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At least 973 records · Page 54Linked to original sources
PubMed2026

Immune-Like Malignant Epithelial Programs Shape Tumor-Immune Interactions and Inform Prognostic Stratification in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is characterized by marked cellular heterogeneity, yet how malignant epithelial states contribute to immune regulation and clinical outcomes remains incompletely defined. We integrated single-cell RNA-sequencing data to map the cellular landscape of LUAD and identify malignant epithelial cells based on inferred copy-number alterations. Epithelial states were further examined through trajectory inference, transcription factor analysis, and cell-cell communication profiling. Single-cell-derived genes were subsequently integrated with TCGA and independent GEO cohorts to construct and validate a machine learning-based prognostic signature. Malignant epithelial cells displayed distinct functional programs, including an immune-like state associated with genomic instability, immune-related transcriptional activity, tumor-immune communication, and patient outcomes. The resulting immune-like malignant epithelial cell signature (IMEC-Sig) consistently stratified survival across multiple cohorts. Low IMEC-Sig scores were accompanied by greater immune infiltration, higher immune checkpoint expression, and increased immunophenoscore, whereas high scores were linked to a comparatively immunosuppressive phenotype. Pan-cancer analyses further identified KRT8 as a gene associated with unfavorable prognosis, and functional experiments showed that KRT8 silencing suppressed proliferation, migration, invasion, and colony formation in LUAD cells. Together, these findings connect malignant epithelial heterogeneity with the immune context and clinical outcomes, support IMEC-Sig as a biologically informed prognostic tool, and nominate KRT8 as a potential therapeutic target in LUAD.

Humans↗
PubMed2004

Stratification of the flexor retinaculum and the course and distribution of the ulnar, median, and palmar digital nerves: an anatomical study.

A gross anatomic study of 169 hands from 94 human adult cadavers was carried out to define the morphology of the flexor retinaculum and the relationship of the flexor retinaculum to the course of the median and ulnar nerves and branching of the palmar digital nerves. The following results were obtained. Three parts of the flexor retinaculum were arranged like overlapping tiles on a roof, and in all cases, the median nerve passed deep to the flexor retinaculum, whereas the ulnar nerve passed through various parts of the flexor retinaculum in 19% of cases irrespective of its proximal form and branching of the palmar digital nerves.

Adult↗
PubMed1995

Prevalence, characteristics, and risk stratification of electrocardiographic and symptomatic silence of myocardial ischemia despite scintigraphically evidenced ischemia in symptomatic patients presenting with severe coronary artery stenosis.

Symptoms of angina pectoris and transient ST-segment depression are most commonly used to evidence acute myocardial ischemia during exercise testing. However, the diagnostic accuracy of either or both criteria in relation to clinical characteristics and the patient's exercise response has been a subject of controversy. The prevalence and severity of symptoms of angina pectoris and/or ST-segment depression were studied prospectively in 147 consecutive patients with a history of daily angina pectoris, scintigraphic evidence of exercise-induced myocardial ischemia, and coronary artery stenosis > 75%. Logistic regression analysis was applied to determine absence of any or both criteria by the clinical characteristics or exercise response of the patient. During exercise testing, ST-segment response failed to prove scintigraphically evidenced myocardial ischemia in 14/147 patients (10%) and 35/147 patients (24%) when ST-segment depression > or = 0.1 in either > or = 1 or > or = 2 ECG leads was chosen. Symptoms of angina pectoris were found to be absent in 69/147 patients (47%). Only 58 patients (40%) suffered from angina and met the ECG criterion at the time of scintigraphic myocardial ischemia. Absence of ST-segment depression was best predicted by clinical variables such as large myocardial infarction (increase: 2.6 times, p = 0.007), number of stenoses < or = 2 (2.0 times, p = 0.023), and presence of diabetes mellitus (4.3 times, p = 0.035). Painless myocardial ischemia was determined by blood response to exercising. Thus, a double product > 23 increased the risk of painless myocardial ischemia by 1.5 times (p = 0.017).(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1998

Relative value of clinical and transesophageal echocardiographic variables for risk stratification in patients with infective endocarditis.

BACKGROUND: Infective endocarditis remains a life-threatening disease, and its optimal management is of paramount importance. Transesophageal echocardiography (TEE) is useful for the diagnosis of endocarditis-induced lesions, but the prognostic significance of the method remains controversial. HYPOTHESIS: The purpose of this study was to relate clinical and TEE characteristics to the occurrence of mortality and/or systemic embolization in a consecutive series of 45 patients with a diagnosis of infective endocarditis. METHODS: All patients underwent at least one monoplane TEE. Clinical data, episodes of embolization, and echocardiographic characteristics were prospectively recorded. Stepwise logistic discriminant analysis was performed to identify the independent variables that best predicted three binary outcomes: systemic embolization, death, and systemic embolization and/or death. RESULTS: Twelve of the 45 patients (27%) died from the endocarditis. Significant univariate predictors of death were the presence of paravalvular abscess (p = 0.025), number of vegetations (p = 0.021), Staphylococcus aureus isolated in blood cultures (p = 0.002), medical treatment alone (p < 0.002), and systemic embolism (p < 0.001). In multivariate analysis, systemic embolism (chi 2 = 29.3; p < 0.01), echocardiographic evidence of paravalvular abscess (chi 2 = 5.6; p = 0.018), Staphylococcus aureus endocarditis (chi 2 = 5.5; p = 0.016), and medical treatment alone (chi 2 = 5.11; p = 0.024) emerged as optimal predictors of death. Systemic embolization occurred in 12 patients. Independent variables predicting systemic embolization were a total length of vegetations > 14 mm (p = 0.01), greater age (p = 0.02), and medical treatment alone (p = 0.03). When two or more vegetations were observed, the total length is the sum of the individual sizes. Independent risk factors for the development of systemic emboli and/or death as a combined end point were total length of vegetations on TEE (chi 2 = 6.4; p = 0.003) and medical treatment alone (chi 2 = 4.1; p = 0.047). CONCLUSIONS: High-risk patients may be identified by the combination of clinical variables and TEE characteristics.

Discriminant Analysis↗
PubMed1999

The role of cardiac troponin-I (cTnI) in risk stratification of patients with unstable coronary artery disease.

In patients with chest pain at rest but no ST-segment elevation on the electrocardiogram, the diagnoses of unstable angina and non-Q-wave myocardial infarction (MI) are usually considered together because they cannot be differentiated clinically or angiographically. Since the extent of myocardial necrosis is an important determinant of the risk of death, it is important to identify serum markers with which to predict prognosis, in order to initiate appropriate medical treatment and/or invasive procedures in these patients. Cardiac troponin-I (cTnI), one of the subunits of the troponin regulatory complex, binds to actin and inhibits interactions between actin and myosin. The presence of elevated cTnI in serum is a significant prognostic indicator in patients with unstable angina and non-Q wave MI. Its independent prognostic potential persists even after adjustment for independent baseline variables known to be significantly associated with an increased risk of cardiac events. The use of cTnI in the triage of patients with unstable coronary disease may identify those at greater risk for adverse cardiac events.

Aged↗
PubMed2003

The relative utility of cardiac troponin I, creatine kinase-MBmass, and myosin light chain-1 in the long-term risk stratification of patients with chest pain.

BACKGROUND: Sensitive and specific cardiac markers convey important short-term prognostic information about patients with an acute coronary syndrome. There are, however, few data assessing their value as long-term predictors. HYPOTHESIS: The aim of the current study was to assess the relative value of three such markers and clinical characteristics in determining the long-term prognosis of patients with chest pain. METHODS: Cardiac troponin I (cTnI), myosin light chain-(MLC-1), and creatine kinase-MBmass levels were obtained on admission (0 h) and at 4, 8, 16, and 24 h in 208 patients with chest pain. Eligible subjects were determined, at the time of hospital admission, to be at >7% risk of acute myocardial infarction (MI), but without new ST-segment elevation on their presenting electrocardiogram. Follow-up was performed a median of 28 (range 1-46) months later. The primary study endpoint was death or nonfatal MI, subsequent to the index admission. RESULTS: Cardiac TnI levels > or = 0.2 ng/ml (odds ratio [OR] 1.93, 95% confidence interval [CI] 1.09-3.40) and MLC-1 levels > or = 1 ng/ml (OR 3.24, 95% CI 1.83-5.73) were both significant predictors of death or MI during long-term follow-up; MLC-1 was, however, the only independent biochemical predictor (OR 2.11,95% CI 1.14-3.93). CONCLUSIONS: Both cTnl and MLC-1 predict the long-term outcome of patients with chest pain, but, in this cohort, MLC-1 proved to be a better predictor of mortality and nonfatal acute MI.

Adult↗
PubMed2004

Classification and risk stratification of patients with acute chest pain using a low discriminatory level of cardiac troponin T.

BACKGROUND: Cardiac troponins are the biochemical markers of choice for the evaluation of acute coronary syndromes (ACS). Using the first-generation test, most studies related adverse outcome to > 0.20 or 0.10 microg/l cardiac troponin T (cTnT) levels. With the highly sensitive and specific second- and third-generation assays, cTnT is undetectable in most healthy individuals. HYPOTHESIS: We evaluated whether a lower cTnT level, within 24 h of admission, could indicate an increased risk of future complications. METHODS: During 1998-1999, clinical data were collected in 260 patients with ACS. Cardiac troponin T was measured at arrival, and 4, 8, and 12-24 h thereafter. The maximum cTnT value was then used to assess, over a 15-month follow-up period, the cumulative risk of death or myocardial infarction (MI), as well as rates of events according to quartiles of cTnT values. RESULTS: Patients with < or = 0.03 microg/l cTnT levels had the lowest rate of adverse events and the best Kaplan-Meier event-free survival curve. Increasing cTnT levels were associated with stepwise increases in mortality rates and with a constant 10-fold increase in MI rates during follow-up. CONCLUSIONS: A low threshold cTnT elevation is recommended to assess the risk of ACS. All cTnT elevations > 0.03 microg/l predict a higher risk of MI during follow-up, whereas increasing values predict mortality in relation to the amount of elevation.

Acute Disease↗
PubMed2004

Role of noninvasive studies in risk stratification for sudden cardiac death.

Sudden cardiac death (SCD) is one of the leading causes of mortality in developing countries. To prevent SCD, it is crucial to have effective tools for identifying patients at risk, given that there are now effective devices and medications that can prevent SCD. Two noninvasive electrocardiographic tools have been approved by the Food and Drug Administration and are being used clinically for identifying patients at risk for SCD: the signal-averaged electrocardiogram (SAECG) and T-wave alternans (TWA). This article reviews each of these approaches and includes a discussion of the mechanisms and a summary of the clinical studies published to date.

Arrhythmias, Cardiac↗
PubMed2004

Cardiovascular risk stratification and cardiovascular risk factors associated with erectile dysfunction: assessing cardiovascular risk in men with erectile dysfunction.

Cardiovascular risk factors are known to be associated with the presence of erectile dysfunction (ED), and ED is more common in men with cardiovascular disease (CVD). The Princeton Guidelines provide a strategy for assessing cardiac risk and planning a safe return to sexual activity. Men at low risk, who have fewer than three cardiac risk factors, can resume intercourse with very little concern for an untoward cardiac event. Men at high risk need to have their primary disease controlled, and should be stabilized before planning to resume sexual activity. Prior to resuming intercourse, men in the indeterminate category are candidates for restratification as either low or high risk. Certain cardiovascular risk factors may be predictors of ED: most notably, hyperlipidemia, hypertension, and diabetes. Advancing age is also a strong predictor of ED. The close correlation between ED and CVD is a signal to evaluate the sexual histories of all men who present for cardiovascular evaluation and, perhaps, of all men in general. Early detection of ED may allow for early diagnosis and management of CVD and diabetes.

Aging↗
PubMed2005

Echocardiography for risk stratification of myocardial infarction in the reperfusion era.

The prediction of functional recovery or ventricular remodeling plays a central role in the prognostic assessment of acute myocardial infarction (MI) in the reperfusion era. This article reviews the advances of echocardiographic techniques, focusing on the role of low-dose dobutamine stress echocardiography, contrast echocardiography, transthoracic Doppler of the left anterior descending coronary artery, and transmitral Doppler in detecting myocardial viability and predicting outcome after an acute MI. Moreover, the definition of risk for further ischemic events is another major objective in conservatively managed patients post infarction. As such, the prognostic and economic implication of stress echocardiography compared with that of traditional exercise electrocardiography was considered.

Coronary Vessels↗
PubMed2005

Epidemiology and stratification of risk for sudden cardiac death.

Sudden cardiac death (SCD) is a major cause of mortality in the United States. Approximately 65% of cases of SCD occur in patients with underlying acute or chronic ischemic heart disease. The incidence of SCD increases 2- to 4-fold in the presence of coronary disease and 6- to 10-fold in the presence of structural heart disease. Ventricular fibrillation (VF) precipitated by ventricular tachycardia (VT) is a common mechanism of cardiac arrest leading to SCD. Triggers for SCD include electrolyte disturbances, heart failure, and transient ischemia. Although a large percentage of patients with out-of-hospital SCD do not survive, successful resuscitation to hospitalization has improved in recent years. One of the challenges for preventing SCD lies in identifying individuals at highest risk for SCD within a lower-risk population. The progression from conventional risk factors of coronary artery disease to arrhythmogenesis and SCD can be represented as a cascade of changes associated with levels of increasing risk. At the first level is atherogenesis, followed by changes in atherosclerotic plaque anatomy, which may be mediated by inflammatory processes. Disruption of active plaque formed during a transitional state initiates the thrombotic cascade and acute occlusion, after which acute changes in myocardial electrophysiology become the immediate trigger for arrhythmogenesis and SCD. Each level of the cascade offers different opportunities for risk prediction. Among the classes of risk predictors are clinical markers, such as ECG measures and ejection fraction. Transient risk markers, such as inflammatory markers, are potentially useful for identifying triggers for SCD. In the future, genetic profiling is expected to allow better assessment of individual risks for SCD.

Arrhythmias, Cardiac↗
PubMed2003

The molecular biology of Euglena gracilis. XV. Recovery from centrifugation-induced stratification.

The contents of Euglena gracilis cells can be separated in vivo by ultracentrifugation. Within the unbroken cell, each set of components forms a distinct layer according to their respective densities. The degree of segregation increases with both the g-force and the time of centrifugation, up to a maximum at 100,000 x g for 1 h, when six distinct strata can be observed. When returned to normal growth conditions, essentially all the cells return to the normal state and growth pattern. Greater g-forces or longer exposures do not alter the observable strata, but the ability of the cells to recover is diminished. Smaller g-forces result in less separation of cellular contents and all cells recover, even after 18 h of exposure. Euglena cells stratified at 100,000 x g for 1 h were returned to normal growth conditions; recovery was followed microscopically and by the rate of utilization of oxygen as well as that of the single carbon source. The cells recovered their normal state within 1 to 2 h, which is only a tenth of the normal doubling time. The mechanism for this recovery involves a natural process of change in cell shape caused by contraction and relaxation of the pellicle, a cell surface structure.

Animals↗
PubMed2002

A survival-stratification model of human colorectal carcinomas with beta-catenin and p27kip1.

BACKGROUND: The stabilization and nuclear translocation of beta-catenin are early events in the majority of sporadic colorectal carcinomas (CRC). beta-catenin up-regulates c-Myc and cyclin D1, which antagonize the association of the cyclin-dependent kinase (Cdk) inhibitor, p27(kip1), with Cdk2, thus allowing cell cycle progression through G1 to S-phase. Lack of p27 is a significant predictor of poor survival in a series of 136 CRC specimens. A combination of molecules in the same pathway may be a better prognostic factor. METHODS: The expression of beta-catenin, c-Myc, and cyclin D1 in relation to patients' survival and clinicopathologic parameters in the same series was evaluated by immunohistochemistry. RESULTS: Intense nuclear overexpression of beta-catenin, but not a lack of cell membrane or cytoplasmic expression, is a significant predictor of poor survival by both univariate (P = 0.0029) and multivariate analyses (P = 0.004, risk ratio =3.8), suggesting that beta-catenin is retained in the nucleus to function as an oncogene. None of the patients with high nuclear beta-catenin and low p27 expression survived 5 years or more whereas 65% of patients with all other combinations of the two markers survived (P < 0.0001). This combination is also a significant and independent prognostic factor (P = 0.001; risk ratio = 9.7). Overexpression of c-Myc is associated with higher mortality rates, but the expression of cyclin D1 has no prognostic significance. CONCLUSIONS: The combined expression of beta-catenin and p27 can stratify patients into markedly different survival groups, possibly via their antagonistic effects on metastasis promotion.

Adenocarcinoma↗
PubMed2003

Scoring algorithm to predict survival after nephrectomy and immunotherapy in patients with metastatic renal cell carcinoma: a stratification tool for prospective clinical trials.

BACKGROUND: The objective of this study was to develop an algorithm capable of stratifying the survival of patients with metastatic renal cell carcinoma (RCC) after nephrectomy and immunotherapy. METHODS: The medical records of 173 patients who underwent radical nephrectomy for metastatic RCC and received recombinant interleukin-2 (IL-2)-based immunotherapy between 1989 and 2000 were evaluated. Survival was the primary endpoint and was assessed based on clinical, surgical, and pathologic parameters. The clinical parameters included age, gender, performance status, existing hypertension, thyroid-stimulating hormone (TSH) levels, location of metastases, and presenting symptomatology. The surgical features included the requirement for blood transfusion or adrenalectomy. The pathologic factors involved tumor stage, tumor size, nuclear grade, lymph node status, and histologic subtype. Disease-specific survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used to determine associations between clinical and pathologic features and survival. RESULTS: The median follow-up was 3.2 years (range, 0.2-9.3 years). Death due to RCC occurred in 123 patients (71%) at a median of 13 months (range, from 0.1 months to 8.4 years) after nephrectomy. Multivariate analysis revealed that the following features were associated with survival: lymph node status (P = 0.002), constitutional symptoms (P = 0.005), location of metastases (P < 0.001), sarcomatoid histology (P = 0.003), and TSH level (P = 0.038). A scoring system based on the features in the multivariate model was created to stratify patients into low-risk, intermediate-risk, and high-risk groups. Estimated survival rates at 1 years, 3 years, and 5 years were 92%, 61%, and 41%, respectively, for the low-risk group and 66%, 31%, and 19%, respectively, for the intermediate risk group. The high-risk group had 1% survival at 1 year and no survivors at 3 years. CONCLUSIONS: In patients with metastatic RCC who were treated with nephrectomy and IL-2 immunotherapy, regional lymph node status, constitutional symptoms, location of metastases, sarcomatoid histology, and TSH levels were associated with survival. The authors present a scoring algorithm based on these features that can be used to predict survival in patients who present with metastatic RCC and to stratify such patients for prospective clinical trials.

Adult↗