Oncology and Cardiac Rehabilitation: An Underrated Relationship.

Cancer and cardiovascular diseases are globally the leading causes of mortality and morbidity. These conditions are closely related, beyond that of sharing many risk factors. The term bidirectional relationship indicates that cardiovascular diseases increase the likelihood of getting cancer and vice versa. The biological and biochemical pathways underlying this close relationship will be analyzed. In this new overlapping scenario, physical activity and exercise are proven protective behaviors against both cardiovascular diseases and cancer. Many observational studies link an increase in physical activity to a reduction in either the development or progression of cancer, as well as to a reduction in risk in cardiovascular diseases, a non-negligible cause of death for long-term cancer survivors. Exercise is an effective tool for improving cardio-respiratory fitness, quality of life, psychological wellbeing, reducing fatigue, anxiety and depression. Finally, it can counteract the toxic effects of cancer therapy. The protection obtained from physical activity and exercise will be discussed in the various stages of the cancer continuum, from diagnosis, to adjuvant therapy, and from the metastatic phase to long-term effects. Particular attention will be paid to the shelter against chemotherapy, radiotherapy, cardiovascular risk factors or new onset cardiovascular diseases. Cardio-Oncology Rehabilitation is an exercise-based multi-component intervention, starting from the model of Cardiac Rehabilitation, with few modifications, to improve care and the prognosis of a patient's cancer. The network of professionals dedicated to Cardiac Rehabilitation is a ready-to-use resource, for implementing Cardio-Oncology Rehabilitation.

Implementing an ICT-Based Polypharmacy Management Program in Italy.

Although there is evidence of a growing awareness of the problem, no official policy statements or regulatory guidelines on polypharmacy have been released up to date by Italian Health Authorities. Medication review, application of appropriateness criteria and computerized prescription support systems are all possible approaches in order to improve the quality of prescribing in older persons. More focused training courses on multimorbidity and polytherapy management are encouraged. Furthermore a multidisciplinary approach integrating different health care professionals (physicians, pharmacists, and nurses) may positively impact on reducing the sense of fear related to discontinue or substitute drugs prescribed by others; the fragmentation of therapy among different specialists; reducing costs; and improving adverse drug reaction detection and reporting. Aiming at achieving the individualized pharmacotherapy, a multidisciplinary approach starting with identification of patients and risk for drug-related problems, followed by medication review overtime and use of inappropriateness criteria, supported by computerized systems has been proposed.

The Tosca Registry: An Ongoing, Observational, Multicenter Registry for Chronic Heart Failure.

The ageing of the population in western countries, the continuous increase of the prevalence of chronic diseases, the frequent coexistence of several morbid conditions (comorbidity) requires health professionals and Institutions to face difficult challenges, including increasing costs, need for more effective and sustainable therapies, and organizational issues. The European Innovation Partnership on Active and Healthy Ageing aims at enabling European citizens to lead healthy, active and independent lives while ageing. We herein discuss some key concepts bearing a special significance in the light of the Partnership aims, and present research and educational projects active in our local environment. Among these, the multicentre project TOSCA (Trattamento Ormonale nello Scompenso CArdiaco) that, although primarily focused on the understanding of the interactions between hormones and chronic heart failure (CHF), is also aimed at developing more effective models of clinical care. We provide the scientific background and current stage of the project. In the context of a growing complexity of the patients' clinical management, the polipharmacy is a new arising challenge for clinicians, bearing direct economic, organizational and clinical implications. A better understanding, characterization and management of this issue represent an additional target of the TOSCA network.

A CHO/fibre diet reduces and a MUFA diet increases postprandial lipaemia in type 2 diabetes: no supplementary effects of low-volume physical training.

The aim of the study was to evaluate the effects of a supervised physical training added to a healthy diet-rich in either carbohydrate and fibre (CHO/fibre) or monounsaturated fatty acids (MUFA)-on postprandial dyslipidaemia, an independent cardiovascular risk factor particularly relevant in type 2 diabetes (T2D). Participants were forty-five overweight/obese subjects with T2D, of both genders, in good blood glucose control with diet or diet+metformin, with normal fasting plasma lipids. According to a parallel groups 2 × 2 factorial design, participants were randomized to an 8-week isoenergetic intervention with a CHO/fibre or a MUFA diet, with or without a supervised low-volume aerobic training programme. The main outcome of the study was the incremental area under the curve (iAUC) of lipid concentrations in the plasma chylomicron+VLDL lipoprotein fraction, isolated by preparative ultracentrifugation (NCT01025856). Body weight remained stable during the trial in all groups. Physical fitness slightly improved with training (VO2 peak, 16 ± 4 vs. 15 ± 3 ml/kg/min, M ± SD, p < 0.05). Postprandial triglyceride and cholesterol iAUCs in plasma and chylomicron+VLDL fraction decreased after the CHO/fibre diet, but increased after the MUFA diet with a significant effect for diet by two-way ANOVA (p < 0.05). The addition of exercise training to either dietary intervention did not significantly influence postprandial lipid response. A diet rich in carbohydrates and fibre reduced postprandial triglyceride-rich lipoproteins compared with a diet rich in MUFA in patients with T2D. A supervised low-volume physical training did not significantly influence these dietary effects.

Measurement of the velocity of neutrinos from the CNGS beam with the large volume detector.

We report the measurement of the time of flight of ∼17 GeV ν(µ) on the CNGS baseline (732 km) with the Large Volume Detector (LVD) at the Gran Sasso Laboratory. The CERN-SPS accelerator has been operated from May 10th to May 24th 2012, with a tightly bunched-beam structure to allow the velocity of neutrinos to be accurately measured on an event-by-event basis. LVD has detected 48 neutrino events, associated with the beam, with a high absolute time accuracy. These events allow us to establish the following limit on the difference between the neutrino speed and the light velocity: -3.8 × 10(-6) < (v(ν)-c)/c < 3.1 × 10(-6) (at 99% C.L.). This value is an order of magnitude lower than previous direct measurements.

Individual patient meta-analysis of exercise training effects on systemic brain natriuretic peptide expression in heart failure.

BACKGROUND: Brain natriuretic peptide (BNP) predicts exercise performance and exercise training may modulate BNP and its N-terminal portion (NT-pro-BNP), we therefore conducted an individual patient analysis of exercise training effects on BNP and NT-pro-BNP. AIMS: To use an individual patient meta-analysis to relate changes in BNP, NT-pro-BNP, and peak VO(2); to link these changes to volume parameters of exercise training programmes (intensity etc.); and to identify patient characteristics likely to lead to greater improvements in BNP, NT-pro-BNP, and peak VO(2). DESIGN: Individual patient meta-analysis. METHODS: A systematic search was conducted of Medline (Ovid), Embase.com, Cochrane Central Register of Controlled Trials, and CINAHL (until July 2008) to identify randomized controlled trials of aerobic and/or resistance exercise training in systolic heart failure patients measuring BNP and/or NT-pro-BNP. Primary outcome measures were change in BNP, NT-pro-BNP, and peak VO2. Subanalyses were conducted to identify (1) patient groups that benefit most and (2) exercise programme parameters enhancing favourable changes in primary outcome measures. RESULTS: Ten randomized controlled studies measuring BNP or NT-pro-BNP met eligibility criteria, authors provided individual patient data for 565 patients (313 exercise and 252 controls). Exercise training had favourable effects on BNP (-28.3%, p < 0.0001), NT-pro-BNP (-37.4%, p = < 0.0001), and peak VO(2) (17.8%, p < 0.0001). The analysis showed a significant change in primary outcome measures; moreover, change in BNP (r = -0.31, p < 0.0001) and NT-pro-BNP (r = -0.22, p < 0.0001) were correlated with peak VO(2) change. CONCLUSION: Exercise training has favourable effects on BNP, NT-pro-BNP, and peak VO(2) in heart failure patients and BNP/NT-pro-BNP changes were correlated with peak VO(2) changes.

Structured exercise training programme versus hypocaloric hyperproteic diet in obese polycystic ovary syndrome patients with anovulatory infertility: a 24-week pilot study.

BACKGROUND: Lifestyle modifications are successfully employed to treat obese and overweight women with polycystic ovary syndrome (PCOS). The aims of the current pilot study were (i) to compare the efficacy on reproductive functions of a structured exercise training (SET) programme with a diet programme in obese PCOS patients and (ii) to study their clinical, hormonal and metabolic effects to elucidate potentially different mechanisms of action. METHODS: Forty obese PCOS patients with anovulatory infertility underwent a SET programme (SET group, n = 20) and a hypocaloric hyperproteic diet (diet group, n = 20). Clinical, hormonal and metabolic data were assessed at baseline, and at 12- and 24-week follow-ups. Primary endpoint was cumulative pregnancy rate. RESULTS: The two groups had similar demographic, anthropometric and biochemical parameters. After intervention, a significant improvement in menstrual cycles and fertility was noted in both groups, with no differences between groups. The frequency of menses and the ovulation rate were significantly (P < 0.05) higher in the SET group than in diet group but the increased cumulative pregnancy rate was not significant. Body weight, body mass index, waist circumference, insulin resistance indexes and serum levels of sex hormone-binding globulin, androstenedione and dehydroepiandrosterone sulphate changed significantly (P < 0.05) from baseline and were significantly different (P < 0.05) between the two groups. CONCLUSIONS: Both SET and diet interventions improve fertility in obese PCOS patients with anovulatory infertility. We hypothesize that in both interventions an improvement in insulin sensitivity is the pivotal factor involved in the restoration of ovarian function but potentially acting through different mechanisms.

Irbesartan effects on renal function in patients with renal impairment and hypertension: a drug-withdrawal study.

The blood-pressure lowering activity, tolerability, and safety of irbesartan was evaluated in 52 hypertensive patients with chronic renal insufficiency. After a 3-week placebo period, once-daily irbesartan was administered for 12 weeks at a daily dose of 150 mg titrated to 300 mg. A second, non-angiotensin-converting enzyme inhibitor, antihypertensive drug was added after 8 weeks as needed. Twenty-four-hour creatinine clearance was determined and renal clearance studies of inulin and para-aminohippurate were done in a subset of 11 patients. Trough sitting blood pressures were reduced at the end of the first week in all groups. At weeks 4, 8, and 12 the reductions in systolic blood pressure/diastolic blood pressure averaged -11.9/-8.7, -10.8/-9.4, and -14.7/-12.1 mm Hg in patients with mild renal insufficiency and -7.7/-6.3, -13.1/-11.8, and -14.1/-10.6 mm Hg in patients with moderate-to-severe renal insufficiency. Creatinine clearance, glomerular filtration rate, and effective renal plasma flow were stable. Irbesartan was withdrawn in only five patients because of adverse clinical or laboratory experience. Hyperkalemia (>6 mEq/l) requiring discontinuation of irbesartan occurred in only one patient. Once-daily irbesartan given as monotherapy at dose of 150-300 mg or in combination with other antihypertensive drugs is effective in reducing blood pressure in hypertensive patients with chronic renal disease. Irbesartan regimens are well tolerated in all groups. In addition, the blood pressure-lowering effect of irbesartan is accompanied by a significant reduction in proteinuria in patients with chronic renal insufficiency.

Effects of enalapril and isradipine alone and in combination on blood pressure, renal function and echocardiographic parameters in mild hypertension.

AIMS AND METHODS: A study was carried out to evaluate the influence of antihypertensive treatment with combined low doses of enalapril plus isradipine (5+5 mg daily) compared with those of either drug at a higher dose level (10 mg daily) by double-blind, three-way crossover study (balanced Latin square design) in 102 subjects (mean age 51.9 +/- 7.42 years) with essential hypertension. Left ventricular mass and function were evaluated by M-B mode echocardiography, renal function by glomerular filtration rate (GFR) and by serum and 24-h urinary Na+ and K+ during wash-out period and after 24 weeks of treatment. RESULTS: The supine blood pressure for subjects given placebo was 171/103 mmHg. After 24 weeks of treatment, systolic and diastolic supine blood pressure were significantly lower with 5 mg isradipine plus 5 mg enalapril (134/84 mmHg) than with 10 mg enalapril (137/84 mmHg) or with 10 mg isradipine (144/85 mmHg). Left ventricular posterior wall and septal thickness were significantly and similarly reduced in all groups. Left ventricular systolic and diastolic end diameters were not significantly changed. Left ventricular mass (LVM) was significantly reduced in E plus I group and enalapril group. GFR was not significantly altered. The 24-h urinary Na+ significantly increased with enalapril, more so than isradipine. The combination was tolerated better than either monotherapy. We observed no clinically significant changes in laboratory variables including blood lipoproteins. CONCLUSIONS: The combination of isradipine plus enalapril reduced blood pressure more effectively and was better tolerated than other drug alone. All three groups showed similar changes in echocardiographic indices and no change in renal function.

Reversal of left ventricular hypertrophy following once daily administration of felodipine for two years to elderly subjects with isolated systolic hypertension.

Left ventricular mass sometimes decreases during the treatment of hypertension. In a two-year open study, we investigated the ability of extended release (ER) felodipine (5 or 10 mg), plus chlorthalidone (25 mg), given once daily, to reduce left ventricular mass in 84 elderly patients with isolated systolic hypertension. Drug dosage was determined in an initial stepped-care titration phase lasting six weeks. Mean systolic blood pressure decreased after two years of treatment with 5 or 10 mg of felodipine (p < 0. 001) and the left ventricular mass index decreased too (p < 0.0001). One or two weeks after withdrawal of therapies, blood pressure returned to pretreatment values. We concluded that left ventricular mass can be reduced in elderly patients with isolated systolic hypertension and ventricular hypertrophy who receive felodipine 5-10 mg once daily. This treatment was generally well tolerated.

Sympathetic deactivation by growth hormone treatment in patients with dilated cardiomyopathy.

AIMS: We examined the effects of growth hormone administration on the sympathetic nervous system in patients with idiopathic dilated cardiomyopathy. BACKGROUND: Growth factor therapy is emerging as a new potential option in the treatment of heart failure. Although growth hormone provides functional benefit in the short term, it is unknown whether it affects the sympathetic nervous system, which plays a role in the progression of heart failure. METHODS: Seven patients with idiopathic cardiomyopathy received 3 months treatment with recombinant human growth hormone (0.15-0.20 IU.kg-1.week-1). Standard medical therapy was unchanged. Myocardial norepinephrine release, both at rest and during submaximal physical exercise, plasma aldosterone, and plasma volume were measured before and after growth hormone treatment. Myocardial norepinephrine release was assessed from arterial and coronary venous plasma concentrations of unlabelled and tritiated norepinephrine and coronary plasma flow (thermodilution). RESULTS: Growth hormone induced a significant fall in myocardial norepinephrine release in response to physical exercise (from 180 +/- 64 to 99 +/- 34 ng.min-1; P < 0.05). Basally, plasma aldosterone was 189 +/- 28 and 311 +/- 48 pg.ml-1 in the supine and upright position, respectively, and fell to 106 +/- 16 (P < 0.01) and 182 +/- 29 pg.ml-1 (P < 0.05) after growth hormone therapy. Growth hormone increased plasma volume from 3115 +/- 493 ml to 3876 +/- 336 ml (P < 0.05), whereas serum sodium and potassium concentrations were unaffected. CONCLUSIONS: The data demonstrate that growth hormone administration to patients with idiopathic cardiomyopathy reduces myocardial sympathetic drive and circulating aldosterone levels. This neurohormonal deactivation may be relevant to the potential, long-term use of growth hormone in the treatment of patients with heart failure.

Depression and anxiety in young children of substance abusers.

144 5- to 13-yr.-old children of substance abusers, enrolled in an expressive arts therapy program, were tested for depression on the Children's Depression Inventory and for anxiety on the Revised Children's Manifest Anxiety Scale prior to treatment. Total scores for anxiety were significantly higher for girls than for boys; however, total depression scores did not differ between boys and girls. Analysis of subscale scores on each of the tests indicated several sex differences. Age was positively correlated with certain symptoms of depression for boys but not for girls. Conversely, age was negatively correlated with certain symptoms of anxiety for boys but not for girls. When compared to known norms for these assessments, girls scored significantly higher on total Depression but not differently than normals on total Anxiety. Boys, however, scored significantly lower on total Anxiety but did not score differently than normals on total Depression. We interpreted these findings as indicating that young children of substance abusers may be at risk for certain symptoms of anxiety and depression following their parents' addiction. Also, these symptoms may be manifest differently by boys and girls of various ages.

Metabolic and hemodynamic effects of peptide leukotriene C4 and D4 in man.

The time course of the effects of intravenous or intracoronary administration of peptide leukotrienes on metabolic parameters and on systemic and coronary hemodynamics was evaluated in 15 patients with normal coronary arteries. Peptide leukotriene C4 (2 nmol given as a bolus intravenous injection) induced an early fall (at 2 min) in mean arterial pressure (P < 0.02) associated with a rise in heart rate (P < 0.001) and in plasma levels of epinephrine (P < 0.05) and norepinephrine (P < 0.005), but without significant changes in coronary blood flow or coronary vascular resistance. Mean arterial pressure, heart rate, norepinephrine, and epinephrine returned to baseline values 10 min after leukotriene C4 administration. In contrast, at 10 min post leukotriene C4, with coronary blood flow and myocardial oxygen consumption unchanged, an increase in coronary vascular resistance (P < 0.05) and in myocardial oxygen extraction (P < 0.01) was observed, which returned to baseline values at 20 min post leukotriene C4. Peptide leukotriene D4 (3 nmol, given in the left coronary artery) induced an early (20 s) and transient fall in mean arterial pressure (P < 0.001) paralleled by a rise in heart rate and plasma levels of epinephrine and norepinephrine, all of which returned to baseline at 10 min. Coronary vascular resistance increased at 10 and 15 min (P < 0.02 and P < 0.05, respectively) and myocardial oxygen extraction at 15 min (P < 0.02). These results suggest that small doses of peptide leukotrienes induce both an early and transient fall in mean arterial pressure associated with secondary sympathoadrenergic activation, and a late increase in small coronary arteriolar resistance.

Affective symptoms in young children of substance abusers correlate with parental distress.

In families that included a chemically addicted father, the nonsubstance abusing mother was assessed using the Brief Symptom Inventory and her children were assessed for depression using the Children's Depression Inventory. The nonsubstance-abusing mothers were psychologically distressed and their distress correlated (positively for girls and negatively for boys) with their children's depression.

Categorization based on attribute versus relational similarity in 4- to 10-month-old infants.

4- to 10-month-old infants were tested in 2 experiments to determine whether they used a similar attribute or a similar relationship among attributes to make visual judgments of similarity and categorization. In Exp. 1 infants were familiarized with a single stimulus composed of several attributes and a prescribed relationship among the attributes, left wing smaller than right wing. When tested in a novelty-preference procedure with novel stimuli that either preserved a single attribute but violated the relationship (Attribute Test Stimulus) or preserved the relationship with a new set of attributes (Relational Test Stimulus), 4-mo.-olds treated the Attribute Test Stimulus as familiar, whereas 6-mo.-olds treated the Relational Test Stimulus as familiar. Neither 8- nor 10-mo.-olds showed a preference for either test stimulus. In Exp.2 a category containing 3 exemplars was constructed. In each exemplar a single attribute, left wing, was held constant, and all 3 exemplars shared the same relational structure, left wing smaller than right wing, but the remaining attributes varied across exemplars. Four, 6-, and 8-mo.-olds in Exp. 2 reliably included the novel Attribute Test Stimulus in the category. These data suggest that, although infants under 8 months can recognize relational information, they may not always use that information when making categorization judgments, particularly if a single, well-defined attribute is available as the basis for categorization.

A preliminary study of growth hormone in the treatment of dilated cardiomyopathy.

BACKGROUND: Cardiac hypertrophy is a physiologic response that allows the heart to adapt to an excess hemodynamic load. We hypothesized that inducing cardiac hypertrophy with recombinant human growth hormone might be an effective approach to the treatment of idiopathic dilated cardiomyopathy, a condition in which compensatory cardiac hypertrophy is believed to be deficient. METHODS: Seven patients with idiopathic dilated cardiomyopathy and moderate-to-severe heart failure were studied at base line, after three months of therapy with human growth hormone, and three months after the discontinuation of growth hormone. Standard therapy for heart failure was continued throughout the study. Cardiac function was evaluated with Doppler echocardiography, right-heart catheterization, and exercise testing. RESULTS: When administered at a dose of 14 IU per week, growth hormone doubled the serum concentrations of insulin-like growth factor I. Growth hormone increased left-ventricular-wall thickness and reduced chamber size significantly. Consequently, end-systolic wall stress (a function of both wall thickness and chamber size) fell markedly (from a mean [+/-SE] of 144+/-11 to 85+/-8 dyn per square centimeter, P<0.001). Growth hormone improved cardiac output, particularly during exercise (from 7.4+/-0.7 to 9.7+/-0.9 liters per minute, P=0.003), and enhanced ventricular work, despite reductions in myocardial oxygen consumption (from 56+/-6 to 39+/-5 ml per minute, P=0.005) and energy production (from 1014+/-100 to 701+/-80 J per minute, P=0.002). Thus, ventricular mechanical efficiency rose from 9+/-2 to 21+/-5 percent (P=0.006). Growth hormone also improved clinical symptoms, exercise capacity, and the patients' quality of life. The changes in cardiac size and shape, systolic function, and exercise tolerance were partially reversed three months after growth hormone was discontinued. CONCLUSIONS: Recombinant human growth hormone administered for three months to patients with idiopathic dilated cardiomyopathy increased myocardial mass and reduced the size of the left ventricular chamber, resulting in improvement in hemodynamics, myocardial energy metabolism, and clinical status.

Reduced left ventricular mechanical efficiency in elderly patients with coronary artery disease.

We evaluated left ventricular (LV) mechanical efficiency in 23 elderly patients (mean age 67 +/- 2) with coronary artery disease (CAD) and in 22 patients younger than 65 years (mean age 49 +/- 8) with similar severity of CAD (2.4 +/- 0.8 and 2.2 +/- 0.8 vessels per patient, respectively) and history of myocardial infarction (34% and 41%, respectively). LV mechanical efficiency was calculated as the ratio of LV work per minute and myocardial O2 consumption. LV stroke volume was calculated from left ventriculography. Coronary blood flow was measured by thermodilution. Older patients had lower values of LV stroke volume (49 +/- 16 vs 73 +/- 16 mL, p < 0.005), ejection fraction (41 +/- 17 vs 58 +/- 17%, p < 0.05), LV stroke work (93 +/- 26 vs 131 +/- 41 g.m., p < 0.02) and LV work per minute (6.7 +/- 2.6 vs 9.3 +/- 2.7 kg.m./min, p < 0.05). Since myocardial O2 consumption was similar in the two groups, LV mechanical efficiency was lower in older CAD patients (16.2 +/- 15 vs 23.8 +/- 12%, p < 0.05). Thus, elderly patients with CAD show a reduced LV mechanical pump performance and efficiency, compared with younger patients with similar disease severity and history of myocardial infarction. These observations may contribute to understanding the higher frequency of congestive heart failure in elderly patients with CAD.

[Reduced endothelium-dependent peripheral vasodilation in the aged]. / Ridotta vasodilatazione periferica endotelio-dipendente nel sogetto anziano.

Endothelial dysfunction may be present years before the clinical manifestations of atherosclerosis, which is particularly frequent in the late decades of life. Therefore, we have evaluated the presence of endothelial dysfunction in the elderly by measuring, by echo-Doppler technique, the vasodilatation of brachial artery in response to the hyperemia following forearm occlusion and decompression, a response that is dependent on endothelial function. We studied 10 subjects > 65 years (mean 72 +/- 8) and 10 subjects < 65 years (mean 40 +/- 6) all without clinical signs and without risk factors for atherosclerosis. The increase in brachial arterial flow during reactive hyperemia was similar in the young and elderly subjects (152 +/- 74% vs 129 +/- 63%, NS). While in the young at peak hyperemia we found a significant increase in brachial artery diameter from 3.4 +/- 0.9 to 4.1 +/- 1.0 mm (p < 0.005), there was no significant change in the elderly (from 3.0 +/- 0.7 to 3.1 +/- 0.7 mm, NS). In both groups sublingual glyceryl trinitrate produced a significant increase in brachial artery diameter (from 3.0 +/- 0.7 to 3.5 +/- 0.8 mm in the elderly, p < 0.01, and from 3.4 +/- 0.9 to 3.9 +/- 0.9 mm in the young subjects, p < 0.01, NS among groups), showing the absence in the elderly of structural vascular changes potentially responsible for absence of dilatation. In conclusion, elderly subjects without clinical signs or risk factors for atherosclerosis have a vascular endothelial dysfunction that may play an important role in pathologic processes of the cardiovascular system in the late decades of life.