A coupled chemo-fluidic computational model for thrombogenesis in infarcted left ventricles.

A coupled chemo-fluidic computational model for investigating flow-mediated thrombogenesis in infarcted left ventricles (LVs) is proposed. LV thrombus (LVT) formation after the acute myocardial infarction (AMI) may lead to thromboembolic events that are associated with high mortality and morbidity, and reliable stratification of LVT risk is the key to managing the treatment of AMI patients. There have been several studies emphasizing the importance of LV blood flow patterns on thrombus formation; however, given the complex interplay between ventricular flow dynamics and biochemistry of thrombogenesis, current understanding is mostly empirical. In the present model, blood flow in the LV is obtained by solving the incompressible Navier-Stokes equations, and this is coupled to the biochemical modeling of the coagulation cascade, platelet activation, and fibrinogen polymerization. The coupled model is used to examine the effect of ventricular flow patterns on thrombogenesis in modeled ventricles. It is expected that the method developed here will enable in-depth studies of thrombogenesis in patient-derived infarcted LV models.

Genetics and personalized medicine--a role in statin therapy?

Pharmacogenetics uses the genetic variation in metabolic pathways to identify groups of patients who may respond differently in terms of therapeutic and adverse effects. Much clinical interest lies in drug metabolism and the opportunity to improve prescribing efficacy and safety. Owing to widespread use and increasing concern regarding side effects, statins are of significant interest in this area. Among other benefits, statins have been shown to improve lipid profiles and reduce coronary heart disease event rates in many populations. However, variability in drug response exists, and genetic variability may be a contributing factor. Our primary goal is to feature the most important genes involved in lipid metabolism, clinical outcomes, and statin-induced side effects, highlighting genome-wide association studies and the candidate gene approach.

The role of C-reactive protein as a risk predictor of coronary atherosclerosis: implications from the JUPITER trial.

Much controversy surrounds the use of high-sensitivity C-reactive protein (hs-CRP) as a marker of cardiovascular (CV) risk. Although data regarding the association of hs-CRP with CV disease is extensive and consistent, its role in clinical practice remains unclear. The American Heart Association (AHA) recently published a scientific statement regarding criteria for evaluation of novel markers of CV risk. This article provides a comprehensive review of data regarding hs-CRP as a risk marker for CV disease in the context of these AHA criteria. The impact of the JUPITER trial on the utility of hs-CRP as a risk marker is emphasized. The review concludes with an evidence-based statement regarding the current role of hs-CRP in CV risk prediction.

A retrospective evaluation of hospitalizations for acute gastroenteritis at 2 sentinel hospitals in central Japan to estimate the health burden of rotavirus.

BACKGROUND: Two rotavirus vaccines have recently been licensed for use in >80 countries worldwide but not in Japan. To assess the value of introducing rotavirus vaccination in Japan, data on the burden of rotavirus disease are needed. METHODS: To describe the epidemiology of severe rotavirus disease among Japanese children aged <5 years, we examined retrospective demographic, clinical, and laboratory data from the period 2003-2007 for children hospitalized with acute gastroenteritis (AGE) at 2 sentinel hospitals in Japan. RESULTS: At each of the 2 hospitals, 17%-21% of all pediatric hospitalizations were for AGE. Three-fourths of all AGE-related admissions occurred during the winter (December-May). Rotavirus testing was performed for approximately three-fourths of patients admitted with AGE in the winter, of which 55% at one hospital and 59% at the other tested positive. By extrapolating the test results to those patients with AGE admitted in the winter who were not tested, we estimated that 39%-44% of year-round and 52%-57% of winter hospitalizations were attributable to rotavirus. The annual incidence of hospitalization for rotavirus AGE in the 2 cities served by the hospitals was estimated to be 3.8 and 4.9 per 1000 person-years. CONCLUSIONS: The burden of severe rotavirus disease among Japanese children is substantial and warrants consideration of vaccination as a prevention strategy.

Increased low density lipoprotein and increased likelihood of positive prostate biopsy in black americans.

PURPOSE: Differences in prostate cancer incidence, grade and stage at diagnosis, and survival in black vs nonblack men are well documented. Recent studies indicate that lipids may have a role in oncogenesis, including that of prostate cancer. We investigated the relationship between circulating lipids in black and nonblack patients, and newly diagnosed prostate cancer. MATERIALS AND METHODS: The study population included consecutive patients who underwent prostate biopsy for increased prostate specific antigen and/or abnormal digital rectal examination at Atlanta Veterans Affairs Medical Center. Age, race, prostate specific antigen, prostate volume, body mass index, family history, high and low density lipoprotein, triglyceride and cholesterol lowering medications were included in data analysis. RESULTS: A total of 1,775 men with complete information were included in data analysis. A total of 521 black and 451 white men had positive biopsies. Using 100 mg/dl or less as the referent the adjusted OR reflecting the association of low density lipoprotein and prostate cancer diagnosis in black men was 1.49 (95% CI 1.04-2.13, p = 0.031), 1.51 (95% CI 0.96-2.39, p = 0.076) and 3.24 (95% CI 1.59-6.92, p = 0.002) for low density lipoprotein greater than 100 to 130, greater than 130 to 160 and greater than 160 mg/dl, respectively. Corresponding results in nonblack men showed no significant association. CONCLUSIONS: Increased serum low density lipoprotein is associated with an increased likelihood of prostate cancer diagnosis in black men but not in nonblack men. This association is strongest in the highest low density lipoprotein risk category. The reasons for the racial differences are unknown but may include genetic, dietary or other environmental factors.

Clinical risk factors alone are inadequate for predicting significant coronary artery disease.

OBJECTIVE: We sought to derive and validate a model for identifying suspected ACS patients harboring undiagnosed significant coronary artery disease (CAD). METHODS: This was a secondary analysis of data from a randomized control trial (RCT). Patients randomized to the CTA arm of an RCT examining a CTA-based strategy for ruling-out acute coronary syndrome (ACS) constitute the derivation cohort, which was randomly divided into a training dataset (2/3, used for model derivation) and a test dataset (1/3, used for internal validation (IV)). ED patients from a different center receiving CTA to evaluate for suspected ACS constitute the external validation (EV) cohort. Primary outcome was CTA-assessed significant CAD (stenosis of ≥50% in a major coronary artery). RESULTS: In the derivation cohort, 11.2% (76/679) of subjects had CTA-assessed significant CAD, and in the EV cohort, 8.2% of subjects (87/1056) had CTA-assessed significant CAD. Age was the strongest predictor of significant CAD among the clinical risk factors examined. Predictor variables included in the derived logistic regression model were: age, sex, tobacco use, diabetes, and race. This model exhibited an area under the receiver operating characteristic curve (ROC AUC) of 0.72 (95% CI: 0.61-0.83) based on IV, and 0.76 (95% CI: 0.70, 0.82) based on EV. The derived random forest model based on clinical risk factors yielded improved but not sufficient discrimination of significant CAD (ROC AUC = 0.76 [95% CI: 0.67-0.85] based on IV). Coronary artery calcium score was a more accurate predictor of significant CAD than any combination of clinical risk factors (ROC AUC = 0.85 [95% CI: 0.76-0.94] based on IV; ROC AUC = 0.92 [95% CI: 0.88-0.95] based on EV). CONCLUSIONS: Clinical risk factors, either individually or in combination, are insufficient for accurately identifying suspected ACS patients harboring undiagnosed significant coronary artery disease.

Effect of intravenous infusion of iodinated contrast media on the coronary blood flow in dogs.

BACKGROUND: Coronary computed tomography angiography (CCTA) is obtained using peripheral intravenous iodinated contrast agents (ICA) injection. There is continuing attempts to derive coronary physiological information like coronary blood flow (CBF) and/or fractional flow reserve from CCTA images. However, no data is available regarding the effect of peripheral intravenous injection of ICA on CBF. METHODS: A series of 4 experiments was performed using healthy mongrel dogs. All dogs underwent anesthesia and open thoracotomy with placement of ultrasound flowmeter to one of the coronary artery to provide real time absolute CBF measurements. Different infusion protocols of Isovue-370 and Visipaque-320 were injected into a peripheral vein. Similar doses of normal saline injection were performed to be used as controls. The effect of iodinated contrast media injection on absolute coronary blood flow was monitored and recorded. RESULTS: Injection of normal saline in the peripheral vein did not produce any significant increase in CBF. Peripheral intravenous injection of ICA resulted in a consistent increase of 40-73% in absolute CBF as recorded 5 minutes post-contrast administration. The contrast effect starts about 30 seconds and peaks at about 2 minutepost-contrast injection then slowly fades away in the following 10-15 min. The increase in the CBF was dose related. There was greater increase in the CBF to 50 ml infusion compared to 25 ml infusion of both Visipaque and Isovue. CONCLUSIONS: Peripheral venous administration of iodinated contrast-media in dogs results in a dose related, significant and prolonged increase in CBF.

Association of coronary plaque burden with fractional flow reserve: should we keep attempting to derive physiology from anatomy?

Coronary computed tomography angiography (CTA) has been used increasingly for the diagnosis of coronary artery disease over the past decade. Compared to invasive coronary angiography (ICA), coronary CTA has the ability to visualize and quantify atherosclerotic plaque both calcified and non-calcified. Traditional measures of evaluating a coronary stenosis such as diameter stenosis, area stenosis, minimal lumen diameter and minimal luminal area are limited in their ability to predict its functional significance especially when diameter stenosis ranges between 30-69% (intermediate range). Measurement of invasive fractional flow reserve (FFR) is considered the gold standard for assessment of the hemodynamic significance of a stenosis. The current study by Nakazato et al. evaluates the performance of an emerging coronary CTA-derived anatomical measure "percent aggregate plaque volume" to improve the detection of hemodynamic significant stenosis as compared with invasive FFR.

Estimating coronary blood flow using CT transluminal attenuation flow encoding: Formulation, preclinical validation, and clinical feasibility.

BACKGROUND: We present the formulation and testing of a new CT angiography (CTA)-based method for noninvasive measurement of absolute coronary blood flow (CBF) termed transluminal attenuation flow encoding (TAFE). CTA provides assessment of coronary plaque but does not allow for detection of vessel specific ischemia. A simple and direct method to calculate absolute CBF from a standard CTA could isolate the functional consequence of disease and aid therapy decisions. METHODS: We present the theoretical framework and initial testing of TAFE. Nine canine models of ischemic heart disease were prepared and underwent CT imaging and microsphere measurements of myocardial blood flow. Additionally, 39 acute chest pain patients with normal coronary arteries underwent coronary CTA. We applied TAFE to calculate absolute CBF in the coronary arteries using 4 vessel input parameters including transluminal attenuation gradient, cross-sectional area, length, and the contrast bolus duration derived from the arterial input function. RESULTS: In animal studies, TAFE-derived CBF in the left anterior descending, left circumflex, and right coronary artery was 20.8 ± 10.4 mL/min, 27.0 ± 13.4 mL/min, and 6.0 ± 3.7 mL/min, respectively. TAFE-derived CBF divided by myocardial mass strongly correlated with microsphere myocardial blood flow (R(2) = 0.90, P < .001). In human studies, TAFE-derived CBF in the left anterior descending, left circumflex, and right coronary artery was 26.4 ± 10.7 mL/min, 20.1 ± 13.0 mL/min, and 43.2 ± 40.9 mL/min, respectively. CBF per unit mass was 0.93 ± 0.48 mL/g/min in patients. Interobserver variability was minimal with excellent correlation (R = 0.96, P < .0001) and agreement (mean difference, 4.2 mL/min). CONCLUSION: TAFE allows for quantification of absolute CBF from a standard CTA acquisition and may provide functional significance of coronary disease without complex computational methods.

2013 ACC/AHA cholesterol treatment guideline: what was done well and what could be done better.

Five years after convening the expert panel, the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults was released. The American College of Cardiology and American Heart Association issued the guideline on the basis of a systematic review of cholesterol treatment trials performed by the National Heart, Lung, and Blood Institute. This report critically appraises the guideline and provides our view of what was done well and what could be done better. In particular, we propose that the guideline succeeds in prioritizing statin therapy, expanding the focus to atherosclerotic cardiovascular disease (including stroke), and emphasizing absolute cardiovascular risk to determine eligibility for statin therapy. We contend that the guideline could be enhanced by refining the use of lipid goals rather than removing them, enhancing guidance on evaluation of cholesterol, and broadening the concept of age underpinning risk-based decision making to include vascular and physiological age. We further suggest that the next guideline panel could comprehensively review current best evidence, build on existing guidelines, and cultivate broader national and international consensus. Overall, we aim to continue discussions about the important contributions and shortfalls of the guideline and create momentum for effective implementation and timely updates.

Rare Elizabethkingia meningosepticum meningitis case in an immunocompetent adult.

Though Elizabethkingia meningosepticum typically causes meningitis in neonates, its occurrence in adult is rare, with sixteen cases described worldwide. We report a case of E. meningosepticum meningitis in an immunocompetent adult. Bacterial identification was made a day earlier than conventional method by using matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) Vitek mass spectrometry RUO (VMS), which resulted in successful treatment with rifampin, trimethoprim-sulfamethoxazole, levofloxacin and minocycline.

Remote monitoring and supervision of urology residents utilizing integrated endourology suites-a prospective study of patients' opinions.

PURPOSE: To report on integrated endourology suites (IES), remote monitoring and supervision (RMS) of urology residents and to evaluate patients' opinions, acceptance, and satisfaction level with IES and RMS. PATIENTS AND METHODS: Patients undergoing flexible cystoscopy in the IES with RMS were surveyed using a questionnaire. All procedures were performed by junior urology residents (UR-1 level) using RMS. Patients were studied using a nine-question survey to evaluate their comfort level, acceptance, and level of satisfaction with RMS. Six questions used a scale of 1 to 10 (1=strongly disagree; 10=strongly agree), and the remaining three questions solicited a "yes" or "no" response. RESULTS: 100 patients were studied (59% Caucasians, 40% African Americans, and 1% Hispanic). Median age was 63 years. The highest level of education was middle school in 2% of patients, high school in 55%, undergraduate in 33%, and postgraduate in 10%. Patients scored a mean of 9.50/10 (highly satisfactory) regarding their comfort with RMS; 96% scored ≥ 7, 4% scored 5 to 6, and none scored <5. Patients were satisfied having a urology resident perform the procedure (9.48/10), other residents and medical students watch the procedure (9.41/10), a video camera in the room (9.40/10), and two-way sound communication (9.40/10). None perceived compromise to their privacy or quality of care. CONCLUSIONS: RMS in IES is highly acceptable to patients undergoing endoscopic procedures. RMS has the potential to positively impact residency training, efficiency, regulatory compliance, safety, and productivity.

Work-related physical activity among cardiovascular specialists.

BACKGROUND: Strong evidence supports positive correlation of physical activity with health benefits. Current recommendations by the American Heart Association are a minimum 30 minutes of moderate physical activity 5 days per week. This goal has been equilibrated with 10,000 steps per day. HYPOTHESIS: Work-related physical activity of cardiovascular (CV) specialists does not meet the currently recommended daily physical activity. METHODS: Eight cardiothoracic (CT) surgeons, 7 general cardiologists, 5 procedural cardiologists, and 8 cardiac anesthesiologists (N = 28) participated in the study. Demographic information on each participant was recorded including age, resting heart rate, body mass index, and medical and social history. Subjects were asked to wear a spring-levered pedometer on their hip for 2 weeks while at work and to record the total number of steps as well as number of hours worked each day. RESULTS: The average daily steps walked during work were 6540, 6039, 5910, and 5553 for general cardiologists, CT surgeons, procedural cardiologists, and cardiac anesthesiologists, respectively. There were no statistically significant differences in the average number of steps taken per day among the groups. CT surgeons worked 12.4 hours per day compared to 9.3 hours by the cardiac anesthesiologists (P = 0.03). CONCLUSIONS: In this small, single-center study, work-related physical activity of CV specialists did not meet the recommended guidelines. Obtaining the recommended activity level might be a challenge, given their busy work schedule. Therefore, CV specialists must engage in additional, out-of-hours exercise to achieve the recommended daily exercise.

Statin-induced myopathy: a review and update.

INTRODUCTION: Statin-induced myopathy is an important cause of statin intolerance and the most common cause of statin discontinuation. Observational studies estimate that 10 - 15% of statin users develop statin-related muscle side effects ranging from mild myalgia to more severe muscle symptoms with significant CPK elevations. AREAS COVERED: This article reviews the epidemiology, clinical features, risk factors and mechanisms of statin-induced myopathy and provides an evidence-based algorithm for managing patients with statin myopathy. EXPERT OPINION: There are multiple risk factors for statin-induced myopathy that are both patient-related (age, genetics, co-morbidities) and drug-related (statin metabolism via the CYP system, drug-drug interactions and statin drug transport). Management options for statin-intolerant patients include statin switching, especially to low-dose, non-daily doses of long-acting statins, such as rosuvastatin and atorvastatin, and other non-statin lipid-lowering agents, such as ezetimibe and colesevelam, and possibly red yeast rice. In conclusion, statin-induced myopathy is a significant clinical problem that contributes considerably to statin therapy discontinuation. However, there exist multiple and effective management options for statin intolerant patients.

Comparison of 12-core versus 8-core prostate biopsy: multivariate analysis of large series of US veterans.

OBJECTIVES: To investigate the impact of additional biopsy cores on prostate cancer diagnosis among US veterans. The reported rate of positive biopsy results varies from 20% to 40%. METHODS: We analyzed 1546 consecutive initial prostate biopsy procedures (8-core and 12-core biopsy protocols) at the Atlanta VA Medical Center. Both biopsy protocols targeted the peripheral zone. Cancer detection rates were compared between the 2 protocols in univariate and multivariate analyses with results expressed as odds ratios and corresponding 95% confidence intervals. Characteristics of cancer detected were also compared. Sensitivity analyses were performed for different population subgroups. RESULTS: The overall positive biopsy rate was 49.9%, 51.2% in the 8-core group and 49.2% in the 12-core group. There was no difference between the 2 biopsy groups (adjusted odds ratio = 0.97, 95% confidence interval = 0.76-1.25). Advanced age and high body mass index were significantly associated with higher likelihood of prostate cancer, whereas larger prostate volumes were associated with lower risk. CONCLUSIONS: In this large series of prostate biopsy procedures, in which the peripheral zone was well targeted, there was no evidence that 12-core biopsy improved the likelihood of prostate cancer diagnosis compared with 8-core biopsy. As such, the results of this cohort from a US veteran population suggest that targeting the peripheral zone is more important than the absolute number of biopsy cores. However, in certain subgroups of patients with specific clinical characteristics, such as those with very large prostates, more cores may be required. Further studies are needed to identify such characteristics.