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Results for “prognostic stratification”

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PubMed1993

[Acquired aplastic anemia: a stereological analysis of bone marrow fatty tissue and its clinical correlations].

BACKGROUND: To analyze the changes of the number and size of bone marrow adipocytes in aplastic anaemia. To discover possible clinical and haematological factors which may be associated with predominant expansion of the number or size of adipocytes. To analyze the prognostic value of the adipocyte number and size. METHODS: The adipose tissue of 25 plastic-embedded bone marrow specimens corresponding to patients with aplastic anaemia was studied stereologically. The correlation study between the results obtained and clinical and haematological data was carried out. RESULTS: The expansion of the adipose tissue is due to the predominant increase of the adipocyte number in some cases and of the adipocyte size in others. Among different clinical and haematological factors, only a lower age is significantly associated with a predominant increase of adipocyte number. In the prognostic stratification performed according to three different systems, neither the adipocyte number nor the size showed a statistically significant association. CONCLUSIONS: In the aplastic anaemia, the younger patients expand their bone marrow adipose tissue by increasing predominantly the adipocyte number, whereas in the older patients this occurs by predominantly increasing the adipocyte size (may be due to the decrease in proliferative potential). On the other hand, both the adipocyte number and size lack prognostic significance.

Adipocytes↗

PubMed1999

Clinically useful information provided by the flow cytometric immunophenotyping of hematological malignancies: current status and future directions.

BACKGROUND: At present, immunophenotyping of hematological malignancies represents one of the most relevant clinical applications of flow cytometry. In recent years, its use has extended from clinical research to diagnostic laboratories. The aim of this report is to critically review the type of information provided by the flow cytometric immunophenotyping of hematological malignancies and its clinical impact as well as to highlight its potential future applications. METHODS: The currently available information, including that provided by different international consensus groups on the phenotypic characterization of hematologic malignancies, was reviewed. Additionally, recent reports on the immunophenotypic analysis of hematological malignancies published in hematology, oncology, pathology, immunology, and cell biology journals were also analyzed. RESULTS: A careful review of the literature showed that in spite of the well-established utility of immunophenotyping for the diagnosis, classification, prognostic stratification, and monitoring of hematological malignancies, only a small part of the information on the immunophenotypic characteristics of pathological hemopoietic cells has been used routinely. Specific and sensitive identification of neoplastic cells and their accurate enumeration and phenotypic characterization represent the major aims of these procedures. Similarities between leukemic and healthy cells allow the establishment of the lineage and maturation stage of the pathologic cells, this information being of great utility for the diagnosis, classification, and prognostic evaluation of different subtypes of hematological malignancies. On the other hand, the phenotypic aberrations displayed by leukemic cells could allow the selection of cases carrying specific genetic abnormalities in which further confirmatory molecular studies will be performed. CONCLUSIONS: The information provided by the flow cytometric immunophenotyping of hematological malignancies is of great clinical utility, with a major challenge for the near future being the standardization of technical procedures, data interpretation, and reporting.

Flow Cytometry↗

PubMed2026

An oxidative stress - and immunotherapy-related six-gene signature defines immune subtypes and predicts prognosis and immunotherapy response in hepatocellular carcinoma.

BACKGROUND: Oxidative stress and the tumor immune microenvironment jointly shape hepatocellular carcinoma (HCC) progression and response to immunotherapy, yet integrated biomarkers linking these processes are lacking. METHODS: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to identify oxidative stress- and immunotherapyrelated differentially expressed genes (OSIRDEGs). Functional enrichment, weighted gene co-expression network analysis (WGCNA) and LASSO-Cox regression were used to construct a prognostic signature. Consensus clustering, TIDE, CIBERSORT and ssGSEA characterized immune phenotypes. Somatic mutation, copy-number and drug-response data were integrated to assess genomic alterations and drug sensitivity. Expression of model genes was validated by qRT-PCR and western blotting in HCC cell lines. RESULTS: We identified 24 OSIRDEGs enriched in cell-cycle and mitotic pathways. WGCNA intersection yielded 18 module genes, from which a six-gene signature (BUB1B, CDKN2A, CENPE, HMMR, PTTG1, SPP1) was derived. The signature robustly stratified patients into high- and low-risk groups with significantly different progression-free and disease-free survival in both TCGA-LIHC and GSE14520. Based on signature expression, two molecular subtypes were defined, exhibiting distinct survival, immune landscapes and predicted immunotherapy responsiveness. Model genes harbored recurrent alterations and showed significant correlations with anticancer agents. All six genes were upregulated at mRNA and protein levels in metastatic HCC cell lines versus normal hepatocytes. CONCLUSIONS: We systematically explored the landscape of OSIRDEGs in HCC, and proposed a validated six-gene signature that refines prognostic stratification, delineates immunerelevant HCC subtypes and highlights candidate biomarkers for therapeutic selection and mechanistic investigation.

Humans↗

PubMed2000

[Echocardiographic follow-up of patients with heart failure. Which parameters should be measured? How often?].

The echocardiographic evaluation keeps a relevant place in the evaluation of patients with heart failure and left ventricular systolic dysfunction, not only for its contribution to the diagnosis, prognostic stratification and comprehension of pathogenetic mechanisms, but also for the analysis of the evolution of the disease and the response to optimal medical therapy. On the other hand, the role of echocardiography in the follow-up of patients with diastolic dysfunction is still unclear. In patients with heart failure and left ventricular systolic dysfunction the analysis of changes in left ventricular function and dimension during follow-up is particularly relevant to recognize the potential benefit of optimal medical therapy with ACE-inhibitors and beta-blockers and their prognostic significance. The echo-Doppler hemodynamic evaluation is also of clinical and prognostic value particularly for the recognition of the persistence or (re)appearance of restrictive filling pattern during follow-up. Moreover, in patients with persistent severe left ventricular systolic dysfunction, the evaluation of right ventricular function may allow for the identification of a subset of patients at high risk for cardiovascular events. A practical flow-chart of echocardiographic assessment of patients with heart failure and left ventricular systolic dysfunction includes the following steps: 1) after 3 to 6 months on optimal therapy, to detect the persistence of restrictive filling pattern, if present at diagnosis; 2) after 12 to 24 months, to analyze the response of left ventricular function and dimension to optimal medical treatment; 3) serial examinations, according to the stage of the disease or to the episodes of worsening heart failure, to identify echocardiographic indicators of disease progression, such as worsening of left ventricular and/or right ventricular function or (re)appearance of restrictive filling pattern. The changes in these parameters seem to have a relevant prognostic significance to define the risk profile of patients with heart failure and left ventricular systolic dysfunction.

Follow-Up Studies↗

PubMed2005

Pulmonary arterial hypertension: evaluation of the newly diagnosed patient.

With a quickly growing range of therapeutic options precise prognostic stratification became particularly important for clinical decision making in patients with pulmonary arterial hypertension (PAH). Assessment of disease-specific functional class remains the simplest method and is a fairly reliable way of assessing severity of PAH, and current guidelines recommend a therapeutic algorithm based on functional class evaluation. Six-minute walk is the most widely used test assessing exercise tolerance both in clinical practice and in clinical trials testing new therapies in PAH. Right heart catheterization with a vasoreactivity test is mandatory to identify a subgroup that has good long-term prognosis when treated with calcium channel blockers alone. Echocardiographic variables of documented prognostic value in PAH are not those directly correlated with pulmonary arterial pressure (PAP). Instead, the presence of pericardial effusion, enlarged right atrium, and elevated Doppler index of right ventricular performance have been the most consistently reported signs of poor prognosis. Low or decreasing brain natriuretic peptide (BNP) suggests a good outcome whereas troponin T leak persisting despite therapy is a poor prognostic sign. Biomarkers seem particularly useful for noninvasive follow-up of patients with PAH, and due to simplicity and low costs may successfully compete with echocardiography.

Biomarkers↗

PubMed2026

Circulating tumor cells identify a disseminated genomic high-risk phenotype within IMS-IMWG 2025 staging in newly diagnosed multiple myeloma.

The 2025 IMS-IMWG consensus genomic staging (CGS) system has improved genomic risk stratification in newly diagnosed multiple myeloma (NDMM), yet does not capture whether high-risk clones have acquired a disseminated phenotype. We investigated whether circulating tumor cells (CTC) refine CGS and enable longitudinal residual disease monitoring. We retrospectively analyzed 631 MM patients from the NICHE cohort (NCT04645199) who underwent CTC assessment across disease phases. Among 410 patients assessed at diagnosis, CTC were detectable in 63.9% and correlated with both bone marrow plasma cell infiltration and accumulation of high-risk cytogenetic abnormalities. In 359 NDMM patients with adequate follow-up, a cohort-derived CTC threshold of 0.38% independently predicted inferior progression-free survival (PFS) after multivariable adjustment. Importantly, CTC refined prognostic stratification specifically within the CGS high-risk subgroup. Patients with CGS high-risk/CTC-high disease had the shortest PFS, thereby defining a disseminated genomic high-risk phenotype comprising 12.4% (39/314) of evaluable NDMM patients. In follow-up cohorts, detectable CTC were associated with inferior outcomes in 127 patients assessed during non-progressive disease states, whereas combined CTC and bone marrow minimal residual disease assessment stratified outcomes in 120 patients with paired measurements. Overall, CTC-integrated CGS supports minimally invasive baseline risk stratification and longitudinal disease monitoring.

Journal Article↗

PubMed1992

[Prognostic value of the dipyridamole-echocardiography test immediately after a non-complicated myocardial infarct: a large scale multicenter study. Echo Persantine Italian Cooperative Study].

BACKGROUND: Any new diagnostic test should follow a pathway similar to that of a new drug, from initial studies in highly selected populations under strictly controlled conditions, up to large scale multicenter trials more likely to represent the true performance of the test in the clinical arena. AIM OF THE STUDY: To evaluate the capability of prognostic stratification of high dose (up to 0.84 mg/kg over 10') dipyridamole-echocardiography test (DET) early after an acute myocardial infarction in a "phase IV" study, based upon 11 different echocardiographic laboratories, all with established experience in stress echo and fulfilling quality control requirements for stress echo readings. STUDY POPULATION: Nine-hundred twenty five patients were evaluated after a mean of 10 days from an acute myocardial infarction and followed up for a mean of 14 months. RESULTS: During DET, one major adverse reaction occurred, consisting of a prolonged ischemia resistant to aminophylline and nitrates, and progressing to small uncomplicated reinfarction. In 11 patients the lower dipyridamole dose (0.56 mg/kg over 4') gave limiting side effects. Patients were followed up for 14 +/- 9.9 months (range = 1.53). During the follow-up, there were 34 deaths and 37 non-fatal myocardial infarctions; 104 patients developed class III or IV angina, and 149 had coronary revascularization procedures (bypass or angioplasty). Considering all spontaneous events (angina, reinfarction and death), the most important univariate predictor was the result of DET (chi-square = 45.8). With a Cox analysis, echocardiographic positivity, age and sex were found to have an independent and additive value. Considering survival (and therefore death as the only event) age was the most meaningful parameter, followed by the Wall Motion Score Index during dipyridamole (chi-square = 12.1); among other parameters, the resting Wall Motion Score Index was a significant predictor of death. By Cox analysis, age (relative risk estimate = 1.02) and Wall Motion Score Index during dipyridamole (relative risk estimate = 14) showed an independent and additional prognostic value. In particular, considering death only, the event rate was of 2% in patients with negative DET, 4% in patients with high dose positive DET and 7% in patients with low dose positive DET. CONCLUSIONS: Dipyridamole echocardiography is feasible and safe early after uncomplicated myocardial infarction and allows an effective risk stratification on the basis of the presence, severity, extent and timing of the induced dyssynergy. In particular, the risk of death doubles in patients with high dose positivity and almost quadruples in patients with low dose positivity.

Adult↗

PubMed1997

[Natriuretic peptides and the heart. Critical review and application].

This paper deals with a literature survey on natriuretic peptides (NP) and their clinical use in prognostic stratification and therapy of arterial hypertension and cardiac failure. After a brief historical introduction, the phylogenesis of NP is analyzed and the reasons of their preservation in the evolution are emphasized. The biochemistry of the NP is then treated, and the structure, synthesis, mechanism of cellular action and systems of regulation are analyzed. Subsequently, the authors have analyzed the physiology of the NP as well as their hemodynamic and biohumoral effects and actions on the central nervous system. A literature review on the significance of NP in arterial hypertension, on their usefulness as indicators of damage and on their therapeutic practice is then made. In particular, the possible future applications in the prevention of atherosclerotic damage are analyzed. The significance of NP and of their metabolites in heart failure and the prognostic implication of these peptides particularly in ischemic heart failure are then discussed. The most important papers on this topic are described. Finally the studies on the use of NP in the therapy of heart failure are analyzed and a guide on research of this topic is defined.

Atrial Natriuretic Factor↗

PubMed2005

Prognostic significance of residual cumulative ST-segment deviation after mechanical reperfusion in patients with ST-segment elevation myocardial infarction.

BACKGROUND: The analysis of ST-segment resolution is a well established and easy method to assess myocardial perfusion after reperfusion therapy for ST-segment elevation myocardial infarction (STEMI). The aim of the current study was to identify an easy and practical instrument for patients' prognostic stratification after angioplasty for STEMI by the use of only postprocedural ST-segment analysis. METHODS: Our population is represented by a total of 1286 patients treated with primary angioplasty for STEMI. Residual ST-segment elevation and deviation were analyzed at 3 hours after revascularization. One-year follow-up data were collected prospectively in all patients. RESULTS: Patients with impaired ST-segment normalization were older, with larger prevalence of diabetes, anterior infarction, hypertension, signs of heart failure at presentation, lower rate of postprocedural thrombolysis in myocardial infarction 3 flow, myocardial blush grades 2 to 3, and successful reperfusion. A linear relationship was found between both residual cumulative ST-segment elevation and deviation with 1-year mortality. At multivariate analysis, postprocedural residual cumulative ST deviation (RR 1.31, 95% CI 1.06-1.63, P = .014), but not residual cumulative ST elevation (RR 0.95, 95% CI 0.55-1.67, P = .87), was an independent predictor of 1-year mortality. Furthermore, we found that residual cumulative ST-segment deviation provides better prognostic information (area receiver operating characteristic [ROC] = 0.733) than ST-segment elevation resolution (area ROC = 0.636) or ST-segment deviation resolution (area ROC = 0.660) in terms of 1-year mortality. These data were confirmed for both anterior and nonanterior infarct location. CONCLUSION: This study showed that postprocedural residual cumulative ST-segment deviation is an independent prognostic parameter in patients treated with primary angioplasty, providing even better prognostic information than ST-segment resolution.

Aged↗

PubMed2001

[Myelodysplastic syndromes. Clinico-pathologic analysis of 54 cases].

For myelodysplastic syndromes (MDS) many scoring systems were developed to improve the prognostic stratification of patients. METHODS AND AIM OF THE STUDY: We enrolled 54 primary MDS patients, having an advanced median age of 78.5 years, that discouraged the choice of aggressive treatments. Then, we employed only the Bournemouth score (without cytogenetic analysis), with the aim to identify the best predictor of death and of AML development. RESULTS: Both for overall and leukemia-free analysis, shorter survival and faster development of AML were found in MDS patients with severe peripheral cytopenia, RAEB-T, major proportion of bone marrow blasts (over 20%) and with the higher Bournemouth score (i.e. 3-4). The multivariate analysis by the Cox's regression model showed that a high percentage of bone marrow blasts presented the best statistical significance. CONCLUSIONS: In our survey we confirmed the value of Bournemouth score in identifying those MDS patients presenting a greater risk of death and AML development. Moreover, a high percentage of bone marrow blasts rose as the best predictor of death and leukemic evolution. The kariotypic analysis, with a stronger prognostic power but also complex and expensive, was not performed in our elderly MDS patients, who were unable to tolerate aggressive treatments.

Aged↗

PubMed2006

Molecular cytogenetic stratification of recurrent oligodendrogliomas: utility of interphase fluorescence in situ hybridization (I-FISH).

In oligodendroglial brain tumours, losses of chromosomal material of the short arm of chromosome 1 and long arm of chromosome 19 have been shown to predict responsiveness to chemotherapy and prolonged patients' survival. Therefore, the correct diagnosis of these genetic alterations in tumours of oligodendroglial origin is particularly important. To detect deletions of 1p36 and/or 19q13.3 in oligodendroglial cells we used dual-colour I-FISH with locus-specific DNA probes. I-FISH was performed on isolated whole cell nuclei, prepared from fresh non-fixed tumour tissue samples resuspended in media and processed using a standard cytogenetic procedure, thus bypassing the problem of nuclear truncation. We examined 16 patients with histologically proved oligodendrogliomas (5x oligodendroglioma, 9x anaplastic oligodendroglioma, 2x anaplastic oligoastrocytoma). The results of molecular cytogenetic analyses were correlated with morphological and clinical findings. Molecular cytogenetic analyses were successful in 15 patients and, due to a non-adequate tissue specimen, were uninformative in one patient only. Combined deletions 1p36/19q13 were proved in 13 patients. However, in six of them additional genetic alterations typical for high-grade astrocytoma were found, which could have negative influence on the prognosis. One patient had isolated deletion of 1p36 and another had a normal genetic pattern without any chromosomal alterations. In summary, I-FISH on isolated cell nuclei is a powerful tool for detecting chromosomal aberrations in tumour cells. A systematic molecular cytogenetic analysis may advance diagnosis, prognostic stratification, and targeted treatment of patients with brain tumours.

Adult↗

PubMed2004

Idiopathic dilated cardiomyopathy: prognostic significance of electrocardiographic and electrophysiologic findings in the nineties.

BACKGROUND: With the exception of a few cases such as aborted sudden cardiac death, sustained ventricular tachycardia, and syncope of unexplained origin, there is no consensus on the clinical findings identifying patients with idiopathic dilated cardiomyopathy with an increased risk of sudden cardiac death or malignant ventricular arrhythmias. METHODS: To verify whether electrocardiographic and arrhythmologic features could be useful for prognostic stratification, 78 consecutive patients with an invasive diagnosis of idiopathic dilated cardiomyopathy, but without symptomatic ventricular arrhythmias, were enrolled in a prospective study. Signal-averaged ECG, 24 to 48 hour ECG monitoring and electrophysiologic study were performed at the time of diagnosis to identify arrhythmogenic predictors of outcome. Transplant-free and arrhythmic event-free survival was evaluated on the basis of initial parameters. RESULTS: During a mean follow-up of 85 months, 9 patients died (6 of sudden cardiac death and 3 of congestive heart failure), 10 patients underwent cardiac transplantation for refractory heart failure, and 3 presented with sustained ventricular tachycardia. The independent predictors for death and cardiac transplantation were an HV interval > 55 ms and the combination of frequent repetitive ventricular ectopics with a poor left ventricular function. A strong index of arrhythmic events proved to be the association of a prolonged HV interval with a wide (> 110 ms) QRS complex (odds ratio 4.53, 95% confidence interval 1.57-13.04, p < 0.005). CONCLUSIONS: An accurate measurement of the HV interval and QRS duration at baseline evaluation may add prognostic information in patients with idiopathic dilated cardiomyopathy. In our experience, abnormal values of both parameters identified a group of patients with a very high risk of late occurring arrhythmic events.

Adolescent↗

PubMed2006

A novel prognostic index to determine the impact of cardiac conditions and co-morbidities on one-year outcome in patients with heart failure.

Prognostic stratification is relevant in clinical decision making in heart failure (HF). Predictors identified during hospitalization or in clinical trials may be unrepresentative of HF in the community. The aim of this study was to derive and validate, in different clinical settings, a risk stratification model for the prediction of stable HF outcomes. The study included 807 patients, 350 enrolled at discharge from the hospital (44%), 309 in the outpatient clinic (38%), and 148 in the home-care setting (18%). There were 292 patients in the derivation cohort and 515 in the validation cohort. A multivariate logistic analysis was performed to obtain the CardioVascular Medicine Heart Failure (CVM-HF) index. One-year mortality was 20.8% in the derivation cohort and 20.7% in the validation cohort. The CVM-HF index included cardiac conditions and co-morbidities and stratified the 1-year mortality risk as low (death rate 4%), average (32%), high (63%), and very high (96%). The area under the curve of the receiver-operating characteristic curve was 0.844 (95% confidence interval [CI] 0.779 to 0.89) for the derivation cohort and 0.812 (95% CI 0.76 to 0.86) for the validation cohort. Model performance was equally good in the 3 different HF settings. In a subgroup of 409 patients, the CVM-HF index (area under the curve 0.821, 95% CI 0.79 to 0.89) outperformed the most-used prognostic models (the Charlson index and the Heart Failure Risk Scoring System). In conclusion, the CVM-HF index, a novel prognostic model that is easy to derive and applicable to unselected patients, may represent a valuable tool for the prognostication of stable HF outcomes.

Aged↗

PubMed1998

Signal-averaged ECG in patients after anthracycline therapy for childhood cancer.

Late cardiac complications after anthracycline therapy is an increasingly common problem among survivors of childhood cancer. Routine clinical examination may be normal, but subclinical cardiac abnormalities, which may progress with time, are documented in high percentage of these patients. Microstructural myocardial alterations may result in production of micropotential level signals (late potentials, LP) and altered frequency components of signal-averaged ECGs (SAECG). SAECG abnormalities are valuable in risk stratification of patients with various heart diseases culminating in fatal arrhythmias or heart failure. Forty-five pediatric oncologic patients (mean age 14.4 +/- 4.1 years) were included in the study. SAECG was performed 3 months-12 years (median 5.5 years) following completion of anthracycline therapy. The total cumulative doses of anthracyclines were 90-555 (median 230) mg/m2. The control group consisted of 30 healthy age-matched volunteers. LP were present in six (13.3%) patients after anthracycline therapy at 40 Hz high-pass filter setting. Using frequency-domain analysis within the QRS complex, area ratio 1 (area of 20 to 50 Hz/area of 0 to 20 Hz) and area ratio 2 (area of 40 to 100 Hz/area of 0 to 40 Hz) were calculated. Twenty (44.4%) and fourteen (31.1%) had abnormal values in area ratios 1 and 2, respectively, within the QRS complex. Area ratios 1 and 2 of patients after anthracycline therapy were significantly higher than those in control group (p = 0.0187 and p = 0.0043). Our preliminary results suggest that chemotherapy with anthracyclines, even in low dosage, is associated with increased incidence of SAECG abnormalities. The potential of this simple, noninvasive method to detect subclinical anthracycline-induced myocardial alterations and facilitate prognostic stratification of cancer survivors is promising, however, the clinical value of SAECG remains to be established in a larger and a longer study.

Adolescent↗

PubMed2005

Incremental prognostic value of stress echo positivity in the left anterior descending coronary artery territory.

BACKGROUND: Dipyridamole stress echo (DSE) positivity is usually titrated according to presence and severity of the induced wall motion abnormalities. The purpose of our study is to assess whether the location of DSE positivity might add to prognostic stratification. METHODS: The study enrolled 112 patients with known or suspected coronary artery disease (CAD) and without a history of prior myocardial infarction. They were consecutively submitted to DSE (0.84 mg/Kg in 10 min followed by atropine administration, when needed) and coronary angiography (within a 15+/-7 day period). End points at follow-up were cardiac death and acute coronary syndromes. RESULTS: Twenty-seven patients had a negative, and 85 a positive DSE (47 in the LAD territory). Angiographically assessed CAD was present in 82 patients (LAD in 59). At a follow-up of 9+/-7 months, there were 28 events of cardiac deaths or acute coronary syndromes. Event-free survival was lower in patients with positive DSE (any location) compared to those with negative DSE (47% vs 89%, p=0.003). In the subset with positive DSE, event-free survival was lower in patients with wall motion abnormalities in the LAD territory compared to those with dysfunction in the left circumflex and right coronary artery territory (31% vs 72%, p=0.00012 ). At multivariate analysis, stress echo positivity in the LAD territory was independently associated with increased risk (HR: 9.51, CI: 1.61 to 56.11, p<0.013) and outperformed angiographically assessed LAD stenosis (HR: 0.36, CI: 0.06 to 2.24, p: NS). CONCLUSIONS: In CAD patients, wall motion abnormalities in the LAD territory during DSE identified a higher risk subgroup. Functional stress echo positivity on the LAD territory overcame the prognostic impact of an anatomic, angiographically assessed LAD disease.

Adult↗

PubMed2005

Risk assessment in patients with acute myeloid leukemia and a normal karyotype.

PURPOSE: The recognition of a number of leukemia-specific cytogenetic abnormalities and their role as independent prognostic factors have provided considerable insights into leukemia pathogenesis and have paved the way to adopt risk-adapted treatment. However, approximately 50% of newly diagnosed acute myeloid leukemia (AML) have a normal karyotype. There has therefore been much interest in identifying molecular markers that could help to improve the prognostic stratification of patients with normal-karyotype AML. EXPERIMENTAL DESIGN: Consecutive untreated AML patients (n = 67) from a single institution all with normal karyotype were analyzed for the presence of mutations in the myeloid transcription factor gene CEBPA (for CCAAT/enhancer binding protein-alpha), for internal tandem duplications (ITD) of the tyrosine kinase receptor gene FLT3 (for fms-like tyrosine kinase 3), and for expression of the BAALC gene (for brain and acute leukemia, cytoplasmic). RESULTS: 17.9% of normal-karyotype AML had mutations in the CEBPA gene, and 28.4% had FLT3-ITD; 65.7% (44 of 67) had high BAALC expression and 34.3% (23 of 67) had low BAALC expression. Patients with CEBPA mutations had a very favorable course of their disease. Median disease-free survival (DFS) and overall survival (OS) were 33.5 and 45.5 months, respectively, compared with 10 (e.g., 12 months in patients without CEBPA mutations; P = 0.0017; P = 0.0007). AML patients with FLT3-ITD had significantly shorter median DFS (P = 0.0328) and OS (P = 0.0148) than patients without FLT3-ITD. High BAALC expression predicted for a shorter DFS (P = 0.0152) and OS (P = 0.0210) compared with AML with low BAALC expression; 53.7% of normal-karyotype AML had neither FLT3-ITD nor CEBPA mutations. We found that high BAALC expression in normal-karyotype AML with neither FLT3-ITD nor CEBPA mutations (18 of 67) indicates adverse prognosis for both DFS and OS (P = 0.0001; e.g., P = 0.0001) compared with the group with low BAALC expression and absent FLT3-ITD and CEBPA mutations (18 of 67). Thus, BAALC expression represents a novel prognostic marker particularly for normal-karyotype AML patients with neither FLT3-ITD nor CEBPA mutations. CONCLUSIONS: Assessment of CEBPA mutations, FLT3-ITD, and BAALC expression permits to split normal-karyotype AML into clinically distinct subgroups.

Acute Disease↗

PubMed2005

Novel classification of idiopathic inflammatory myopathies based on overlap syndrome features and autoantibodies: analysis of 100 French Canadian patients.

Our objective was to improve the currently imperfect classifications of idiopathic inflammatory myopathies (IIM). In clinical practice, overlap features are common in IIM. This provided a rationale for positioning overlap clinical features at the core of a new classification system. We conducted a longitudinal study of 100 consecutive adult French Canadian patients with IIM. Clinical and laboratory data were obtained by retrospective chart review. Sera were analyzed for autoantibodies (aAbs) by protein A-assisted immunoprecipitation and double immunodiffusion. Overlap aAbs encompassed aAbs to synthetases, systemic sclerosis-associated aAbs, anti-signal recognition particle (SRP) and anti-nucleoporins. Patients were classified both at IIM diagnosis, based on data at presentation, and at the end of follow-up, based on cumulative findings. Three classifications were used: 1) the Bohan and Peter original classification, 2) a new version of that classification as modified by us, and 3) a novel clinicoserologic classification. As investigators were blinded to aAb results, the modified classification is strictly a clinical classification. Its core concept is the attribution of diagnostic significance to the presence of overlap features, that is, their presence resulted in a diagnosis of overlap myositis (OM). This approach allowed direct comparison with the original Bohan and Peter classification. By integrating aAb results to the modified classification, we also defined the clinicoserologic classification, which allowed to examine the added value of aAbs to diagnostic, therapeutic and prognostic stratification. Whereas polymyositis (PM) was the most common IIM according to the original classification, accounting for 45% of the cohort at diagnosis, its frequency fell to 14% with the modified classification. Conversely, while the frequency of myositis associated with connective tissue disease was 24% according to the original classification, the frequency of OM was 60% when using the modified classification. At last follow-up, the frequency of PM fell further to only 9%, while the frequency of OM rose to 67%. Systemic sclerosis was the most common connective tissue disease associated with IIM, accounting for 42.6% of OM patients and 29% of the cohort. The frequencies of overlap aAbs in the cohort and in OM patients were 48% and 70.5% (n =48/68), respectively. The presence of overlap aAbs at IIM diagnosis identified additional OM patients unrecognized by the modified classification. The sensitivity of the modified classification for OM at diagnosis was 87%, suggesting that clinicians may rely on the modified classification for identification of most OM patients, while awaiting results of aAb assays. The new classifications predicted the response to prednisone and IIM course. Using stringent definitions, IIM was classified as responsive or refractory after an adequate initial corticosteroid therapy, and the disease course as monophasic or chronic after a single adequate trial of prednisone. PM was always chronic and was associated with the highest rate (50%) of refractoriness to initial corticosteroid treatment. Dermatomyositis was almost always chronic (92% rate); however, its responsiveness to initial corticosteroid treatment was high (87%). OM was almost always responsive to corticosteroids (89%-100% rates). When OM patients were divided according to aAb subsets, anti-synthetase, SRP, or nucleoporin aAbs were markers for chronic myositis, whereas aAbs to U1RNP, Pm-Scl, or Ku were markers for monophasic myositis. We conclude that the original Bohan and Peter classification should be abandoned as it leads to misclassification of patients. Much of IIM is composed of OM. The proposed modified and clinicoserologic classifications have diagnostic, prognostic, and therapeutic value.

Adolescent↗

PubMed2002

Effectiveness of nurses as providers of birth labor support in North American hospitals: a randomized controlled trial.

CONTEXT: North American cesarean delivery rates have risen dramatically since the 1960s, without concomitant improvements in perinatal or maternal health. A Cochrane Review concluded that continuous caregiver support during labor has many benefits, including reduced likelihood of cesarean delivery. OBJECTIVE: To evaluate the effectiveness of nurses as providers of labor support in North American hospitals. DESIGN: Randomized controlled trial with prognostic stratification by center and parity. Women were enrolled during a 2-year period (May 1999 to May 2001) and followed up until 6 to 8 postpartum weeks. SETTING: Thirteen US and Canadian hospitals with annual cesarean delivery rates of at least 15%. PARTICIPANTS: A total of 6915 women who had a live singleton fetus or twins, were 34 weeks' gestation or more, and were in established labor at randomization. INTERVENTION: Patients were randomly assigned to receive usual care (n = 3461) or continuous labor support by a specially trained nurse (n = 3454) during labor. MAIN OUTCOME MEASURES: The primary outcome measure was cesarean delivery rate. Other outcomes included intrapartum events and indicators of maternal and neonatal morbidity, both immediately after birth and in the first 6 to 8 postpartum weeks. RESULTS: Data were received for all 6915 women and their infants (n = 6949). The rates of cesarean delivery were almost identical in the 2 groups (12.5% in the continuous labor support group and 12.6% in the usual care group; P =.44). There were no significant differences in other maternal or neonatal events during labor, delivery, or the hospital stay. There were no significant differences in women's perceived control during childbirth or in depression, measured at 6 to 8 postpartum weeks. All comparisons of women's likes and dislikes, and their future preference for amount of nursing support, favored the continuous labor support group. CONCLUSIONS: In hospitals characterized by high rates of routine intrapartum interventions, continuous labor support by nurses does not affect the likelihood of cesarean delivery or other medical or psychosocial outcomes of labor and birth.

Canada↗