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Results for “prognostic stratification”

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At least 307 records · Page 17Linked to original sources

PubMed2026

Pathomics-based machine learning models for predicting METTL5 expression and prognosis in lung adenocarcinoma.

BACKGROUND: METTL5, an N6-methyladenosine (m6A) RNA methyltransferase, has been implicated in tumor progression, but its prognostic value and non-invasive prediction in lung adenocarcinoma (LUAD) remain unclear. This study aimed to develop a pathomics-based machine learning model to predict METTL5 expression from histopathological images and evaluate its prognostic significance in LUAD. METHODS: A total of 327 LUAD patients from The Cancer Genome Atlas (TCGA) with matched hematoxylin and eosin (H&E) slides, transcriptomic, and clinical data were included and randomly divided into training and validation sets (7:3). Quantitative histopathological features were extracted using PyRadiomics. Feature selection was performed via maximum relevance minimum redundancy (mRMR) and recursive feature elimination (RFE), followed by construction of a Gradient Boosting Machine (GBM) model. A pathomics score (PS) was generated to assess prognostic relevance. Survival analyses, gene set variation analysis (GSVA), tumor mutational burden (TMB), immune infiltration analysis, and in vitro functional assays were conducted. RESULTS: METTL5 overexpression was independently associated with poor overall survival [hazard ratio (HR) =1.637, P=0.007]. The model achieved good predictive performance [area under the curve (AUC) =0.847 in the training set and 0.752 in the validation set]. High PS was significantly associated with worse survival and remained an independent prognostic factor (HR =1.563, P=0.03). Elevated PS correlated with altered metabolic pathways, increased TMB, and immune microenvironment changes. METTL5 knockdown reduced proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in A549 cells. CONCLUSIONS: The pathomics-based model accurately predicts METTL5 expression and provides prognostic stratification in LUAD, supporting its potential as a practical imaging-derived biomarker.

Methyltransferase-like 5↗

PubMed2026

Methylation-Associated Differentiation Features Define Biological and Prognostic Heterogeneity in CMS4 Colorectal Cancer.

Consensus molecular subtype 4 (CMS4) colorectal cancer (CRC) is associated with an aggressive clinical course and poor survival, yet the biological basis of heterogeneity within this subtype remains incompletely understood. DNA methylation is an epigenetic mechanism involved in transcriptional regulation, cellular differentiation, and colorectal tumorigenesis. Here, we integrated single-cell RNA sequencing (scRNA-seq), bulk data, and promoter DNA methylation data to characterize CMS4-associated cancer cell states and methylation-related features. Using the scAB algorithm, we integrated scRNA-seq with bulk CMS4 data and identified CMS4-related cells distributed across multiple patients. Single-cell analyses of cell-cell communication and transcriptional regulation revealed a CMS4-related cancer cell population characterized by macrophage migration inhibitory factor (MIF)-centered intercellular communication, enhanced caudal type homeobox 1 (CDX1) and Kruppel-like factor 5 (KLF5) regulon activity, and gene modules enriched in differentiation-related pathways. CytoTRACE analysis further stratified CMS4 cancer cells into poorly and well-differentiated states, yielding 802 differentially expressed genes (DEGs). Linking these differentiation-associated DEGs with bulk expression and promoter methylation data identified 218 methylation-associated DEGs showing significant inverse methylation expression correlations, suggesting a link between differentiation-related heterogeneity and promoter methylation. Univariable Cox regression followed by LASSO regression further prioritized eight genes for construction of the methylation and differentiation-related prognostic model (MeDiff-PM). MeDiff-PM consistently stratified overall survival in the TCGA CMS4 cohort and two independent validation cohorts, with cutoff-independent continuous Cox analyses further supporting its prognostic association across cohorts. And MeDiff-PM remained prognostically significant after adjustment for available clinical variables. High MeDiff-PM risk scores were associated with activation of P53, WNT, and ubiquitin-mediated proteolysis pathways and with consistent predicted drug response differences for compounds across three CMS4 cohorts. While individual in silico knockout analysis suggested links between MeDiff-PM genes and metallothionein-related and immune-associated transcriptional responses. Collectively, these findings indicate that methylation-associated differentiation features represent a molecular dimension of intra-CMS4 heterogeneity and provide a biologically informed framework for prognostic stratification within CMS4 CRC.

Humans↗

PubMed1998

[Prevalence of simple sporadic goiter in relation to other non-neoplastic thyroid pathologies in an internal medicine department].

BACKGROUND AND AIM: Thyroid pathologies, in particular goiter, are commonly found in everyday clinical practice in hospitalised patients. METHODS: The authors carried out a prospective type survey lasting 80 months in a mountain community with about 30,000 inhabitants with uniform socio-demographical characteristics. A total of 8,034 subjects (4,131 males and 3,903 females) were included in the study who were hospitalised in an Internal Medicine Department. All patients underwent screening using standard diagnostic criteria. RESULTS: Thyroid pathology was identified and classified into its various forms. There was a net prevalence of goiter which, owing to the unique features identified by the study, was defined as the sporadic form. The study demonstrated a marked prevalence in females, the familial pattern, the homogeneity of distribution throughout the area, the progression of disease with age and its evolution into immersed forms, the prevalence in both sexes in adults, the frequent use of surgery and its inherent problems, the inadequacy of treatment. CONCLUSIONS: The authors affirm that this pathology is regularly underestimated because it is not adequately identified, treated and monitored. They suggest a clinical and methodological approach based on a correct nosological definition, adequate diagnostic and prognostic stratification, an appropriate therapeutic protocol and clinical controls performed over time.

Adult↗

PubMed2000

[Endothelins and chronic cardiac insufficiency].

Endothelins (ET) comprise a group of substances which are produced and have regulatory functions in different systems of the organism. The main cardiovascular ET is ET-1 which is so far the most potent vasoconstrictor substance. In the pathophysiology of cardiac insufficiency ET-1 promotes cardiac hypertrophy, is involved in vasoconstriction, delayed relaxation and reduced left ventricular contractility. The ET-1 level correlates with pulmonary vascular hypertension. By vasoconstriction of renal arteries ET leads to volume retention. Big-ET is a very efficient neurohumoral marker in the diagnosis of developed cardiac failure which can lead to more accurate prognostic stratification. ET-1 is probably important for assessment of the diagnosis of cardiac insufficiency only in severe cardiac failure. The favourable effect of ET block in cardiac insufficiency was proved for the non-selective ETA/ETB blocker and selective ETA blocker. The selective ETB blocker has an adverse haemodynamic effect in treatment of heart failure but by suppression of aldosterone it can prevent fluid retention. In the treatment of cardiac failure blockers of endothelin converting enzyme seem perspective as they reduce adversely activated neurohumoral factors.

Endothelins↗

PubMed2000

Electrophysiological instability in the acute phase: prognostic significance of early ventricular fibrillation in acute myocardial infarction.

BACKGROUND: In the prognostic stratification of patients affected by AMI is important to evaluate, besides the assessment of left ventricular function and residual ischemia, the presence of electrophysiological instability. METHODS: We have analysed 15 patients all affected by AMI complicated by early ventricular fibrillation. During the hospital phase we evaluated the E.F.% (ECHO) and the presence of late ventricular potentials (SAECG). After hospital discharge we followed up the patients for 6 months. RESULTS: None of the patients died during the hospital phase while the posthospital cardiac mortality was 20%. The three patients dead during the follow-up had an AMI localized in the anterolateral wall of the left ventricle, an E.F.% less than 40% and LVP positive in the hospital phase. Besides the clinical course was complicated by cardiac failure. CONCLUSIONS: We conclude that these three patients are a "high risk profile subgroup" and should be submitted to extensive evaluation with cardiac catheterization, coronary arteriography and programmed ventricular stimulation.

Adult↗

PubMed2000

[Non-invasive evaluation of the hemodynamic profile in patients with heart failure: estimation of pulmonary arterial pressure].

Continuous-wave Doppler echocardiography is an accurate method for the non-invasive estimation of pulmonary artery pressure because the pressure gradient across a regurgitant valve can be estimated accurately by measuring the high flow velocity of the regurgitant jet and by applying the simplified Bernoulli equation. Measurable tricuspid and/or pulmonary regurgitation can be observed in a great percentage of patients with heart failure (approximately 90% of patients if the examination is performed by an experienced sonographer) and the method has a wide clinical applicability. Recently, new attention has been focused on the possibility of evaluating the right ventricular function by echocardiography. Although the measurement of the volumes of this cardiac chamber is undoubtedly difficult with ultrasound (as it is with most imaging techniques), it must be recognized that echocardiography allows for the measurement of simple M-mode and two-dimensional parameters which are extremely useful in the prognostic stratification of patients with congestive heart failure.

Blood Flow Velocity↗

PubMedDate not supplied

Independent prognostic importance of microvessel density in clinically localized prostate cancer.

BACKGROUND: Previous studies have reported a possible prognostic importance of microvessel density (MVD) in prostate cancer, although the significance after radical prostatectomy is not clear. The purpose of this study was to assess the prognostic value of MVD in clinically localized prostatic adenocarcinomas, focusing on moderately-differentiated tumours. MATERIALS AND METHODS: We examined a series of 104 patients treated for presumed organ-confined cancer in the period 1988-94. The area of highest tumour grade was selected from the prostatectomy specimens and vessels were high-lighted by staining for factor-VIII-related antigen. MVD was quantitated in the "hot spot" area and related to biochemical failure and clinical recurrence. RESULTS: In moderately differentiated tumours (WHO grade) (n = 66), MVD was associated with preoperative s-PSA and positive surgical margins. In univariate 5-year analysis, microvessel density (MVDmean > 122 mm-2, median) (p = 0.0074), s-PSA, tumour dimension, capsular penetration, seminal vesicle invasion and positive surgical margins were all significant predictors of biochemical failure, while MVDmean (p = 0.0084) was the only statistically significant predictor of clinical recurrence. In multivariate Cox' analysis, MVDmean (p = 0.0003), capsular penetration and tumour dimension remained as independent predictors of biochemical failure. CONCLUSION: Assessment of MVD in moderately differentiated prostatic adenocarcinomas may improve the prognostic stratification of patients after radical prostatectomy.

Adenocarcinoma↗

PubMedDate not supplied

Immunohistochemical expression of T, Tn and sialyl-Tn antigens and clinical outcome in human breast carcinoma.

BACKGROUND: The extent of expression of reactive T (Thomsen-Friedenreich), Tn and sialyl-Tn antigens has been assumed to predict carcinoma aggressiveness. We studied the expression of T, Tn and sialyl-Tn antigens in a relatively large cohort of breast carcinoma patients with known long-term outcome to assess the clinical and biological significance of these antigens. MATERIALS AND METHODS: T, Tn and sjalyl-Tn antigens were examined in 72 consecutive primary breast carcinomas by immunohistochemistry using well defined monoclonal antibodies and their semiquantitative values were correlated with established clinicopathologic prognostic parameters of the disease to determine their relationship with long-term clinical outcome. RESULTS: Of the 72 carcinomas, 63 (87.5%) each expressed T or Tn antigens, while 16 (22%) expressed sialyl-Tn antigens. Most carcinomas (81%) expressed more than one of the antigens simultaneously, being the most frequent combination T/Tn antigen expression. No significant correlation was noted between the expression of T, Tn and sialyl-Tn antigens (whether individually or in combination) and the prognostic parameters including patient age, disease stage, tumor size, lymph node status, nuclear and histologic grades, histologic types, hormone receptor status and menopausal status. Univariate survival analyses showed that disease stage, tumour size and lymph node metastasis were significant predictors of overall survival. Interestingly, a significant inverse correlation was found between the Tn antigen expression (p = 0.04), as well as the combined T/Tn (p = 0.03) and Tn/sialyl-Tn (p = 0.02) antigen expressions and long-term overall survival. In a multivariate Cox proportional hazard model, disease stage and a negative or low Tn antigen expression emerged as significant predictors of overall survival. CONCLUSION: Our data suggested that the expression of T, Tn and sialyl-Tn antigens does not appear to predict the outcome of patients with breast carcinoma in a long-term run. Moreover, the findings signified a potential value for a negative or low Tn antigen expression in prognostic stratification of breast carcinomas.

Adult↗

PubMed2001

Cardiac neurotransmission imaging.

Cardiac neurotransmission imaging with SPECT and PET allows in vivo assessment of presynaptic reuptake and neurotransmitter storage as well as of regional distribution and activity of postsynaptic receptors. In this way, the biochemical processes that occur during neurotransmission can be investigated in vivo at a micromolar level using radiolabeled neurotransmitters and receptor ligands. SPECT and PET of cardiac neurotransmission characterize myocardial neuronal function in primary cardioneuropathies, in which the heart has no significant structural abnormality, and in secondary cardioneuropathies caused by the metabolic and functional changes that take place in different diseases of the heart. In patients with heart failure, the assessment of sympathetic activity has important prognostic implications and will result in better therapy and outcome. In diabetic patients, scintigraphic techniques allow the detection of autonomic neuropathy in early stages of the disease. In conditions with a risk of sudden death, such as idiopathic ventricular tachycardia and arrhythmogenic right ventricular cardiomyopathy, PET and SPECT reveal altered neuronal function when no other structural abnormality is seen. In patients with ischemic heart disease, heart transplantation, drug-induced cardiotoxicity, and dysautonomias, assessment of neuronal function can help characterize the disease and improve prognostic stratification. Future directions include the development of tracers for new types of receptors, the targeting of second messenger molecules, and the early assessment of cardiac neurotransmission in genetically predisposed subjects for prevention and early treatment of heart failure.

Cardiomyopathies↗

PubMed2001

[Exercise test after acute myocardial infarction: on medical therapy?].

Given the great relevance of beta-blockers after myocardial infarction, we focused our attention on this therapy, considering also the difficulty of its management: it takes a long time to up titrate as well as to wash out. Other anti-ischemic therapies, i.e. nitroderivatives and calcium-antagonists, are easier to manage and there is less need of precise schedules. Our belief is that predischarge exercise testing should be performed on beta-blocker therapy, since we deem unadvisable to interrupt this treatment in the early phase of the postinfarction clinical course, and the reasons are detailed in the text. After myocardial infarction, beta-blockers may reduce the sensitivity of predischarge exercise testing for the diagnosis of inducible ischemia; however, their interference does not seem to affect negatively the prognostic stratification of the test, also in the "thrombolytic era". This may be true since beta-blockers hide, but also cure, those forms of inducible ischemia of lower clinical importance, and only inducible ischemia occurring in spite of such therapy might be dangerous and should be treated with myocardial revascularization. Patients receiving thrombolytic treatment are a selected minority at lower clinical risk; it is necessary to emphasize that predischarge exercise testing is more frequently positive in these patients, probably because of the presence of residual stenosis of the infarct-related vessel that may often have a trivial relevance. The test has a lower negative predictive value in these patients, mainly for the higher incidence of reinfarction and ischemic events related to plaque instability, events that none of the provocative tests can predict accurately.

Adrenergic beta-Antagonists↗

PubMed2001

Prognosis in patients with heart failure and preserved left ventricular systolic function.

BACKGROUND: It is recognized that heart failure patients with preserved left ventricular systolic function have better prognosis; nevertheless, there are some studies with conflicting results. Also, there is a paucity of data concerning the prognostic factors in this group of patients. OBJECTIVES: To determine possible variables with prognostic relevance in heart failure patients with preserved left ventricular systolic function (ejection fraction > 40%). METHODS: 157 consecutive ambulatory patients with heart failure were assessed; those patients with ejection fraction > 40% were included in the study (n = 46). All patients were evaluated by clinical interview and physical examination, ECG, echocardiogram (M-mode, 2D and pulsed Doppler of mitral flow), biochemical study and determination of type B natriuretic peptide (BNP). The patients were grouped according to the rhythm presented on ECG: Group I--patients with atrial fibrillation; Group II--patients in sinus rhythm Group II was further subdivided in two groups according to the presence or absence of restrictive left ventricular filling pattern. All patients had a clinical follow-up, with recording of events (death or hospitalization from cardiac cause). The mean follow-up time was 682.2 +/- 55 days. RESULTS: The mean age of the patients was 70.4 +/- 1.2 years; 54.3% were women; mean ejection fraction was 49.6 +/- 1%; mean BNP levels were 202.9 +/- 41.3 pg/ml. Mortality was 19.6% and the combined event death or hospitalization from cardiac cause) occurred in 26.1% of the patients. Among the clinical, demographic, biochemical, echocardiographic and neurohumoral parameters, only BNP levels had prognostic significance in the whole population. In Group II patients, BNP levels, heart rate and restrictive left ventricular filling pattern were identified as having prognostic significance. Kaplan-Meyer curve analysis showed that both BNP and restrictive left ventricular filling pattern seemed to be important prognostic markers. CONCLUSIONS: This preliminary study suggests thar neurohumoral activity (determined by plasma BNP levels) and a restrictive ventricular filling pattern may be important factors in prognostic stratification of heart failure patients with preserved left ventricular systolic function.

Aged↗

PubMedDate not supplied

[The role of exercise testing in evaluation of functional capacity at patients with ischemic ventricular dysfunction].

UNLABELLED: The assessment of functional capacity represents an important parameter in the prognostic stratification of patients with heart failure. The objective of the paper is the testing of exercise capacity at patients with ischemic ventricular dysfunction. METHODS: There have been selected 80 patients with coronary heart disease (old myocardial infarction, angina pectoris, ischemic cardiomiopathy) admitted in the Department of Internal Medicine, Rehabilitation Hospital, Iasi, during 1.01.1998-31.12.1999. They were divided into two groups: group A (46 patients) with proper ventricular function and ejection fraction (EF) above 50% and group B (34 patients) with EF under 50%. They underwent exercise testing at the ergometric bicycle. RESULTS: Patients of group B had higher values of resting heart rate (74 +/- 9 vs 70 +/- 11, p = 0.04). There were registered similar levels at the maximal exercise at both groups (time-tension index, watt, MET). The evolution of the group with ventricular dysfunction is distinguished by a lower length of time of exercise (8.6 +/- 4.4 vs 9.8 +/- 5.2 min, p = 0.05) and by a significantly greater value of the ST depression (1.6 +/- 1.4 vs 0.9 +/- 1.1 mm, p = 0.01). DISCUSSION AND CONCLUSIONS: The higher resting heart rate at patients with heart failure suggests the activation of neuroumoral mechanisms, especially the adrenergic activation. These patients reach maximal levels similar to those with good systolic function but in a shorter length of time, due to a physical deconditioning or to the same neuroumoral mechanisms. Ischemia is higher at these patients.

Adult↗

PubMed1992

Target organ status and cardiovascular risk in borderline hypertension.

In order to assess the prevalence of target organ damage 78 men with borderline hypertension, according to the World Health Organization criteria, and 67 normotensive controls underwent echocardiographic, electrocardiographic and fundoscopic examination, followed by ambulatory blood pressure monitoring for 24 hours. Echocardiographic left ventricular hypertrophy was found in 13 borderline hypertensive subjects (16.6%), while no electrocardiographic or fundoscopic abnormalities could be detected. Our data suggest that noninvasive assessment of cardiovascular status, including echocardiography, allows recognition of a subset of borderline subjects with an increased risk for subsequent cardiac morbid events, thereby improving prognostic stratification.

Adult↗

PubMed1992

Expanding applications of the 12-lead ECG in suspected acute infarction.

In the setting of acute myocardial infarction, the importance of the 12-lead electrocardiogram has increased tremendously. In addition to facilitating diagnosis of acute ischemic syndromes, including acute myocardial infarction, the 12-lead electrocardiogram may provide invaluable assistance in determining which patients are most suitable for thrombolytic therapy, and it may provide information that is useful in prognostic stratification.

Acute Disease↗

PubMed2003

[Consensus document. Type B natriuretic peptide in the Italian cardiology clinical reality: update of the experience].

The research on natriuretic peptides in cardiology has now reached the clinical setting in cardiology. The scientific literature on the brain natriuretic peptide (BNP) or on its N-terminal peptide (NT-proBNP) in heart failure is steadily growing, but Italian groups are under-represented in this context, even if there are some published or ongoing studies. This document summarizes the experience, mostly ongoing and unpublished, of 12 Italian groups in that field, as presented in a recent national meeting, suggests recommendations about the collection of blood samples and analytical procedures for BNP assay, and presents a brief consensus on the use of BNP in heart failure, for different areas: a) population screening, b) differential diagnosis of heart failure in case of dyspnea in general practice and c) in the emergency room, d) prognostic stratification in patients with diagnosed heart failure, and e) hormone-guided treatment of heart failure.

Heart Failure↗

PubMed2004

[Stress imaging in coronary artery disease: state of the art].

To date, several diagnostic tools allow an accurate non-invasive evaluation of coronary artery disease; this is due to the great progress in echocardiographic and nuclear imaging techniques in the last 10 years. The large availability of different stress imaging techniques allows to choose the most appropriate technique for each patient according to the clinical characteristics. This paper presents the state of the art of echocardiographic and nuclear stress imaging for the diagnosis of coronary artery disease and for the prognostic stratification of infarcted patients. Advantages and limits of the different techniques are described rather than putting in competition echo and nuclear cardiology as has often been done in the past. Cardiologists should select among the various techniques on the basis of clinical characteristics of single patients, center's experience and an objective evaluation of economical aspects.

Coronary Disease↗

PubMed2004

[Doppler echocardiography for the assessment of left ventricular diastolic function: methodology, clinical and prognostic value].

To date, left ventricular diastolic function can be clinically assessed by Doppler echocardiography. The Doppler recording of mitral inflow and pulmonary venous flow provides main information about ventricular diastolic properties. At the level of the mitral inflow we can measure the early diastolic peak velocity (E), atrial peak velocity and derive their ratio, the E velocity deceleration time and isovolumic relaxation time, and calculate atrial filling fraction. At the level of the pulmonary veins, the peak systolic velocity (S), the peak diastolic velocity (D), the S/D ratio, the peak of reverse atrial velocity and its duration, above all in terms of difference with the mitral A duration, characterize the different patterns of diastolic function. Also the new ultrasound technologies are clinically useful to define ventricular diastolic properties. The myocardial early diastolic velocity (Em) detectable by pulsed tissue Doppler at the level of the mitral annulus, and the flow propagation velocity (Vp) recordable by color M-mode of left ventricular inflow, both relatively preload-independent, are measurements related to tau, the reference hemodynamic variable. The E/Em and E/Vp ratios provide accurate estimation of the changes in left ventricular end-diastolic pressure. They allow us to distinguish the pseudonormal and restrictive patterns from the normal pattern and are, therefore, alternative tools to Valsalva maneuver of mitral inflow and pulmonary venous flow. The predictive value of the pattern of abnormal relaxation (grade I of diastolic dysfunction) and both the reversible and irreversible restrictive patterns (grade III and IV respectively) is now demonstrated and permits important prognostic stratification and appropriate therapeutic management.

Diastole↗

PubMed2004

[Inflammation in acute coronary syndromes: mechanisms and clinical implications].

Inflammation plays a pivotal role in the pathogenesis of atherosclerosis and its complications. In particular, atherosclerosis is an active process and the inflammatory component appears to be particularly correlated with the development of acute coronary syndromes (ACS). Accumulating data demonstrate that in ACS, elevated levels of circulating inflammatory markers, such as C-reactive protein, predict an unfavorable cardiovascular outcome. A better knowledge of the molecular and cellular mechanisms of inflammation might not only further improve prognostic stratification but also allow us to identify novel therapeutic targets. The present review summarizes the mechanisms of the inflammatory response in ACS, its clinical implications, and the potential treatment strategies to contrast this phenomenon.

Acute Disease↗