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In this paper, the indications for myocardial perfusion scintigraphy, the stress methods, the radiopharmacy and the most used methodology are reviewed. The clinical applications of myocardial perfusion scintigraphy, regarding the diagnosis and prognostic stratification in stable angina are emphasised.
OBJECTIVES: Follicular lymphoma (FL) is generally considered an indolent disorder but a significant subset of patients shows a worse outcome. Aim of this study was to validate the FLIPI score in an independent series of follicular lymphoma patients and to correlate prognostic categories with the period of diagnosis and the use of anthracycline. METHODS: We evaluated the clinical characteristics, prognostic stratification, and outcome of 338 patients with follicular lymphoma consecutively diagnosed and followed at our Institution between 1975 and 2002. RESULTS: The distribution of patients within the prognostic categories of the IPI and FLIPI score, while confirming the indolent outcome of follicular lymphoma, shows that a subset of patients has a worse prognosis. With the IPI score, 62% of patients are in the low risk, 26% in the low-intermediate, and 12% in the high (high-intermediate+high) risk group. With the FLIPI score, 48% of patients are categorized as low risk, 31% as intermediate risk, and 21% as poor risk. With the IPI score, median OS is 17.3 years for the low risk; 6.3 for the intermediate risk, and 5.2 years for the high risk group (p=0.0004). With the FLIPI system, median OS is 15.5 years for the low risk, 8.3 years for the intermediate risk, and 5.2 for the poor risk group (p=0.0002). Prognostic scores were calculated also after dividing patients according to the time of diagnosis: in three periods (before 1987, between 1988 and 1997, and from 1998), as well as in two periods (before and after 1998). In all the periods studied survival of patients classified according to IPI and FLIPI categories was significantly different. CONCLUSION: This study shows in an independent series that the FLIPI score is a reproducible prognostic index of clinical utility for the initial assessment of patients with follicular lymphoma.
Non-invasive quantitative indices of atherosclerosis are promising new parameters for an improved prognostic stratification of patients with risk factors that aim at individualized risk factor assessment and modification. In a recently published ACC/AHA consensus document, further data on the diagnostic and prognostic value of coronary calcified plaque quantification were strongly encouraged prior to its use in the general population. In this present work we summarize data published since, which contribute significantly to the prognostic value of fast CT-based noninvasive coronary calcified plaque quantification. It is a measure of atherosclerostic disease activity and is hence an index for the likelihood of future cardiovascular events. Current data indicate that noninvasive quantification of coronary atherosclerosis has incremental prognostic value beyond conventional single risk factor assessment. However, it is not clear yet whether it has a significant value beyond quantitative combined risk assessment using complex risk prediction models such as Framingham charts. Results from ongoing prospective trials such as the MESA study in the US and the Heinz Nixdorf Recall study in Germany will clarify some of the pending issues. In addition, it is still unclear, at what stage of the disease process, which of the available imaging tools will provide optimal diagnostic and prognostic value for the individual patient.
BACKGROUND: The nervous system is increasingly recognized to play a critical role in tumor initiation and progression. Central to this complex relationship are the interactions between neurotransmitters secreted by neurons and their receptors (neurotransmitter receptors, NTRs) expressed on cancer cells, which activate multiple intracellular signaling pathways. However, the spectrum of NTR dysregulation and its association with biochemical recurrence (BCR) in prostate cancer (PCa) has not been explored. Therefore, the aim of this study was to fill this gap. METHODS: We systematically characterized the expression profiles of 130 NTR genes by integrating bulk and single-cell transcriptomic data. Consistently dysregulated NTR (cdNTR) genes were identified and used to construct a PCa signature (PCaSig) using elastic-net regression. The robustness of PCaSig was evaluated across three independent cohorts. In addition, the associations of PCaSig with clinicopathological characteristics, genomic alterations, tumor immune-related characteristics, and biological pathways were comprehensively investigated. RESULTS: Thirteen cdNTR genes with strong cell-type specificity, particularly in luminal epithelial cells, were identified. PCaSig robustly stratified patients into distinct BCR risk groups across multiple independent cohorts and remained an independent predictor after adjustment for clinicopathological factors. High PCaSig scores were associated with aggressive clinicopathological features, elevated tumor mutation burden (TMB), suppression of neurotransmitter-related signaling, and activation of cell-cycle and immune-related pathways. Notably, PCaSig refined prognostic stratification regardless of TMB status and was associated with distinct immune-related characteristics, including immune checkpoint expression and immune cell infiltration. Incorporation of PCaSig into a clinical nomogram significantly improved prognostic accuracy and clinical net benefit. CONCLUSIONS: These findings establish NTR dysregulation as a previously underappreciated dimension of PCa and support PCaSig as a clinically relevant tool for personalized management.
PURPOSE: We validate the prognostic value of a symptom based classification (S classification) in a multi-institutional study. MATERIALS AND METHODS: A total of 2,242 patients from 5 European centers were included in this study. Based on symptoms at diagnosis, patients were stratified into 3 groups of S1-asymptomatic tumors, S2-tumors with local symptoms and S3-tumors with systemic symptoms. Variables such as age, gender, tumor size, TNM stage, Fuhrman grade, Eastern Cooperative Oncology Group (ECOG) performance status, perinephric fat, renal vein and adrenal invasion were also considered for prognostic value. The end point of the study was cancer specific survival. Survival assessment was made with univariate and multivariate analyses using the Kaplan-Meier method and Cox regression analysis. RESULTS: Of the patients 1,018 (45.4%) were classified as S1, 865 (38.6%) S2 and 339 (16.0%) S3. The S classification correlated to tumor stage, grade and ECOG (p <0.001). On univariate analysis ECOG performance status, S classification, tumor size, TNM stage, Fuhrman grade, and adrenal, perinephric fat or vein invasion were significant prognostic factors (p <0.001). The S classification provided a significant prognostic stratification in the aggregate as well at each of the 5 centers. On multivariate analysis the S classification, TNM stage, Fuhrman grade, and perinephric fat and renal vein invasion remained independent prognostic factors (p <0.001). CONCLUSIONS: This study confirms that it is possible to graduate symptoms for a prognostic purpose. The proposed symptom score should be evaluated for its integration in prognostic algorithms.
The observed variability in the clinical course of follicular lymphoma (FL), along with the diverse range of therapeutic options available, necessitates accurate prognostic stratification of the individual patient. A number of clinical, laboratory, and pathologic parameters have been associated with both good and poor risk disease; in some instances these have been incorporated into readily calculable prognostic indices. With new insights into disease biology and the resulting identification of biomarkers that have arisen from the analysis of both the genome and the transcriptome, more accurate individualization of prognosis will be realized. At present the clinical application of such biomarkers, however, remains largely in its infancy. This review examines the clinical and molecular prognostic features that have been identified as of value in FL.
The sympathetic nervous system has great influence on cardiovascular physiology, and the importance of cardiac innervation abnormalities in the physiopathology of various cardiac diseases has been emphasized. Cardiac neurotransmission imaging with single-photon emission computed tomography (SPECT) allows in vivo assessment of the myocardial nervous system. At present, the most commonly used SPECT tracer to assess cardiac neurotransmission is metaiodobenzylguanidine labelled with iodine-123 ((123)I-MIBG). In patients with heart transplantation, ischemic heart disease, dysautonomias and drug-induced cardiotoxicity, assessment of neuronal function can help characterise the disease and improve the prognostic stratification. Cardiac (123)I-MIBG scintigraphy allows autonomic neuropathy to be detected in the early stages of diabetes mellitus. In patients with heart failure, the assessment of cardiac sympathetic activity has important prognostic implications. Future directions in cardiac sympathetic neurotransmission include the development of new tracers, targeting of second-messenger molecules and early assessment of cardiac neurotransmission in genetically predisposed subjects for prevention of heart failure.
INTRODUCTION AND OBJECTIVES: Cardiovascular disease is the main cause of death in patients with kidney failure. Moreover, the presence of impaired renal function is an important prognostic factor in patients with heart disease, and is a determinant of outcome during follow-up. The main aim was to investigate the relationship between kidney failure at admission and one-year mortality in patients with non-ST-elevation acute coronary syndrome. PATIENTS AND METHOD: We studied 1029 consecutive patients admitted to our institution. The serum creatinine level and glomerular filtration rate were determined at admission, and classical risk factors and biochemical markers were assessed. The primary endpoint was all-cause mortality at one year. RESULTS: Patients who died were older, more frequently had a history of diabetes or coronary artery disease, were more likely to have heart failure at admission, had higher troponin-I, myoglobin and creatinine levels, and were less likely to have dyslipidemia or to be a smoker. Multivariate analysis showed that the independent predictors of all-cause mortality at one year were age, diabetes, troponin-I level, Killip class > 1, male gender, creatinine level, and glomerular filtration rate. There was a linear correlation between increased risk and creatinine level. CONCLUSIONS: Creatinine level at admission is one of the most important covariates in early prognostic stratification in these patients. A high serum creatinine level (or a low glomerular filtration rate) increases the probability of death due to all causes. The serum creatinine level is, moreover, an inexpensive, easy-to-use, and widely available prognostic marker.
Cancer is one of the most common causes of death in dogs. The availability of multiple treatment modalities and novel therapeutic targets make the correct diagnosis, prognostic stratification, and the identification of treatment effect predictive factors an issue of major debate in cancer management. Selection of high and low risk patients and the type of systemic or local treatment is important in cancer management. The search for better prognostic markers and predictive factors is now focused on the molecular mechanisms which underlie tumour behaviour, such as altered cell cycle progression, proliferation, apoptosis, and angiogenesis. The ultimate goal is to identify reliable markers that can accurately diagnose and stage a tumour and predict tumour's clinical behaviour, prognosis and response to therapy. In this review, the current state of prognostication in canine tumours and promising new molecular markers are discussed. The markers are allocated to four groups according to their function: (i) proliferation markers, (ii) apoptosis, (iii) extracellular matrix and cell adhesion molecules, (iv) angiogenesis and (v) cell cycle regulators. Clinicopathological factors and histopathological grading remain the most practical parameters in decision-making. Although experimental research has shown that molecular markers have a good potential to be used as diagnostic, prognostic or predictive markers in canine tumours, insufficient evidence exists on their efficacy for routine use in veterinary oncology.
OBJECTIVES: We sought a better understanding of the coupling between right ventricular ejection fraction (RVEF) and pulmonary artery pressure (PAP), as it might improve the accuracy of the prognostic stratification of patients with heart failure. BACKGROUND: Despite the long-standing view that systolic function of the right ventricle (RV) is almost exclusively dependent on the afterload that this cardiac chamber must confront, recent studies claim that RV function is an independent prognostic factor in patients with chronic heart failure. METHODS: Right heart catheterization was performed in 377 consecutive patients with heart failure. RESULTS: During a median follow-up period of 17 +/- 9 months, 105 patients died and 35 underwent urgent heart transplantation. Pulmonary artery pressure and thermodilution-derived RVEF were inversely related (r = 0.66, p < 0.001). However, on Cox multivariate survival analysis, no interaction between such variables was found, and both turned out to be independent prognostic predictors (p < 0.001). It was found that RVEF was preserved in some patients with pulmonary hypertension, and that the prognosis of these patients was similar to that of the patients with normal PAP. In contrast, when PAP was normal, reduced RV function did not carry an additional risk. CONCLUSIONS: These observations emphasize the necessity of combining the right heart hemodynamic variables with a functional evaluation of the RV when trying to define the individual risk of patients with heart failure.
It is of primary importance for the clinical cardiologist to keep in mind the parameters allowing an adequate prognostic stratification in post-infarct patients in view of making the best diagnostic and therapeutic choices. A diagnostic strategy, based on a pathophysiologic approach, should evaluate four aspects: spontaneous and stress-induced ischemia, myocardial viability, and ventricular arrhythmias. Spontaneous ischemia has an undefined prognostic value, especially in the thrombolytic era; therefore it seems reasonable to perform invasive procedures in patients who are not stabilized by an adequate medical therapy or with large jeopardized areas. In asymptomatic patients, a provocative stress test allows a more articulated decisional iter. It is preferably to perform the test by the most physiological exercise EKG, together with the echocardiographic imaging, after the acute phase. It has a high negative predictive value, but a low positive predictive value. The detection of myocardial viability is frequently performed, mainly in patients with large post-ischemic myocardial dysfunction. Among all the proposed methods, the echo-dobutamine test mainly allows to estimate patients in whom revascularization may result in more benefit. The role of ventricular arrhythmias as an independent prognostic factor is debated and has to be always considered in relationship to other parameters, particularly left ventricular function. Regarding the therapeutic strategy, the indications from recent trials, related to antithrombotic drugs, beta-blockers, ACE-inhibitors, nitrates, Ca-blockers and antiarrhythmic drugs, are emphasized.
AIMS: The 6-min walk test has been incorporated into studies on the efficacy of new therapies and into prognostic stratification for chronic heart failure patients. Firm conclusions on the usefulness of the test in clinical practice are still lacking. The aim of this study was to investigate (1) the correlation between walk test performance and standard indices of cardiac function and exercise capacity, and (2) the prognostic value of the walk test with respect to peak VO2 and NYHA class. METHODS AND RESULTS: Three hundred and fifteen chronic heart failure patients (age: 53+/-9 years, NYHA class: II (182), III (133)) underwent a functional evaluation and a 6-min walk test. Of these, 270 were followed-up for a minimum of 6 months (mean 387+/-177 days). Walked distance was 396+/-92 m. There was no significant correlation between distance walked and central haemodynamic data. Functional capacity, as measured by ergometry, correlated moderately with distance walked (duration: r=0.48, peak VO2: r=0.59, anaerobic threshold: r=0.54; all P<0.001). During follow-up, 46 patients died from cardiovascular causes and 12 were urgently transplanted. Either of these events were considered end points of the study. Survival analysis was performed from a continuous walk test and peak VO2 measurements or after categorization of (a) quartile segmentation, (b) cut-off points from the literature and (c) thresholds from receiver operating characteristic curves. At univariate survival analysis (Cox regression), the association of the walk test with survival was of significance (P=0.03, continuous variable), or borderline significance (0.05< or =P< or =0.1, after categorization). Peak VO2 was always significant, independent of the scale used (0.005< or =P< or =0.03). The strongest association was found for NYHA class (P<0.001), which showed the highest sensitivity and specificity for the prediction of the event (0.64 and 0.65, respectively). When walk test performance, continuous or categorized, was entered into a multivariate model with NYHA class or peak VO2, it lost any significant association with survival (P>0.76 in all models with NYHA class and P>0.27 in all models with peak VO2). CONCLUSION: In moderate-to-severe chronic heart failure patients, the 6-min walk test is not related to cardiac function and only moderately related to exercise capacity. Walking performance does not provide prognostic information which can complement or substitute for that provided by peak VO2 or NYHA class. Hence the test is of limited usefulness as a decisional indicator in clinical practice.
Positron emission tomography (PET) has initially developed as a research tool, primarily for cardiological and neurological application. In the past decade, the paramount clinical potential of this imaging procedure has been recognized, reaching its full expression in the oncological field. The number of scientific publications demonstrating the clinical accuracy of the tracer [fluorine-18]-fluoro-2-deoxy-D-glucose ([18F]FDG) in the diagnosis, grading, staging, monitoring the response to treatment and in prognostic stratification of the oncological patient is continuously expanding. Nowadays, the clinical use of PET with [18F]FDG is approved in the majority of the countries (even in those with strict health regulations) for the metabolic imaging of proliferative diseases of the lung, breast, colon, and for the adequate diagnostic and prognostic evaluation of the patient with lymphoma and melanoma. Encouraging results have been also obtained in cancers of the head and neck, ovary and musculoskeletal system. Although about 90% of clinical investigations in oncology are performed using [18F]FDG as the tracer, radiopharmaceutical research is continuously developing new and more specific tumor targeting agents, whose efficacy is being explored more and more in the wide scale.
Frank cachexia is usually evident in the clinical evaluation, but important metabolic alterations in tumour-bearing patients with slight weight changes are frequently overlooked. Since several factors are involved in cancer-induced malnutrition (marasmus type descriptive of general inadequate food intake, kwashiorkor type descriptive of inadequate protein intake/increased turnover), medical/dietary history and physical examination (dynamic weight loss, vitamin/mineral deficiency) should be complemented by simple additional laboratory tests. Minimal baseline testing may include: weight loss (> 5%/month = severe) and serum albumin (< 24 g/l = severe). Anthropometric measurements (triceps skin fold, midarm muscle circumference) for the assessment of fat deposits and lean body mass are rarely used in a routine clinical setting owing to great variations among individuals and interobserver measurement variability. The Prognostic Nutritional Index (PNI), including serum parameters, immune competence testing and anthropometrics (but no further dietary parameters, i.e. dynamic weight loss), has proved to be quite a reliable method of predicting postoperative morbidity/mortality and of selecting cancer patients for aggressive preoperative nutritional interventions. For clinical studies including the evaluation of nutritional status (stratification, prognostic impact) and/or outcome (nutritional interventions), a simple standardized and validated assessment protocol including dietary history, specific physical examination and widely available laboratory testing should be implemented to document significant nutritional alterations. Body weight alone will often fail to demonstrate important disease- or therapy-related changes in caloric intake or metabolic rate.
BACKGROUND: Numerous investigations have examined prognostic factors for patients with primary cutaneous melanoma. However, only a few studies have been published on the definition of prognostic groups. The first aim of the present study was to determine the relative importance of different prognostic factors in a large collective study. The second aim was to define prognostic groups of patients based on combinations of prognostic factors and to define a model that allows the estimation of individual survival probability. METHODS: Long term follow-up of 5264 patients with invasive primary cutaneous melanoma was performed from 1970 to 1988 at four German University Departments of Dermatology (Berlin-Steglitz, Münster-Hornheide, Tübingen, and Würzburg). The multivariate Cox model was used to analyze 5093 patients, and 4371 patients with complete information were included in a classification and regression tree analysis (CART). RESULTS: Tumor thickness, sex, anatomic location, and level of invasion were highly significant prognostic factors according to the multivariate analysis (P < 0.0001). However, histologic subtype and age influenced prognosis less significantly (P < 0.05). The CART analysis resulted in 12 groups defined mainly by tumor thickness, sex, and anatomic location, which were combined into five prognostic groups. The prognostic stratification defined by the five groups was superior compared with the standard TNM model. Ten-year survival rates of the five groups ranged from 97% to 14% (P < 0.0001), and an equation was used to calculate individual survival probabilities based on the significant factors of the Cox model. CONCLUSIONS: Consideration of all significant prognostic factors of patients with primary cutaneous melanoma investigated in the present study allows for the definition of prognostic groups with a more reliable estimation of prognosis than by previous staging systems and also enables calculation of individual survival probabilities.
In early rheumatoid arthritis (RA), the objectives of therapeutic strategies are to obtain remission and prevent joint destruction as early as possible. These goals may be reached with conventional disease-modifying antirheumatic drugs (DMARDs) or with biological agents. In clinical practice, initial treatments are usually chosen according to the degree of disease activity at baseline, and adapted according to a step-up strategy. A more elegant therapeutic approach would be to choose the most appropriate treatment based on the prognosis of RA. Therefore, prognostic stratification could improve the relative roles and benefits of initial DMARD or biological therapy for early RA. For RA with a severe prognosis, a combination of DMARDs or biologicals could be initiated as the first-line therapy. However, we need to know how to predict outcome in early RA for this type of strategy. This review attempts to answer this question by reporting the most reliable prognostic factors and some predictive models proposed for classification into benign, mild and severe RA.
The challenge of medical practice today is to identify individuals who are at risk of developing disease, determine the severity of the disease and distinguish the responders from the nonresponders to therapy (individualized medicine). Advances in molecular genetics and biology have shifted the paradigm for identification of markers from large-scale epidemiologic studies to studies on genomic- and proteomic-based techniques. Consequently, a large number of biologic markers, referred to as biomarkers, are being identified and validated to serve for risk stratification, prognostication and individualization of therapy. Identification of biomarkers for cardiovascular diseases could also provide insight into the pathogenesis of the phenotype, which is fundamental for the development of specific therapies. The list of biomarkers for cardiovascular disease is expanding rapidly. Nonetheless, the field is in the early stages of evolution and large-scale clinical studies are required to validate the utility of newly identified biomarkers in diagnosis, risk stratification and treatment of cardiovascular diseases. Selected biomarkers for coronary atherosclerosis, acute coronary syndromes and heart failure are discussed in this review.
BACKGROUND: A potential limitation to the clinical utilization of dobutamine stress echocardiography is the higher incidence of side effects in respect to other noninvasive tests for the diagnosis of coronary artery disease reported by some authors. Due to the increased utilization of this test for the evaluation of chest pain and for prognostic stratification in patients with a recent myocardial infarction, we analyzed the results of 373 consecutive tests to evaluate the incidence and clinical significance of side effects induced by dobutamine. METHODS: Dobutamine stress echocardiography was performed in 256 patients (69%) for the evaluation of chest pain; 85 out of 256 (33%) suffered from a previous myocardial infarction. 117 patients (31%) were studied in the early phase after an acute myocardial infarction for prognostic purposes. Dobutamine was infused starting with the dose of 5 gamma/kg/min over 3 minutes with incremental steps of 10-20-30-40 gamma/kg/min over 3 minutes under 2D-echocardiographic and 12-lead electrocardiographic monitoring. RESULTS: In 95% of cases the test was stopped at the achievement of a target end point: wall motion abnormalities (60%), significant ECG changes (5%), 85% of the age-predicted maximal heart rate (13%), maximal dose (17%); only in 5% of cases a limiting side effect requiring a premature interruption of the test occurred: hypertension (systolic blood pressure over 240 mm Hg and/or diastolic over 120 mm Hg) (2%); symptomatic hypotension (0.5%); severe chest pain (1%); nausea (0.5%); cardiac arrhythmias (1%). Cardiac arrhythmias were the most frequently registered non limiting side effect. During the test 79 episodes of supraventricular arrhythmias and 211 episodes of ventricular arrhythmias occurred. Supraventricular arrhythmias consisted usually of benign sporadic premature beats; only 3 cases of self-limiting supraventricular tachycardia or atrial fibrillation were recorded. Sporadic ventricular premature beats were the most frequently recorded arrhythmias; 10 patients developed a ventricular tachycardia; however in no case this arrhythmia was sustained, associated with subjective symptoms and required the administration of a specific antiarrhythmic drug or the premature interruption of the test. Patients were divided according to the absence (Group 1, G1, n = 193, 52%) or the presence (Group 2, G2, n = 180, 48%) of cardiac arrhythmias during the test. Patients of G2 differed from patients of G1 only in respect of the maximal dose of dobutamine infused (33.5 vs 28.6 gamma/kg/min, p < 0.0005) and the incidence of a wall motion abnormality in the basal echocardiogram (66% vs 53%, p < .01). The second most recorded non limiting side effect (71/373 pts) (19%) was the occurrence of systolic hypotension, a drop of systolic blood pressure > or = 20 mm Hg in respect of the antecedent infusion step. In all cases no symptoms developed and the great majority of patients with this finding had a normal echocardiographic response to dobutamine at the time of his occurrence. CONCLUSIONS: Dobutamine echo stress test is limited by the occurrence of significant side effects only in a minority of patients (5%); however in all cases, including complex ventricular arrhythmias, these side effects were self limiting and promptly recovered after interruption of the drug infusion. Non limiting side effects, in particular cardiac arrhythmias and systolic hypotension, are usually well tolerated and not associated with the occurrence of myocardial ischemia or left ventricular disfunction; thus, dobutamine echo stress test may be considered a safe test for the evaluation of the presence and severity of coronary artery disease both in patients with a previous or recent myocardial infarction and in patients without myocardial infarction.