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PubMed1991

Myocardial perfusion imaging in ischemic heart disease anno 1990.

The field of radionuclide myocardial perfusion imaging is in a rapid state of change. Stress-rest myocardial imaging is important not only for the detection of coronary artery disease but also for prognostic stratification of patients. In particular, assessment of myocardial viability in patients with left ventricular dysfunction is a recent focus of investigation. Single-photon emission computed tomography has become widely accepted as the preferred (albeit challenging) imaging modality for myocardial perfusion imaging. Silent myocardial ischemia and its clinical significance continues to be an intriguing aspect of the clinical manifestation of coronary artery disease. Myocardial perfusion imaging is an invaluable independent method to unravel this problem. Dipyridamole was approved for pharmacologic vasodilation in conjunction with myocardial perfusion imaging. At the same time, direct infusion of adenosine was proposed as an alternative method of effecting vasodilatory stress. In 1990, several new technetium-99m-labeled myocardial perfusion imaging agents have been introduced (teboroxime and hexakis-2-methoxyisobutyl-isonitrile [sestaMIBI]) that may have a profound impact on imaging techniques and applications of myocardial perfusion imaging.

Coronary Disease↗
PubMed2003

Value of echocardiography in predicting future cardiac events after acute myocardial infarction.

Short- and long-term survival after acute myocardial infarction mainly depends on three factors: the amount of myocardium that had become necrotic, the area of myocardium at further risk of becoming necrotic, and the patency of the infarct-related artery. Echocardiography is a low-cost, safe, bedside, repeatable tool, particularly useful for prognostic stratification after myocardial injury. Two-dimensional echocardiography analyzes left ventricular function, the most powerful predictor of survival immediately after acute myocardial infarction. Myocardial contrast echocardiography measures the infarct size and detects viable myocardium. Stress echocardiography stratifies patients with viable myocardium and/or multivessel coronary artery disease who need further diagnostic and therapeutic interventions. Transthoracic coronary Doppler ultrasonography assesses effective recanalization and coronary flow reserve of the left anterior descending coronary artery. Further technologic advances are needed to allow direct noninvasive measurement of flow by transthoracic Doppler ultrasonography in other coronary arteries.

Acute Disease↗
PubMed1997

Survival in patients with nosocomial pneumonia: impact of the severity of illness and the etiologic agent.

OBJECTIVE: To assess the impact of severity of illness at different times, using the Mortality Probability Models (MPM II), and the impact of etiologic agent on survival in patients with nosocomial pneumonia. DESIGN: Retrospective, observational study. SETTING: Fourteen-bed medical-surgical intensive care unit (ICU) in a teaching hospital. PATIENTS: Sixty-two patients with nosocomial pneumonia who were receiving early appropriate antibiotic treatment. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Severity of illness at the time of admission to the ICU (M0), 24 hrs after admission (M24), and at the time of pneumonia diagnosis (M1) was determined using MPM II. Bacteriology was established by quantitative cultures from bronchoscopic samples. The outcome measure was the crude mortality rate. The crude mortality rate in the ICU was 59.7%, compared with average predicted mortality rates of 43.5% (M0), 36.4% (M24), and 52.2% (M1). We observed significant differences in mean MPM II determinations between survivors and nonsurvivors at M1 (39.3% vs. 60.9%, p = .001) but not at M0 and M24. In the univariate analysis, the variables most predictive of mortality were the presence of coma (p = .02), inotropic medication use (p = .001), and an MPM II determination of > 50% (p = .001) when pneumonia was diagnosed (M1). Multivariate analysis showed that, in the absence of Pseudomonas aeruginosa, an MPM II determination of > 50% at M1 was associated with a relative risk of death of 4.8. The presence of P. aeruginosa was associated with an increase in the risk of death of 2.6 and 6.36 in both populations with MPM II determinations at M1 of < or = 50% and > 50%, respectively. CONCLUSIONS: Severity of illness when pneumonia is diagnosed is the most important predictor of survival, and this determination should be used for therapeutic and prognostic stratification. In addition, the presence of P. aeruginosa contributed to an excess of mortality that could not be measured by MPM II alone, suggesting the importance of the pathogen in prognosis.

Aged↗
PubMed2004

Clinical usefulness of ambulatory blood pressure monitoring.

During the past decade, several prospective studies showed that ambulatory BP (ABP) measurements provide a better prediction of major cardiovascular events when compared with clinic BP measurements. This review summarizes the available evidence supporting the use of ABP monitoring to refine prognostic stratification in hypertension. On the basis of available evidence, an operational flowchart is suggested to interpret results of ABP for better treatment of patients with elevated BP.

Blood Pressure Monitoring, Ambulatory↗
PubMed2006

Update on anti-tumor necrosis factor therapy in the spondyloarthropathies including psoriatic arthritis.

PURPOSE OF REVIEW: The introduction of the macromolecule tumor necrosis factor inhibitors etanercept, infliximab, and adalimumab has proven very successful for patients with spondyloarthropathies. The greatest experience has accrued in ankylosing spondylitis and psoriatic arthritis. This paper reviews data from clinical trials with tumor necrosis factor inhibitors in ankylosing spondylitis and psoriatic arthritis. RECENT FINDINGS: Treatment with tumor necrosis factor inhibitors has not only resulted in substantial improvement in the signs and symptoms of arthritis but has also improved functional status and quality of life in ankylosing spondylitis and psoriatic arthritis. Improvements in associated inflammatory features, such as enthesitis in psoriatic arthritis and uveitis in ankylosing spondylitis, have also been observed. Moreover, treatment has been shown to inhibit the progression of radiographic joint damage in psoriatic arthritis and to attenuate spinal inflammation in ankylosing spondylitis. The notable success of tumor necrosis factor inhibitors has not only changed the treatment paradigms for these conditions but has also stimulated studies aimed at improving diagnosis, prognostic stratification, and other aspects of clinical care. SUMMARY: The introduction of tumor necrosis factor inhibitors for patients with ankylosing spondylitis and psoriatic arthritis has had a tremendous impact on daily clinical care.

Adalimumab↗
PubMed2006

The changing scene of adult acute lymphoblastic leukemia.

PURPOSE OF REVIEW: The review focuses on the most recent advances in the diagnostic and prognostic work-up of adult acute lymphoblastic leukemia (ALL) and its implications in the clinical management of the disease. RECENT FINDINGS: ALL can be identified on the basis of morphologic, cytochemical and immunophenotypic criteria; modern management of ALL is also based on cytogenetic and genetic evaluations. New technologies, such as gene expression profile analysis, may allow us to further unravel the intrinsic biology of the disease, to improve diagnostic and prognostic stratification, and to design innovative therapeutic strategies. In potentially all cases, specific markers of the disease can be found and utilized together with the rearrangement of immunoglobulin and T-cell receptor genes to monitor minimal residual disease during clinical follow-up. These biologically-defined subgroups of patients may have a different clinical course, response to treatment and variable prognosis. SUMMARY: Recent biologic advancements are progressively realising the possibility of designing targeted and individualized therapeutic strategies according to the more refined, molecularly defined features of leukemic cells and the presence or absence of residual disease in adult ALL.

Adult↗
PubMed2006

Blood pressure in acute ischemic stroke and mortality: a study with noninvasive blood pressure monitoring.

BACKGROUND: In acute ischemic stroke, a transient elevation of blood pressure is common; its significance and its relationship with the neurological outcome are still unclear. METHODS: In 71 consecutive patients with acute ischemic stroke, aged 25-94 years, admitted to our unit, we investigated the relationships between the blood pressure variation during the first 24 h and mortality at 3 months (study endpoint). Neurological status was assessed with the National Institutes of Health Stroke Scale. Blood pressure was measured with bedside noninvasive blood pressure monitoring every 15 min. The mean of four measurements at the emergency department and the mean of 12 measures (during a 3-h interval) at 12 and at 24 h after stroke onset were considered for analysis. Antihypertensive treatment was given in accordance with the Recommendations for Stroke Management of European Stroke Initiative. RESULTS: In the whole series, 21% were atherothrombotic, 32% cardioembolic, 34% lacunar, and 13% of unknown or other cause. Blood pressure was 160+ or -3/86+ or -2 mmHg at the emergency department, 148+ or -3/82+ or -2 mmHg at 12 h, and 147+ or -3/81+ or -2 mmHg at 24 h (P<0.05). Four patients (11%) of those in whom mean blood pressure decreased >5 mmHg, and 12 (33%) of the others, in whom mean blood pressure decreased < or =5 mmHg or did not decrease, reached the endpoint (P<0.05). According to the multivariate Cox model, NIHSS score at the emergency department (95% confidence interval: 1.025-1.238, P=0.013) and age (95% confidence interval: 1.007-1.259, P=0.038) were predictors of reaching the endpoint, whereas mean blood pressure reduction 24 h after stroke onset had a protective effect (95% confidence interval: 0.845-0.995, P=0.038). Diabetes, mean blood pressure at the emergency department and the need for antihypertensive therapy did not correlate with the outcome. CONCLUSIONS: Noninvasive blood pressure monitoring during the first 24 h of acute ischemic stroke may be useful in the prognostic stratification by showing moderate blood pressure decrease, either spontaneous or drug induced, which is associated with a favorable prognosis at 3 months.

Adult↗
PubMed2006

Cardiovascular risk in patients receiving double therapy with false and true nonresponder hypertension.

OBJECTIVE: The aim of this study was to evaluate cardiovascular risk in hypertensive patients receiving double therapy with false and true nonresponder hypertension. METHODS: The occurrence of fatal and nonfatal cardiovascular events was evaluated in 730 patients receiving double therapy with uncontrolled clinic blood pressure. Two hundred and seventy had false nonresponder hypertension (clinic blood pressure > or =140 or 90 mmHg and daytime blood pressure <135/85 mmHg) and 460 had true nonresponder hypertension (clinic blood pressure > or =140 or 90 mmHg and daytime blood pressure > or =135 or 85 mmHg). RESULTS: During the follow-up (4.77+/-2.9 years, range 0.2-11.7 years), 55 cardiovascular events occurred. The event rates per 100 patient-years in patients with false and true nonresponder hypertension were 1.03 and 1.9, respectively. Event-free survival was significantly different between the groups (P<0.05). After adjustment for several covariates, including clinic blood pressure (forced into the model), Cox regression analysis showed that cardiovascular risk was significantly higher in true than in false nonresponder hypertension (relative risk 2.33, 95% confidence interval 1.14-4.77, P=0.02). CONCLUSIONS: This study shows that, among treated hypertensive patients receiving double therapy with uncontrolled clinic blood pressure those with true nonresponder hypertension are at higher cardiovascular risk. Ambulatory blood pressure monitoring should be performed in this population to achieve a better prognostic stratification.

Aged↗
PubMed2026

Genetic regulation of CPEB3-mediated alternative polyadenylation associated with survival of patients with hepatocellular carcinoma.

BACKGROUND: Alternative polyadenylation (APA) is a key post-transcriptional mechanism that regulates gene expression by modulating 3'UTR length, its dysregulation has been implicated in carcinogenesis. How genetic variants influence APA to affect hepatocellular carcinoma (HCC) prognosis remains unclear. METHODS: Prognosis-APA quantitative trait loci (apaQTL) were performed using genotype and APA profiling from TCGA data. A two-stage survival analysis in 848 Chinese and 369 TCGA LIHC patients and functional validation were used to identify prognostic apaQTL in HCC progression. RESULTS: A total of 2,025 and 817 significant APA events were identified in Chinese and TCGA cohort, respectively. Besides, 859 events were associated with poor prognosis in HCC and enriched in RNA splicing / metabolism pathways. We detected 32,034 significant apaQTLs, predominantly enriched in 3'UTRs and RBP-binding regions. CPEB3 was prioritized as a key APA regulator RBP; its low expression correlated with poor patient survival and promoted proliferation, migration, and invasion in HCC cells. Notably, a functional apaQTL variant rs2037547, located in GSK3B and mediated by CPEB3, demonstrated a poor survival of HCC patients in both cohort (pooled HR=1.29, p=0.016). Mechanistically, rs2037547 promoted aberrant APA at proximal poly(A) sites of GSK3B through CPEB3, leading to increased expression of short 3'UTR isoform. This regulatory alteration enhanced HCC cell proliferation, invasion, and migration, and contributed to HCC progression. CONCLUSION: These findings elucidated the distinct role of apaQTL-mediated APA dysregulation in HCC prognosis, providing insights for prognostic stratification and potential targets for personalized therapy in HCC.

RNA-binding proteins↗
PubMed1982

A placebo-controlled study to determine the efficacy of oral disopyramide phosphate for the prophylaxis of ventricular dysrhythmias after acute myocardial infarction.

1 To evaluate oral disopyramide phosphate in the prophylaxis of dysrhythmias occurring in acute myocardial infarction (MI) patients (presenting within 12 h of symptoms, age 21-70 years), a placebo-controlled, randomized double-blind, in hospital trial was conducted. After prognostic stratification (anterior and non-anterior MI at each of 4 regional hospitals) patients were randomly assigned to receive oral disopyramide phosphate (loading dose 150, 200, or 300 mg followed 6 h later by 100, 150, or 200 mg every 6 h for patients assessed to weigh less than 55, 55-85, or greater than 85 kg, respectively or matching placebo. The primary exclusion criteria were overt heart failure, systolic BP less than 100 mmHg, significant heart block or history of urinary retention. Active drug or placebo was continued for 7 days or until (a) detection of "warning arrhythmias' requiring i.v. lignocaine intervention (greater than 5 for 7 days or until (a) detection of "warning arrhythmias' requiring i.v. lignocaine intervention (greater than 5 premature ventricular contractions (PVCs)/min, R on T PVCs, multifocal PVCs, bigeminal PVCs, ventricular tachycardia or ventricular fibrillation) or (b) onset of exclusion criteria. In addition, plasma drug concentrations were determined and 24 h electrocardiographic tapes were obtained on day 1, and on one of days 4-7 but these results are not presented here. 2 Out of 121 patients entering the trial, 101 had confirmatory ECG and enzyme changes. Of these, 9 of 47 patients receiving disopyramide phosphate required lignocaine compared to 20 of 54 receiving placebo (19% v 37%; P = 0.047). Corresponding numbers for patients discontinuing trial medication for other non-fatal complications of MI were 5 and 3, and for those dying, were 3 (2 infarct extensions and 1 massive infarction), and 0, respectively. Respective numbers discontinuing trial medication for possible drug side effects (viz. urinary retention requiring catheterization) were 6 and 1 (P = 0.031). 3 In circumstances where i.v. therapy is deemed impractical, use of oral disopyramide phosphate given prophylactically in patients with acute MI may reduce the incidence of "warning arrhythmias' by a clinically significant extent.

Adult↗
PubMed2006

Classification of pleomorphic sarcomas: where are we now?

Until a decade ago, so-called pleomorphic and storiform malignant fibrous histiocytoma (MFH) represented the most frequently diagnosed sarcoma, accounting for approximately 40% of adult mesenchymal malignancies. However, the latest World Health Organization classification of soft tissue tumours considers MFH a synonym for undifferentiated pleomorphic sarcoma. Historically, the term MFH was introduced in the medical literature in 1963 by Ozzello, O'Brien and Stout, on the basis of the acquisition of phagocytic properties observed in cultured fibroblasts. The existence of MFH as a well-defined clinicopathological entity became rapidly very popular and by the mid 1980s MFH represented the most common sarcoma in adults. With the advent of electron microscopy, immunohistochemistry and molecular genetics, it became clear that the so-called "facultative fibroblast" theory had no scientific grounds and, in 1992, a milestone paper eventually brought attention to the concept that MFH merely represented a morphological pattern shared by a wide variety of poorly differentiated malignant neoplasms, which include specific subtypes of pleomorphic sarcomas. Currently, accurate subclassification of pleomorphic sarcomas is mandatory as it enables recognition of non-sarcomatous lesions as well as pleomorphic neoplasms not associated with aggressive behaviour. Furthermore, as myogenic differentiation predicts aggressive clinical behaviour among pleomorphic sarcomas, precise histotyping allows prognostic stratification of patients.

Humans↗
PubMed1990

Risk assessment in myelodysplastic syndromes: value of clinical, hematologic and bone marrow histologic findings at presentation.

We analyzed the prognostic value of clinical, hematologic and bone marrow (BM) histologic findings at presentation in 94 patients with myelodysplastic syndromes (MDS) (28 RA; 2 RARS; 34 RAEB; 6 CMML; 24 RAEB-t). With survival as the dependent variable, stepwise multivariate analysis indicated as the prognostically most important factors among the MDS taken as a whole: latency from the first symptoms to diagnosis, age, and percentage of BM blasts. In each main MDS group the most unfavorable initial characteristics were: 1) low Hb, no macro-megaloblastosis, male sex for RA/RARS; 2) low Hb and low platelet levels for RAEB/CMML; 3) granuloblastic hyperplasia and high BM blastosis for RAEB-t. Of the BM histologic parameters, only the percentage of blasts had significant prognostic value. Histologic assessment of BM blastosis, however, did not differ statistically from that based on cytologic examination of BM smears, so that marrow histology seemed not essential for initial prognostic assessment in MDS patients. The finding of abnormal localization of immature precursors (ALIP) in BM biopsies was associated with a negative trend without reaching statistical significance. Using four objective parameters of proven significance (age, Hb, platelets, and BM blasts) we devised a staging system of immediate clinical utility for prognostic stratification and risk-adapted therapeutic choices.

Biopsy, Needle↗
PubMed2006

Best evidence topic report. Brain natriuretic peptide as a potential marker of acute coronary syndromes.

A short cut review was carried out to establish whether brain natriuretic peptide (BNP) can be used as a marker for acute coronary syndromes. 685 citations were found, of which eight presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. The clinical bottom line is that BNP shows promise as an early cardiac marker and may enhance prognostic stratification. NPV and PPV may be unacceptably low to enable use as a sole cardiac marker. Incorporation into a multimarker strategy and serial estimations may be necessary.

Acute Disease↗
PubMed1981

Analysis of prognostic significance of ventricular arrhythmias after myocardial infarction. Shortcomings of Lown grading system.

The Lown grading system for ventricular arrhythmias has been used in observational and experimental studies of ischaemic heart disease. This grading system uses three levels of ventricular premature depolarisation frequency and four complex features to assign patients to one of seven grades. We tested several of the major assumptions of the Lown grading system in a group of 400 patients who had recently experienced acute myocardial infarction. The Lown grading system assumes that the frequency of ventricular extrasystoles exerts a negligible risk force in patients who have complex ventricular extrasystoles. We found, however, that the frequency of ventricular extrasystoles contributed significant additional risk for cardiac death even in the three highest Lown grades, 4A, 4B, and 5. The Lown grading system assumes that, of the four complex features used, R on T ventricular extrasystoles have the greatest risk for subsequent cardiac death. We found that paired ventricular extrasystoles and ventricular tachycardia had more prognostic significance than R on T ventricular extrasystoles. It is important for prognostic stratification that subgroups which are merged into a given Lown grade should be relatively homogeneous with respect to outcome. We found a lack of homogeneity in the three highest Lown grades. Grade 5 contained 16 subgroups with a mortality risk which ranged from 0 to 75 per cent; statistically significant differences in subsequent mortality were found among these subgroups. Most of the shortcomings of the Lown grading system in our acute myocardial infarction population resulted from failure to give sufficient weight to ventricular extrasystoles frequency and to repetitive ventricular extrasystoles.

Aged↗
PubMed1994

Dilated cardiomyopathy in children: determinants of outcome.

OBJECTIVE: To determine the outcome of dilated cardiomyopathy presenting in childhood and the features that might be useful for prognostic stratification. SETTING: Supraregional paediatric cardiology unit. DESIGN: Retrospective analysis. BACKGROUND: The natural history of dilated cardiomyopathy in children is not well characterised. Previous studies have shown a variable relation between age at presentation and outcome, and sudden death has been infrequent. METHODS: Retrospective study of 63 consecutive patients with idiopathic dilated cardiomyopathy presenting between 1979 and 1992. Survival curves were constructed by the Kaplan-Meier method. RESULTS: Age at diagnosis ranged from 1 day to 15 years (median 12 months) and follow up ranged from 1 day to 13 years (median 19 months). Actuarial survival from presentation was 79% at one year (95% confidence interval (95% CI) 66%-88%) and 61% (44%-74%) at five years. Univariate analysis showed that mural thrombus, left ventricular end diastolic pressure > 20 mm Hg, and age at presentation > 2 years were predictors of adverse outcome, but on multivariate analysis only age at presentation was significant. Left ventricular echocardiographic indices either did not improve or deteriorated in 36 children (17 of whom died, four suddenly, and three were transplanted), partially improved in 16 (three of whom died, all suddenly), and returned to normal in 11 (all of whom have survived). CONCLUSIONS: Older age at presentation and lack of improvement in systolic function are associated with an adverse outcome, and early transplantation should be considered in these patients. There is a persistent risk of late sudden death in those children in whom echocardiographic dimensions remain abnormal.

Adolescent↗
PubMed2002

Molecular mechanisms of inherited cardiomyopathies.

Cardiomyopathies are diseases of heart muscle that may result from a diverse array of conditions that damage the heart and other organs and impair myocardial function, including infection, ischemia, and toxins. However, they may also occur as primary diseases restricted to striated muscle. Over the past decade, the importance of inherited gene defects in the pathogenesis of primary cardiomyopathies has been recognized, with mutations in some 18 genes having been identified as causing hypertrophic cardiomyopathy (HCM) and/or dilated cardiomyopathy (DCM). Defining the role of these genes in cardiac function and the mechanisms by which mutations in these genes lead to hypertrophy, dilation, and contractile failure are major goals of ongoing research. Pathophysiological mechanisms that have been implicated in HCM and DCM include the following: defective force generation, due to mutations in sarcomeric protein genes; defective force transmission, due to mutations in cytoskeletal protein genes; myocardial energy deficits, due to mutations in ATP regulatory protein genes; and abnormal Ca2+ homeostasis, due to altered availability of Ca2+ and altered myofibrillar Ca2+ sensitivity. Improved understanding that will result from these studies should ultimately lead to new approaches for the diagnosis, prognostic stratification, and treatment of patients with heart failure.

Animals↗
PubMed2006

Risk factors for short-term mortality in older subjects with acute ischemic stroke.

BACKGROUND: Stroke is the third cause of death in older individuals living in Western Countries. The identification of predictors for mortality after stroke has a major importance for clinicians in order to allow the implementation of therapeutic and preventive strategies. OBJECTIVE: To evaluate the association between clinical and laboratory parameters and 30-days total mortality in a large sample of older patients with stroke. METHODS: 469 older patients (median age: 80.0 years) consecutively hospitalized for acute ischemic stroke were enrolled. The data recorded included: (1) clinical features of stroke; (2) routine clinical chemistry analyses; (3) medical history, and (4) 12-lead ECG. All patients underwent computed tomography scan of the brain. Stroke type was classified by the Oxfordshire Community Stroke Project system. RESULTS: 130 subjects died within 30 days after stroke, with an overall mortality of 27.7%. At univariate analysis, altered levels of consciousness (ALC), congestive heart failure, atrial fibrillation, previous stroke, high blood glucose, fibrinogen and blood sedimentation rate levels, higher white blood cell count, lower serum albumin and iron levels were associated with mortality. Multivariate logistic regression analysis indicated that short-term mortality was associated with ALC (OR: 11.80; CI 95%: 5.50-24.00), congestive heart failure (OR: 3.06; CI 95%: 1.04-8.80), and age (OR: 1.04; CI 95%: 1.002-1.09) independent of gender, previous stroke, AF, fasting blood glucose, serum albumin, serum iron, and white blood cell count. In patients with ALC (high-mortality rate: 63.6%), only hyperglycemia (III vs. I tertile, OR: 9.60; CI 95%: 1.65-52.50) was associated with mortality after multivariate adjustment. CONCLUSION: Our study highlights the role of ALC and congestive heart failure in the short-term prognostic stratification of older patients with acute ischemic stroke. Furthermore, our results support the value of post-stroke hyperglycemia as a marker for short-term mortality also in advanced age, and particularly in the presence of ALC and in nondiabetic individuals.

Aged↗