Individual Patient Risk Assessment Research Articles

Increased neutrophil-lymphocyte ratio is a poor prognostic factor in patients with primary operable and inoperable pancreatic cancer

Background:The neutrophil-lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammatory response. Previous findings from small-scale studies revealed conflicting results about its independent prognostic significance with regard to different clinical end points in pancreatic cancer (PC) patients. Therefore, the aim of our study was the external validation of the prognostic significance of NLR in a large cohort of PC patients.Methods:Data from 371 consecutive PC patients, treated between 2004 and 2010 at a single centre, were evaluated retrospectively. The whole cohort was stratified into two groups according to the treatment modality. Group 1 comprised 261 patients with inoperable PC at diagnosis and group 2 comprised 110 patients with surgically resected PC. Cancer-specific survival (CSS) was assessed using the Kaplan–Meier method. To evaluate the independent prognostic significance of the NLR, the modified Glasgow prognostic score (mGPS) and the platelet-lymphocyte ratio univariate and multivariate Cox regression models were applied.Results:Multivariate analysis identified increased NLR as an independent prognostic factor for inoperable PC patients (hazard ratio (HR)=2.53, confidence interval (CI)=1.64–3.91, P<0.001) and surgically resected PC patients (HR=1.61, CI=1.02–2.53, P=0.039). In inoperable PC patients, the mGPS was associated with poor CSS only in univariate analysis (HR=1.44, CI=1.04–1.98).Conclusion:Risk prediction for cancer-related end points using NLR does add independent prognostic information to other well-established prognostic factors in patients with PC, regardless of the undergoing therapeutic modality. Thus, the NLR should be considered for future individual risk assessment in patients with PC.

High-sensitive Troponin T increase after exercise in patients with pulmonary arterial hypertension

BackgroundThe current study aimed to investigate the release of myocardial high-sensitive Troponin T (hsTnT) in patients with pulmonary arterial hypertension (PAH) in response to maximal physical exercise.MethodsIn 24 patients with PAH, symptom-limited cardiopulmonary exercise testing was performed. hsTnT was measured by the novel hsTnT assay with a lower limit of detection of 2 ng/L and a total imprecision of less than 10% at the 99th percentile value. hsTnT was related to NT-proBNP, WHO functional class and right ventricular (RV) function. Serial measurement was performed before and 30 min, 180 min, and 300 min after exercise. Healthy volunteers served as a control group.ResultsIn 21 PAH patients, hsTnT levels were detectable before exercise with a close correlation between hsTnT and NT-proBNP. hsTnT was detectable in all PAH patients after exercise and significantly increased from 7.5 ng/L at baseline to 14.62 ng/L after 300 min, whereas levels of NT-proBNP remained constant with time.ConclusionsUsing the novel hsTnT assay, the current study provides first evidence that hsTnT levels increase in PAH patients after maximal physical exercise, while levels of other biomarkers remain constant after exercise testing. This might provide new insights into pathophysiology and individual risk assessment in patients with PAH.

A Risk Factor-based Predictive Model of Outcomes in Carotid Endarterectomy

Accurate knowledge of individualized risks and benefits is crucial to the surgical management of patients undergoing carotid endarterectomy (CEA). Although large randomized trials have determined specific cutoffs for the degree of stenosis, precise delineation of patient-level risks remains a topic of debate, especially in real world practice. We attempted to create a risk factor-based predictive model of outcomes in CEA. We performed a retrospective cohort study involving patients who underwent CEAs from 2005 to 2010 and were registered in the American College of Surgeons National Quality Improvement Project database. Of the 35 698 patients, 20 015 were asymptomatic (56.1%) and 15 683 were symptomatic (43.9%). These patients demonstrated a 1.64% risk of stroke, 0.69% risk of myocardial infarction, and 0.75% risk of death within 30 days after CEA. Multivariate analysis demonstrated that increasing age, male sex, history of chronic obstructive pulmonary disease, myocardial infarction, angina, congestive heart failure, peripheral vascular disease, previous stroke or transient ischemic attack, and dialysis were independent risk factors associated with an increased risk of the combined outcome of postoperative stroke, myocardial infarction, or death. A validated model for outcome prediction based on individual patient characteristics was developed. There was a steep effect of age on the risk of myocardial infarction and death. This national study confirms that that risks of CEA vary dramatically based on patient-level characteristics. Because of limited discrimination, it cannot be used for individual patient risk assessment. However, it can be used as a baseline for improvement and development of more accurate predictive models based on other databases or prospective studies.

How to Apply follow-up in Relation to Risk Group

The term 'Non-muscle invasive bladder cancer' identifies a heterogeneous disease due to different natural history of its various appearances. T1 stage represents a non-predictable population, which might respond to non-operative treatment strategies or to the need of a more aggressive treatment, in order to avoid the progression to invasive, and possibly to metastatic stages. In the first year following transurethral resection of bladder (TURB), tumor recurrence is seen in up to 45% of the population; of this, 15% may progress to muscle invasive or metastatic disease, or both. In order to control the recurrence and progression and identify invasive tumors at the earliest possible stage, it is strongly necessary to define individual patient risk assessment follow-up. To obtain exact staging, besides a proper transurethral resection of bladder, a restaging transurethral resection of bladder should be performed in T1 patients. Data from literature support the immediate postoperative intravesical instillation of different chemotherapeutic agents in low-risk patients. Multifocal papillary lesions might require a more intensive adjuvant regimen, whereas intravesical immunotherapy using Bacillus Calmette-Guérin is recommended in patients at high risk of progression. Early cystectomy should be considered in patients with recurrent T1 tumors or refractory carcinoma in situ to avoid unfavorable tumor progression.

Individual risk assessment in bladder cancer patients based on a multi-marker panel

To investigate whether a combined application of urine cytology (CYT) and molecular markers for bladder cancer (BC) can predict tumor aggressiveness. The study comprised 2,113 patients who underwent urethrocystoscopy and transurethral resection of the bladder. CYT, fluorescence in situ hybridization (FISH), immunocytology (uCyt+) and nuclear matrix protein 22 test (NMP22-ELISA) were performed. Results of the individual tests and of a multi-marker panel were correlated with pT-stages and tumor grades. Five hundred and two of 2,113 (23.8 %) patients had BC. False-negative test rates of CYT (p < 0.001), FISH (p = 0.01) and NMP22-ELISA (p = 0.05) were lower in patients with muscle-invasive BC compared with patients with non-muscle-invasive BC. Furthermore, false-negative rates of CYT (p < 0.001), FISH (p = 0.0002) and NMP22-ELISA (p < 0.001) were lower in patients with G3/CIS compared with patients with G1-G2 BC. In patients with evidence of tumor in urethrocystoscopy, the presence of simultaneously positive CYT and NMP22 was associated with a 20-fold risk for G3/CIS (p < 0.0001). This is the first study investigating the combined use of four urine markers in addition to cystoscopy to predict tumor aggressiveness. Our results indicate that combined application of urine markers as an adjunct to cystoscopy may facilitate identification of patients harboring high-grade tumors.

International Patterns of Practice in the Management of Radiation Therapy-induced Nausea and Vomiting

To investigate international patterns of practice in the management of radiation therapy-induced nausea and vomiting (RINV). Oncologists prescribing radiation therapy in the United States, Canada, The Netherlands, Australia, New Zealand, Spain, Italy, France, Hong Kong, Singapore, Cyprus, and Israel completed a Web-based survey that was based on 6 radiation therapy-only clinical cases modeled after the minimal-, low-, moderate-, and high-emetic risk levels defined in the antiemetic guidelines of the American Society of Clinical Oncology and the Multinational Association of Supportive Care in Cancer. For each case, respondents estimated the risks of nausea and vomiting separately and committed to an initial management approach. In total, 1022 responses were received. Risk estimates and management decisions for the minimal- and high-risk cases varied little and were in line with guideline standards, whereas those for the low- and moderate-risk cases varied greatly. The most common initial management strategies were as follows: rescue therapy for a minimal-risk case (63% of respondents), 2 low-risk cases (56% and 80%), and 1 moderate-risk case (66%); and prophylactic therapy for a second moderate-risk case (75%) and a high-risk case (95%). The serotonin (5-HT)₃ receptor antagonists were the most commonly recommended prophylactic agents. On multivariate analysis, factors predictive of a decision for prophylactic or rescue therapy were risk estimates of nausea and vomiting, awareness of the American Society of Clinical Oncology antiemetic guideline, and European Society for Therapeutic Radiology and Oncology membership. Risk estimates and management strategies for RINV varied, especially for low- and moderate-risk radiation therapy cases. Radiation therapy-induced nausea and vomiting are under-studied treatment sequelae. New observational and translational studies are needed to allow for individual patient risk assessment and to refine antiemetic guideline management recommendations.

Increased arterial stiffness is associated with high cardiovascular mortality in male Fabry patients

Cardiovascular survival in a cohort of 33 male Fabry patients followed for a median of 7.3 years at a single centre was most strongly associated in a Cox proportional hazard regression model with age and elevated arterial stiffness at baseline. Seven patients died of cardiovascular causes. The presence of cardiomyopathy and renal involvement (either clinical nephropathy or CKD stage >1) were also negatively associated with survival when analysed as single factors. In this small study, presence of hypertension and hypercholesterolemia at baseline did not significantly predict cardiovascular death. The significant effect of elevated arterial stiffness, especially in a small cohort, argues for its clinical utility in individual patient risk assessment and for further intervention studies focusing on therapeutic reduction.

Impact of immediate TRUS rebiopsy in a patient cohort considering active surveillance for favorable risk prostate cancer

Introduction and ObjectiveActive surveillance (AS) is an option for the management of favorable risk prostate cancer (CaP) in the PSA era. Published studies have reported variable inclusion criteria for cohort selection. Accurate assessment of individual patient risk in AS is dependent not only upon rigorous selection criteria, but also reliability of diagnosis at tissue biopsy. To date, the impact of immediate transrectal ultrasound (TRUS) rebiopsy in confirming candidates for AS has been incompletely defined. MethodsFrom a total of over 567 men, 67 met criteria for AS (Gleason <7, PSA <10, PSAD <0.15, <3 cores with <50% involvement of any 1 core). Fifty-two men agreed to a 12-core TRUS rebiopsy within 6 months of first diagnosis performed in clinic. Statistical analysis was performed using Wilcoxon signed rank test and logistic regression to determine predictors of rebiopsy characteristics, histopathologic outcomes, and impact on treatment choice. ResultsMean cohort age was 63.9 years (range 56–72 years), PSA 5.9 ng/ml (4.1–10), and PSA density 0.12 ng/ml/cc at initial biopsy. Tumor involved 1.1 cores and 3.2% (range 1%–5%) of the total tissue. Average time to rebiopsy was 2.7 months. Notably, 29 of 52 men (56%) demonstrated no evidence of CaP on repeat biopsy; 14 of 23 men with a positive repeat biopsy showed either an increase in cancer volume (2.8% mean increase) and 9 (18%) were upgraded to Gleason pattern 3+4 = 7. Rebiopsy demonstrated 9 (17%) patients exceeded AS criteria. Nine patients chose curative surgical intervention (radical prostatectomy) based on increased cancer volume or grade (4) or an elective desire for treatment (5). All had organ confined disease with negative margins on final pathologic analysis. Statistical review revealed that initial Gleason score, PSA density, and number of positive cores at first biopsy were not predictive of men with higher volume/grade on re-biopsy. ConclusionsImmediate TRUS repeat biopsy after diagnosis frequently fails to redemonstrate prostate cancer confirming the favorable-risk nature of disease burden in this group being considered for AS. A subset of patients are upgraded (17%) leading to reconsideration of AS. We conclude this clinic-based approach provides valuable additional information to discriminate appropriate AS candidates.

Functional genomics applied to cardiovascular medicine.

Since completion of the draft sequence of the human genome in 2000, the landscape of biomedical research has undergone a rapid transformation. Growing knowledge of genome structure and variation has spawned the development of technologies that allow researchers to study thousands of genes, transcripts, and proteins simultaneously. This has expanded biomedical science beyond reductionist approaches that test the function of individual genes to less biased approaches that study the behavior of many or all genes in homeostasis and disease. Such studies have been grouped under the broad label of functional genomics, which can be defined as the branch of biology that seeks to uncover the properties and function of the entirety of the genes and gene products of an organism.1 Functional genomics is fueling an explosion of new insights in biology and medicine, and many of these insights were completely unanticipated. Because these advances have begun to influence clinical practice,2,3 physicians will be expected to understand the potential uses and limitations of functional genomics in clinical settings. The purpose of this review is to provide a conceptual overview of functional genomics applied to the practice of cardiovascular medicine. We begin with a review of commonly used terms and approaches and then describe examples of their use for screening, diagnosis, and treatment selection in clinical cardiology. We also highlight emerging trends and speculate about where the field is headed in the near term. Although some predictions will be overly optimistic and some major advances unanticipated, we hope this review will help prepare cardiologists for their role in the application of genome science to the diagnosis and treatment of disease. This review is part of a series that introduces several related areas of cardiovascular genetics and genomics.4 We refer to these other contributions to guide further reading …

Usefulness of Multiple Biomarkers for the Prediction of Significant Fibrosis in Chronic Hepatitis B

It has not been explicitly addressed whether new biomarkers, in addition to readily available clinical data, make a contribution to the prediction of liver fibrosis. A total of 209 patients with chronic hepatitis B who underwent liver biopsy were recruited. The Clinical Score (CS) model using only routine clinical data and the Biomarker Score (BS) model using 7 putative biomarkers were derived from the derivation set (n=105), and these models were applied to a separate patients group (n=104) to investigate whether the addition of BS improved the diagnostic accuracy in predicting significant fibrosis beyond an assessment based solely on CS. The most informative biomarkers for predicting significant fibrosis were hyaluronic acid and matrix metalloproteinase-2. The BS was an independent predictive factor for significant fibrosis even after accounting for CS in both sets. Among the derivation set, the incorporation of the BS into the CS model did not significantly increase the receiver operating characteristic area, with only a small improvement of about 2% (P=0.11). Similarly, in the validation set, a combined model with CS and BS showed no superior diagnostic accuracy over the CS model alone, with an improvement of approximately 2% [0.83 (0.75 to 0.92) vs. 0.81 (0.70 to 0.91); P=0.16]. The simultaneous addition of several biomarkers adds only modestly to clinical predictive factors for risk assessment of individual patients. These results highlight the need for the models to be validated in another cohort with a broader distribution of fibrosis severity.

Not Very Meaningful

In principle, funduscopy is a fascinating method to investigate in vivo the intracranial vasculature for hypertension related changes. The authors rightly point out, however, that vascular changes in themselves (stages I and II of hypertensive retinopathy) are not very meaningful. The overlap with “normal” (for example, age related) vascular changes is too big for the ophthalmologist to be able to contribute to risk assessment in individual patients. In patients with parenchymatous changes of stages III and IV, due to highly elevated blood pressure any treating general practitioner or specialist in internal medicine knows that urgent treatment is required. Ophthalmologists can therefore not contribute any further information that would be of additional benefit in this scenario either. However, Professor Schmieder’s article (2) suggests that using new, computer supported methods for vascular analysis of the ocular fundus improves prediction of patients’ individual risk of developing hypertensive complications. Some individual health services (that patients have to pay for) create the same impression. A recent literature review does not support this assumption (1). Rather, it summarizes that computer aided methods to detect less pronounced vascular changes currently contribute little additional information to risk prediction made by the internal medical specialist.

Physicians’ perceptions of the definition of major bleeding in major orthopedic surgery: results of an international survey

Decisions regarding choice of thromboprophylaxis in patients undergoing major orthopedic surgery are based on assessment of individual patient risk for thrombosis versus risk for bleeding. An international survey sought physician views on definitions and relative importance of different types of major bleeding. A random sample of physicians from five countries (100 physicians per country, mainly surgeons) completed an internet-based 13-question survey on perceptions, concerns, and relevance of bleeding associated with thromboprophylaxis in major orthopedic surgery. Over 80% of responders were concerned or very concerned about bleeding with >70% considering surgical-site bleeding as the most concerning, and relevant type and site for bleeding. Nearly 80% of responders considered surgical-site bleeding to increase patient length of hospital stay, and >70% noted that it complicates patient rehabilitation. After fatal bleeding, bleeding leading to re-operation was ranked as the most concerning type of major bleed. Less than half of responders reported closely reading the major-bleeding definitions in clinical study publications. Most responders favored anticoagulants that could offer a reduced bleeding risk and similar venous thromboembolism (VTE) prevention compared to current anticoagulants rather than a decrease in VTE and similar bleeding risk. There is a disconnect between the definitions of major bleeding that surgeons would apply to describe bleeding associated with VTE thromboprophylaxis, and those used in clinical studies reporting the safety profiles of newer anticoagulant agents. Misperceptions about the benefit-to-harm profiles of thromboprophylactic therapies may incorrectly inform treatment choices in patients at high risk for post-operative VTE.

Structural neuroimaging for individual patient risk assessment in mild cognitive impairment

Structural neuroimaging for individual patient risk assessment in mild cognitive impairment

What procalcitonin brings to management of sepsis in the ICU

In inflammatory states, particularly in response to infectious stimuli, local procalcitonin (PCT) production rises, and because these tissues cannot further process PCT into calcitonin, serum levels increase. In the critical care setting, PCT should be considered a useful tool to help physicians in some specific, although frequent, situations. Serial measurements of PCT levels may indicate the effectiveness of medical decisions such as the appropriateness of antibiotic therapy, the detection of new infections, and the exclusion of a diagnosis of sepsis. PCT-guided algorithms may also help to decrease the duration of antimicrobial therapy. However, the role of PCT as a prognostic marker in critically ill patients is controversial. In a study by Karlsson and colleagues, PCT concentrations did not differ between hospital survivors and nonsurvivors, but the outcome was better in patients whose PCT concentrations decreased more than 50%. The study of PCT kinetics thus could offer an individual risk assessment in patients with severe sepsis.

Abstract CN02-01: Circulating tumor cells as targets for cancer therapy

Abstract Metastatic relapse of carcinoma patients is mainly due to clinically occult micrometastases present at primary diagnosis, but undetectable even by high-resolution imaging technologies. Frequently, traditional prognostic factors are insufficient to predict metastasis and treatment decisions are mainly based on statistical risk parameters. Highly sensitive and specific cytometric and molecular methods enable now the detection of disseminated tumor cells (DTC) in bone marrow (BM) and circulating tumor cells (CTC) in peripheral blood of breast carcinoma patients. The presence of DTC has independent prognostic impact for patients with primary breast cancer with regard to metastatic relapse and overall survival(1) and DTC may even contribute to local relapse (2). Interestingly, bone marrow seems to be a common homing organ for cells derived from various epithelial tumors including breast, prostate, lung and colon cancer (3); (4)). This surprising finding is consistent with recent results obtained in mouse models (5),, supporting the hypothesis that BM might be an important reservoir for metastatic cells from where they can re-circulate into various organs and may be even back to the primary site (6); (7); (8). DTC may have adapted to the special environmental conditions in the BM and may survive in so called “bone marrow niches” over decades. This hypothesis has important clinical implications for the design of future clinical trials with drugs that are able to specifically block the interaction between tumor cells and the bone marrow microenvironement (e.g., bisphosphonate or antibodies to RANK ligand). However, a significant fraction of DTC remain over years in a “dormant” stage, and little is known about the conditions required for the persistence of dormancy or the escape from the dormant phase into the active phase of metastasis formation (9). Transition from a dormant into a dynamic phase may be caused by genetic changes within the disseminated tumor cells (i.e. acquisition of growth factor receptor Her-2/neu amplification (10); (11) but also by the influence of the surrounding bone marrow microenvironment. Furthermore, BM has a particular capability to host stem cells, which may also contribute to keep DTC in a stem cell-like state. This assumption is also supported by the fact that most DTC in BM and blood are in a nonproliferating state and survive systemic chemotherapy (12); (13). Moreover, most DTC in breast cancer patients showed a breast stem cell phenotype (CD44+/CD24- or MUC1-/CK19+) (14); (15). Moreover, epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2) - two known stem cell factors - were relevant for the in vitro growth of DTC obtained from BM of cancer patients (16). Nevertheless, strong direct evidence that some of the few DTC or CTC detected in the BM or blood samples have cancer stem cell properties is still missing. Future studies including xenotransplantation of DTC/CTC into immunodeficient mice need to demonstrate that these cells are the actual founder cells of overt metastasis. BM analyses are not well accepted by the medical community for the clinical management patients in breast cancer and other solid tumors. Therefore, most current research efforts are directed to evaluate the clinical utility of CTC detection (17). Because of the high variability of results obtained by different cytometric and molecular approaches, standardization of current technologies is urgently required (18); (19). While the prognostic significance of CTC could be demonstrated for metastatic breast cancer patients (20), studies on the impact of CTC in primary breast cancer patients are still ongoing but the intermediate results are so far promising (21). Moreover, encouraging results on monitoring CTC during primary systemic or adjuvant chemotherapy in breast cancer patients were obtained in recent studies. Further characterization of CTC is pivotal to understand the biology of tumor cell dissemination (22). The molecular characterization of CTC with special emphasis on potential cancer stem cell features and therapeutically relevant targets such as HER2 (23) might improve individual risk assessment and stratification of patients for targeted therapies. This characterization will contribute to more “tailored” and personalized anti-metastatic therapies. At present, the success or failure of anti-cancer therapies is only assessed retrospectively by the absence or presence of overt metastases during the postoperative follow up period. Real-time monitoring of peripheral blood (i.e., during and after systemic adjuvant therapy) for CTC might provide unique information for the clinical management of the individual cancer patient and allow an early change in therapy years before the appearance of overt metastases signals incurability (24). Future clinical trials will show whether the assessment and monitoring of therapeutic targets (e.g., EGF-R, HER2 or VEGF) on CTC (and probably DTC) might become an important diagnostic tool for cancer patients undergoing targeted therapies and may provide new insights into the selection of tumor cells under biological therapies. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):CN02-01.

Frontiers in Thyroid Cancer: December 2009

Frontiers in Thyroid Cancer: December 2009

Risk-based antifungal prophylaxis in hematologic malignancy and stem cell transplantation

Invasive fungal infection (IFI) is an important cause of morbidity and mortality in patients with hematologic malignancy, prolonged neutropenia, or after hematopoietic stem cell transplant. Antifungal prophylaxis prevents IFI in high-risk hematology patients. This article discusses recent developments in antifungal prophylaxis, focusing on those expected to affect patient management. Significant advances have occurred in understanding risk stratification and assessment of individual patient risk for drug-drug interactions, toxicity, or variations in pharmacokinetics; choice of antifungal prophylaxis strategy, drug, dose, route, and regimen; therapeutic drug monitoring; cost effectiveness of prophylaxis; and the significance of breakthrough IFI. Research over the coming decade is likely to fundamentally alter antifungal prophylaxis by allowing clinicians to make individualized decisions for their patients informed by rapid, detailed, and personalized risk-benefit analyses.

18F-4V for PET–CT Imaging of VCAM-1 Expression in Atherosclerosis

The aim of this study was to iteratively develop and validate an (18)F-labeled small vascular cell adhesion molecule (VCAM)-1 affinity ligand and demonstrate the feasibility of imaging VCAM-1 expression by positron emission tomography-computed tomography (PET-CT) in murine atherosclerotic arteries. Hybrid PET-CT imaging allows simultaneous assessment of atherosclerotic lesion morphology (CT) and may facilitate early risk assessment in individual patients. The early induction, confinement of expression to atherosclerotic lesions, and accessible position in proximity to the blood pool render the adhesion molecule VCAM-1 an attractive imaging biomarker for inflamed atheroma prone to complication. A cyclic, a linear, and an oligomer affinity peptide, internalized into endothelial cells by VCAM-1-mediated binding, were initially derivatized with DOTA to determine their binding profiles and pharmacokinetics. The lead compound was then (18)F-labeled and tested in atherosclerotic apoE(-/-) mice receiving a high-cholesterol diet as well as wild type murine models of myocardial infarction and heart transplant rejection. The tetrameric peptide had the highest affinity and specificity for VCAM-1 (97% inhibition with soluble VCAM-1 in vitro). In vivo PET-CT imaging using (18)F-4V showed 0.31 +/- 0.02 SUV in murine atheroma (ex vivo %IDGT 5.9 +/- 1.5). (18)F-4V uptake colocalized with atherosclerotic plaques on Oil Red O staining and correlated to mRNA levels of VCAM-1 measured by quantitative reverse transcription polymerase chain reaction (R = 0.79, p = 0.03). Atherosclerotic mice receiving an atorvastatin-enriched diet had significantly lower lesional uptake (p < 0.05). Furthermore, (18)F-4V imaging in myocardial ischemia after coronary ligation and in transplanted cardiac allografts undergoing rejection showed high in vivo PET signal in inflamed myocardium and good correlation with ex vivo measurement of VCAM-1 mRNA by quantitative polymerase chain reaction. (18)F-4V allows noninvasive PET-CT imaging of VCAM-1 in inflammatory atherosclerosis, has the dynamic range to quantify treatment effects, and correlates with inflammatory gene expression.

Antithrombotic management in patients with prosthetic valves: a comparison of American and European guidelines

Prosthetic heart valves have been in use for almost 50 years and warfarin has been available as an oral anticoagulant drug for almost 60 years. One might expect that after...

Particulate air pollution, coronary heart disease and individual risk assessment: a general overview

Both long-term and short-term exposure to air pollution is associated with a marked increase in cardiovascular morbidity and mortality because of the coronary syndrome and its complications. The exact molecular mechanism that is responsible for these acute and chronic effects is not elucidated yet. Potential pathophysiological pathways, however, include vascular dysfunction, inflammation, and oxidative stress and altered cardiac autonomic dysfunction. Actually, the cardiovascular risk assessment for individual patients with regard to air pollution is still complicated. To support decision-making in clinic, we propose a risk model, named 'CardioVascular and AIR pollution' risk table, composed of acknowledged factors in the relationship of cardiovascular disease and air pollution.