The effect of the plasminogen activator inhibitor-1 4G/5G polymorphism on the thrombotic risk

Plasminogen activator inhibitor (PAI-1), is the central component of the fibrinolytic system. A deletion/insertion (4G/5G) polymorphism in the promoter region of the PAI-1 gene has been correlated with levels of plasma PAI-1. The 4G allele is associated with higher levels of PAI-1, and might increase the risk for intravascular thrombosis. However, the contribution of this genetic variant to the risk for thrombosis, both arterial and venous, has not been clearly established. A broad spectrum of findings regarding the effect of the 4G allele on thrombotic risk in different target organs has been reported. Our aim is to summarize the variable influence of this polymorphism on thrombotic events in different tissues or organs and explain the underlying mechanisms accounting for these differences.     

Value of myocardial viability estimation using dobutamine stress echocardiography in assessing risk preoperatively before noncardiac vascular surgery in patients with left ventricular ejection fraction <35%

Patients with heart failure (HF) scheduled for vascular surgery have an increased risk of adverse postoperative outcome, and stratification usually depends on dichotomous risk factors. A quantitative prognostic model for patients with HF was developed using wall motion patterns during dobutamine stress echocardiography (DSE). A total of 295 consecutive patients (mean age 67 +/- 12 years) with ejection fraction < or =35% were studied. During DSE, wall motion patterns of dysfunctional segments were scored as scar, ischemia, or sustained improvement. Cardiac death and myocardial infarction were noted perioperatively and during 5 years of follow-up. Of 4,572 dysfunctional segments; 1,783 (39%) had ischemia, 1,280 (28%) had sustained improvement, and 1,509 (33%) had scar. In 212 patients, > or =1 ischemic segment was present; 83 had only sustained improvement. Perioperative and late cardiac event rates were 20% and 30%, respectively. Using multivariate analysis, number of ischemic segments was associated with perioperative cardiac events (odds ratio per segment 1.6, 95% confidence interval 1.05 to 1.8), whereas number of segments with sustained improvement was associated with improved outcome (odds ratio per segment 0.2, 95% confidence interval 0.04 to 0.7). Multivariate independent predictors of late cardiac events were age and ischemia. Sustained improvement was associated with improved survival. In conclusion, DSE provides accurate risk stratification of patients with HF undergoing vascular surgery.     

Cost-effectiveness of frequent in-center hemodialysis

Published evidence suggests that frequent hemodialysis (more than three times per week) for patients with ESRD may improve health-related quality of life and has the potential to increase longevity and reduce hospitalization and other complications. Here, a Monte Carlo simulation model was used to compare varying combinations of in-center hemodialysis frequency (three to six treatments per week) and session length (2 to 4.5 h per session) with regard to unadjusted and quality-adjusted life-years and total lifetime costs for a cohort of 200,000 patients, representing the prevalent ESRD population. The incremental cost-effectiveness ratio was calculated for the various regimens relative to a conventional hemodialysis regimen (three treatments per week, 3.5 h per session). Using conservative assumptions of the potential effects of more frequent hemodialysis on outcomes, most strategies achieved a cost-effectiveness ratio of <$125,000, although all had a cost-effectiveness ratio of >$75,000. The cost-effectiveness ratio increased with the frequency of hemodialysis. More frequent in-center hemodialysis strategies could become cost-neutral if the cost per hemodialysis session could be reduced by 32 to 43%. No other change in model assumptions achieved cost neutrality. In conclusion, given the extraordinarily high costs of the ESRD program, the viability of more frequent hemodialysis strategies depends on significant improvements in the economic model underlying the delivery of hemodialysis.     

A prognostic risk index for long-term mortality in patients with peripheral arterial disease

BACKGROUND: Prognostic information in peripheral arterial disease (PAD) may provide the basis for optimal management strategies at an early stage. This study aimed to develop a prognostic risk index for long-term mortality in patients with PAD. METHODS: In a single-center observational cohort study, 2642 patients with an ankle-brachial index of 0.90 or lower were randomly divided into derivation (n = 1332) and validation (n = 1310) cohorts. Cox regression analysis with stepwise backward elimination identified predictors of 1-year, 5-year, and 10-year mortality in the derivation cohort. Weighted points were assigned to each predictor. Index discrimination was determined in both the derivation and validation cohorts. RESULTS: During 10 years of follow-up, 42.2% and 40.4% of patients died in the derivation and validation cohorts, respectively. The risk index for 10-year mortality (+ points) included renal dysfunction (+12), heart failure (+7), ST-segment changes (+5), age greater than 65 years (+5), hypercholesterolemia (+5), ankle-brachial index lower than 0.60 (+4), Q-waves (+4), diabetes (+3), cerebrovascular disease (+3), and pulmonary disease (+3). Statins (-6), aspirin (-4), and beta-blockers (-4) were associated with reduced 10-year mortality. Patients were stratified into low (<0 points), low-intermediate (0-5 points), high-intermediate (6-9 points), and high (>9 points) risk categories, according to risk score. Ten-year mortality rates were 22.1%, 32.2%, 45.8%, and 70.4%, respectively (P < .001) and comparable to mortality in the validation cohort. C statistics demonstrated good discrimination in both the derivation (0.72) and validation cohorts (0.73). CONCLUSIONS: A prognostic risk index for long-term mortality stratified patients with PAD into different risk categories. This may be useful for risk stratification, patient counseling, and medical decision making.     

Use of statins and risk of haematological malignancies: a meta-analysis of six randomized clinical trials and eight observational studies

AIMS: Statins have been suggested to prevent haematological malignancies. Several epidemiological studies have evaluated this association, while randomized controlled trials (RCTs) on cardiovascular outcomes have provided relevant data as secondary end-points. Our aim was to examine the strength of this association through a detailed meta-analysis of the studies published in peer-reviewed literature. METHODS: A comprehensive search for articles published up to December 2006 was performed, reviews of each study were conducted and data abstracted. Prior to meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the random effects model. RESULTS: Fourteen studies (six RCTs, seven case-control and one cohort study) contributed to the analysis. Studies were grouped on the basis of study design, and two separate meta-analyses were conducted. There was no evidence of an association between statin use and haematological malignancies among either RCTs (RR = 0.92, 95% CI 0.72, 1.16) or the observational studies (RR = 0.83, 95% CI 0.53, 1.29). Similarly, we found no evidence of publication bias. However, high heterogeneity was detected among the observational studies. CONCLUSION: Our meta-analysis findings do not support a potential role of statins in the prevention of haematological malignancies.     

Accuracy of cardiac auscultation in asymptomatic neonates with heart murmurs: comparison between pediatric trainees and neonatologists

The aim of this study was to assess whether cardiac auscultation performed by pediatric trainees and neonatologists can reliably distinguish innocent from pathologic heart murmurs in asymptomatic neonates. From January 2008 to April 2009 the pediatric trainees of our institution were requested to refer all asymptomatic neonates with a murmur and classify the murmurs as ??innocent,?? ??pathologic,?? or ??possibly pathologic.?? Prior to echocardiography, each neonate was evaluated by two experienced neonatologists. The echocardiographic studies of 169 neonates were analyzed. Abnormal cardiac anatomy was found in 55 neonates (32.6%). The overall ability of pediatric trainees in identifying congenital heart disease (CHD) was moderate [area under the curve (AUC)?=?0.855] and significantly lower compared to neonatologists (AUC?=?0.919, p?=?0.007). However, at ??lower?? levels of clinical confidence (i.e., clinical diagnosis of possibly pathologic murmurs), pediatric trainees had good ability in excluding CHD (sensitivity 94.6%; negative likelihood ratio?=?0.09). The ability of cardiac auscultation for diagnosing CHD in asymptomatic neonates is limited and dependent on the physician??s experience and level of clinical confidence. Echocardiography should remain an option for all neonates with a possibly pathologic murmur.     

Automated foveal location detection on spectral-domain optical coherence tomography in geographic atrophy patients

Graefe's Archive for Clinical and Experimental Ophthalmology - To develop a fully automated algorithm for accurate detection of fovea location in atrophic age-related macular degeneration...     

Total and free PSA kinetics in patients without prostate cancer undergoing radical cystoprostatectomy

BACKGROUND: Radical cystoprostatectomy and radical prostatectomy are the two major operations where prostate is totally and radically removed. Radical cystoprostatectomy is usually performed in patients with invasive bladder cancer. The aim of the study was to examine Total PSA, Free PSA, and Free/Total Ratio elimination kinetics after radical cystoprostatectomy. METHODS: Serum PSA, Free PSA, and Free/Total Ratio were determined preoperatively, at the time of cystoprostatectomy specimen removal and then at 3, 6, 12, 24, 48, 72, and 168 hr, from seven patients with muscle invasive bladder cancer, who underwent radical cystoprostatectomy. Free and Total PSA concentrations were measured with non-competitive immunological procedures. The elimination rates and half-lives of Total, Free PSA and Free/Total Ratio were studied using a nonlinear regression analysis. RESULTS: Surgical manipulations caused about 1.5-fold increase of PSA, 5-fold increase in Free PSA and 3-fold increase in Free/Total Ratio. PSA and Free PSA followed a biphasic elimination pattern of a rapid exponential (a) phase with a half-life of 4.27 and 2.14 hr and a terminal, nonexponential (b) phase with a half-life of 63 and 173.2 hr, respectively. Free/Total PSA Ratio followed, also, a biphasic kinetic pattern of a rapid exponential decline with a half-life of 3.34 and a terminal non-exponential increase with a doubling time of 43 hr. CONCLUSIONS: Comparing PSA kinetics after radical cystoprostatectomy with those of radical prostatectomy, it appears that PSA follows the same elimination pattern in both models. In contrast, Free PSA and Free/Total Ratio elimination kinetics' patterns differ between the two surgical models.