Towards personalized Internet health information: the STEPPS architecture

PRIMARY OBJECTIVE: STEPPS (STructured Evaluated Personalized Patient Support) proposes a strategy for integration of electronic patient records with Internet health-related content and its consequent use in personalized information retrieval for patient education. The application domain is the post-discharge support of burn patients in the Netherlands. MATERIALS AND METHODS: We developed an electronic patient record interface for structured data collection in burn care. The system's thesaurus was projected to UMLS terms and the corresponding codes were incorporated in our software. A list of topics central to burn patient education was identified and a collection of related Web pages was compiled using meta-search software (Copernic2001Pro). The HTML pages were filed into catalogues by the Collexis indexing-matching software, using the UMLS Metathesaurus as indexing vocabulary. RESULTS: The bilingual (English and Dutch) structured data interface is currently used to create a database of retrospective patient data. Each patient's profile, i.e. set of characteristics employed to personalize information retrieval, can be automatically extracted. We have assembled a collection of more than 2500 Internet pages containing relevant information for burn patients. When patient data is available, the Collexis matching engine will accept the patient's profile as input and retrieve the most relevant HTML documents available in the catalogues. DISCUSSION: We have addressed some basic issues around the technical feasibility of linking electronic patient record data to online content. Although the functionality of STEPPS is not yet optimal, it contributes to the efforts towards improved relevance of information retrieval. Electronic patient record applications in conjunction with Internet resources can give a significant boost to the availability of tailored health education material. In this context, quality assurance of online health information is an indispensable element.     

FOLFIRINOX and translational studies: Towards personalized therapy in pancreatic cancer

Pancreatic cancer is an extremely aggressive disease; although progress has been made in the last few years, the prognosis of these patients remains dismal. FOLFIRINOX is now considered a standard treatment in first-line setting, since it demonstrated an improved overall and progression-free survival vs gemcitabine alone. However, the enthusiasm over the benefit of this three-drug regimen is tempered by the associated increased toxicity profile, and many efforts have been made to improve the feasibility of this schedule. After a more recent phase Ⅲ trial showing an improved outcome over gemcitabine, the combination of gemcitabine/nab-paclitaxel emerged as another standard first-line treatment. However, this treatment is also associated with more side effects. In addition, despite initial promising data on the predictive role of SPARClevels, recent studies showed that these levels are not associated with nab-paclitaxel efficacy. The choice to use this treatment over FOLFIRINOX is therefore a topic of debate, also because no validated biomarkers to guide FOLFIRINOX treatment are available. In the era of actionable mutations and target agents it would be desirable to identify molecular factors or biomarkers to predict response to therapy in order to maximize the efficacy of treatment and avoid useless toxic effects for non-responding patients. However, until today the milestone of treatment for pancreatic cancer remains chemotherapy combinations, without predictive or monitoring tools existing to optimize therapy. This review analyzes the state-of-the-art treatments, promises and limitations of targeted therapies, ongoing trials and future perspectives, including potential role of microR NAs as predictive biomarkers.     

Towards personalized perioperative treatment for advanced gastric cancer

Gastric cancer is one of the most frequently diagnosed cancers worldwide. Although the rate of gastric cancer has declined dramatically over the past decades in most developed Western countries, it has not declined in East Asia. Currently, a radical gastrectomy is still the only curative treatment for gastric cancer. Over the last twenty years, however, surgery alone has been replaced by a multimodal perioperative approach. To achieve the maximum benefit from the perioperative treatment, a thorough evaluation of the tumor must first be performed. A complete assessment of gastric cancer is divided into two parts: staging and histology. According to the stage and histology of the cancer, perioperative chemotherapy or radiochemotherapy can be implemented, and perioperative targeted therapies such as trastuzumab may also play a role in this field. However, perioperative treatment approaches have not been widely accepted until a series of clinical trials were performed to evaluate the value of perioperative treatment. Although multimodal perioperative treatment has been widely applied in clinical practice, personalization of perioperative treatment represents the next stage in the treatment of gastric cancer. Genomic-guided treatment and efficacy prediction using molecular biomarkers in perioperative treatment are of great importance in the evolution of treatment and may become an ideal treatment method.     

Assessment of residual tissue viability by exercise testing in recent myocardial infarction: comparison of the electrocardiogram and myocardial perfusion scintigraphy.

The assessment of residual myocardial viability in infarcted areas is relevant for subsequent management and prognosis but requires expensive technology. To evaluate the possibility that simple, easily obtainable clinical markers may detect the presence of within-infarct viable tissue, the significance of exercise-induced ST elevation occurring in leads exploring the area of a recent Q wave myocardial infarction was assessed. Twenty-five patients with recent (less than 6 months) myocardial infarction were studied. All had angiographically documented coronary artery disease, diagnostic Q waves (n = 24) or negative T waves (n = 25) on the rest 12-lead electrocardiogram and exhibited during exercise greater than or equal to 1.5 mm ST segment elevation (n = 17) or isolated T wave pseudonormalization (n = 8) in the infarct-related leads. ST-T wave changes were reproduced in all patients during thallium-201 exercise myocardial scintigraphy. A fixed perfusion defect was observed in 24 of the 25 patients. A reversible defect was seen in 16 (94%) of 17 patients who exhibited transient ST elevation during exercise but in only 4 (50%) of the 8 patients who had only T wave pseudonormalization. In conclusion, in patients with recent myocardial infarction, analysis of simple ST segment variables obtained during exercise testing may allow a first-line discrimination of those who may potentially benefit from a revascularization procedure.     

Clinical decision-making and myocardial viability: current perspectives

Not all myocardium involved in a myocardial infarction is dead or irreversibly damaged. The balance between the amount of scar and live tissue, and the nature of the live tissue, determine the likelihood that contractile function will improve after revascularisation. This improvement (which defines viability) may be predicted with about 80% accuracy using several techniques. This review examines the determinants of functional recovery and how they may be integrated in making decisions regarding revascularisation.     

Assessment of myocardial viability using myocardial contrast echocardiography

Myocardial contrast echocardiography (MCE) is a technique that uses microbubbles as a tracer during simultaneous ultrasound of the heart. The microbubbles can be used to provide quantitative information regarding the adequacy of myocardial blood flow (MBF), as well as the spatial extent of microvascular integrity. In acute myocardial infarction, MCE can identify the presence of collateral flow within the risk area, and can therefore predict preservation of myocardial viability and ultimate infarct size even prior to reperfusion. After reperfusion, the extent of microvascular no-reflow can be determined, and has significant implications for recovery of left ventricular function. In chronic ischemic heart disease, MCE has also been shown to successfully differentiate viable from necrotic myocardium. This technique can accurately predict recovery of function after revascularization. More importantly, MCE can be used to identify viable segments that may help to prevent infarct expansion and remodeling, and thus improve patient outcomes.     

Assessment of myocardial viability with myocardial contrast echocardiography

The application of noninvasive imaging techniques to assess myocardial viability has become an important part of routine management of patients with acute myocardial infarction and chronic coronary artery disease. Information regarding the presence and extent of viability may help identify patients likely to benefit from revascularization or therapy directed at attenuating left ventricular remodeling. Myocardial contrast echocardiography (MCE) is capable of defining the presence and extent of viability by providing an accurate assessment of microvascular integrity needed to maintain myocellular viability. It is especially suited for the spatial assessment of perfusion, even when myocardial blood flow is reduced substantially in the presence of severe epicardial stenoses or in a bed dependent on collateral perfusion. The routine use of MCE to evaluate viability in patients with acute and chronic coronary artery disease is now feasible with the advent of new imaging technologies and microbubble agents capable of myocardial opacification from venous injections. The utility of this technique for determining treatment strategies has not been established but is forthcoming.     

心肌声学造影定量心肌血流判断存活心肌的实验研究

目的　评价经静脉心肌声学造影 (MCE)判断存活心肌的可行性。方法　建立急性心肌梗死犬模型 ,经外周静脉持续滴注微泡造影剂 ,通过计算A·β值测定心肌相对血流量。以放射性微球法测定的心肌血流量 (MBF)为标准 ,了解A·β值测定MBF的准确性。通过A·β值估测心肌存活与否 ,病理检查验证其可靠性。结果　放射性微球法所测的正常区、缺血区、坏死区的MBF分别为 ( 1 5± 0 3)、( 0 7± 0 3)、( 0 3± 0 2 )ml·min-1·g-1;MCE测得的A·β值分别为 5 2 46± 15 0 9、2 4 36±3 89、3 74± 3 80 ;正常区、缺血区、坏死区的MBF和A·β值“标化”后分别为 1 0± 0 0、0 44± 0 17、0 17± 0 11和 1 0± 0 0、0 48± 0 0 9、0 0 7± 0 0 8,二者的相关性良好 (r=0 81,P =0 0 0 1)。MCE对坏死心肌的判定结果与病理结果吻合。结论　心肌声学造影可用于活体状态下评价存活心肌 ,“标化”后的A·β值 <0 2 3提示心肌坏死。     

Prognostic utility of myocardial viability assessment

Myocardial viability assessment is useful in patients with severe coronary artery disease and severe left ventricular dysfunction. Whereas most studies have focused on recovery of regional function, there are emerging data on patient outcome. Review of these data suggests that patients with chronic ischemia, cardiomyopathy, and viable myocardium who are treated medically have a worse, outcome than those treated with coronary revascularization. However, there are no prospective randomized trials. We present perspectives for future studies.     

The noninvasive assessment of myocardial viability

The major objective of noninvasive imaging for detection of myocardial viability is to assist in the improved selection of patients with coronary artery disease and severe left ventricular dysfunction who would benefit most from revascularization. The techniques most commonly used to identify viable myocardium are thallium-201 (TI) scintigraphy, positron emission tomography (PET) using a flow tracer in combination with a metabolic tracer, technetium-99m (Tc) sestamibi imaging, and dobutamine echocardiography. On stress TI scintigraphy, asynergic regions showing normal thallium uptake, an initial defect with delayed redistribution at 3–4 h, late redistribution at 24 h, or defect reversibility after reinjection of a second dose of TI at rest all suggest preserved viability. The greater the final uptake of TI in areas of regional myocardial dysfunction preoperatively, the greater the improvement in ejection fraction after coronary revascularization. Demonstration of uptake of fluoro-18 deoxyglucose (FDG) in regions of diminished blood flow on PET imaging also correlates well with improved systolic function after revascularization. Tc sestamibi may also be useful for assessment of myocardial viability, particularly after thrombolytic therapy for acute myocardial infarction. Dobutamine echocardiography has good positive predictive value for viability determination, but absence of systolic thickening in an akinetic zone in response to intravenous infusion of the drug may still be associated with viable myocardium in 25–50% of segments. Of all the techniques cited above, quantitative resting TI scintigraphy may be the best approach for distinguishing between viable and irreversibly injured myocardium.     

Combined carotid endarterectomy and myocardial revascularization: personal experience

A significant percentage of patients undergoing myocardial revascularization suffer from extracranial cerebrovascular disease; recognition of such combined lesions identifies patients at risk for cerebrovascular accidents during the cardiac procedure. Simultaneous or staged coronary artery bypass graft (CABG) and carotid endarterectomy operations have been performed for the last 20 years, however, the clinical indications and the timing of the procedures remain controversial issues. Between November 1988 and January 1994, 1122 patients underwent myocardial revascularization at our Institute and in 35 cases (3.7%) carotid endarterectomy was simultaneously performed; 502 isolated carotid endarterectomies were performed in the same period. Trivascular coronary artery disease was found in 27 cases and low ejection fraction in six. Each patient received an average of 3.7 coronary grafts. Hospital mortality was 5.7% and major neurologic morbidity 2.8%. We believe that a simultaneous approach is recommended in patients with unstable angina and symptomatic carotid artery disease; in patients with a critical but asymptomatic carotid artery stenosis the indication for operation is subject to individual clinical judgment.