Homocysteine-Lowering Therapy and Early Progression of Transplant Vasculopathy: A Prospective, Randomized, IVUS-Based Study

Although observational studies suggest that hyperhomocysteinemia may be a risk factor for coronary allograft vasculopathy (CAV), prospective data on homocysteine-lowering interventions and CAV development are lacking. We, therefore, randomized 44 de novo heart transplant (HT) recipients to 15 mg/day of 5-methyl-tetrahydrofolate (n=22), or standard therapy (control group, n=22) to investigate the effect of homocysteine lowering on the change in coronary intimal hyperplasia during the first 12 months after transplant, as detected by intra-vascular ultrasound (IVUS). Although 12 months after HT, homocysteinemia was lower in folate-treated patients (p<0.001), coronary intimal area increased similarly in the two groups (p>0.4). Conversely, hypercholesterolemia and cytomegalovirus infection were both associated with increased intimal hyperplasia (p<0.04), independently from folate intake. Sub-group analysis revealed that folate therapy reduced intimal hyperplasia in patients with hyperhomocysteinemia before randomization (n=19; p=0.02), but increased intimal hyperplasia in patients with normal homocysteine plasma concentrations (p=0.02). This bimodal effect of folate therapy persisted significantly after adjusting for cytomegalovirus infection and hypercholesterolemia. Despite effective in prevent hyperhomocysteinemia after heart transplantation, folate therapy does not seem to affect early CAV onset. However, sub-group analysis suggests that folate therapy may delay CAV development only in patients with baseline hyperhomocysteinemia, while may favor CAV progression in recipients with normal baseline homocysteinemia.     

Sensory retraining is key to biofeedback therapy for formed stool fecal incontinence

OBJECTIVES: Biofeedback is a nonsurgical treatment that reportedly produces good results in 65-75% of fecally incontinent patients. However, previous studies have not ruled out nonspecific treatment effects. It is also unknown whether biofeedback works primarily by improving the strength of the striated pelvic floor muscles or by improving the rectal perception. We aimed to 1) evaluate the efficacy of biofeedback in formed-stool fecal incontinence, 2) assess the relative contribution of sensory and strength retraining to biofeedback outcomes, and 3) identify patient characteristics that predict a good response to treatment. METHODS: Twenty-four patients with frequent (at least once a week) solid-stool incontinence were provided with three to four biofeedback sessions. They were taught to squeeze in response to progressively weaker rectal distentions. Patients were re-evaluated by anorectal manometry and symptom diary 3 months after completing training and by diary and interview 6-12 months after training. RESULTS: Seventeen (71%) were classified responders; 13 became continent and four reduced incontinence frequency by at least 75%. Clinical improvements were maintained at 12-month follow-up. At 3-month follow-up, responders had significantly lower thresholds for perception of rectal distention and for sphincter contraction, but squeeze pressures did not significantly differ from those of nonresponders. Baseline measures that predicted a favorable response were sensory threshold (50 ml or less), urge threshold (100 ml or less), lower threshold for sphincter contraction, and lower threshold for the rectoanal inhibitory reflex; neither anal squeeze pressure nor severity of incontinence predicted treatment outcome. CONCLUSIONS: In solid-stool fecal incontinence biofeedback training effects are robust and seem not to be explained by expectancy or nonspecific treatment effect. Sensory retraining appears to be more relevant than strength training to the success of biofeedback.     

Recognition of patients with cardiovascular disease by artificial neural networks

BACKGROUND: Artificial neural networks (ANNs) are computer algorithms inspired by the highly interactive processing of the human brain. When exposed to complex data sets, ANNs can learn the mechanisms that correlate different variables and perform complex classification tasks. AIMS: A database, of 949 patients and 54 variables, was analysed to evaluate the capacity of ANNs to recognise patients with (VE+, n = 196) or without (VE-, n = 753) a history of vascular events on the basis of vascular risk factors (VRFs), carotid ultrasound variables (UVs) or both. METHOD: The performance of ANN was assessed by calculating the percentage of correct identifications of VE+ and VE- patients (sensitivity and specificity, respectively) and the prediction accuracy (weighted mean between sensitivity and specificity). RESULTS: The results showed that ANNs can be trained to identify VE+ and VE- subjects more accurately than discriminant analyses. When VRFs and UVs were used as input variables, the prediction accuracies of the ANN providing the best results were 80.8% and 79.2%, respectively. The addition of gender, age, weight, height and body mass index to UVs increased accuracy of prediction to 83.0%. When the ANNs were allowed to choose the relevant input data automatically (I.S. system-Semeion), 37 variables were selected among 54, five of which were UVs. Using this set of variables as input data, the performance of the ANNs in the classification task reached a prediction accuracy of 85.0%. with the 92.0% correct classification of VE+ patients. CONCLUSIONS: Artificial neural network technology is highly promising in the development of accurate diagnostic tools designed to recognize patients at high risk of cardiovascular diseases.     

Chronic hepatitis B in children after e antigen seroclearance: final report of a 29-year longitudinal study

Chronic hepatitis B is usually a benign disease in Caucasian children; however, the long-term prognosis remains unsettled. This report describes the results of a 29-year longitudinal study including 99 white children with chronic hepatitis B, mainly acquired horizontally: 91 were hepatitis B e antigen (HBeAg) positive (4 had cirrhosis), and 8 were HBeAg negative at presentation. Of the 91 HBeAg-positive children, 89 underwent HBeAg seroconversion after a mean period of 5.2 +/- 4.0 years and were included in the study. Of the 85 children without cirrhosis, one had HBeAg-negative hepatitis and the other 84 became inactive carriers. During a mean follow-up of 14.5 +/- 6.1 years after HBeAg seroclearance, 4 carriers experienced reactivation, and 3 of them had HBeAg-negative hepatitis at the last follow-up. Of the 8 initially HBeAg-negative children, 2 had HBeAg-negative hepatitis, and 6 were inactive carriers. Of the 4 children with cirrhosis, 2 had hepatocellular carcinoma (HCC) and remained alive and 2 lost the histological features of cirrhosis in adulthood. Two patients with HBeAg-negative hepatitis and 1 with cirrhosis had experienced drug abuse. At the end of follow-up, 15 of the 89 initially HBeAg-positive patients and 2 of 8 initially HBeAg-negative children had cleared hepatitis B surface antigen. In conclusion, the overall prognosis for chronic hepatitis B in horizontally infected Caucasian children is favorable; however, some patients progress to HCC and HBeAg-negative hepatitis. Long-term monitoring is important, as is counseling on cofactors of liver damage, such as alcohol and drug abuse.     

The use of echocardiography for the non-invasive evaluation of coronary artery disease

In the Western world, there are now millions of patients who undergo clinical procedures that evaluate coronary artery status each year. Methods span from direct imaging using angiography, computerized tomography, to nuclear magnetic imaging as well as to functional studies, such as positron emission tomography. These techniques have provided significant information to physicians, but there is still need for an improved accessibility. Angiographic methods are expensive and expose the patient to significant amounts of radiation, undesirable in younger patients. Among the novel technologies for coronary diagnostics, transthoracic echocardiography (TTE) of coronary arteries has provided an important alternative, particularly in everyday practice. Diagnostic arterial TTE can allow determination of the coronary wall lumen in at least three major coronary segments (left main [LM], left arterial descending [LAD] and right coronary artery [RCA]). Coronary wall thickness using the LAD has been preliminarily shown to be related to the risk of coronary events. Since it is well ascertained that coronary lesions found in any location indicate that at least 80% of the coronary tree is affected, this is very important clinical information. Evaluation of coronary status by TTE is a novel technology providing important information in ischemic syndromes, in cases of coronary malformations and other coronary diseases.

• KEY MESSAGES

• Coronary evaluation can be carried out by a variety of both invasive and non-invasive methods, many requiring radiation exposure or patient immobility.

• Transthoracic echocardiography (TTE) of the coronaries can, in particular, evaluate the coronary wall thickness, and this may be directly related to the coronary disease risk.

• TTE is a useful method for the monitoring of coronary flow reserve and can allow the detection of coronary malformations.

     

Serial versus isolated assessment of clinical and instrumental parameters in heart failure: prognostic and therapeutic implications

Background

In heart failure (HF), it is not known whether analysis of serial changes in prognostic parameters provides incremental information with respect to comprehensive isolated clinical and instrumental assessments.

Methods

We analyzed time-related changes in a period ≥6 months in a broad panel of clinical and instrumental (electrocardiographic, echocardiographic, hemodynamic, and cardiopulmonary) parameters in 105 patients with HF (age, 53 ± 10 years; 88% men; 55% New York Heart Association classification III-IV; EF, 24% ± 6%).

Results

Among the time-related parameters, QRS widening (adjusted RR per 10 ms, 1.21; 95% CI, 1.10-1.48; P = .003) and peak oxygen uptake (pVO2) decrease (adjusted RR per mL/Kg/min, 1.11; 95% CI, 1.01-1.22; P = .034) provided independent, incremental information for predicting cardiac death/need for heart transplantation (CD/HT) with respect to the entire panel of isolated readings. The overall rate of CD/HT-free survival after 12 months was 60% ± 5%. Patients who were clinically stable with QRS widening and pVO2 decrease values of <10% had a better CD/HT event-free survival rate at 1 year (92% ± 5% vs 50% ± 6%; P <.001).

Conclusions

This study indicates that analysis of time-related changes in prognostic parameters provides relevant incremental prognostic information and may help in the risk stratification of patients with HF and the selection of candidates for HT. In particular, patients who were clinically stable and had QRS widening and a pVO2 decreases <10% in a period ≥6 months appear to be characterized by a good prognosis and may not be suitable candidates for HT.     

Measurement of carotid artery intima-media thickness in dyslipidemic patients increases the power of traditional risk factors to predict cardiovascular events

A longitudinal observational study investigated whether the measurement, in clinical practice, of carotid maximum intima-media thickness (Max-IMT) could be combined with the Framingham risk score (FRS) to improve the predictability of cardiovascular events in dyslipidemic patients who are at low or intermediate risk. Max-IMT was measured by ultrasound in 1969 patients attending a lipid clinic. The "best threshold values" (BTVs) above which we considered the Max-IMT to be abnormally high were calculated for our dyslipdemic population for each 10-year age interval in men and women. Two hundred and forty-two patients (age 54+/-10 years; 43.8% women) with an FRS <20%, i.e. at low or intermediate risk, were monitored for more than 5 years. Twenty-four of these patients suffered a cardiovascular event within 5.1+/-2.3 years. Both FRS and Max-IMT proved to be independent outcome predictors (p<0.04, both), with a hazard ratio (HR) of 6.7 (95% CI 1.43, 31.04; p=0.015) in patients in whom FRS was 10-20% and Max-IMT was above the BTV (60th percentile of Max-IMT distribution for men or 80th for women). In Kaplan-Meier analysis, the Max-IMT significantly improved the predictive value of the FRS (chi(2)=8.13, p=0.04). Patients with FRS 10-20% (currently considered intermediate-risk) and also elevated Max-IMT values came into the same high-risk category as patients with FRS 20-30%. The combination of FRS with Max-IMT measurement can be used in routine clinical practice to greatly enhance the predictability of cardiovascular events in the large number of patients who fall into the intermediate-risk category, which currently does not call for aggressive preventive measures.     

Epidemiological profile of 806 Italian children with hepatitis C virus infection over a 15-year period

BACKGROUND/AIMS: To evaluate the epidemiological profile of Italian children with hepatitis C virus (HCV) infection over a 15-year period. METHODS: Fifteen tertiary care centers, belonging to a national Observatory established in 1998, retrospectively/prospectively recruited 806 consecutive HCV-infected, otherwise healthy, children seen from 1990 to 2004. RESULTS: Seven hundred and sixty four were Italian and 42 from foreign countries. Newly-diagnosed cases declined from 332 in 1995-1999 to 196 in 2000-2004, while the proportion of foreign children rose from 3% to 13%. Transfusion-transmitted infection disappeared after 1992. Maternal infection (with drug abuse in 63% of cases in the North) has become the most important mode of HCV diffusion throughout Italy and the exclusive source for all children infected in 2000-2004. The prevalence of HCV genotypes 3 and 4 increased and that of genotype 1b decreased significantly (p<0.02). Male/female ratio was significantly (p<0.001) lower among vertically infected (0.6) than in transfused children (1.3). CONCLUSIONS: The number of children with newly-diagnosed HCV infection is declining in Italy and most post-transfusion cases are now young adults. Thus foreign children could significantly contribute to the reservoir of pediatric infection in years to come. New infections result from maternal transmission and seem to privilege females and genotypes 3 and 4.