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Prospective assessment of presenting serum markers for cardiac risk stratification.

OBJECTIVE: To quantify the association of initial ED serum cardiac markers with the risk for life-threatening events (LEs) or need for lifesaving interventions (LIs) or administration of IV nitroglycerin. METHODS: A prospective, observational study was performed using a cohort of hemodynamically stable, hospitalized patients (age > or = 25 years) presenting with nontraumatic chest discomfort. Patients with ST-segment elevation on their initial ECGs were excluded. Presenting serum samples were assayed for serum myoglobin and creatine kinase-MB isomer (CK-MB) using the Opus and Stratus systems. Target cases were defined as patients having LEs (e.g., cardiogenic shock, ventricular fibrillation, cardiac arrest), requiring LIs (e.g., intubation, cardioversion, pacing, reperfusion therapy), or needing IV nitroglycerin within 48 hours. Manufacturer's thresholds defined abnormal marker levels. Abnormal ECGs were defined using the Brush criteria. RESULTS: Of the 178 eligible patients, 44 (25%) were target cases. Most (55%) target cases had blood drawn for assays within four hours of chest discomfort onset. The relative risk and sensitivity of the serum markers and the ECG for target cases follow: [table: see text] Of the seven patients with an LE/LI, six had blood drawn four hours or less after symptom onset; two LE/LI patients had abnormal myoglobin levels--no LE/LI patient had an abnormal CK-MB level. CONCLUSIONS: Isolated serum myoglobin and CK-MB levels obtained at patient ED presentation were not strongly associated with the 48-hour risk for LEs, LIs, or the use of IV nitroglycerin. Future studies of risk stratification should address the merits of serial serum marker measurements that extend up to 12 hours beyond patient symptom onset.

Adult↗

Development of an HCV infection risk stratification algorithm for patients on chronic hemodialysis.

OBJECTIVE: The prevalence of hepatitis C virus (HCV) in patients on chronic hemodialysis (HD) is near 9%. Transaminases, which are lower in HD patients, are not effective in screening for HCV. Our aim was to design an HCV risk stratification strategy incorporating lowered aminotransferase levels and other clinical parameters. METHODS: Patient serum from 168 consecutive HD patients was analyzed for AST, ALT, ferritin, and hepatitis C antibody. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for lower transaminase values. Multivariate classification and regression tree analysis was used to determine the best combination of variables to predict risk for HCV infection. RESULTS: Median AST and ALT levels were higher in anti-HCV Ab(+) patients (p < 0.05). Applying a lower cutoff value for ALT of 16 IU/L resulted in a sensitivity of 61.1%, a specificity of 66.7%, a positive predictive value of 33.9%, and a negative predictive value of 86.0% for detection of HCV infection. Multivariate classification and regression tree analysis derived an algorithm using patient age, months on HD, and AST, resulting in a 97.2% sensitivity and a 51.9% specificity for the detection of HCV(+) HD patients. CONCLUSIONS: A lower normal cutoff value of 18 IU/L for AST and 16 IU/L for ALT increased sensitivity and specificity for the detection of HCV infection in HD patients. An algorithm combining lower transaminases with clinical parameters improved both sensitivity and specificity in HCV detection. Prospective confirmation of this algorithm would allow more selective HCV enzyme immunoassay and polymerase chain reaction testing in dialysis units.

Alanine Transaminase↗

Prognostic stratification for the mandibular pain dysfunction syndrome.

Combinations of the symptoms and signs of the mandibular pain dysfunction syndrome (MDS) provoked by movements of the mandible are complex and patients are treated as a homogeneous group. The process of prognostic stratification applied to an inception cohort of 169 MDS patients, separated groups of patients according to affected movements of the mandible associated with similar outcomes of treatments. From the data, two staging systems for the dysfunction were derived and evaluated. It is suggested that further analyses of more data would distinguish groups of patients with comparable prognoses enabling universal and valid comparisons of treatment of the dysfunction to be made.

Humans↗

Epidermal stratification reduces the effects of UVB (but not UVA) on keratinocyte cytokine production and cytotoxicity.

Ultraviolet (UV) radiation induces cytokine release from cultured keratinocytes as well as from epidermis in vivo. The purpose of this study was to determine whether differentiation of cultured keratinocytes into stratified epithelium decreases the effects of UVA and UVB radiation on cytokine release. Interleukin-1 (IL-1) alpha, IL-1 beta and tumor necrosis factor (TNF)-alpha release from human keratinocytes and reconstituted human epidermis was measured after exposure to UVA or UVB radiation. Release of IL-1 alpha, IL-1 beta, and TNF-alpha was induced by both UVA and UVB radiation from both keratinocytes and reconstituted epidermis. Release of these cytokines was correlated with cytotoxicity. Keratinocyte cultures were far more sensitive to UVB radiation than reconstituted epidermis, in terms of both cytotoxicity and cytokine release. In contrast, epidermal stratification/differentiation had much less effect on the sensitivity to UVA radiation. We conclude that epidermal stratification and the formation of a stratum corneum provide protection against UVB radiation but have limited barrier effect against UVA radiation.

Anti-Inflammatory Agents↗

Stratification of activity and bacterial community structure in biofilms grown on membranes transferring oxygen.

Previous studies have shown that membrane-aerated biofilm (MAB) reactors can simultaneously remove carbonaceous and nitrogenous pollutants from wastewater in a single reactor. Oxygen is provided to MABs through gas-permeable membranes such that the region nearest the membrane is rich in oxygen but low in organic carbon, whereas the outer region of the biofilm is void of oxygen but rich in organic carbon. In this study, MABs were grown under similar conditions but at two different fluid velocities (2 and 14 cm s(-1)) across the biofilm. MABs were analyzed for changes in biomass density, respiratory activity, and bacterial community structure as functions of biofilm depth. Biomass density was generally highest near the membrane and declined with distance from the membrane. Respiratory activity exhibited a hump-shaped profile, with the highest activity occurring in the middle of the biofilm. Community analysis by PCR cloning and PCR-denaturing gradient gel electrophoresis of 16S rRNA genes demonstrated substantial stratification of the community structure across the biofilm. Population profiles were also generated by competitive quantitative PCR of gene fragments specific for ammonia-oxidizing bacteria (AOB) (amoA) and denitrifying bacteria (nirK and nirS). At a flow velocity of 14 cm s(-1), AOB were found only near the membrane, whereas denitrifying bacteria proliferated in the anoxic outer regions of the biofilm. In contrast, at a flow velocity of 2 cm s(-1), AOB were either not detected or detected at a concentration near the detection limit. This study suggests that, under the appropriate conditions, both AOB and denitrifying bacteria can coexist within an MAB.

Bacteria↗

Risk stratification of patients with syncope in an accident and emergency department.

OBJECTIVES: This study categorised syncopal patients, in a British accident and emergency (A&E) department, into three prognostic groups, using American College of Physicians (ACP) guidelines. The one year mortality of the three groups was studied to see if risk stratification using these guidelines is applicable to these patients and also whether admission improved outcome. METHODS: The records of all syncopal patients presenting to the Leeds General Infirmary A&E department during an eight week period from 2 November 1998 were identified. The cohort was grouped according to ACP guidelines into those who had an absolute indication for admission (group 1), a probable indication for admission (group 2) and no indication for admission (group 3). The actual disposal was recorded and for each patient mortality data were retrieved from general practices or health authorities one year later. The three groups were compared. RESULTS: Two hundred and ten records (1.7% of all new patients aged 16 years or above) were analysed. Forty per cent of the cohort were not assigned a diagnosis after their assessment in A&E. Forty seven (22%) were placed in ACP group 1, 63 (30%) in ACP group 2 and 100 (48%) in ACP group 3. Thirty six per cent of those in group 1 had died within a year, 14% of those in group 2 and none of those in group 3. In neither group 1 patients ("high risk") nor group 2 patients ("moderate risk") did admission to the hospital seem to influence outcome. However, three patients died within a week of their presentation, and two of them had been discharged from A&E. CONCLUSION: It is possible to stratify syncopal patients presenting acutely to A&E, according to prognosis, using ACP guidelines. Disposal decisions for these patients should be based on their apparent prognosis (as defined in the ACP guidelines) and not on the diagnosis, which is often difficult to make.

Adult↗

Chronic heart failure in the elderly: value of cardiopulmonary exercise testing in risk stratification.

OBJECTIVE: To assess the value of cardiopulmonary exercise testing in predicting prognosis in a cohort of elderly patients with chronic heart failure (CHF). DESIGN: A retrospective cohort study of all patients with CHF over the age of 70 years assessed between January 1992 and May 1997. SETTING: Tertiary centre. PATIENTS: 50 patients (mean (SD) age 75.9 (4.5) years, 8 women) with CHF New York Heart Association (NYHA) class I (3 patients), II (25 patients), III (20 patients), and IV (2 patients). Follow up was complete for two years in all patients. RESULTS: The patients underwent cardiopulmonary exercise testing (peak oxygen consumption 15.2 (4.5) ml/kg/min, minute ventilation/carbon dioxide production (VE/VCO(2)) slope 38.7 (11.8)); radionucleide ventriculography (left ventricular ejection fraction 32.8 (14.3)%); serum sodium measurement (139 (2.8) mmol/l); and echocardiography (left ventricular end diastolic dimension 6.1 (1.1) cm, left ventricular end systolic dimension 4.7 (1.5) cm). At the end of follow up in May 1999, 26 patients had died. The median follow up of the survivors was 47.7 months (interquartile range 31. 5-53.5 months). On univariate analysis VE/VCO(2) slope (p < 0.0001), NYHA class (p < 0.001), peak oxygen uptake (VO(2)) (p < 0.01), left ventricular end systolic dimension (p < 0.05), and serum sodium concentration (p < 0.05) had significant predictive power. Stepwise multivariate analysis identified only VE/VCO(2) slope (p < 0.01), NYHA class (p < 0.05), and peak VO(2) (p< 0.05) as conveying significant independent prognostic information. CONCLUSION: Elderly patients with CHF have a high mortality, with the majority dead within two years. Cardiopulmonary exercise testing provides important information for risk stratification within this group and its use should not be neglected.

Aged↗

Role of myocardial perfusion imaging for risk stratification in suspected or known coronary artery disease.

Nuclear cardiology is an evolving specialty that has recently benefited from technological and radiopharmaceutical advances. As a result there has been an increase in the accuracy of myocardial perfusion imaging (MPI) with gated single photon emission computed tomography (SPECT) for assessing the diagnosis and prognosis of coronary artery disease. Moreover, ECG gated SPECT allows the simultaneous assessment of both myocardial perfusion and left ventricular function, which provides additional prognostic value. With increasing concern over early detection of coronary artery disease and its effective treatment, myocardial perfusion imaging is ideally placed to provide a full "one stop" functional assessment for any patient, irrespective of their exercise capacity. This applies not only to patients with chest pain but also to those with myocardial infarction, revascularisation, and heart failure, and those being assessed for non-cardiac surgery. The focus of this review is the use of myocardial perfusion imaging in risk stratification for coronary artery disease.

Coronary Artery Disease↗

Pre-discharge stress echocardiography and exercise ECG for risk stratification after uncomplicated acute myocardial infarction: results of the COSTAMI-II (cost of strategies after myocardial infarction) trial.

OBJECTIVE: To compare in a prospective, randomised, multicentre trial the relative merits of pre-discharge exercise ECG and early pharmacological stress echocardiography concerning risk stratification and costs of treating patients with uncomplicated acute myocardial infarction. DESIGN: 262 patients from six participating centres with a recent uncomplicated myocardial infarction were randomly assigned to early (day 3-5) pharmacological stress echocardiography (n = 132) or conventional pre-discharge (day 7-9) maximum symptom limited exercise ECG (n = 130). RESULTS: No complication occurred during either stress echocardiography or exercise ECG. At one year follow up there were 26 events (1 death, 5 non-fatal reinfarctions, 20 patients with unstable angina requiring hospitalisation) in patients randomly assigned to early stress echocardiography and 18 events (2 reinfarctions, 16 unstable angina requiring hospitalisation) in the group randomly assigned to exercise ECG (not significant). The negative predictive value was 92% for stress echocardiography and 88% for exercise ECG (not significant). Total costs of the two strategies were similar (not significant). CONCLUSION: Early pharmacological stress echocardiography and conventional pre-discharge symptom limited exercise ECG have similar clinical outcome and costs after uncomplicated infarction. Early pharmacological stress echocardiography should be considered a valid alternative even for patients with interpretable baseline ECG who can exercise.

Adult↗

Stress echocardiography for the diagnosis and risk stratification of patients with suspected or known coronary artery disease: a critical appraisal. Supported by the British Society of Echocardiography.

Stress echocardiography today has matured into a robust and reliable technique not only for the diagnosis of suspected coronary artery disease (CAD) but also for the accurate risk stratification of patients with suspected and established CAD. This is mainly because of rapid advances in image acquisition, digital display, and the development of harmonic and contrast imaging. Stress echocardiography today is also utilised in patients with heart failure both for assessing the cause of heart failure and determining the extent of hibernating myocardium. With advances in myocardial perfusion imaging, stress echocardiography now allows simultaneous assessment of myocardial function and perfusion. Tissue Doppler imaging allows quantitation of wall motion. Ready availability and reliability makes stress echocardiography a cost effective technique for the assessment of CAD.

Aged↗

Prognostic stratification of patients after myocardial infarction.

An attempt was made to stratify risk of subsequent cardiac events in post-infarct patients according to a combination of the results of clinical assessment, routine diagnostic investigations, and pre-discharge exercise testing in 350 consecutive patients who were followed up for one year. Patients were classified prospectively on the basis of the extent of myocardial damage as assessed by peak enzyme release, reciprocal change on the electrocardiogram at the time of myocardial infarction, Norris prognostic index, ability to perform a pre-discharge exercise test (and test result), and ability to tolerate beta adrenergic blockade on discharge. Of the 50 patients with contraindications to pre-discharge exercise testing, 26% died or had reinfarctions compared with 9% of the 300 exercised patients; the 24 non-exercised patients with evidence of extensive myocardial damage or reciprocal changes on the electrocardiogram were particularly at risk. Similarly, among the 300 exercised patients, extensive myocardial damage, reciprocal change on the electrocardiogram, and ST depression on exercise testing were the major risk markers in that each identified at least 75% of the patients who had subsequent cardiac events. The 63 exercised patients who had all three of these major risk markers constituted a high risk group: 18 (29%) died or had reinfarction. Of the remaining 237 patients, only 9 (4%) had cardiac events. The 35 high risk patients with exercise induced angina pectoris or clinical contraindications to beta blockade were particularly at risk; 15 (43%) died or had reinfarction. This approach to risk stratification identified a small cohort of high risk patients in a large population of myocardial infarction survivors; it also identified a large group with a very low risk of subsequent cardiac events.

Electrocardiography↗

Reassessment of treadmill stress testing for risk stratification in patients with acute myocardial infarction treated by thrombolysis.

OBJECTIVES: To evaluate the role of a treadmill stress test for identifying patients at risk of recurrent ischaemic events after acute myocardial infarction treated by thrombolysis. BACKGROUND: The natural history of myocardial infarction has changed with the introduction of thrombolytic treatment; there is a lower mortality but a higher incidence of recurrent thrombotic events (reinfarction, unstable angina). The treadmill stress continues to be recommended for risk stratification after acute myocardial infarction even though its value has never been formally reassessed in the thrombolytic era. METHODS: Prospective observational study in which 256 consecutive patients who presented with acute myocardial infarction treated by thrombolysis underwent an early treadmill stress test and were followed up for 10 (range 6-12) months. RESULTS: Recurrent ischaemic events occurred in 41 patients (unstable angina 15, reinfarction 21, death five) and a further 21 required revascularisation. Both ST depression at a low workload and low exercise tolerance (< 7 metabolic equivalents of the task (METS) were predictive of recurrent events, with respective hazard ratios of 1.93 (95% confidence interval (95% CI) 1.17-3.20; p < 0.01)) and 1.67 (95% CI 1.0-2.78; p < 0.05). These variables identified 50% and 70% of patients who subsequently sustained a recurrent ischaemic event, but the corresponding values for positive predictive accuracy were only 26% and 21%. Thus they are of limited value as a screening measure for identifying patients likely to benefit from invasive investigation and revascularisation. None of the other variables (ST elevation, haemodynamic responses, ventricular extrasystoles, angina) was significantly associated with recurrent ischaemic events. CONCLUSIONS: The treadmill stress test is of limited value for identifying patients at risk of recurrent ischaemic events after acute myocardial infarction treated by thrombolysis.

Adult↗

Inherited thrombophilia and stratification of ischaemic stroke risk among users of oral contraceptives.

BACKGROUND: Whether use of oral contraceptives is a risk factor for arterial ischaemic stroke is controversial. In particular, few data are available on what criteria should be adopted to establish an individual profile of risk before the start of oral contraceptives. PATIENTS AND METHODS: The effects of oral contraceptives and their interaction with the G1691A polymorphisms of the factor V gene, the G20210A polymorphisms of the prothrombin gene and the C677T polymorphisms of the MTHFR gene on the risk of cerebral ischaemia were determined in a series of 108 consecutive women aged <45 years with ischaemic stroke and 216 controls, in a hospital-based case-control study design. RESULTS: Use of oral contraceptives was associated with an increased risk of cerebral ischaemia (odds ratio (OR) 3.95; 95% confidence interval (CI) 2.29 to 6.78). ORs for stroke were 2.25 (95% CI 1.15 to 4.40), 3.94 (95% CI 2.28 to 6.81) and 8.87 (95% CI 3.72 to 21.1) for non-oral contraceptive users with the TT MTHFR genotype, oral contraceptive users without the TT MTHFR genotype and oral contraceptive users with the TT MTHFR genotype, respectively, when compared with non-oral contraceptive users without the TT MTHFR genotype, with a multiplicative independent effect. Compared with non-oral contraceptive users, ORs for stroke were 2.65 (95% CI 1.46 to 4.81) for oral contraceptive users with none of the studied polymorphisms and 22.8 (95% CI 4.46 to 116.00) for oral contraceptive users with at least one of the studied polymorphisms, with a synergistic effect. CONCLUSIONS: Exposure to the effects of oral contraceptives may increase the risk of ischaemic stroke in women with an inherited prothrombotic background. Testing for these genetic variants may allow more accurate stratification of the population at risk before long-term use of oral contraceptives is prescribed.

Adult↗

DIA proteomics of FFPE renal biopsies reveals two molecular subtypes of lupus nephritis and identifies APOL1 as candidate biomarker for stratification.

INTRODUCTION: Lupus nephritis (LN) exhibits substantial clinical and pathological heterogeneity. We aimed to define proteomics-based molecular subtypes of LN and identify candidate biomarkers for subtype discrimination. METHODS: We analysed formalin-fixed paraffin-embedded (FFPE) renal biopsy specimens from 292 patients with biopsy-proven LN from four tertiary hospitals using data-independent acquisition (DIA)-liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics. Molecular subtypes were identified by non-negative matrix factorisation. Differential proteins, functional enrichment, immune pathway activity, protein-protein interaction networks and subtype-associated clinical/pathological features were evaluated. Extreme Gradient Boosting (XGBoost) with SHapley Additive exPlanations (SHAP) and Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression were used to identify key subtype-related features and derive a protein panel distinguishing proliferative (class III/IV) from membranous (class V) LN. RESULTS: Two stable molecular subtypes were identified, with 1002 differential proteins between them. Subtype_2 was enriched for interferon-related innate immunity, complement activation, phagocytosis-endocytosis-lysosome pathways and ribosome biogenesis/RNA metabolism, whereas Subtype_1 was characterised by keratinisation and epithelial structural remodelling. Subtype_2 was associated with higher serum creatinine, lower estimated glomerular filtration rate and higher chronicity index. APOL1 showed discriminatory value between subtypes, and serum ELISA demonstrated a consistent pattern with FFPE proteomic findings. A five-protein LASSO panel achieved an area under the curve of approximately 0.76 for distinguishing class III/IV from class V LN. CONCLUSION: DIA-based proteomic profiling of FFPE renal biopsies identifies biologically and clinically relevant LN molecular subtypes and may support tissue-informed classification and risk stratification.

Humans↗

Stratification in the gallbladder on intravenous cholangiography. The value of delayed or 24-hour radiographs.

Errors in interpretation of intravenous cholangiograms are often made if 24-hour radiographs are not obtained. Three cases are presented in which radiographs, obtained 1/2--4 hours after administration of contrast material, failed to demonstrate gallstones in the visualized gallbladder. However, 24-hour radiographs revealed calculi in all three patients. Stratification of bile is thought to be the mechanism responsible. Delayed radiographs assure proper mixing of contrast material and bile, and provide optimal visualization of the gallbladder in patients undergoing intravenous cholangiography.

Adult↗

Examining population stratification via individual ancestry estimates versus self-reported race.

Population stratification has the potential to affect the results of genetic marker studies. Estimating individual ancestry provides a continuous measure to assess population structure in case-control studies of complex disease, instead of using self-reported racial groups. We estimate individual ancestry using the Federal Bureau of Investigation CODIS Core short tandem repeat set of 13 loci using two different analysis methods in a case-control study of early-onset lung cancer. Individual ancestry proportions were estimated for "European" and "West African" groups using published allele frequencies. The majority of Caucasian, non-Hispanics had >50% European ancestry, whereas the majority of African Americans had <20% European ancestry, regardless of ancestry estimation method, although significant overlap by self-reported race and ancestry also existed. When we further investigated the effect of ancestry and self-reported race on the frequency of a lung cancer risk genotype, we found that the frequency of the GSTM1 null genotype varies by individual European ancestry and case-control status within self-reported race (particularly for African Americans). Genetic risk models showed that adjusting for individual European ancestry provided a better fit to the data compared with the model with no group adjustment or adjustment for self-reported race. This study suggests that significant population substructure differences exist that self-reported race alone does not capture and that individual ancestry may be confounded with disease status and/or a candidate gene risk genotype.

Black People↗

Combined histopathological and molecular cytogenetic stratification of medulloblastoma patients.

This study examined the utility of stratifying children with medulloblastomas by a combination of refined histopathological classification and molecular cytogenetic evaluation. Detailed histopathological classification of tumors from a cohort of patients (n = 87) composed mainly of children entered into the International Society of Pediatric Oncology (SIOP)/United Kingdom Children's Cancer Study Group PNET3 trial (n = 65), included identification of the large cell/anaplastic phenotype. Fluorescence in situ hybridization was used to detect chromosome 17 abnormalities, losses of 9q22 and 10q24, and amplification of the MYCC and MYCN oncogenes. The large cell/anaplastic phenotype, which was present in 20% of medulloblastomas, emerged as an independent prognostic indicator. Loss of 17p13.3 (38% of medulloblastomas) was found across all of the histopathological variants, whereas MYCC/MYCN amplification (6%/8% of medulloblastomas) was significantly associated with the large cell/anaplastic phenotype. Both of these genetic abnormalities emerged as prognostic indicators. Loss of 9q22 was associated with the nodular/desmoplastic medulloblastoma variant, whereas loss of 10q24 was found in all of the variants. Together with metastatic tumor at presentation, the large cell/anaplastic phenotype, 17p13.3 loss, or high-frequency MYC amplification defined a high-risk group of children whose outcome was significantly (P = 0.0002) poorer than a low-risk group without these tumor characteristics. Combined evaluation of novel histopathological features and molecular cytogenetic abnormalities promises to allow stratification of patients with medulloblastoma, such that those likely to be cured will be spared the side effects of maximal therapy, which can be targeted at those with aggressive disease.

Cerebellar Neoplasms↗

Molecular stratification of diagnostically challenging high-grade gliomas composed of small cells: the utility of fluorescence in situ hybridization.

PURPOSE: There is considerable morphologic overlap between various entities of high-grade gliomas, and, therefore, a further planning of their optimal treatment is a controversial issue. The aim of this study was molecular stratification of morphologically ambiguous high-grade gliomas composed from small cells. Fluorescence in situ hybridization (FISH) with commercially available probes was used for this purpose. EXPERIMENTAL DESIGN: We analyzed a set of 114 high-grade small-cell gliomas that were difficult to interpret diagnostically because of their distinct cytological origin. FISH assay with locus probes for EGFR, p16, PTEN, and 1p and 19q was done. RESULTS: Morphologically uniform high-grade gliomas composed of small cells varied greatly in terms of molecular features and clinical outcome. Four clinically relevant subsets of patients whose tumors showed distinctly different molecular profiles were identified as follows: (a) 13 patients whose tumors exhibited no discernable molecular alterations (5-year survival rate, 83%); (b) 20 patients whose tumors harbored either 1p/19q codeletion or isolated deletion of 19q unaccompanied by other molecular abnormalities (5-year survival rate, 59%); (c) 35 patients whose tumors showed p16 and/or PTEN deletions unaccompanied by EGFR amplification (5-year survival rate, 8%); and (d) 46 patients whose tumors harbored EGFR amplification (5-year survival rate, 0). CONCLUSIONS: The FISH method provides clinically useful information in the molecular analysis of morphologically ambiguous malignant small-cell gliomas that could potentially enhance the quality of patient care.

Adolescent↗