Impact of serum leptin and adiponectin levels on brain infarcts in patients with mild cognitive impairment and Alzheimer's disease: a longitudinal analysis.

Introduction: The adipokines leptin and adiponectin have been associated with atherosclerosis and the risk of cerebral infarcts. Pre-clinical studies, however, suggest a protective role against ischemic brain damage. In this study we analyzed the relationship between serum leptin and adiponectin levels and the onset or progression of brain infarcts in subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Methods: All data were extracted from the ADNI database. The final population included 566 subjects, with 58 healthy controls, 396 MCI and 112 AD. All patients with available serum leptin and adiponectin levels at baseline were selected. Demographics, neuropsychological test results, CSF biomarkers, regional brain metabolism with FDG-PET data and the number of brain infarcts on longitudinal MRI scans were extracted. Results: Leptin levels were significantly lower in patients with MCI than controls at baseline, while adiponectin levels were not different between the groups. Multivariate logistic regression analysis at baseline for the presence of brain infarcts showed a predictive value for leptin but not for adiponectin. Multivariate longitudinal analysis showed that age was the only significant predictor of brain infarcts development at 15-year follow-up, while serum leptin and adiponectin levels did not play a role in this population. Discussion: The evidence on the pathogenetic or protective role of adipokines on ischemic brain damage is mixed. In this MCI and AD population, serum leptin and adiponectin were not associated with the development of brain infarcts; therefore, these results do not support the use of adipokines as biomarkers of cerebrovascular pathology in this population.

Role of frailty on cardiac rehabilitation in hospitalized older patients.

BACKGROUND: Cardiovascular diseases are the leading cause of mortality, morbidity, and disability in the world, especially in the older adults. A relevant proportion of patients admitted to Cardiac Rehabilitation (CR) may suffer from frailty, a complex geriatric syndrome with multifactorial aetiology. AIMS: The hypothesis underlying the study is that frailty complicates the management of older patients undergoing CR. The main objective is, therefore, to determine the relationship between frailty and CR outcomes in hospitalized older adults. METHODS: The participants have been recruited among patients aged ≥ 65 years admitted at the hospital for CR. A Comprehensive Geriatric Assessment (CGA)-based Frailty Index (FI) was created following a standard procedure. The outcome was measured as the ratio between 6-min walk test (6MWT) distance at the end of CR and normal predicted values for a healthy adult of same age and gender, according to reference equations. RESULTS: The study population consisted of 559 elderly patients, 387 males (69.2%), with age of 72 (69-76) years. The most frequent diagnosis at admission was ischaemic heart disease (231, 41.5%) and overall 6MWT ratio was 0.62 ± 0.21. At the multivariable regression analysis, gender, diagnosis and FI were significantly and independently associated with 6MWT ratio (p ≤ 0.0001, p ≤ 0.001 and p ≤ 0.0001, respectively), while no significant association emerged for age. CONCLUSION: FI resulted independently correlated to 6MWT ratio in a population of older patients undergoing in-hospital CR programs. Frailty is a multifactorial geriatric syndrome whose assessment is essential for prognostic evaluation of older patients, also in CR clinical setting.

Muscle Ultrasound as Imaging Domain of Frailty.

Introduction: Frailty is a geriatric syndrome, a clinical state of vulnerability for developing dependency and/or death. Due to its multidimensional nature, Comprehensive Geriatric Assessment (CGA) constitutes the best strategy to evaluate frailty in older patients. Accumulation of deficits model synthesizes the global assessment of geriatric domains in the Frailty Index (FI) score. Muscle Ultrasound (MUS) has been employed to evaluate muscle mass wasting as tool to assess sarcopenia in late life. The present study aims to evaluate the association between CGA-based FI and MUS measures in a population of hospitalized older adults. Methods: Patients aged ≥65 years underwent CGA for the evaluation of the domains of health and functional status, psycho-cognition, nutritional status, socio-environmental condition. Following standard procedure, a CGA-based FI was elaborated, taking into account 38 multidimensional items. Muscle thicknesses (MT) of rectus femoris plus vastus intermedius were measured through MUS axial cross-section. Multivariable regression analysis was employed to determine factors associated with FI. Results: The study population consisted of 136 older patients, 87 men (63.9%), with median age of 74 (70-81) years, FI of 0.3 (0.21-0.46), and MT of rectus femoris plus vastus intermedius 29.27 (23.08-35.7) mm. At multivariable regression analysis, FI resulted significantly and independently associated with age and MT. Conclusion: Muscle thicknesses of rectus femoris plus vastus intermedius, measured through MUS, resulted to be significantly related to FI in a population of hospitalized older patients. In the CGA-based assessment of frailty, MUS may constitute an additional imaging domain.

Impact of the number of comorbidities on cardiac sympathetic derangement in patients with reduced ejection fraction heart failure.

INTRODUCTION: Heart failure (HF) is frequently associated with comorbidities. 123I-metaiodobenzylguanidine (123I-mIBG) imaging constitutes an effective tool to measure cardiac adrenergic innervation and to improve prognostic stratification in HF patients, including the risk of major arrhythmic events. Although comorbidities have been individually associated with reduced cardiac adrenergic innervation, thus suggesting increased arrhythmic risk, very comorbid HF patients seem to be less likely to experience fatal arrhythmias. We evaluated the impact of the number of comorbidities on cardiac adrenergic innervation, assessed through 123I-mIBG imaging, in patients with systolic HF. METHODS: Patients with systolic HF underwent clinical examination, transthoracic echocardiography and cardiac 123I-mIBG scintigraphy. The presence of 7 comorbidities/conditions (smoking, chronic obstructive pulmonary disease, diabetes mellitus, peripheral artery disease, atrial fibrillation, chronic ischemic heart disease and chronic kidney disease) was documented in the overall study population. RESULTS: The study population consisted of 269 HF patients with a mean age of 66±11 years, a left ventricular ejection fraction (LVEF) of 31±7%, and 153 (57%) patients presented ≥3 comorbidities. Highly comorbid patients presented a reduced late heart to mediastinum (H/M) ratio, while no significant differences emerged in terms of early H/M ratio and washout rate. Multiple regression analysis revealed that the number of comorbidities was not associated with mIBG parameters of cardiac denervation, which were correlated with age, body mass index and LVEF. CONCLUSION: In systolic HF patients, the number of comorbidities is not associated with alterations in cardiac adrenergic innervation. These results are consistent with the observation that very comorbid HF patients suffer lower risk of sudden cardiac death.

Impact of Galectin-3 Circulating Levels on Frailty in Elderly Patients with Systolic Heart Failure.

Background: Heart Failure (HF), a leading cause of morbidity and mortality, represents a relevant trigger for the development of frailty in the elderly. Inflammation has been reported to play an important role in HF and frailty pathophysiology. Galectin-3 (Gal-3), whose levels increase with aging, exerts a relevant activity in the processes of cardiac inflammation and fibrosis. The aim of the present study was to investigate the potential of Galectin-3 to serve as a biomarker of frailty in HF patients. Methods: 128 consecutive patients aged 65 and older with the diagnosis of systolic HF underwent a frailty assessment and blood sample collection for serum Gal-3 detection. A multivariable regression analysis and decision curve analysis (DCA) were used to identify significant predictors of frailty. Results: Frailty was present in 42.2% of patients. Age: Odds Ratio (OR) = 3.29; 95% Confidence Interval CI (CI) = 1.03-10.55, Cumulative Illness Rating Scale Comorbidity Index (CIRS-CI): OR = 1.85; 95% CI = 1.03-3.32, C-Reactive phase Protein (CRP) OR = 3.73; 95% CI = 1.24-11.22, N-terminal-pro-Brain Natriuretic Peptide (NT-proBNP): OR = 2.39; 95% CI = 1.21-4.72 and Gal-3: OR = 5.64; 95% CI = 1.97-16.22 resulted in being significantly and independently associated with frailty. The DCA demonstrated that the addition of Gal-3 in the prognostic model resulted in an improved clinical 'net' benefit. Conclusions: Circulating levels of Gal-3 are independently associated with frailty in elderly patients with systolic HF.

Impact of body mass index on cardiac adrenergic derangement in heart failure patients: a 123I-mIBG imaging study.

PURPOSE: To assess the impact of body mass index (BMI) on cardiac adrenergic derangement, measured by iodine-123 meta-iodobenzylguanidine (123I-mIBG) imaging in heart failure (HF) patients. Overweight and obesity represent relevant health issues, and augmented sympathetic tone has been described in patients with increased BMI. An extensive literature supports that HF-dependent cardiac denervation, measured through mIBG parameters, is an independent predictor of cardiovascular outcomes and mortality. However, the influence of BMI on cardiac mIBG uptake has not been largely investigated. METHODS: We prospectively enrolled patients with systolic HF, collecting demographic, clinical, echocardiographic data, and mIBG imaging parameters. In order to detect the factors associated with mIBG parameters, a model building strategy, based on the Multivariable Fractional Polynomial algorithm, has been employed. RESULTS: We studied 249 patients with systolic HF, mean age of 66.4 ± 10.6 years, and mean left ventricular ejection fraction (LVEF) of 30.7% ± 6.4, undergoing cardiac 123I-mIBG imaging to assess HF severity and prognosis. Seventy-eight patients (31.3%) presented a BMI ≥ 30 kg/m2 and obese patients showed a significant reduction in early heart to mediastinum (H/M) ratio (1.66 ± 0.19 vs. 1.75 ± 0.26; p = 0.008) and a trend to reduction in washout rate (33.6 ± 18.3 vs. 38.1 ± 20.1; p = 0.092) compared with patients with BMI < 30 kg/m2. Multiple regression analysis revealed that BMI, age, and LVEF were significantly correlated with early and late H/M ratios. CONCLUSIONS: Results of the present study indicate that BMI, together with LVEF and age, is independently correlated with cardiac mIBG uptake in HF patients.

Inter-relationships between Gender, Frailty and 10-Year Survival in Older Italian Adults: an observational longitudinal study.

Aim of the present study was to assess the impact of gender on the relationship between long-term mortality and clinical frailty. In an observational, longitudinal study on 10-year mortality, we examined 1284 subjects. The Frailty Staging System was used to assess frailty. The Cox model was employed to assess variables independently associated with survival using a backward stepwise algorithm. To investigate the possible interactions between gender and the selected variables, an extension of the multivariable fractional polynomial algorithm was adopted. Women were more likely to be older, have a higher disability, present with more comorbidities, consume more drugs, be frail and have a higher rate of survival at the follow-up than were men. At the Cox multivariate analysis only age (HR 2.26), female gender (HR 0.43), and number of drugs (HR 1.57) were significant and independent factors associated with all-cause mortality. In the survival analyses, only frailty (vs no frailty) showed significant interaction with gender (p < 0.001, HR = 1.92). While the presence of frailty reduced the survival rate in women, no effect was observed in men. Importantly, frail women showed higher survival rates than did both frail and no frail men. The main finding of the present study is that gender shapes up the association between frailty and long-term survival rates.

Prognosis of severe acquired brain injury: Short and long-term outcome determinants and their potential clinical relevance after rehabilitation. A comprehensive approach to analyze cohort studies.

BACKGROUND: Accurate prognostic evaluation is a key factor in the clinical management of patients affected by severe acute brain injury (ABI) and helps planning focused therapies, better caregiver's support and allocation of resources. Aim of the study was to assess factors independently associated with both the short and long-term outcomes after rehabilitation in patients affected by ABI in the setting of a single Rehabilitation Unit specifically allocated to these patients. METHODS AND FINDINGS: In all patients (567) with age ≥ 18 years discharged from the Unit in the period 2006/2015 demographic, etiologic, comorbidity indicators, and descriptors of the disability burden (at hospital admission and discharge) were evaluated as potential prognostic factors of both short-term (4 classes of disability status at discharge) and long-term (mortality) outcomes. A comprehensive analytical method was adopted to combine several tasks. Select the factors with a significant independent association with the outcome, assess the relative weights and the "stability" (by bootstrap resampling) of them and estimate the role of the prognostic models in the clinical framework considering "cost" and "benefits". The generalized ordered logistic model for ordinal dependent variables was used for the short-term outcome while the Cox proportional hazard model was used for the long-term outcome. The final short-term model identified 7 factors that independently account for 37% of the outcome variability as shown by pseudo R2 (pR2) = 0.37. The disability status descriptors show the strongest association since they account for more than 60% of the pR2, followed by age (14.8%), the presence of percutaneous endoscopic gastrostomy or nasogastric intubation (14.4%), a longer stay in the acute ward (5.9%) and concomitant coronary disease (1.3%). The final multivariable Cox model identified 4 factors that independently account for 52% of the outcome variability (R2 = 0.52). The disability extent and the disability recovered lead the long-term mortality since they account for the 53% of the global R2. The relevant effect of age (42%) is appreciable only after 2 years given the significant interaction with time. A longer stay in the acute ward explains the remaining fraction (5%). Considering 'cost and benefits', the decision curve analysis shows that the clinical benefit achieved by using both prognostic models is greater than the other possible action strategies, namely 'treat all' and 'treat none. Several less obvious characteristics of the prognostic models are appreciated by integrating the results of multiple analytical methods. CONCLUSION: The comprehensive analytical tool aimed to integrate statistical significance, weight, "stability" and clinical "net" benefit, gives back a prognostic framework explaining a relevant portion of both outcomes' variability in which the strong association of the disability status with both outcomes is comparable to and followed by a time modulated role of age. Our data do not support a differentiated association of traumatic vs non-traumatic etiology. The results encourage the use of integrated approach to analyze cohort data.

Impact of Malnutrition on Long-Term Mortality in Elderly Patients with Acute Myocardial Infarction.

BACKGROUND: Malnutrition is a frequent condition in the elderly, and is associated with prolonged hospitalization and increased mortality. However, the impacts of malnutrition among elderly patients with acute myocardial infarction have not been clarified yet. METHODS AND RESULTS: We enrolled 174 patients aged 65 years and over, admitted with the diagnosis of acute myocardial infarction (AMI), who underwent evaluation of nutritional status by Mini Nutritional Assessment (MNA) and evaluation of mortality risk by GRACE Score 2.0. All-cause mortality was the outcome considered for this study. Over a mean follow-up of 24.5 ± 18.2 months, 43 deaths have been registered (24.3%). Non-survivors were more likely to be older, with worse glomerular filtration rate, lower systolic blood pressure, lower albumin and MNA score, higher prevalence of Killip classification III-IV grade, and higher Troponin I levels. Multivariate Cox proportional analysis revealed that GRACE Score and MNA showed a significant and independent impact on mortality, (HR = 1.76, 95%, CI = 1.34⁻2.32, and HR = 0.56, 95% CI = 0.42⁻0.73, respectively). Moreover, the clinical decision curve revealed a higher clinical net benefit when the MNA was included, compared to the partial models without MNA. CONCLUSION: Nutritional status is an independent predictor of long-term mortality among elderly patients with AMI. MNA score in elderly patients with AMI may help prognostic stratification and identification of patients with, or at risk of, malnutrition in order to apply interventions to improve nutritional status, and maybe survival in this population.

Long-term effect of weight loss induced by bariatric surgery on asthma control and health related quality of life in asthmatic patients with severe obesity: A pilot study.

BACKGROUND: The weight loss induced by bariatric surgery (BS) improves asthma clinical control evaluated usually after a short time. The long-term effects of weight loss attained by BS on asthma control and health related-quality of life (HRQoL) in patients affected by asthma and obesity are not known. OBJECTIVE: To investigate the five-year effect of weight reduction induced by BS on asthma control, quality of life and pulmonary functional parameters in severely obese intermittent or mild-to-moderate asthmatic patients. METHODS: Twenty-six consecutive severe obese subjects with previous diagnosis of asthma with indication for laparoscopic adjustable gastric banding (LAGB) were enrolled into the study. Fifteen of them agreed to undertake the surgery (treatment group, TG) while the remaining eleven non-operated patients represented the control group (CG). Body mass index (BMI), Asthma Control Test (ACT), Mini Asthma Quality of Life Questionnaire (mini-AQLQ) and spirometric parameters were evaluated at baseline and after one and five years from surgery. RESULTS: Mean BMI of TG significantly decreased at one and five years after the surgery, while it remained unchanged in CG. After surgery, both the overall ACT and the mini-AQLQ score significantly improved in TG after one year, persisting improved after 5-years (p < 0.001), while these outcomes remained unchanged in CG. As compared with the pre-surgery values, the percentage of predicted FEV1 and FVC significantly increased at five-year follow-up from surgery in TG, while it remained unchanged in CG. CONCLUSIONS: In severe obese asthmatic patients, the significant improvement of asthma control test and HRQoL, observed one year after LAGB, persists five years after surgery.

Impact of aging on cardiac sympathetic innervation measured by 123I-mIBG imaging in patients with systolic heart failure.

PURPOSE: Sympathetic nervous system (SNS) hyperactivity is a salient characteristic of chronic heart failure (HF) and contributes to the progression of the disease. Iodine-123 meta-iodobenzylguanidine (123I-mIBG) imaging has been successfully used to assess cardiac SNS activity in HF patients and to predict prognosis. Importantly, SNS hyperactivity characterizes also physiological ageing, and there is conflicting evidence on cardiac 123I-mIBG uptake in healthy elderly subjects compared to adults. However, little data are available on the impact of ageing on cardiac sympathetic nerve activity assessed by 123I-mIBG scintigraphy, in patients with HF. METHODS AND RESULTS: We studied 180 HF patients (age = 66.1 ± 10.5 years [yrs]), left ventricular ejection fraction (LVEF = 30.6 ± 6.3 %) undergoing cardiac 123I-mIBG imaging. Early and late heart to mediastinum (H/M) ratios and washout rate were calculated in all patients. Demographic, clinical, and echocardiographic data were also collected. Our study population consisted of 53 patients aged >75 years (age = 77.7 ± 4.0 year), 67 patients aged 62-72 years (age = 67.9 ± 3.2 years) and 60 patients aged ≤61 year (age = 53.9 ± 5.6 years). In elderly patients, both early and late H/M ratios were significantly lower compared to younger patients (p < 0.05). By multivariate analysis, H/M ratios (both early and late) and washout rate were significantly correlated with LVEF and age. CONCLUSIONS: Our data indicate that, in a population of HF patients, there is an independent age-related effect on cardiac SNS innervation assessed by 123I-mIBG imaging. This finding suggests that cardiac 123I-mIBG uptake in patients with HF might be affected by patient age.

Prognostic Value of Lymphocyte G Protein-Coupled Receptor Kinase-2 Protein Levels in Patients With Heart Failure.

RATIONALE: Sympathetic nervous system hyperactivity is associated with poor prognosis in patients with heart failure (HF), yet routine assessment of sympathetic nervous system activation is not recommended for clinical practice. Myocardial G protein-coupled receptor kinase-2 (GRK2) is upregulated in HF patients, causing dysfunctional ß-adrenergic receptor signaling. Importantly, myocardial GRK2 levels correlate with levels found in peripheral lymphocytes of HF patients. OBJECTIVE: The independent prognostic value of blood GRK2 measurements in HF patients has never been investigated; thus, the purpose of this study was to evaluate whether lymphocyte GRK2 levels predict clinical outcome in HF patients. METHODS AND RESULTS: We prospectively studied 257 HF patients with mean left ventricular ejection fraction of 31.4±8.5%. At the time of enrollment, plasma norepinephrine, serum NT-proBNP, and lymphocyte GRK2 levels, as well as clinical and instrumental variables were measured. The prognostic value of GRK2 to predict cardiovascular (CV) death and all-cause mortality was assessed using the Cox proportional hazard model including demographic, clinical, instrumental, and laboratory data. Over a mean follow-up period of 37.5±20.2 months (range, 3-60 months), there were 102 CV deaths. Age, left ventricular ejection fraction, New York Heart Association class, chronic obstructive pulmonary disease, chronic kidney disease, N-terminal-pro brain natriuretic peptide, and lymphocyte GRK2 protein levels were independent predictors of CV mortality in HF patients. GRK2 levels showed an additional prognostic and clinical value over demographic and clinical variables. The independent prognostic value of lymphocyte GRK2 levels was also confirmed for all-cause mortality. CONCLUSIONS: Lymphocyte GRK2 protein levels can independently predict prognosis in patients with HF.

Renal function impairment predicts mortality in patients with chronic heart failure treated with resynchronization therapy.

BACKGROUND: The use of cardiac resynchronization therapy (CRT) and implantable cardioverter- defibrillator (ICD) for advanced heart failure (HF) is increasing. Renal dysfunction is a common condition in HF which is associated with a worse survival. The study aims at identifying in patients with advanced HF treated with CRT the effect of baseline glomerular filtration rate (GFR), GFR improvement and left ventricular ejection fraction (LVEF) change, after 6-months of CRT implant, on survival. METHODS: The study population consisted of 375 advanced HF patients who received a CRT between 1999 and 2009, of these 277 received also an ICD implant. Clinical characteristics (New York Heart Association [NYHA] functional class, ischemic vs. non-ischemic etiology, atrial fibrillation, diabetes, hypertension, LVEF, QRS duration and GFR were recorded. The use of common used drugs was evaluated. Cox proportional hazards analysis was calculated in order to evaluate variables associated to mortality. RESULTS: During a median follow-up of 43.0 months, 93 (24.8%) patients died. Patients deceased during the study had at baseline higher NYHA class and lower LVEF and GFR. In Cox regression analysis, GFR predicts long-term mortality (hazard ratio [HR] 0.983; 95% confidence interval [CI] 0.969-0.998; p = 0.023) independently from the effect of others covariates. In addition, a positive GFR improvement 6 months after CRT implant is significantly associated with a lower hazard of mortality (for each 10 mL/min of GFR improvement HR 0.86; 95% CI 0.75-0.99; p = 0.038). CONCLUSIONS: GFR is a significant predictor of mortality in advanced HF patients who received CRT. A GFR improvement 6 months after CRT implant is significantly associated with a lower hazard of mortality.

Warfarin anticoagulant therapy: a Southern Italy pharmacogenetics-based dosing model.

BACKGROUND AND AIM: Warfarin is the most frequently prescribed anticoagulant worldwide. However, warfarin therapy is associated with a high risk of bleeding and thromboembolic events because of a large interindividual dose-response variability. We investigated the effect of genetic and non genetic factors on warfarin dosage in a South Italian population in the attempt to setup an algorithm easily applicable in the clinical practice. MATERIALS AND METHODS: A total of 266 patients from Southern Italy affected by cardiovascular diseases were enrolled and their clinical and anamnestic data recorded. All patients were genotyped for CYP2C9 2, 3, CYP4F2 3, VKORC1 -1639 G>A by the TaqMan assay and for variants VKORC1 1173 C>T and VKORC1 3730 G>A by denaturing high performance liquid chromatography and direct sequencing. The effect of genetic and not genetic factors on warfarin dose variability was tested by multiple linear regression analysis, and an algorithm based on our data was established and then validated by the Jackknife procedure. RESULTS: Warfarin dose variability was influenced, in decreasing order, by VKORC1-1639 G>A (29.7%), CYP2C9 3 (11.8%), age (8.5%), CYP2C9 2 (3.5%), gender (2.0%) and lastly CYP4F2 3 (1.7%); VKORC1 1173 C>T and VKORC1 3730 G>A exerted a slight effect (<1% each). Taken together, these factors accounted for 58.4% of the warfarin dose variability in our population. Data obtained with our algorithm significantly correlated with those predicted by the two online algorithms: Warfarin dosing and Pharmgkb (p<0.001; R(2) = 0.805 and p<0.001; R(2) = 0.773, respectively). CONCLUSIONS: Our algorithm, which is based on six polymorphisms, age and gender, is user-friendly and its application in clinical practice could improve the personalized management of patients undergoing warfarin therapy.

Effects of Lactobacillus rhamnosus strain GG in pediatric obesity-related liver disease.

OBJECTIVE: Various lines of evidence suggest that malfunctioning of the gut-liver axis contributes to hepatic damage of rodents and humans with nonalcoholic fatty liver disease. We evaluated the effects of short-term probiotic treatment in children with obesity-related liver disease who were noncompliant with lifestyle interventions. PATIENTS AND METHODS: Twenty obese children (age 10.7 ± 2.1 years) with persisting hypertransaminasemia and ultrasonographic (US) bright liver were enrolled in this double-blind, placebo-controlled pilot study. At baseline, patients underwent clinical and laboratory anthropometric evaluation, measurement of the US hepatorenal ratio, standard liver function tests, oral glucose tolerance test, serum tumor necrosis factor-alpha, the glucose hydrogen breath test, and evaluation of serum antibodies to antipeptidoglycan-polysaccharide polymers. After exclusion of causes of liver disease other than obesity, patients received either probiotic Lactobacillus rhamnosus strain GG (12 billion CFU/day) or placebo for 8 weeks. RESULTS: Multivariate analysis after probiotic treatment revealed a significant decrease in alanine aminotransferase (average variation vs placebo P = 0.03) and in antipeptidoglycan-polysaccharide antibodies (average variation vs placebo P = 0.03) irrespective of changes in BMI z score and visceral fat. Tumor necrosis factor-alpha, and US bright liver parameters remained fairly stable. CONCLUSIONS: Probiotic L rhamnosus strain GG warrants consideration as a therapeutic tool to treat hypertransaminasemia in hepatopathic obese children noncompliant with lifestyle interventions.

Effects of ACE inhibition on circulating endothelial progenitor cells, vascular damage, and oxidative stress in hypertensive patients.

PURPOSE: The pathogenic role of angiotensin-converting enzyme (ACE) inhibition in hypertensive patients regarding endothelial progenitor-cell (EPC) function is still poorly understood. The aim of the study was to evaluate EPC number, function, and relationship to carotid intima media thickness (IMT) progression. METHODS: We studied 36 newly diagnosed mildly hypertensive patients free of cardiovascular disease and related risk factors without prior or concurrent therapy with ACE inhibitors. Patients were randomized to receive enalapril 20 mg/day (n = 18) or zofenopril 30 mg/day (n = 18). EPC number and migrating capacity, plasma nitrite and nitrate (NOx), and isoprostane concentrations were evaluated. Carotid IMT was determined by ultrasonography at baseline and after 1 and 5 years of follow-up. RESULTS: EPC number increased during the follow-up, with no statistical differences between treatment groups. There was an inverse correlation between circulating EPCs and IMT increase over time. Plasma NOx decreased during the study without evident differences between treatment groups. Isoprostanes decreased more markedly in zofenopril-treated patients. Multiple linear regression model demonstrated that carotid IMT was significantly inversely correlated with EPC but not with migratory cells after adjusting for confounders. CONCLUSIONS: The study demonstrated that EPC levels increased during the follow-up in both groups of newly diagnosed hypertensive patients treated with ACE inhibitors. These drugs prevented progression of vascular damage, with an inverse correlation between circulating EPC levels and IMT values.

Prevalence and long-term course of macro-aspartate aminotransferase in children.

OBJECTIVES: To investigate the prevalence, association with clinical conditions, and long-term course of macro-aspartate aminotransferase (macro-AST). STUDY DESIGN: Forty-four children with an isolated elevation of serum AST were screened for macro-AST with electrophoresis and % polyethylene glycol (PEG) precipitable activity (PPA). RESULTS: All children were healthy, except they had elevated AST values. Seventeen children (38.6%) were macro-AST-positive. They had higher AST values than the 27 children who were macro-AST-negative (P = .001). Values <67.1% PPA and >82.2% PPA were associated with a very low probability of being macro-AST-positive and macro-AST-negative, respectively. Thirty-eight children underwent clinical and laboratory follow-up (mean, 4.7 +/- 3.8; range, 1-16 years). All remained symptom-free. AST levels decreased significantly only in children who were macro-AST-negative (P = .006). Macroenzyme persisted in 6 of the 9 children who were macro-AST-positive after 6.0 +/- 4.1 years. CONCLUSIONS: Macro-AST was present in more than one-third of children with an isolated increase of AST levels. The lack of pathological correlates in a long period argues for the benign nature of this phenomenon in childhood. We suggest that our %PPA thresholds can be used as a screening test and that electrophoresis be reserved for confirming positive screen test results and cases in which %PPA levels are of intermediate discriminant accuracy.

Citrulline blood levels as indicators of residual intestinal absorption in patients with short bowel syndrome.

Plasma citrulline is known to be a marker of absorptive enterocyte mass in humans. We evaluated whether citrulline and other blood amino acids are indicators of residual small intestinal length and therefore potential predictors of dependence on parenteral nutrition in the long term. We studied 25 patients with short bowel syndrome (SBS) after at least 18 months since last digestive circuit modification; 24 of them were again evaluated 1 year later. Ten patients were weaned off parenteral nutrition and 15 were dependent on parenteral nutrition. Fifty-four healthy volunteers (28 women and 26 men) served as controls. Amino acid levels were determined on serum with high-performance liquid chromatography (HPLC) as well as on blood and serum with tandem mass spectrometry analysis. Five amino acids (citrulline, leucine, isoleucine, valine and tyrosine) were significantly lower in all SBS patients than in controls, whereas glutamine, measured only by HPLC, was significantly higher. Nevertheless, only serum citrulline measured with HPLC was significantly related to small bowel length. We conclude that HPLC remains the reference methodology to evaluate blood or serum amino acid levels in adult population with SBS.

Left ventricular remodelling in patients with moderate systolic dysfunction after myocardial infarction: favourable effects of exercise training and predictive role of N-terminal pro-brain natriuretic peptide.

AIMS: To investigate the effects of exercise training (ET) on left ventricular (LV) volumes, cardiopulmonary functional capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in postinfarction patients with moderate LV dysfunction. METHODS: Sixty-one postinfarction patients were randomized into two groups: group T [n=30, LV ejection fraction (EF) 41.6+/-11.3%, mean+/-SD] entered a 6-month ET programme, whereas group C (n=31, EF 42.0+/-7.6%, P=NS) did not. NT-proBNP assay, Doppler-echocardiography and cardiopulmonary exercise test were performed upon enrolment and at sixth months. RESULTS: At sixth months, trained patients showed an improvement in workload (+26%, P<0.001), Vo2peak (+31%, P<0.001), LV end-diastolic volume index (LVEDVI; -9%, P<0.001), a reduction in NT-proBNP (-71%, P<0.001) and a significant correlation between changes in NT-proBNP and in LVEDVI (r=0.858, P<0.001). Baseline NT-proBNP correlated with changes in LVEDVI in both trained (r=0.673, P<0.001) and untrained (r=0.623, P<0.001) patients. Group C showed unfavourable LVEDVI dilation (+8%, P<0.001; T vs. C group, P<0.001) and a smaller reduction in NT-proBNP (-40%, P<0.001; T vs. C group, P<0.001). CONCLUSIONS: Six month ET induced a favourable LV remodelling and a marked fall in NT-proBNP that could predict LV remodelling in postinfarction patients with moderate LV dysfunction.

Effect of losartan in treatment of exercise-induced myocardial ischemia.

Because no controlled clinical studies are available about the possible role of angiotensin II receptor blockers in preventing effort myocardial ischemia, we evaluated the effect of angiotensin II receptor blocker/losartan in preventing exercise-induced myocardial ischemia in patients with coronary artery disease. Twenty-four sedentary patients with chronic stable ischemia were prospectively randomized to 28 days (double blind) of losartan 100 mg or losartan placebo in 2 divided doses. In each patient the treatment was crossed over to the alternative regimen (28 days, double blind) after a 1-week placebo period (single blind). At the end of each phase a new exercise stress test was performed. At baseline, systolic blood pressure was significantly decreased after losartan 100 mg compared with losartan placebo. At submaximal exercise, systolic blood pressure and rate-pressure product were lower after losartan 100 mg administration compared with losartan placebo, and these findings remained significant at 1-mm ST depression and at peak exercise. Losartan 100 mg administration versus losartan placebo significantly delayed the time to 1-mm ST-depression onset and decreased ST-segment depression at peak exercise and time to recovery of ST-segment depression. Losartan 100 mg administration compared with losartan placebo was able to significantly increase exercise duration and maximal workload during exercise stress testing. In conclusion, in our study, losartan decreased electrocardiographic parameters of myocardial ischemia in patients with coronary artery disease, suggesting a possible role of this drug in treatment of patients with effort myocardial ischemia.