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(18)F-FDG PET provides high-impact and powerful prognostic stratification in staging newly diagnosed non-small cell lung cancer.

UNLABELLED: Survival of lung cancer patients remains poor despite increasingly aggressive treatment. Conventional staging has well-described limitations. (18)F-FDG PET has been shown to stage lung cancer more accurately than does CT scanning, but the impact on patient treatment and outcome is poorly defined. This study evaluated this impact in routine clinical practice within a tertiary oncology facility. METHODS: For 153 consecutive patients with newly diagnosed non-small cell lung cancer, the treatment plan based on conventional staging methods was compared with the treatment plan based on incorporation of PET findings. Survival was analyzed using the Cox proportional hazards regression model. RESULTS: For broad groupings of stage, 10% of cases were downstaged and 33% upstaged by PET. When assessable, the PET stage was confirmed in 89% of patients. PET had a high impact on 54 patients (35%), including 34 whose therapy was changed from curative to palliative, 6 whose therapy was changed from palliative to curative, and 14 whose treatment modality was changed but not the treatment intent. For 39 patients (25%), a previously selected therapy was altered because of the PET findings. The Cox model indicated that the pre-PET stage was significantly associated with survival (P = 0.013) but that the post-PET stage provided much stronger prognostic stratification (P < 0.0001) and remained significant after adjustment for treatment delivered. CONCLUSION: Staging that incorporated PET provided a more accurate prognostic stratification than did staging based on conventional investigations. Further, the additional information provided by PET significantly and appropriately changed management in the majority of patients.

Aged↗

Fibroblast growth factor-7 regulates stratification of the bladder urothelium.

PURPOSE: The cellular and molecular mechanisms that regulate the organization of bladder urothelium into basal, intermediate and superficial cell layers remain poorly understood. We tested the hypothesis that fibroblast growth factor (FGF)-7 is essential for generating a multilayered stratified bladder epithelium. MATERIALS AND METHODS: The morphological and molecular characteristics of bladder urothelium in age and sex matched FGF-7 +/+ wild-type and -/- null mice were evaluated. In addition, the effect of exogenous FGF-7 on the growth and differentiation of primary murine urothelial cells was assessed. RESULTS: Morphometric analyses demonstrate that FGF-7 null urothelium is markedly thinned compared with wild-type urothelium. Electron microscopy revealed that null urothelium lacks the intermediate cell layers and molecular marker analyses confirmed this observation. In vitro cell culture experiments indicated that FGF-7 regulates urothelial cell growth, differentiation and stratification. Primary urothelial cultures maintained without FGF-7 ceased to divide and expressed proteins characteristic of terminally differentiated umbrella cells. In contrast, cultures maintained with exogenous FGF-7 contained proliferating epithelial cells with protein expression patterns consistent with those of intermediate cells in addition to terminally differentiated, post-mitotic umbrella cells. Importantly, isolated urothelial cells maintained with exogenous FGF-7 formed a multilayered epithelium in vitro. CONCLUSIONS: Collectively these data indicate that FGF-7 is essential for normal bladder urothelial stratification, specifically the formation of the intermediate cell layers. Fibroblast growth factor-7 stimulates urothelial proliferation and delays the differentiation of these cells into post-mitotic umbrella cells.

Animals↗

[Arrhythmia risk stratification based on clinical and functional data].

The term "sudden death" indicates a natural and rapid death, an unexpected event in patients with high mortality rates such as those with heart failure. Sudden death in patients with heart failure is responsible for some of 40% of all deaths. A detailed clinical evaluation in patients with heart failure is extremely helpful for risk stratification. Although sex has been shown to have no prognostic relevance, heart failure due to coronary artery disease is associated with a higher mortality rate when compared to other etiologies. Left ventricular ejection fraction is the independent risk factor with the highest predictive value of survival. However, in patients with heart failure, except for the advanced stages, sudden death shows an incidence comparable with that of progressive pump failure. Like left ventricular ejection fraction, even the functional classifications of heart failure (such as NYHA) are to be considered as a non-specific marker of overall mortality. In fact, despite the close relation between advanced disease stages and a higher mortality rate, a large overlap has been demonstrated for the intermediate classes. The noninvasive assessment of oxygen consumption during cardiopulmonary exercise testing has been recognized as an independent risk factor and patients with a peak oxygen consumption < 10 ml/kg/min should be recommended for cardiac transplantation. In these patients no clear relation with an increased risk of sudden death has been demonstrated. In conclusion, the commonly employed clinical-functional indexes (left ventricular ejection fraction, functional classifications, peak oxygen consumption during cardiopulmonary testing) are significant predictors of overall mortality, however they are useless in the risk stratification for death due to fatal arrhythmias.

Arrhythmias, Cardiac↗

[Brugada's syndrome: epidemiology, risk stratification, and clinical management].

Brugada syndrome is an arrhythmogenic disease, characterized by syncope and sudden cardiac death, with a typical electrocardiographic pattern: right bundle branch block and ST segment elevation in the right precordial leads. Only recently, the first gene causing Brugada syndrome has been demonstrated by the identification of mutations in SCN5A, the gene encoding for the cardiac sodium channel, also responsible for the LQT3 subtype of long QT syndrome. Despite the knowledge on Brugada syndrome has dramatically improved in the recent years, the clinical management is still often empirical and limited by the lack of pharmacological therapies. Therefore, the implantable cardioverter-defibrillator (ICD) is the only life-saving option for high-risk patients. However, life-long implant in young individuals may have a major impact on the quality of life and it is not free from complications. Therefore, the identification of a robust risk stratification algorithm is of outmost importance to limit the use of ICD to the higher risk individuals. Programmed electrical stimulation has been proposed but this approach appears to have a low positive predictive value, thus leading to implants in many asymptomatic patients. Recently, we analyzed data from 200 Brugada syndrome patients, one of the largest groups so far reported, and we showed that the best predictor of cardiac events is the presence of a spontaneous abnormal ECG pattern associated with history of syncope. In the present article we will review the clinical characteristic of Brugada syndrome and point out a possible risk stratification scheme.

Arrhythmias, Cardiac↗

Preoperative risk stratification using stress myocardial perfusion scintigraphy with electrocardiographic gating.

UNLABELLED: This study was designed to assess the prognostic value of stress myocardial perfusion SPECT with electrocardiographic (ECG) gating in patients undergoing noncardiac surgical treatment. METHODS: The study included 481 consecutive patients who underwent noncardiac surgery and had been referred for preoperative myocardial perfusion scintigraphy. Myocardial scintigraphy used (99m)Tc-labeled perfusion agents and dipyridamole stress with ECG gating, permitting qualitative and quantitative analyses of both myocardial perfusion and cardiac function. Reconstructed perfusion images were analyzed qualitatively and semiquantitatively. The Quantitative Gated SPECT (QGS) program was used for gated SPECT analysis to calculate global left ventricular ejection fraction and estimate regional wall motion. We assessed the relationships between perioperative cardiac events and various predictors, including clinical risk factors, radionuclide perfusion, and functional variables. RESULTS: Univariate analysis indicated that age (P < 0.001), diabetes mellitus (P < 0.01), history of heart failure (P < 0.05) or perfusion imaging (P < 0.0001), and QGS analysis (P < 0.0001) yielded significant risk stratification. According to multivariate analysis, age, diabetes mellitus, perfusion imaging, and QGS analysis were independent predictors of perioperative cardiac events. The event rate was correlated with quantitative scintigraphic indices of perfusion images (rest perfusion and ischemic scores) and QGS analysis (global ejection fraction and the number of hypokinetic segments). Although QGS functional data offered no significant incremental prognostic value in patients with abnormal perfusion, it classified patients with normal perfusion into 2 risk groups (P < 0.0001). A combination of clinical risk factors, scintigraphic perfusion results, and functional data allowed further detailed risk stratification. CONCLUSION: Stress myocardial perfusion SPECT with ECG gating has an incremental prognostic value over conventional nongated stress perfusion imaging in predicting perioperative cardiac events.

Aged↗

[Population size and areas of stratification in the variational model of ecosystem].

The formulations of the variational task for finding the relative population size of species in community at a stationary stage of growth and of the theorem of stratification are given. Algorithms of finding the relative size of populations for communities consisting of two and three species consuming two or three resources were obtained. The borders of areas of stratification were described in which one, two, or three resources are limiting. For two species and two resources, the formulae of the dependence of relative size on the ratio of resources were derived, and the shape of this dependence for real requirements of species was demonstrated.

Algorithms↗

Do-not-resuscitate and stratification-of-care forms in Rhode Island.

Congress passed the Patient Self-Determination Act of 1990 to ensure that patients are informed of their rights to express healthcare preferences in advance of loss of capacity. Thus, a patient may elect to forgo cardiopulmonary resuscitation in favor of a treatment approach that favors comfort over survival. Do-not-resuscitate and stratification-of-care forms provide a means for expression of healthcare preferences in hospitals. These forms can often guide the important discussion of healthcare preferences. Unfortunately, no clear standard exists for what should be included in do-not-resuscitate or stratification-of-care forms that institutions seeking to improve in this vital area of practice could use for guidance. Existing forms in use at adult general hospitals throughout Rhode Island were reviewed.

Adult↗

Quantifying biases in causal models: classical confounding vs collider-stratification bias.

It has long been known that stratifying on variables affected by the study exposure can create selection bias. More recently it has been shown that stratifying on a variable that precedes exposure and disease can induce confounding, even if there is no confounding in the unstratified (crude) estimate. This paper examines the relative magnitudes of these biases under some simple causal models in which the stratification variable is graphically depicted as a collider (a variable directly affected by two or more other variables in the graph). The results suggest that bias from stratifying on variables affected by exposure and disease may often be comparable in size with bias from classical confounding (bias from failing to stratify on a common cause of exposure and disease), whereas other biases from collider stratification may tend to be much smaller.

Bias↗

[Nutritional status by social stratification in Venezuelan school children].

UNLABELLED: This study assessed nutritional status of 590 children from Naguanagua, Valencia, attending school, aged between 4 and 14 years and its relation to social stratification, age and gender. Body dimension indicators were used for nutritional diagnosis. NCHS/OMS and Frisancho references were used for height/age (HA) weight/height (WH) cut-off points, and body mass index (BMI). Graffar modified by Mendez was used to establish socioeconomic status. Statistical analyses included descriptives, x2 and student-test. RESULTS: 91% of the children were in poverty, (71% relative and 20% critical). For HA, 6.4% classified as short, 27.6% in risk, and 4.9% tall for age without significative differences between sex. For WH, 0.6% were in nutritional deficit, 10.2% in risk and 22.1% in excess. For BMI, 12.9% had nutritional deficit, 7.3% excess but no significative differences for sex. Stunting and deficit were present in all age groups, but more significantly in those older than 10 years (12%; 23.9% respectively). Social stratification was associated with WH and BMI being deficit more prevalent in III and V class, predominating excess in IV class. The high prevalence of obesity makes this group as a high risk one for chronic degenerative diseases.

Adolescent↗

Comparison of various score systems for risk stratification in heart surgery.

UNLABELLED: Its is important to predict patients having the highest risk of surgery. Risk stratification systems need to be tested in different surgical populations and whether they are or not appropriate to our population remains unknown. OBJECTIVE: To test various risk stratification systems for our region population having cardiac surgery in our institution during 2002. MATERIALS AND METHODS: Between January 1, 2002 and November 1, 2002, all adult patients undergoing heart surgery with cardiopulmonary bypass in our institution were included in the study and scored using the EuroSCORE, Parsonnet, Ontario, and QMMI. Study was completed by 444 patients. We analyzed score systems predicting characteristics by assessing receiver operating characteristics (ROC). RESULTS: Observed mortality was 25 (5.63%). Mean score for alive and dead patients for EuroSCORE was -7.8+/-3.1 and 10.8+/-3.2, p<0.005; Parsonnet - 14.2+/-11 and 32.5+/-13.8, p<0.0005; Ontario - 3.6+/-2.7 and 6.4+/-3.5, p<0.005; QMMI score - 10.4+/-6.9 and 20.3+/-8.7, p<0.0001. ROC curve analysis for mortality showed best predicting characteristics for the Parsonnet and QMMI, best accuracy for QMMI score - 84.4 %. CONCLUSIONS: Most (71.2%) of our investigated patients having heart surgery are at high-risk group for death. All investigated score systems have significance in mortality prediction. Among the investigated score systems, the QMMI score and Ontario score systems yielded the highest predictive value in our patient population. Highest accuracy of prediction patient population showed QMMI score. Our study highlighted over prediction of mortality for Parsonnet score and EuroSCORE systems for our population.

Adult↗

A switch in cytokeratin expression and intermediate filament organization associated with epithelial stratification.

Low density gingival epithelial cells were cultured on the side of glass slides facing rat's tail collagen lattices. Under these conditions and in the presence of physiological level of calcium, colony formation was enhanced and stratification was slowed down. The strong attachment of the cells to glass slides permitted immunocytochemical examination of cytokeratin (CK) expression and their organization within individual cells during the different stages of epithelial maturation. The present results showed that during the stage of cell migration and colony formation, the cells express the same set of cytokeratins (basal cell marker 14, simple epithelial markers 8, 18 and 19, and marker of hyperproliferation 16) which forms a well-defined network of organized filaments. At the stratification stage, the filament network became dense by the additional expression of the markers of differentiation in non-keratinized stratified epithelia (CK 4 and 13). These appeared once individual cells started to overlap the basal cells, a period during which the cell-temporarily changed morphology. Whilst the suprabasal cells exhibited dense filament network labelled for CK 4 and 13, the density of labelled filaments for CK 14, 8 and 18 was much lower, indicating that these cells contained newly-formed filaments lacking the basal and simple epithelial keratins. The simple epithelial cytokeratins became weakly labelled in older cultures. The uncoupling of paired expression of cytokeratins 4 and 13 was observed in non-colony forming aged cells. This provides an example of altered program of cytokeratin expression during epithelial maturation.

Adult↗

[Application of risk stratification scores in acute myocardial infarction. Results of RICO (observation of infarction in the Ivory Coast)].

Several risk stratification scores for myocardial infarction have been developed in recent years, based on clinical trials. The object of this study was to assess the application of these scores in an unselected population of myocardial in farction in a French department. One thousand and fifty-four patients with acute myocardial infarction were included in the RICO observatory in the Côte d'Or. Those with ST elevation (SST), N = 746, had 30 day-mortality rates which increased with the TIMI and GUSTO scores (khi2 tendency, p < 0.001). There was a good discriminatory power of both these scores (correlations of 0.71 and 0.69 respectively). Similarly, logistic regression analysis showed a significant relationship between TIMI and GUSTO scores and 30 day mortality (p < 0.001). No correlation was observed between mortality and increased TIMI score in cases of infarction without ST elevation, N = 308, p = 0.344. Moreover, this score had a low discriminatory value in the study population with a correlation of 0.54. On the other hand, regression analysis showed a strong predictive value of the PURSUIT score in infarction without ST elevation for mortality. In addition, there was a correlation between death and the value of this score (p < 0.05). This score also showed a good discriminatory power with a correlation of 0.71. This study shows that, in an unselected population, risk stratification scores may be used as a routine in myocardial infarction, especially in cases with ST elevation.

Aged↗

Risk stratification for arrhythmic events in patients with idiopathic dilated cardiomyopathy: a review of the literature and current perspectives.

The prognosis for patients with idiopathic dilated cardiomyopathy (DCM) has markedly improved during the last decade, mainly because of advancements in therapeutic strategies. However, sudden death still accounts for a significant part of the total mortality in patients with moderate disease. Recent primary prophylactic trials failed to demonstrate any benefit of cardioverter-defibrillator implantation in an unselected group of idiopathic DCM patients and thus the identification of the subgroup of patients at high arrhythmic risk is crucial. Although different risk stratification methods have been evaluated in risk assessment, the reported clinical value differs in studies, mainly because of differences in either methodology and/or patient selection. The present review focuses on arrhythmic events in idiopathic DCM and on the value of noninvasive methods and electrophysiological study in the risk stratification of this group of patients.

Arrhythmias, Cardiac↗

Asthma population management: development and validation of a practical 3-level risk stratification scheme.

OBJECTIVE: To define and validate a practical risk stratification scheme based on administrative data for use in identifying patients at high, medium, and low risk of requiring emergency hospital care for asthma. STUDY DESIGN: Retrospective cohort. PATIENTS AND METHODS: Predictors in 1999 were evaluated in relation to 2000 asthma emergency hospital care (any asthma hospitalization or emergency department visit) in a training set (n = 8789, 2000 emergency hospital care = 5.5%) and a testing set (n = 6104, 2000 emergency hospital care = 7.9%). Logistic regression was used to assign risk points in the training set, and positive and negative predictive values, sensitivities, and specificities were calculated in the training and testing sets. RESULTS: High risk was defined as asthma emergency hospital care in the previous year or use of >14 beta-agonist canisters and oral corticosteroid use; medium risk was defined as no emergency hospital care but use of either >14 beta-agonist canisters or oral corticosteroids; and low risk was defined as none of the above. For the high-risk groups in the training and testing sets, positive predictive values were 12.9% and 22.0%, sensitivities were 24.8% and 25.4%, specificities were 90.3% and 92.0%, and negative predictive values were 95.4% and 93.2%, respectively. The medium-risk groups identified another 32.6% of patients in the training set and 28.3% in the testing set requiring subsequent asthma emergency hospital care. CONCLUSION: This simple risk stratification scheme is useful for identifying patients from administrative data who are at increased risk of experiencing emergency hospital care for asthma.

Adolescent↗

"Learning curves" of cardiac surgery in relation to risk stratification and hospital location.

AIM: The purpose of this study was to determine any significant differences in "learning curves" between private and public hospitals when the same senior surgeon was responsible during the initial phases of open-heart surgery programs development, in relation to risk stratification and hospital location. METHODS: A prospective review of 610 patients records was performed at a newly-opened cardiothoracic program in a public University Hospital (PUH) in the periphery of Greece, and a private institution (PI) with an experienced intensive care unit (ICU) in the capital city of Athens. Preoperative risk stratification, mortality and postoperative length of stay (LOS) were analysed between 1999 to 2001. RESULTS: At PUH 298 patients were operated and 312 patients at PI. There were 136 low risk (EuroSCORE 0-2) and 474 medium and high-risk patients (EuroSCORE > or =3). There was no significantly elevated mortality or learning curve in low risk surgery either at PUH (57 patients with 1 death) or PI (79 patients and 1 death). In medium and high-risk surgery at PI there was no mortality in 68 patients operated by the senior surgeon and no learning curve in all 233 such patients. In 240 medium and high-risk patients at PUH there was a learning curve despite the involvement of the same senior surgeon. In 1999 and 2000 the observed mortality (OM) in 150 patients was 15.33%, EuroSCORE 5.98, and in 2001 in 91 patients OM 3.29%, EuroSCORE 5.95 with p=0.00.8 when "experienced" ICU staff was employed. LOS was significantly reduced in 97 patients in 2001 at PUH (8.7 d +/- 2.81 vs 11.07 days +/- 7.9 in 1999 and 2000, p=0.046) confirming the existence of a learning curve at the PUH. No such change was observed at PI (8.2 days vs 7.8, p=0.45). CONCLUSION: No mortality differences or learning curve characteristics were detected for low risk operations either at PUH or PI. For medium and high risk surgery there appears to be a learning curve in PUH but not in PI despite senior surgeon involvement in both. The presence of an experienced ICU appears to play a critical role in the outcome of operations in newly opened cardiothoracic programs.

Analysis of Variance↗

[Risk stratification after acute myocardial infarction: limitations of dobutamine stress echocardiography in females].

BACKGROUND: Dobutamine stress echocardiography (DSE) is an imaging test widely used for risk stratification of patients after acute myocardial infarction. METHODS: We evaluated the sensitivity of DSE with respect to the gender and the stenotic coronary artery in patients who survived a myocardial infarction and with angiographic evidence of single-vessel coronary artery disease. RESULTS: The sensitivity of DSE was generally low. In particular, it was significantly lower in the presence of stenosis of the left circumflex and right coronary arteries with respect to the left anterior descending coronary artery. In females it was lower, especially when the stenosis involved the right coronary and left circumflex arteries. CONCLUSIONS: Our data suggest that in female gender the use of other imaging tests and particularly of coronarography should be strongly recommended for risk stratification after acute myocardial infarction.

Coronary Angiography↗

Efficacy of anticoagulation for stroke prevention and risk stratification in atrial fibrillation: translating trials into clinical practice.

As one of the most powerful independent risk factors for ischemic stroke and the most clinically relevant arrhythmia, atrial fibrillation (AF) poses a serious clinical and public health threat as the global population ages. AF increases the risk of ischemic stroke 4- to 5-fold although this statistic varies with age of the patient. Indeed, the prevalence rises to 1 in 25 people aged > or =60 years and 1 in 10 people aged > or =80 years. More than 2.3 million Americans have diagnosed AF, and that number is expected to increase dramatically over the coming decades. Ischemic stroke causes the most major disability and remains the third leading cause of death in the United States. Therapeutic strategies and optimal risk stratification offer the best hope for decreasing the burden of AF-related thromboembolism. This article focuses on the randomized trial evidence for the efficacy and safety of oral vitamin K antagonists (eg, warfarin) for stroke prevention in AF. In particular, this article explores how well these findings translate into clinical practice, especially among patients with AF treated outside of clinical trials. Discussion centers on using evidence-based data to guide treatment for patients who are at increased risk for stroke. Such strategies would enhance the net benefit of oral anticoagulation. Concluding points provide information on improving risk stratification for stroke in patients with AF.

Anticoagulants↗

Gene expression profiles and risk stratification in childhood acute lymphoblastic leukemia.

BACKGROUND AND OBJECTIVES: Childhood acute lymphoblastic leukemia (ALL) is a heterogeneous disease. There are several distinct genetic subtypes, characterized by typical changes in gene expression pattern. In addition to cytogenetic markers, the in vivo response to treatment is an emerging prognostic marker for risk stratification. However, it has not yet been reported whether gene expression profiles can predict risk group stratification already at the time of diagnosis. DESIGN AND METHODS: We analyzed bone marrow samples of 31 ALL patients to identify changes in gene expression that are associated with the current risk assignment, irrespective of the genetic subtype. Gene expression profiles were established using oligonucleotide microarrays. RESULTS: Considering all low- and high-risk patients, no gene was capable of predicting the risk assignment already at time of diagnosis. However, screening for risk group associated genes using more homogeneous subsets of patients revealed 10(6) discriminatory probe sets. The prognostic significance of these probe sets was subsequently determined for the entire series of patients. Using the selected subgroups as the training set and the remaining samples as an independent test set, logistic regression using 3 predictor variables could accurately predict current risk assignment for 10 out of 12 patients. INTERPRETATION AND CONCLUSIONS: Gene expression profiles established from a cytogenetically heterogeneous study group are not, as yet, sufficiently accurate to be used prognostically in a clinical setting. Additional risk-associated gene expression analyses need to be performed in more homogeneous sets of patients.

Child↗