Cancer and myositis: Who,when, and how to screen

Cancer screening in idiopathic inflammatory myopathies (IIMs) is essential because an increased risk of cancer in IIMs has been well demonstrated. However, a consensus regarding cancer screening approaches is lacking. Therefore, the approach presented in this review reflects available evidence and our clinical experiences. Patients with IIMs should be evaluated for 3 distinct types of risk categories: (a) clinical with their history, physical examination, and laboratory parameters; (b) based on IIMs subtypes; and (c) based on serology – myositis specific and associated autoantibodies. Further, according to these characteristics, patients should be classified as low risk, moderate risk, and high risk for cancer. In our approach, all patients with IIM within 3 years of disease onset should undertake cancer screening according to their risk stratification. First, irrespective of risk, all patients should undergo age and gender-appropriate screening as per local guidelines. Patients at low-risk stratification should undertake basic cancer screening with routine blood counts, labs, and imaging; at moderate-risk stratification, patients should undertake enhanced cancer screening including CT chest; and at high-risk stratification, patients should undertake comprehensive cancer screening including PET/CT at baseline. Consensus guidelines among all major stakeholders, including rheumatologists, neurologists, dermatologists, and oncologists representing different parts of the world, establishing uniform cancer screening approaches in patients with IIM, are the need of the hour.     

Current status of imaging in nonalcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD) is the most common diffuse liver disease, with a worldwide prevalence of 20% to 46%. NAFLD can be subdivided into simple steatosis and nonalcoholic steatohepatitis. Most cases of simple steatosis are non-progressive, whereas nonalcoholic steatohepatitis may result in chronic liver injury and progressive fibrosis in a significant minority. Effective risk stratification and management of NAFLD requires evaluation of hepatic parenchymal fat, fibrosis, and inflammation. Liver biopsy remains the current gold standard; however, non-invasive imaging methods are rapidly evolving and may replace biopsy in some circumstances. These methods include well-established techniques, such as conventional ultrasonography, computed tomography, and magnetic resonance imaging and newer imaging technologies, such as ultrasound elastography, quantitative ultrasound techniques, magnetic resonance elastography, and magnetic resonancebased fat quantitation techniques. The aim of this article is to review the current status of imaging methods for NAFLD risk stratification and management, including their diagnostic accuracy, limitations, and practical applicability.     

Investigating health and subjective well-being: substantive challenges

Both the nature of health and the nature of subjective well-being are multifaceted and are in great need of precise differentiable dimensions. The articles in this special issue perform two much-needed tasks. First, they have utilized effectively the knowledge now at hand from the work of many investigators. Second, they have pointed us in the direction in which we ought to be heading. The author sees a long series of new productive hypotheses regarding the relationships between health and subjective well-being become possible as the conceptual and measurement issues surrounding each of the two separate constructs become resolved.     

Innovative approaches to lung volume reduction for emphysema

The 10 years of resurgent interest in lung volume reduction surgery (LVRS) and recent National Emphysema Treatment Trial findings for emphysema have stimulated a range of innovative alternative ideas aimed at improving outcomes and reducing complications associated with current LVRS techniques. Concepts being actively investigated at this time include surgical resection with compression/banding devices, endobronchial blockers, sealants, obstructing devices and valves, and bronchial bypass methods. These novel approaches are reaching the stage of clinical trials at this time. Theory, design issues, methods, potential advantages and limitations, and available results are presented. Extensive research in the near future will help to determine the potential clinical applicability of these new approaches to the treatment of emphysema symptoms.     

Transient ischemic attack: risk stratification and treatment

A major challenge facing the physician evaluating patients with transient ischemic attack is determining which patients are at highest short-term risk of stroke. A number of stratification schemes have been recently developed incorporating easily obtainable clinical information about the individual patient. Further, emerging data suggest a role for brain and vascular imaging in risk stratification. Many aspects of acute management of transient ischemic attack, such as which patients should be hospitalized and choice of acute antithrombotic therapy, remain controversial because of a lack of evidence from controlled trials. For longer-term prevention, there is much firmer evidence from multiple large randomized trials, and these data are reviewed in this article.     

Genetic testing for thrombophilia mutations

Venous thrombosis is a multicausal disease due to the interaction of genetic and environmental risk factors. Some of the recently discovered genetic risk factors, such as factor V Leiden and prothrombin G20210A mutations, are quite common in the population. Accordingly, laboratory investigation of thrombophilic disorders has expanded to incorporate molecular assays, which unlike functional assays, are unequivocal with no borderline values. When testing for these mutations, specific issues of patient management need to be addressed, such as the duration of anticoagulant therapy, risk stratification for primary or secondary prophylaxis, and family studies. Criteria used to select specific DNA methodologies will center on the issues of cost, automation, speed, reliability, and simplicity. A variety of molecular methods fulfill many but not all of these criteria, whereas the new, semiautomated methodologies of real-time polymerase chain reaction and DNA microarrays offer the potential for widespread application and utility in the future.     

Diabetes and cardiovascular risk evaluation and management in primary care: progress and unresolved issues - rationale for a nationwide primary care project in Germany.

This review highlights established and more recently recognized risk factors for coronary heart disease (CHD) relevant for patients seen in primary care, emphasizing the key role of diabetes mellitus type 2. Recent trends in risk factor research as well as current methods of risk stratification, and new systemic markers are discussed. Beyond the need for more forceful public health strategies to improve early recognition and intervention, the necessity of an integrated comprehensive investigation of the overall characteristics of cardiovascular disease, especially in primary care patients as a prerequisite for future concerted actions is pointed out. Based on this, a large-scale epidemiological investigation focusing on CHD and diabetes in the primary care sector is suggested.     

Cardiac events in patients undergoing noncardiac surgery: shifting the paradigm from noninvasive risk stratification to therapy

Internists and cardiologists are often asked to estimate the risk for perioperative myocardial infarction or cardiac death in patients being considered for noncardiac surgery. Estimating this risk in an individual patient is difficult and complex. Although noninvasive imaging tests are often used for this purpose, a review of the literature reveals that the positive predictive value of noninvasive imaging tests is uniformly low and that they do not provide information beyond that obtained by assessing simple clinical risk variables. Moreover, no evidence exists that noninvasive imaging tests lead to a therapeutic strategy that reduces the risk for perioperative myocardial infarction or cardiac death. Since the publication of guidelines for preoperative risk stratification by the American College of Cardiology/American Heart Association in 1996 and the American College of Physicians in 1997, three clinical trials have shown that beta-blocker therapy reduces the risk for perioperative cardiac events. This paper focuses on the relationship between risk stratification and subsequent therapy to minimize or eliminate risk. In short, the paradigm is shifting from predicting which patient is at high risk for having a perioperative cardiac event to minimizing the likelihood of such an event with specific perioperative pharmacologic therapy.     

Stenting “Vulnerable” But Fractional Flow Reserve–Negative Lesions: Potential Statistical Limitations of Ongoing and Future Trials

Can imaging provide sufficient risk stratification to warrant revascularization of a stable plaque with negative fractional flow reserve (FFR)? Prophylactic stenting could at best be applied selectively since the composite group of FFR-negative lesions has a death or myocardial infarction rate of approximately 1%/year or less but modern stents have a rate of 2% to 3.5%/year. Because vulnerable features exist in a minority of lesions, at least 9,000 patients must be screened in order to enroll a cohort with sufficient risk. While several ongoing randomized trials are testing the concept of plaque sealing in FFR-negative lesions, preventive stenting depends on such a small effect that sample sizes to validate or refute its benefit become prohibitive. Since FFR provides a quantitative, straightforward, and reproducible metric of plaque vulnerability and burden without the need for or expense of additional catheter devices, intracoronary imaging cannot meaningfully guide prophylactic stenting when faced with a negative FFR.     

Adenosine single photon emission computed tomography for assessing risk after myocardial infarction: recent developments

PURPOSE OF REVIEW: While the prognostic power of adenosine single photon emission computed tomography myocardial perfusion imaging has been validated in multiple patient populations including those with known or suspected coronary artery disease, the utility of this modality in assessing risk after an acute myocardial infarction in the primary angioplasty era is still a topic of debate. RECENT FINDINGS: The INSPIRE trial showed that early adenosine single photon emission computed tomography myocardial perfusion imaging is capable of identifying low-risk patients for early hospital discharge after acute myocardial infarction. This novel study demonstrated that intensive medical therapy is a reasonable strategy in low, intermediate, and high-risk post-myocardial infarction patients with preserved left ventricular function. SUMMARY: The INSPIRE trial established the role for early adenosine single photon emission computed tomography myocardial perfusion imaging as a tool for risk stratification in stable patients after an acute myocardial infarction and provided evidence that intensive medical therapy is comparable to coronary revascularization in suppressing ischemia and presumably improving cardiac outcomes. It remains to be seen whether these new findings will alter current American College of Cardiology/American Heart Association guidelines, which emphasize a primary role of coronary revascularization in acute coronary syndromes.     

Clinical review: Clinical applications of vertebral fracture assessment by dual-energy x-ray absorptiometry

CONTEXT: Vertebral fracture (VF) is the most common type of fragility fracture, yet most VFs are not clinically apparent. VFs are associated with a significant increase in morbidity, mortality, and risk of future fracture. Many patients with VFs do not have T-scores classified as osteoporosis. Knowledge of VFs may change diagnostic classification, estimation of future fracture risk, and clinical management. VF assessment (VFA) by dual-energy x-ray absorptiometry is a method for imaging the spine to diagnose VFs. EVIDENCE ACQUISITION: Background information and medical evidence on the technology and clinical applications of VFA was acquired by electronic searching of PubMed for appropriate terms that included vertebral fracture, imaging, diagnosis, dual-energy x-ray absorptiometry, and cost effectiveness. Matches with the highest levels of medical evidence were selected for review, recognizing that the new and evolving nature of the field required inclusion of some material that relied partly on expert opinion. EVIDENCE SYNTHESIS: The sensitivity and specificity of VFA compare favorably with spine radiographs in the ability to diagnose grade 2 and 3 VFs. VFA involves less radiation, lower cost, and often greater patient convenience than spine radiography. Cost effectiveness modeling suggests that imaging of the spine in selected patients provides essential diagnostic and therapeutic information at a nominal cost. Patients with T-scores that are classified as low bone mass (osteopenia) who are selected for pharmacological therapy based on the presence of a VF benefit by reduction in fracture risk. Guidelines for the clinical application of VFA have been developed by the International Society for Clinical Densitometry. CONCLUSIONS: VFA is a technology for diagnosing VFs that may alter diagnostic classification, improve fracture risk stratification, and identify patients likely to benefit from pharmacological therapy who otherwise might not be treated.     

Partnering for better lung health: improving tobacco and tuberculosis control.

Tuberculosis and tobacco together constitute a considerable threat to global health. Several recent initiatives by non-governmental organisations and the World Health Organization have highlighted the need for concerted approaches to lung health that require addressing both of these major threats. However, the emphasis has been on independent effects on health and on independent strategies to control. There is a clear case for closer partnering between researchers, service providers and policy makers in addressing tuberculosis and tobacco. This is based upon growing epidemiological and laboratory evidence that indicate that tobacco is a risk factor for tuberculosis and for death from tuberculosis. Despite the fact that a very high percentage of tuberculosis patients smoke in all settings for which data are available, opportunities to treat tobacco dependence in such patients are under-utilised. This paper will recommend areas that require research, policy development and immediate action.     

Identifying high-risk individuals for gastric cancer surveillance from western and eastern perspectives: Lessons to learn and possibility to develop an integrated approach for daily practice

Current evidence shows that individuals with gastric dysplasia, severe and extensive gastric atrophy, extensive gastric intestinal metaplasia and the incomplete subtype of intestinal metaplasia are at high risk for gastric cancer(GC) development. There are several approaches to identifying these subjects,including noninvasive methods, esophagogastroduodenoscopy and histology.The main approach in Western countries is histology-based while that in Eastern countries with a high prevalence of GC is endoscopy-based. Regarding asymptomatic individuals, the key issues in selecting applicable approaches are the ability to reduce GC mortality and the cost-effectiveness of the approach. At present, population-based screening programs have only been applied in a few Asian countries with a high risk of GC. Pre-endoscopic risk assessment based on demographic and clinical features, such as ethnicity, age, gender, smoking and Helicobacter pylori status, is helpful for identifying subjects with high pre-test probability for a possibly cost-effective approach, especially in intermediate-and low-risk countries. Regarding symptomatic patients with indications for esophagogastroduodenoscopy, the importance of opportunistic screening should be emphasized. The combination of endoscopic and histological approaches should always be considered as endoscopy provides a real-time assessment of the patient's risk level. In addition, imaging enhanced endoscopy(IEE) has been shown to facilitate targeted biopsies resulting in better correlation between endoscopic and histological findings. Currently, the use of IEE is recommended for endoscopic examinations, and the Operative Link for Gastric Intestinal Metaplasia or Operative Link on Gastritis Assessment grading systems are recommended for histological examinations whenever available. However,resource limitations are an important barrier in many regions worldwide. Thus,for an approach to be applicable in real-life practice, it should be not only evidence-based but also resource-sensitive. In this review, we discuss the current understanding and approaches to identifying high-risk individuals from western and eastern perspectives, as well as the possibility of an integrated, resourcesensitive approach.     

Recent advances in the diagnostic evaluation of pancreatic cystic lesions

Pancreatic cystic lesions (PCLs) are becoming more prevalent due to more frequent abdominal imaging and the increasing age of the general population. It has become crucial to identify these PCLs and subsequently risk stratify them to guide management. Given the high morbidity associated with pancreatic surgery, only those PCLs at high risk for malignancy should undergo such treatment. However, current diagnostic testing is suboptimal at accurately diagnosing and risk stratifying PCLs. Therefore, research has focused on developing new techniques for differentiating mucinous from non-mucinous PCLs and identifying high risk lesions for malignancy. Cross sectional imaging radiomics can potentially improve the predictive accuracy of primary risk stratification of PCLs at the time of detection to guide invasive testing. While cyst fluid glucose has reemerged as a potential biomarker, cyst fluid molecular markers have improved accuracy for identifying specific types of PCLs. Endoscopic ultrasound guided approaches such as confocal laser endomicroscopy and through the needle microforceps biopsy have shown a good correlation with histopathological findings and are evolving techniques for identifying and risk stratifying PCLs. While most of these recent diagnostics are only practiced at selective tertiary care centers, they hold a promise that management of PCLs will only get better in the future.     

Do Current Clinical Trials Meet Society’s Needs? : A Critical Review of Recent Evidence

This paper describes some important controversies regarding the current state of clinical trials research in cardiology. Topics covered include the inadequacy of trial research on medical devices, problems with industry-sponsored trials, the lack of head-to-head trials of new effective treatments, the need for wiser handling of drug safety issues, the credibility (or lack thereof) of trial reports in medical journals, problems with globalization of trials, the role of personalized (stratified) medicine in trials, the need for new trials of old drugs, the need for trials of treatment withdrawal, the importance of pragmatic trials of treatment strategies, and the limitations of observational comparative effectiveness studies. All issues are illustrated by recent topical trials in cardiology. Overall, we explore the extent to which clinical trials, as currently practiced, are successful in meeting society’s expectations.     

Intraoperative use of indocyanine green fluorescence imaging in rectal cancer surgery: The state of the art

Indocyanine green (ICG) fluorescence imaging is widely used in abdominal surgery. The implementation of minimally invasive rectal surgery using new methods like robotics or a transanal approach required improvement of optical systems. In that setting, ICG fluorescence optimizes intraoperative vision of anatomical structures by improving blood and lymphatic flow. The purpose of this review was to summarize all potential applications of this upcoming technology in rectal cancer surgery. Each type of use has been separately addressed and the evidence was investigated. During rectal resection, ICG fluorescence angiography is mainly used to evaluate the perfusion of the colonic stump in order to reduce the risk of anastomotic leaks. In addition, ICG fluorescence imaging allows easy visualization of organs such as the ureter or urethra to protect them from injury. This intraoperative technology is a valuable tool for conducting lymph node dissection along the iliac lymphatic chain or to better identifying the rectal dissection planes when a transanal approach is performed. This is an overview of the applications of ICG fluorescence imaging in current surgical practice and a synthesis of the results obtained from the literature. Although further studies are need to investigate the real clinical benefits, these findings may enhance use of ICG fluorescence in current clinical practice and stimulate future research on new applications.     

Risk stratification for ST segment elevation myocardial infarction in the era of primary percutaneous coronary intervention

Acute coronary syndromes presenting with ST elevation are usually treated with emergency reperfusion/revascularisation therapy. In contrast current evidence and national guidelines recommend risk stratification for non ST segment elevation myocardial infarction(NSTEMI) with the decision on revascularisation dependent on perceived clinical risk. Risk stratification for STEMI has no recommendation. Statistical risk scoring techniques in NSTEMI have been demonstrated to improve outcomes however their uptake has been poor perhaps due to questions over their discrimination and concern for application to individuals who may not have been adequately represented in clinical trials. STEMI is perceived to carry sufficient risk to warrant emergency coronary intervention [by primary percutaneous coronary intervention(PPCI)] even if this results in a delay to reperfusion with immediate thrombolysis. Immediate thrombolysis may be as effective in patients presenting early, or at low risk, but physicians are poor at assessing clinical and procedural risks and currently are not required to consider this. Inadequate data on risk stratification in STEMI inhibits the option of immediate fibrinolysis, which may be cost-effective. Currently the mode of reperfusion for STEMI defaults to emergency angiography and percutaneous coronary intervention ignoring alternative strategies. This review article examines the current risk scores and evidence base for risk stratification for STEMI patients. The requirements for an ideal STEMI risk score are discussed.     

What are the Thromboembolic Risks of Heart Failure Combined With Chronic or Paroxysmal AF?

BackgroundHeart failure (HF) and atrial fibrillation (AF) are common disorders that frequently occur together and are associated with an increased risk of thromboembolism. This thromboembolic risk may be reduced by anticoagulation with warfarin but not without introducing new hemorrhagic risks.Methods and ResultsCurrent guidelines recommend the use of anticoagulation in patients with HF and chronic AF and paroxysmal AF (PAF) that is symptomatic or frequent and prolonged enough to be detected by electrocardiogram. However, the evidence supporting these recommendations is weak and does not take account of research indicating that the prothrombotic risk is higher in more severe HF.ConclusionsAn area not addressed by current guidelines is anticoagulation in patients with HF and short, asymptomatic episodes of AF. These issues need to be resolved with further studies using implanted devices to detect such asymptomatic PAF.     

Defining optimal research study design for cardiovascular imaging using computed tomography angiography as a model

Patients, physicians, and payers are facing a significant increase in cardiovascular (CV) imaging use, resulting in skyrocketing societal costs, without clear improvement in patient outcomes. The need for studies evaluating the effects of CV imaging that assess appropriate end points is critical to address continued concerns over the lack of well-designed clinical studies. Thus, the investigators propose a framework, using computed tomographic angiography as a model, that should be considered in the optimal design of future imaging research and would potentially provide payers with data to make appropriate reimbursement decisions. The inclusion of risk stratification, randomization, multiple-site participation, and multigeography site enrollment are key elements in the construction of such studies. Meaningful end points with regard to operating characteristics, downstream testing, CV event rates, outcomes, and costs are essential to appropriately evaluate any new imaging technology. Only once better level evidence is formed to support CV imaging can the central issues of quality and appropriateness of CV imaging truly be evaluated. If the CV community does not embrace this type of scientific evaluation of CV imaging modalities and fails to adequately identify the value in these techniques, it may ultimately lose the ability to use them to provide optimal care to its patients.