survivors, regardless of whether they were treated with anthracyclines or radiation, should be monitored for systemic inflammation and the risk of premature cardiovascular disease. Echocardiographic screening must be supplemented with screening for biomarkers of cardiotoxicity and perhaps by identification of genetic susceptibilities to cardiovascular diseases; optimal strategies need to be identified. The health burden related to cancer treatment will increase as this population expands and ages.

Cardiotoxicity and cardioprotection in childhood cancer.

Children diagnosed with cancer are now living longer as a result of advances in treatment. However, some commonly used anticancer drugs, although effective in curing cancer, can also cause adverse late effects. The cardiotoxic effects of anthracycline chemotherapy, such as doxorubicin, and radiation can cause persistent and progressive cardiovascular damage, emphasizing a need for effective prevention and treatment to reduce or avoid cardiotoxicity. Examples of risk factors for cardiotoxicity in children include higher anthracycline cumulative dose, higher dose of radiation, younger age at diagnosis, female sex, trisomy 21 and black race. However, not all who are exposed to toxic treatments experience cardiotoxicity, suggesting the possibility of a genetic predisposition. Cardioprotective strategies under investigation include the use of dexrazoxane, which provides short- and long-term cardioprotection in children treated with doxorubicin without interfering with oncological efficacy, the use of less toxic anthracycline derivatives and nutritional supplements. Evidence-based monitoring and screening are needed to identify early signs of cardiotoxicity that have been validated as surrogates of subsequent clinically significant cardiovascular disease before the occurrence of cardiac damage, in patients who may be at higher risk.

Anthracycline-related cardiotoxicity in childhood cancer survivors.

PURPOSE OF REVIEW: Anthracyclines have markedly improved the survival rates of children with cancer. However, anthracycline-related cardiotoxicity is also well recognized and can compromise the long-term outcome in some patients. The challenge remains of how to balance the chemotherapeutic effects of anthracycline treatment with its potentially serious cardiovascular complications. Here, we review the pathophysiology, risk factors, clinical manifestations, prevention, and treatment of anthracycline-related cardiotoxicity. RECENT FINDINGS: Some risk factors and biomarkers associated with an increased probability of anthracycline-related cardiotoxicity have been identified. Modifying the structural forms and dosages of anthracyclines and coadministering cardioprotective agents may prevent some of these cardiotoxic effects. Cardiovascular complications have also been treated with angiotensin-converting enzyme inhibitors, ß-blockers, and growth hormone replacement therapy. Cardiac transplantation remains the treatment of last resort. SUMMARY: Despite major advances in cancer treatment, anthracycline-related cardiotoxicity remains a major cause of morbidity and mortality in survivors of childhood cancer. Promising areas of research include: use of biomarkers for early recognition of cardiac injury in children receiving chemotherapy, development and application of cardioprotective agents for prevention of cardiotoxicity, and advancements in therapies for cardiac dysfunction in children after anthracycline treatment.

Aggregate risk of cardiovascular disease among adolescents perinatally infected with the human immunodeficiency virus.

BACKGROUND: Perinatally HIV-infected adolescents may be susceptible to aggregate atherosclerotic cardiovascular disease risk, as measured by the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary arteries and abdominal aorta risk scores, as a result of prolonged exposure to HIV and antiretroviral therapy. METHODS AND RESULTS: Coronary arteries and abdominal aorta PDAY scores were calculated for 165 perinatally HIV-infected adolescents, using a weighted combination of modifiable risk factors: dyslipidemia, cigarette smoking, hypertension, obesity, and hyperglycemia. Demographic and HIV-specific predictors of scores ≥1 were identified, and trends in scores over time were assessed. Forty-eight percent and 24% of the perinatally HIV-infected adolescents had coronary arteries and abdominal aorta scores ≥1, representing increased cardiovascular disease risk factor burden. Significant predictors of coronary arteries scores ≥1 included male sex, history of an AIDS-defining condition, longer duration of use of a ritonavir-boosted protease inhibitor, and no prior use of tenofovir. Significant predictors of abdominal aorta scores ≥1 included suppressed viral load, history of an AIDS-defining condition, and longer duration of boosted protease inhibitor use. No significant changes in coronary arteries and abdominal aorta risk scores were observed over the 4-year study period. CONCLUSIONS: A substantial proportion of perinatally HIV-infected youth have high PDAY scores, reflecting increased aggregate atherosclerotic cardiovascular disease risk factor burden. High scores were predicted by HIV disease severity and boosted protease inhibitor use. PDAY scores may be useful in identifying high-risk youth who may benefit from early lifestyle or clinical interventions.

Treatment-related cardiotoxicity in survivors of childhood cancer.

Treatment advances and higher participation rates in clinical trials have rapidly increased the number of survivors of childhood cancer. However, chemotherapy and radiation treatments are cardiotoxic and can cause cardiomyopathy, conduction defects, myocardial infarction, hypertension, stroke, pulmonary oedema, dyspnoea and exercise intolerance later in life. These cardiotoxic effects are often progressive and irreversible, emphasizing a need for effective prevention and treatment to reduce or avoid cardiotoxicity. Medical interventions, such as angiotensin-converting enzyme inhibitors, ß-blockers, and growth hormone therapy, might be used to treat cardiotoxicity in childhood cancer survivors. Preventative strategies should include the use of dexrazoxane, which provides cardioprotection without reducing the oncological efficacy of doxorubicin chemotherapy; less-toxic anthracycline derivatives and the use of antioxidant nutritional supplements might also be beneficial. Continuous-infusion doxorubicin provides no benefit over bolus infusion in children. Identifying patient-related (for example, obesity and hypertension) and drug-related (for example, cumulative dose) risk factors for cardiotoxicity could help tailor treatments to individual patients. However, all survivors of childhood cancer are at increased risk of cardiotoxicity, suggesting that survivor screening recommendations for assessment of global risk of premature cardiovascular disease should apply to all survivors. Optimal, evidence-based monitoring strategies and multiagent preventative treatments still need to be identified.

Effect of ethnicity on weight loss among adolescents 1 year after bariatric surgery.

AIM: To investigate whether or not bariatric surgery weight outcomes vary by ethnicity in a large, nationally representative sample of adolescents. METHODS: The Bariatric Outcomes Longitudinal Database was used for analysis and contains data on surgeries performed on adolescents from 2004 to 2010 from 423 surgeons at 360 facilities across the United States Adolescents (n = 827) between 11 and 19 years old who underwent either gastric bypass or adjustable gastric banding surgery were included in the analysis. Outcome measures included changes in anthropometric measurements [weight (kg) and body mass index] from baseline to 3 (n = 739), 6 (n = 512), and 12 (n = 247) mo after surgery. RESULTS: A year after patients underwent either gastric bypass (51%) or adjustable gastric banding (49%) surgery, mean estimated weight loss for all ethnic groups differed by a maximum of only 1.5 kg, being 34.3 kg (95%CI: 30.0-38.5 kg) for Hispanics, 33.8 kg (95%CI: 27.3-40.3 kg) for non-Hispanic blacks, and 32.8 kg (95%CI: 30.9-34.7 kg) for non-Hispanic whites. No overall pairwise group comparisons were significant, indicating that no ethnic group had better weight loss outcomes than did another. CONCLUSION: Bariatric surgery substantially reduces the weight of severely obese adolescents at 1 year post-procedure with little variation by ethnicity and/or gender. These results suggest that bariatric surgery is a safe and reasonable treatment for all severely obese adolescents with the appropriate indications.

Impact of hemochromatosis gene mutations on cardiac status in doxorubicin-treated survivors of childhood high-risk leukemia.

BACKGROUND: Doxorubicin is associated with progressive cardiac dysfunction, possibly through the formation of doxorubicin-iron complexes leading to free-radical injury. The authors determined the frequency of hemochromatosis (HFE) gene mutations associated with hereditary hemochromatosis and their relationship with doxorubicin-associated cardiotoxicity in survivors of childhood high-risk acute lymphoblastic leukemia. METHODS: Peripheral blood was tested for 2 common HFE allelic variants: C282Y and H63D. Serum cardiac troponin-T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP), which are biomarkers of cardiac injury and cardiomyopathy, respectively, were assayed during therapy. Left ventricular (LV) structure and function were assessed with echocardiography. RESULTS: A total of 184 patients had DNA results for at least 1 variant, and 167 had DNA results for both: 24% carried H63D and 10% carried C282Y. Heterozygous C282Y genotype was associated with multiple elevations in cTnT concentrations (P = .039), but not NT-proBNP. At a median of 2.2 years (range, 1.0 years-3.6 years) after diagnosis, the mean Z-scores for LV fractional shortening (-0.71 [standard error (SE), 0.25]; P = .008), mass (-0.84 [SE, 0.17]; P < .001), and end-systolic (-4.36 [SE, 0.26], P < .001) and end-diastolic (-0.68 [SE, 0.25]; P = .01) posterior wall thickness were found to be abnormal in children with either allele (n = 32). Noncarriers (n = 63) also were found to have below-normal LV mass (-0.45 [SE, 0.15]; P = .006) and end-systolic posterior wall thickness (-4.06 [SE, 0.17]; P < .001). Later follow-up demonstrated similar results. CONCLUSIONS: Doxorubicin-associated myocardial injury was associated with C282Y HFE carriers. Although LV mass and wall thickness were found to be abnormally low overall, they were even lower in HFE carriers, who also had reduced LV function. Screening newly diagnosed cancer patients for HFE mutations may identify those at risk for doxorubicin-induced cardiotoxicity.

Cardiac effects in perinatally HIV-infected and HIV-exposed but uninfected children and adolescents: a view from the United States of America.

INTRODUCTION: Human immunodeficiency virus (HIV) infection is a primary cause of acquired heart disease, particularly of accelerated atherosclerosis, symptomatic heart failure, and pulmonary arterial hypertension. Cardiac complications often occur in late-stage HIV infections as prolonged viral infection is becoming more relevant as longevity improves. Thus, multi-agent HIV therapies that help sustain life may also increase the risk of cardiovascular events and accelerated atherosclerosis. DISCUSSION: Before highly active antiretroviral therapy (HAART), the two-to-five-year incidence of symptomatic heart failure ranged from 4 to 28% in HIV patients. Patients both before and after HAART also frequently have asymptomatic abnormalities in cardiovascular structure. Echocardiographic measurements indicate left ventricular (LV) systolic dysfunction in 18%, LV hypertrophy in 6.5%, and left atrial dilation in 40% of patients followed on HAART therapy. Diastolic dysfunction is also common in long-term survivors of HIV infection. Accelerated atherosclerosis has been found in HIV-infected young adults and children without traditional coronary risk factors. Infective endocarditis, although rare in children, has high mortality in late-stage AIDS patients with poor nutritional status and severely compromised immune systems. Although lymphomas have been found in HIV-infected children, the incidence is low and cardiac malignancy is rare. Rates of congenital cardiovascular malformations range from 5.6 to 8.9% in cohorts of HIV-uninfected and HIV-infected children with HIV-infected mothers. In non-HIV-infected infants born to HIV-infected mothers, foetal exposure to ART is associated with reduced LV dimension, LV mass, and septal wall thickness and with higher LV fractional shortening and contractility during the first two years of life. CONCLUSIONS: Routine, systematic, and comprehensive cardiac evaluation, including a thorough history and directed laboratory assays, is essential for the care of HIV-infected adults and children as cardiovascular illness has become a part of care for long-term survivors of HIV infection. The history should include traditional risk factors for atherosclerosis, prior opportunistic infections, environmental exposures, and therapeutic and illicit drug use. Laboratory tests should include a lipid profile, fasting glucose, and HIV viral load. Asymptomatic cardiac disease related to HIV can be fatal, and secondary effects of HIV infection often disguise cardiac symptoms, so systematic echocardiographic monitoring is warranted.

Dietary quality, caloric intake, and adiposity of childhood cancer survivors and their siblings: an analysis from the cardiac risk factors in childhood cancer survivors study.

Childhood cancer survivors are at increased risk of cardiovascular disease, in part because of adiposity. Whether survivors have healthy diets and whether dietary quality is associated with adiposity among survivors are not known. Survivors and siblings from the Cardiac Risk Factors in Childhood Cancer Survivors Study completed 3-day food records that were used to estimate daily caloric intake relative to recommended and dietary quality using the Healthy Eating Index-2005 (HEI). Medical records were reviewed for cancer therapies. Body composition was measured by dual-energy x-ray absorptiometry. Of 91 childhood cancer survivors and 30 sibling controls, there were no marked differences in mean daily caloric intakes (98% vs. 100% of recommended) or HEI total scores (55.5 vs. 53.3), respectively, with both groups scoring worst for the consumption of dark green vegetables and whole grains. Survivors exposed to cranial irradiation had lower total HEI scores (-6.4, P = 0.01). Among survivors, better dietary quality, as reflected by the total HEI score, was associated with decreasing percent body fat (ß = -0.19, P = 0.04). Survivors consume diets similar to their siblings although these diets are only moderately adherent to current guidelines. Decreased dietary quality is associated with higher body fat and receipt of cranial irradiation in survivors.

Reduction in cardiometabolic disease risk following gastric bypass surgery among Hispanic adults.

BACKGROUND: The increasing prevalence of US morbid obesity is associated with serious health consequences and high medical costs, particularly among ethnic minority groups. Little information is available on the long-term weight and chronic disease risk reduction effectiveness of bariatric surgery among Hispanics. METHODS: A retrospective medical chart analysis of 633 Hispanic adults (76% female, mean age at surgery 41.3 years) from Central and South America and the Caribbean who underwent gastric bypass surgery from 2002 to 2010 was conducted. A presurgery and 1-year postsurgery comparative means analysis of weight, body mass index (BMI), and cardiometabolic disease risk factors [systolic (SBP) and diastolic blood pressure (DBP), fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), and triglycerides (TGs) was performed. RESULTS: Mean weight (127-109 kg) and BMI (46.4-39.9 kg/m(2)) significantly decreased and all cardiometabolic disease risk factors improved from before to 1 year after surgery. Males were significantly more likely than females to show postsurgery improvement in weight (-21.7 kg versus -16.9 kg, P<0.0001), HbA1c (-1.1% versus -0.7%, P=0.02), HDL (3.2 mg/dL versus -0.6 mg/dL, P=0.04), and TGs (-97.2 mg/dL versus -54.5 mg/dL, P=0.006) versus females. Conversely, women were significantly more likely than men to have postsurgery improvements in LDL (-24.5 mg/dL versus -12.7 mg/dL, P=0.04). CONCLUSIONS: Gastric bypass surgery results in significant weight loss and cardiometabolic disease risk reduction among Hispanic adults 1 year after surgery. These improvements vary by gender. Gastric bypass surgery is an effective treatment option for weight loss and chronic disease risk improvements in Hispanic adults who are not Mexican American.

A high school-based voluntary cardiovascular risk screening program: issues of feasibility and correlates of electrocardiographic outcomes.

Risk factors for adult cardiovascular events can be identified from the prenatal period through childhood. We performed a cardiovascular risk-screening program in students from grades 9-12 in 7 high schools in Hillsborough County, FL. We obtained blood pressure (BP) measurements and calculated body mass index (BMI) as risk factors for future cardiovascular events as well as obtained an electrocardiogram (ECG) for the purposes of detecting possible life-threatening arrhythmias. Of ~14,000 students contacted, 600 (4 %) participated in the screening. Of these, 517 (86 %) were diagnosed with normal, 71 (12 %) with borderline, and 12 (1 %) with abnormal ECGs. Although no participant had any cardiac history, two of the abnormal ECGs indicated a cardiac diagnosis associated with the potential for sudden cardiac death. Both systolic and diastolic BP increased as the ECG diagnosis moved from normal (115.6/73.8) through borderline (121.0/75.9) to an abnormal (125.0/80.7) diagnosis (all P ≤ .0016). An increase in BMI was only observed when an ECG diagnosis was abnormal (P = .0180). Boys had a greater prevalence (18.97 %) of borderline or abnormal ECGs compared with girls (6.75 %), whereas no discernible differences were seen in ECG diagnosis between white and nonwhite individuals (15.09 and 12.26 %, respectively). Although participation rates were low, a high school-based cardiovascular risk-screening program including ECG is feasible. Although ECG diagnosis tended to be related to other known cardiovascular risk factors (BP, BMI), the utility of an abnormal ECG in adolescence as a predictor of future cardiovascular risk will require further evaluation in more controlled settings.

Effectiveness of bariatric surgery in reducing weight and body mass index among Hispanic adolescents.

BACKGROUND: Ethnic minority adolescents, Hispanics in particular, are disproportionately affected by extreme obesity and its associated co-morbidities. Bariatric surgery is one of the few effective treatments for morbid obesity, yet little information about weight outcomes after surgery in this demographic are available. We determined the effectiveness of bariatric surgery in reducing weight and body mass index (BMI) in adolescents, a majority of whom were non-Mexican American Hispanic and originated from Central and/or South America and the Caribbean Basin region. METHODS: Adolescents (16-to-19 years old) who had undergone gastric bypass or adjustable gastric band surgery between 2001 and 2010 and who had complete follow-up data available (91 %) were included in the analysis. Mean weight and BMI before and 1-year after surgery were compared. RESULTS: Among 71 adolescents (80 % Hispanic, 77 % female), mean BMI and weight, and z-scores and percentile transformations were all significantly lower after surgery for the entire sample (P < 0.001). Gastric bypass surgery showed significantly better weight loss outcomes for all anthropometric measures versus adjustable gastric band surgery (P < 0.05). Weight loss was similar among Hispanics and non-Hispanics. No peri-operative complications were reported. Three patients who stopped taking supplements as prescribed experienced iron deficiency anemia within the year following surgery. CONCLUSIONS: Our results show that bariatric surgery, gastric bypass procedure in particular, can markedly reduce weight among a predominantly Hispanic adolescent patient sample. These findings indicate that bariatric surgery has the potential to be safe and effective in substantially reducing weight in a group of adolescents who are at a particularly high risk for obesity-related health consequences.

Changes in weight and co-morbidities among adolescents undergoing bariatric surgery: 1-year results from the Bariatric Outcomes Longitudinal Database.

BACKGROUND: Bariatric surgery is 1 of the few effective treatments of morbid obesity. However, the weight loss and other health-related outcomes for this procedure in large, diverse adolescent patient populations have not been well characterized. Our objective was to analyze the prospective Bariatric Outcomes Longitudinal Database (BOLD) to determine the weight loss and health related outcomes in adolescents. The BOLD data are collected from 423 surgeons at 360 facilities in the United States. METHODS: The main outcome measures included the anthropometric and co-morbidity status at baseline (n = 890) and at 3 (n = 786), 6 (n = 541), and 12 (n = 259) months after surgery. Adolescents (75% female; 68% non-Hispanic white, 14% Hispanic, 11% non-Hispanic black, and 6% other) aged 11 to 19 years were included in the present analyses. RESULTS: The overall 1-year mean weight loss for those who underwent gastric bypass surgery was more than twice that of those who underwent adjustable gastric band surgery (48.6 versus 20 kg, P < .001). Similar results were found for all other anthropometric changes and comparisons within 1 year between surgery types (P < .001). In general, the gastric bypass patients reported more improvement than the adjustable gastric band patients in co-morbidities at 1 year after surgery. A total of 45 readmissions occurred among gastric bypass patients and 10 among adjustable gastric band patients, with 29 and 8 reoperations required, respectively. CONCLUSIONS: The weight loss at 3, 6, and 12 months after surgery is approximately double in adolescent males and females who underwent gastric bypass surgery versus those who underwent adjustable gastric band surgery. Bariatric surgery can safely and substantially reduce weight and related co-morbidities in morbidly obese adolescents for ≥1 year.

Cranial irradiation as an additional risk factor for anthracycline cardiotoxicity in childhood cancer survivors: an analysis from the cardiac risk factors in childhood cancer survivors study.

Anthracycline-treated childhood cancer survivors experience cardiac damage that results in decreased left ventricular (LV) mass, leading to increased LV wall stress, which underlies their greater risk of cardiomyopathy. Many of these survivors also are at risk of growth hormone (GH) abnormalities from cranial irradiation exposure, although it is unknown whether such exposure is associated with cardiotoxicity. Echocardiograms and insulin-like growth factor-1 (IGF-1), a marker of GH, were measured in 130 anthracycline-treated childhood cancer survivors, 59 of whom had been exposed to cranial irradiation, a mean 10 years after their cancer diagnosis. Echocardiographic parameters and IGF-1 were standardized relative to age or body surface area using data from sibling control subjects and expressed as the percentage difference from normal values. The results showed that after adjustment for other risk factors, survivors exposed to cranial irradiation had an additional 12 % decrease in LV mass compared with unexposed survivors (P < 0.01) and an additional 3.6 % decrease in LV dimension (P = 0.03). Survivors exposed to cranial irradiation also had a 30.8 % decrease in IGF-1 relative to normal values, which was greater than the 10.5 % decrease in unexposed survivors (P < 0.01). The above findings led us to conclude that in anthracycline-treated childhood cancer survivors a mean 10 years after their diagnosis, those with cranial irradiation exposure had significantly greater decreases in LV mass and dimension. Because cranial irradiation also was associated with decreased IGF-1, it is possible that GH deficiencies mediated this effect, suggesting that GH replacement therapy may help to prevent the development of cardiotoxicity.

Exercise capacity in long-term survivors of pediatric cancer: an analysis from the Cardiac Risk Factors in Childhood Cancer Survivors Study.

BACKGROUND: Childhood cancer survivors may have premature symptomatic cardiovascular and non-cardiovascular diseases that contribute to reduced capacity for physical activity. Studies of exercise capacity and identification of risk factors for reduced capacity in survivors are limited. PROCEDURE: We assessed maximal myocardial oxygen consumption (V(O(2)max), a measure of exercise capacity) in survivors at least 4 years after cancer diagnosis and sibling controls. We evaluated associations between V(O(2)max) and age, sex, treatments, cardiac structure and function, biomarkers, endocrine function, and physical activity. RESULTS: Of 72 survivors (mean age, 22 years; range, 8.0-40 years) and 32 siblings (mean age, 20.2 years; range, 8-46 years), about half were male. Mean time since diagnosis was 13.4 years (range, 4.5-31.6 years). In age- and sibling-pair adjusted analyses, V(O(2)max) was lower in survivors than siblings (males, 28.53 vs. 30.90 ml/kg/minute, P = 0.08; females, 19.81 vs. 23.40 ml/kg/minute, P = 0.03). In males, older age (P = 0.01), higher percent body fat (P < 0.001) and high or low left ventricular (LV) mass Z-scores (P = 0.03) predicted lower V(O(2)max). In females, older age (P < 0.001), methotrexate exposure (P = 0.01), and higher, but normal, LV load-dependent contractility (P = 0.02) predicted lower V(O(2)max). CONCLUSIONS: Fitness for most survivors and controls was poor and generally lower in survivors, particularly females. Older age, higher body fat, methotrexate exposure, and extremes of LV mass/function were associated with lower V(O(2)max) in survivors. Because physical activity can improve nutritional and cardiac conditions, survivors should be encouraged to exercise regularly with close monitoring.

Continuous Versus Bolus Infusion of Doxorubicin in Children With ALL: Long-term Cardiac Outcomes.

BACKGROUND AND OBJECTIVES: Doxorubicin, effective against many malignancies, is limited by cardiotoxicity. Continuous-infusion doxorubicin, compared with bolus-infusion, reduces early cardiotoxicity in adults. Its effectiveness in reducing late cardiotoxicity in children remains uncertain. We determined continuous-infusion doxorubicin cardioprotective efficacy in long-term survivors of childhood acute lymphoblastic leukemia (ALL). METHODS: The Dana-Farber Cancer Institute ALL Consortium Protocol 91-01 enrolled pediatric patients between 1991 and 1995. Newly diagnosed high-risk patients were randomly assigned to receive a total of 360 mg/m(2) of doxorubicin in 30 mg/m(2) doses every 3 weeks, by either continuous (over 48 hours) or bolus-infusion (within 15 minutes). Echocardiograms at baseline, during, and after doxorubicin therapy were blindly remeasured centrally. Primary outcomes were late left ventricular (LV) structure and function. RESULTS: A total of 102 children were randomized to each treatment group. We analyzed 484 serial echocardiograms from 92 patients (n = 49 continuous; n = 43 bolus) with ≥1 echocardiogram ≥3 years after assignment. Both groups had similar demographics and normal baseline LV characteristics. Cardiac follow-up after randomization (median, 8 years) showed changes from baseline within the randomized groups (depressed systolic function, systolic dilation, reduced wall thickness, and reduced mass) at 3, 6, and 8 years; there were no statistically significant differences between randomized groups. Ten-year ALL event-free survival rates did not differ between the 2 groups (continuous-infusion, 83% versus bolus-infusion, 78%; P = .24). CONCLUSIONS: In survivors of childhood high-risk ALL, continuous-infusion doxorubicin, compared with bolus-infusion, provided no long-term cardioprotection or improvement in ALL event-free survival, hence provided no benefit over bolus-infusion.