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PubMed1987

Prognosis in chronic myeloid leukaemia: biology of the disease vs. treatment.

CML is best regarded as a benign neoplasm, which regularly transforms into a rapidly fatal malignant one. Survival is determined by the timing of disease transformation. The rate of transformation and death is low initially and increases gradually to a stable annual rate, reached during the third year after diagnosis. This averages 25% per year in large populations of Ph positive patients. Transformation appears to occur randomly; a patient's risk of transformation can be defined, but the time when it will occur cannot be predicted. There is no evidence that conventional antileukaemic therapy changes the risk of transformation; thus, survival is determined principally by the intrinsic biology of the disease. A number of features recorded at the time of diagnosis correlate significantly with survival and can serve as prognostic parameters. Multivariate regression and Cox model analyses can generate hazard ratio formulae which provide quantitative estimates of patients' risk. Several Cox models have been described by different groups, and it is possible that two or more models may describe survival equally well. A four-variable model described by the International CGL Prognosis Study Group in 1984 has recently been tested in a prospective study by the Italian Cooperative Study Group on Chronic Myeloid Leukaemia, and successfully classified patients into three groups with significantly different outcomes. This model produces excellent results in analyses of large patient populations, but is less satisfactory when applied to smaller series. It is likely that current prognostic models can be improved substantially to provide more accurate definition of patient risk over a broader range of hazard ratio values. Such models should prove useful in evaluating therapeutic schedules, selecting patients for investigational or hazardous treatment and making decisions regarding bone marrow transplantation.

Bone Marrow Transplantation↗

PubMed2006

[Prognostic analysis of chronic myeloid leukemia with Cox model and the Sokal, Hasford score].

This study was aimed to analyze the prognostic factors of the patients with chronic myeloid leukemia (CML). Survival curve and survival rate of 204 patients with CML were estimated with Kaplan-Meier method and Logrank respectively. Univariate and multivariate analysis of prognostic factors carried out by Cox's regression model. The Sokal and Hasford score were used to discriminate the relative risk of Hu and IFN group. The results showed that among the 204 patients, the median survival time was 50 (32-65) months, and 5 year survival rate was 32.3% (95% CI, 23.7%-42.6%). The median survival times of IFN and Hu group were 56 (41-67) and 41 (19-56) months, and 5 year survival rates were 45.4% (95% CI, 37.5%-54.2%) and 26.8% (95% CI, 21.6%-33.3%) (P < 0.001) respectively. From the Cox stepwise regression model, Ph chromosome negative, high LDH, low Hct, percentage of peripheral blood basophils > or = 10%, marrow blasts + promyelocytes > or = 10% and presence of nucleated RBCs was associated with poor prognosis, and the treatment also played an important role in CML. According to the Sokal score, the high, intermediate and low risk rates of Hu group were 72.9%, 21.5% and 5.6%, the median survival time reached 34 (23-49) months, 43 (32-58) and 50 (38-62) months respectively; while censored by the Hasford score, the high, intermediate and low risk rates of IFN group were 17.6%, 25.1% and 57.3% respectively, the median survival time was 44 (33-57), 56 (45-70) and 66 (52-76) months respectively. It is concluded that Ph chromosome, concentration of LDH, percentage of Hct, peripheral blood basophils, marrow blasts, promyelocytes, presence of nucleated RBCs and treatment are the most important prognostic factors for CML. The Sokal score can not discriminate the relative risk of Hu group well, while the Hasford score can discriminate the relative risk of IFN group.

Adolescent↗

PubMed2006

Anabolic deficiency in men with chronic heart failure: prevalence and detrimental impact on survival.

BACKGROUND: The age-related decline of circulating anabolic hormones in men is associated with increased morbidity and mortality. We studied the prevalence and prognostic consequences of deficiencies in circulating total testosterone (TT) and free testosterone, dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor-1 (IGF-1) in men with chronic heart failure (CHF). METHODS AND RESULTS: Serum levels of TT, DHEAS, and IGF-1 were measured with immunoassays in 208 men with CHF (median age 63 years; median left ventricular ejection fraction 33%; New York Heart Association class I/II/III/IV, 19/102/70/17) and in 366 healthy men. Serum levels of free testosterone were estimated (eFT) from levels of TT and sex hormone binding globulin. Deficiencies in DHEAS, TT, eFT, and IGF-1, defined as serum levels at or below the 10th percentile of healthy peers, were seen across all age categories in men with CHF. DHEAS, TT, and eFT were inversely related to New York Heart Association class irrespective of cause (all P<0.01). DHEAS correlated positively with left ventricular ejection fraction and inversely with N-terminal pro-brain natriuretic peptide (both P<0.01). Circulating TT, eFT, DHEAS, and IGF-1 levels were prognostic markers in multivariable models when adjusted for established prognostic factors (all P<0.05). Men with CHF and normal levels of all anabolic hormones had the best 3-year survival rate (83%, 95% CI 67% to 98%) compared with those with deficiencies in 1 (74% survival rate, 95% CI 65% to 84%), 2 (55% survival rate, 95% CI 45% to 66%), or all 3 (27% survival rate, 95% CI 5% to 49%) anabolic endocrine axes (P<0.0001). CONCLUSIONS: In male CHF patients, anabolic hormone depletion is common, and a deficiency of each anabolic hormone is an independent marker of poor prognosis. Deficiency of >1 anabolic hormone identifies groups with a higher mortality.

Adult↗

PubMed2006

Association of high-level MRP1 expression with poor clinical outcome in a large prospective study of primary neuroblastoma.

PURPOSE: We have previously shown in a retrospective study that expression of the multidrug transporter gene MRP1 (ABCC1) is associated with outcome in neuroblastoma. We have now undertaken a prospective analysis to examine the independent prognostic significance of MRP1 expression in a large cohort of primary untreated neuroblastomas. PATIENTS AND METHODS: Two hundred nine diagnostic neuroblastoma samples from patients prospectively enrolled onto the Pediatric Oncology Group biology protocol 9047 were analyzed for expression of the MRP1, MDR1, MYCN, and TRKA genes using real-time polymerase chain reaction. Expression levels were correlated with established prognostic indicators and disease outcome. RESULTS: MRP1 expression was detected in all tumors analyzed, and levels were significantly higher in tumors with versus without MYCN amplification (P < .0001). High levels of MRP1 were highly predictive of both event-free survival (EFS; P < .001) and overall survival (OS; P < .001). High-level MYCN and low-level TRKA were also predictive of poor outcome. MDR1 expression demonstrated no prognostic significance. After adjustment for the effect of statistically significant prognostic indicators in multivariate models, MRP1 expression retained significant prognostic value for both EFS (hazard ratio = 3.0; P = .0011) and OS (hazard ratio = 2.5; P = .0095), whereas MYCN amplification did not have prognostic significance. CONCLUSION: The results of this prospective study confirm our earlier findings and support a clinically relevant role for MRP1 gene expression in neuroblastoma. These findings have implications for the biology, prognosis, and treatment of this disease and provide evidence that MRP1 is a bone fide molecular target for reversing chemotherapy resistance in aggressive drug-refractory neuroblastoma.

Adolescent↗

PubMed1979

Short-term prognostic index in acute myocardial infarction. Multivariate analysis by Cox model.

A new multivariate stepwise linear regression analysis (Cox's model) with survival time as prognostic endpoint was utilized in 281 patients with acute myocardial infarction. From 18 prognostic factors occurring during the first 5 days in the Coronary Care Unit a new prognostic index was calculated for the chance of survival in the first 36 days after admission. The significant prognostic variables were heart failure, cardiogenic shock, atrioventricular block and age. The total group of patients was classified in 6 subgroups with different mean indices and prognosis. There were 2 large groups of patients with relative bad and good prognosis (with and without heart failure). Over half of the patients had no prognostic variables. There was a trend of overestimating the expected deaths. A definite cardiac cause of death was shown by 23 patients (82%). This prognostic index based on the 4 variables can for the individual patient predict the chance of survival, which can be the basis of an individualized duration of hospital stay.

Age Factors↗

PubMed1999

Analyzing prognostic factors in breast cancer using a multistate model.

In breast cancer clinical research, an important goal is to analyze how factors are seen to affect the disease process. Meanwhile, the disease progression is not fully modelled using standard analysis since transitions between intermediate events such as local-regional recurrences (LRR) or metachronous contralateral breast cancer (MCBC) are not considered. In the present study, the progression of disease was modelled using a multistate model. By this approach, we assessed transitions during the course of the disease and studied prognostic factors for each transition. The model was applied to 6,185 patients with unilateral ductal invasive breast cancer, clinical stage I through III, treated between 1981 and 1988 at the Curie Institute. At first diagnosis, high clinical stage, high histological grade, positive lymph nodes, and age less than 40 years were associated with increased risks of LRR, metastases, or death. Except age, the same factors remained predictive for metastases or death following LRR. Chemotherapy for the first cancer was associated with a decreased risk for developing MCBC. As the time interval from diagnosis of the primary tumor to that of a local or contralateral recurrence increased, the risk of metastases or death decreased. Nodal status for the first tumor and clinical stage for the contralateral tumor increased the risk of metastases or death following MCBC. Conversely, the risk decreased for patients who received adjuvant hormone therapy following MCBC. In conclusion, the multistate model offers us a much more appropriate way to study prognostic factors for each transition in breast cancer disease.

Adult↗

PubMed1991

Prognosis for recovery from prolonged posttraumatic unawareness: logistic analysis.

This study reviews the course and outcome of 130 patients who remained in a state of prolonged unawareness 30 days after severe cranio-cerebral trauma. Prognostic indicators and outcome were fitted by a logistic model. The significant prognostic factors observable in the first week after trauma were found to be ventilatory status, motor reactivity and significant extraneural trauma. The significant prognostic factors after the first month of unawareness were early ventilatory status, early motor reactivity, late epilepsy and hydrocephalus. The estimated probability of recovery of awareness (that is, consciousness) ranged from 0.94 in patients with early decorticate posturing in the absence of both extraneural trauma and ventilatory disturbance to 0.06 in patients with flaccidity, extraneural trauma and ventilatory disturbance in the first week after injury.

Arousal↗

PubMed1988

Model for breast cancer survival: relative prognostic roles of axillary nodal status, TNM stage, estrogen receptor concentration, and tumor necrosis.

The independent prognostic effects of certain clinical and pathological variables measured at the time of primary diagnosis were assessed with Cox multivariate regression analysis. The 859 patients with primary breast cancer, on which the proportional hazards model was based, had a median follow-up of 60 months. Axillary nodal status (categorized as N0, N1-3 or N4+) was the most significant and independent factor in overall survival, but inclusion of TNM stage, estrogen receptor (ER) concentration and tumor necrosis significantly improved survival predictions. Predictions made with the model showed striking subset survival differences within stage: 5-year survival from 36% (N4+, loge[ER] = 0, marked necrosis) to 96% (N0, loge[ER] = 6, no necrosis) in TNM I, and from 0 to 70% for the same categories in TNM IV. Results of the model were used to classify patients into four distinct risk groups according to a derived hazard index. An 8-fold variation in survival was seen with the highest (greater than 3) to lowest index values (less than 1). Each hazard index level included patients with varied combinations of the above factors, but could be considered to denote the same degree of risk of breast cancer mortality. A model with ER concentration, nodal status, and tumor necrosis was found to best predict survival after disease recurrence in 369 patients, thus confirming the enduring biological significance of these factors.

Adult↗

PubMed1986

Prognostic factors in small cell lung cancer: multivariate model based on 778 patients treated with chemotherapy with or without irradiation.

The relationships between prognostic factors and duration of survival in small cell lung cancer were investigated in a consecutive series of 874 patients treated with combination chemotherapy with or without irradiation. The series included 443 patients with limited and 431 patients with extensive stage disease based on staging including bone marrow examination and peritoneoscopy with liver biopsy but no routine scans. The median durations of survival for the two disease categories were 48 and 30 weeks, respectively. The influence on survival of various pretreatment factors was investigated by use of univariate methods and Cox's multivariate regression model. Patients in each stage were treated according to one of three controlled trials. Variations among the applied treatment regimens did not result in significant differences in duration of survival among patients with limited disease. An alternating regimen was superior to continuous therapy in patients with extensive disease and raised serum lactate dehydrogenase. Prognosis was correlated with disease extent. Surgical resection as well as limited stage disease thus both contributed to survival. Poor performance status, reduced hemoglobin concentration, and raised values for serum lactate dehydrogenase were significantly associated with a reduced duration of survival in both stages. Females with limited disease lived significantly longer than males while advanced age was a negative prognostic factor in extensive disease. Plasma sodium and serum urate were both predictive of survival in limited disease. Proved metastatic disease affecting specific sites or total number of metastatic sites did not carry significant prognostic information in a model including a general variable characterizing stage of disease. Fifty of the 778 patients, on whom the multiple regression model was based, were alive and disease free 2 years after the start of the treatment. Two-year survival rates were strongly correlated to groupings based on prognostic factors, and information about disease extent was not mandatory for predicting the probability of long term disease-free survival.

Adult↗

PubMed2000

Expression and prognostic significance of survivin in de novo acute myeloid leukaemia.

Survivin is an inhibitor of apoptosis (programmed cell death) overexpressed in various human cancers, but undetectable in normal differentiated tissues. A potential distribution and prognostic significance of survivin in patients with de novo acute myeloid leukaemia (AML) was investigated. By immunofluorescence of bone marrow specimens and peripheral blood mononuclear cells, survivin was detected in 75 out of 125 interpretable AML cases (60%), with reactivity in 50-90% of AML cells. Survivin expression correlated with a lower white blood cell count (WBC) (P = 0.008 by the Mann-Whitney test) and was associated, in the 55 cases of FAB M0/M1/M2, with leukaemic granulocytic maturation (one out of five M/L0, 11 out of 22 M/L1 and 23 out of 28M/L2; P = 0.007 by the Fisher test). In 69 patients treated with the Acute Leukaemia French Association (ALFA) 9000 protocol, survivin expression was significantly associated with a lower WBC (P = 0.03 by the Mann-Whitney test) and favourable/intermediate cytogenetics (P= 0.03 by the Fisher test). There was no significant difference in complete remission rate or overall survival between survivin-positive and survivin-negative AML patients (P = 0.15 by the log-rank test). However, survivin expression became an independent negative prognostic factor for survival when adjusted with the Cox model for established prognostic factors in AML (cytogenetics, age and WBC) or for the ALFA 9000 treatment arm (RR = 2.8 and P = 0.026, by the likelihood-ratio test). These data suggest that survivin expression may be considered as a new unfavourable prognostic factor of de novo AML and suggest a role for apoptosis inhibition in influencing disease outcome.

Acute Disease↗

PubMed2002

The 1-year and 3-month prognostic utility of the AST/ALT ratio and model for end-stage liver disease score in patients with viral liver cirrhosis.

OBJECTIVES: The AST/ALT ratio has shown good diagnostic accuracy in patients with chronic viral liver disease. However, its prognostic utility has never been tested. Recently, the Model for End-Stage Liver Disease (MELD) has been proposed as a simple and effective tool to predict survival in patients with liver cirrhosis. The aims of this study were to assess the 3-month and 1-yr prognostic ability of the AST/ALT ratio in a series of patients with virus-related liver cirrhosis, and to evaluate the relationship between the AST/ALT ratio and the MELD score and to compare their prognostic ability. METHODS: The AST/ALT ratios and MELD scores of 99 patients with liver cirrhosis of viral etiology (73 patients with hepatitis C virus and 26 with hepatitis B virus) who had been followed-up for at least 1 yr were retrospectively calculated and correlated with the patients' 3-month and 1-yr prognosis. Receiver operating characteristic curves were used to determine the AST/ALT ratio and the MELD score cut-offs with the best sensitivity (SS) and specificity (SP) in discriminating between patients who survived and those who died. Univariate survival curves were estimated by the Kaplan-Meier method using the cut-offs identified by means of receiver operating characteristic curves. RESULTS: AST/ALT ratios and MELD scores showed a significant correlation (r(s) = 0.503, p = 0.0001). In all, 8% and 30% of the patients had died after 3 months and 1 yr of follow-up, respectively. AST/ALT ratios and MELD scores were significantly higher among the patients who died during both 3-month and 1-yr follow-up. An AST/ALT ratio cut-off of 1.17 had 87% SS and 52% SP, whereas a MELD cut-off of 9 had 57% SS and 74% SP in discriminating between patients who survived and those who died after I yr. The combined assessment of the AST/ALT ratio and/or MELD score had 90% SS and 78% SP. Survival curves of the patients showed that both parameters clearly discriminated between patients who survived and those who died in the short term (AST/ALT ratio, p = 0.0094; MELD score, p = 0.0089) as well as in the long term (AST/ALT ratio, p < 0.0005; MELD score, p = 0.004). CONCLUSIONS: In patients with virus-related cirrhosis, the AST/ALT ratio has prognostic capability that is not significantly different from that of an established prognostic score such as MELD. Combined assessment of the two parameters increases the medium-term prognostic accuracy.

Alanine Transaminase↗

PubMed1992

Making the most of your prognostic factors: presenting a more accurate survival model for breast cancer patients.

Determining an appropriate level of adjuvant therapy is one of the most difficult facets of treating breast cancer patients. Although the myriad of prognostic factors aid in this decision, often they give conflicting reports of a patient's prognosis. What we need is a survival model which can properly utilize the information contained in these factors and give an accurate, reliable account of the patient's probability of recurrence. We also need a method of evaluating these models' predictive ability instead of simply measuring goodness-of-fit, as is currently done. Often, prognostic factors are broken into two categories such as positive or negative. But this dichotomization may hide valuable prognostic information. We investigated whether continuous representations of factors, including standard transformations--logarithmic, square root, categorical, and smoothers--might more accurately estimate the underlying relationship between each factor and survival. We chose the logistic regression model, a special case of the commonly used Cox model, to test our hypothesis. The model containing continuous transformed factors fit the data more closely than the model containing the traditional dichotomized factors. In order to appropriately evaluate these models, we introduce three predictive validity statistics--the Calibration score, the Overall Calibration score, and the Brier score--designed to assess the model's accuracy and reliability. These standardized scores showed the transformed factors predicted three year survival accurately and reliably. The scores can also be used to assess models or compare across studies.

Breast Neoplasms↗

PubMed2006

Serial plasma osteopontin levels have prognostic value in metastatic breast cancer.

PURPOSE: Osteopontin is a malignancy-associated protein measurable in blood and tumor tissue. To evaluate its prognostic value in advanced disease, we conducted a prospective clinical study measuring serial osteopontin plasma levels in women with metastatic breast cancer throughout the course of their disease. EXPERIMENTAL DESIGN: One hundred fifty-eight women with newly diagnosed metastatic breast cancer were enrolled in the study. Plasma osteopontin was measured using our validated ELISA, at baseline and every 3 to 12 weeks during and after therapy until death. Multivariate time-dependent survival analyses were conducted using models that right censored patient outcomes 3, 6, and 12 months after the last known osteopontin measurement. RESULTS: Osteopontin was measured in 1,378 samples (median, 9 per patient). Ninety-nine patients had elevated baseline osteopontin (median, 177 ng/mL; range, 1-2,648 ng/mL). In univariate analysis, elevated baseline osteopontin was associated with short survival (P = 0.02). In a multivariate model incorporating standard prognostic factors, baseline osteopontin was significantly associated with survival duration (relative risk, 1.001; P = 0.038). Metastasis-free interval, visceral metastases, and Eastern Cooperative Oncology Group status 2 to 4 also retained significance. In a multivariate model incorporating standard prognostic factors and changes in sequential osteopontin levels, an osteopontin increase of >250 ng/mL at any time was the variable with the most prognostic value for poor survival (relative risk, 3.26; P = 0.0003), and poor Eastern Cooperative Oncology Group status also retained significance. CONCLUSIONS: This is the first study to show that in women with metastatic breast cancer, increases in osteopontin levels over time are strongly associated with poor survival. Sequential monitoring of osteopontin may have use in making treatment decisions for these patients.

Adult↗

PubMed1999

Variation over time of the effects of prognostic factors in a population-based study of colon cancer: comparison of statistical models.

The authors compare the performance of different regression models for censored survival data in modeling the impact of prognostic factors on all-cause mortality in colon cancer. The data were for 1,951 patients, who were diagnosed in 1977-1991, recorded by the Registry of Digestive Tumors of Côte d'Or, France, and followed for up to 15 years. Models include the Cox proportional hazards model and its three generalizations that allow for hazard ratio to change over time: 1) the piecewise model where hazard ratio is a step function; 2) the model with interaction between a predictor and a parametric function of time; and 3) the non-parametric regression spline model. Results illustrate the importance of accounting for non-proportionality of hazards, and some advantages of flexible non-parametric modeling of time-dependent effects. The authors provide empirical evidence for the dependence of the results of piecewise and parametric models on arbitrary a priori choices, regarding the number of time intervals and specific parametric function, which may lead to biased estimates and low statistical power. The authors demonstrate that a single, a priori selected spline model recovers a variety of patterns of changes in hazard ratio and fits better than other models, especially when the changes are non-monotonic, as in the case of cancer stages.

Aged↗

PubMed2002

Studies on angiogenesis in the benign and malignant ovarian neoplasms with the use of color and pulsed Doppler sonography and serum CA-125, CA-19.9, CA-72.4 and vascular endothelial growth factor measurements.

The aim of the study was to investigate whether a combination of serum CA-125, CA-72.4; CA-19.9 and VEGF levels along with several currently used gray-scale criteria and pulsed and semiquantitative color Doppler blood flow assessment can be useful in preoperative discrimination of ovarian tumors. Ultrasound examinations were performed between 1994 and 1999 with the use of transvaginal probes 5-6.5-7.0 MHz and transabdominal 3.5 MHz probe (B&K Medical 3535 and 2002 ADI, Denmark). Preoperative serum CA-125 and CA-19.9 (Roche, Switzerland) and CA-72.4 (Centocor, USA) were measured with EIA II immunoassays. VEGF (R&D Systems, USA) serum levels were measured by microplate immunoenzymatic method. Retrospective study included 4,876 women referred for sonography of pelvic structures. For final analysis 451 patients with persistent adnexal tumors were available. In all these women age, menopausal status, tumor size, volume and morphology as well as blood flow indices (PI, RI, PSV) and semiquantitative color assessment were noted. In women who were not operated the cysts were followed for 10-12 weeks until resolution which was confirmed by repeated sonography. Multiple regression analysis was used to determine which of the independent variables had prognostic significance in the constructed predictive model. ROC curves were plotted and areas under ROC for each test were calculated and compared. 286 women were operated and in 118 patients their tumors regressed. The sensitivity for Doppler indices was between 85% (RI), 67% (PSV) and 66% (PI). For the subjective color assessment sensitivity was 87%. 294 women had their CA-125 serum levels available. For CA-19.9, CA-72.4 and VEGF the corresponding numbers were 109, 92 and 116 patients, respectively. Optimal cutoff level for CA-125 was 67.5 U/ml and this produced diagnostic accuracy of 69.4%. For CA-19.9 the best predictive value was 13.4 U/ml (accuracy of 74%) and for the cut-off CA-72.4 level of 4.1 U/ml the accuracy of the test was 77.8%. Multiple regression analysis revealed that only RI measurements and subjective color assessment had significant influence on the constructed predictive model. The best cut-off value of regression index "Z" was obtained following ROC curves construction for sensitivity (true positive rate) and 1-specificity (false positive rate). In all 116 patients who had Doppler indices with both CA-125 and VEGF levels measured the highest accuracy was associated with "Z" = 1.45 in postmenopausal women. The prognostic model proposed in this study can be log transformed and further used in the estimation of the true probability of malignancy of a given mass in the new set of prospectively studied patients with ovarian tumors. Color and pulsed Doppler can improve preoperative diagnosis of adnexal tumors when compared to transvaginal sonography alone or tumor markers assessment. The proposed semiquantitative evaluation of tumor vascularity increases the predictive value in terms of sensitivity and specificity. VEGF serum concentration was not useful in the preoperative discrimination of malignant and benign ovarian tumors.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed2000

Prognostic usefulness of the tricuspid annular plane systolic excursion in patients with congestive heart failure secondary to idiopathic or ischemic dilated cardiomyopathy.

The prognostic value of ultrasound evaluation of right ventricular (RV) performance in patients with congestive heart failure (CHF) is still a matter of investigation. We studied 140 consecutive patients with chronic CHF and a left ventricular ejection fraction <35%. All patients underwent a complete echocardiographic evaluation that systematically included the measurement of the tricuspid annular plane systolic excursion (TAPSE). During a follow-up period of 24 +/- 14 months, 45 patients died and 7 underwent emergency heart transplantation. At the multivariate survival analysis (Cox regression model) backward stepwise selection identified a prognostic model with 2 parameters: New York Heart Association (NYHA) class III or IV and TAPSE < or =14 mm (p <000). In a subgroup of 97 patients in sinus rhythm in whom mitral inflow Doppler variables could be measured, survival was further analyzed according to a model in which the significant parameters were included in the same order as usually used in routine clinical practice: clinical variables first, left ventricular function data second, mitral Doppler variables third, and indexes of right ventricular (RV) function last. TAPSE < or =14 mm added significant (p <0.03) prognostic information to NYHA class III or IV, left ventricular ejection fraction of <20%, and mitral deceleration time of < 125 ms. In conclusion, in patients with CHF, TAPSE adds significant prognostic information to the NYHA clinical classification, to the echocardiographic evaluation of left ventricular function, and to mitral Doppler variables. Furthermore, the measurement of TAPSE is easy to obtain in all patients, irrespective of heart rate and rhythm.

Cardiac Catheterization↗

PubMed2005

Detection of disseminated lung cancer cells in regional lymph nodes by assay of CK19 reverse transcriptase polymerase chain reaction and its clinical significance.

PURPOSE: To set up a molecular method (i.e. RT-PCR) that can be used to detect disseminated tumor cells (DTCs) in regional lymph nodes (LNs) in patients with lung cancer and to evaluate its clinical significance. METHODS: Cytokeratin 19 (CK(19)) was used as marker. Serial dilution study for LC-5 cells (a lung squamous cell line) was performed to detect sensitivity of the molecular protocol. Regional LNs (n = 261) and primary lung cancer tissue (n = 40) were obtained from 40 patients with lung cancer who underwent lobectomy or pneumonectomy. They were randomly categorized into two groups: group I (LN-based study, n = 20) and group II (patient-based study, n = 20). Each LN was halved. One half of a LN was subjected to histological examination (HE) and the other half was subjected to RT-PCR amplification of CK(19) mRNA. The effect on survival was analyzed. The cumulative survival was calculated by the Kaplan-Meier method and compared by the log rank test. The Cox model analyzed the prognostic factors. RESULTS: CK(19) mRNA expressed in all tumor tissues as well as LC-5, PAa cells (a lung adenocarcinoma cell line), but not in normal control LNs. Serial dilution study for LC-5 cells demonstrated that CK(19) mRNA was detectable at a concentration as low as 10 LC-5 cells in 1x10(7) LN cells. There was no significant difference between the detecting result of single LN and that of mixed LNs (P > 0.05). In 18 of 40 patients, the metastasis in regional LNs was found by both HE and RT-PCR. Of 22 patients without pathologically involved nodes, six (27%) were found to express CK(19) mRNA in regional LNs. According to the results of regional LNs in 40 patients by molecular assay, the presence of the CK(19) product in LNs was related to tumor size (chi(2) = 5.76, P < 0.025) as well as cell differentiation of the tumor (chi(2) = 7.08, P < 0.01). Following a median observation time of 26 months (range, 4 to 60 months), patients with DTCs in nodes showed significant shorter disease-free survival duration than node-negative patients (log-rank test, P = 0.001). The independence of this prognostic significance was demonstrated by a multivariate analysis (Cox regression model, P = 0.004). The results diagnosed by HE had no significant effect on prognoses (P = 0.455). CONCLUSIONS: Comparing with HE, RT-PCR can make more accurate assessment of metastatic status in LNs, which is helpful for screening the patients in whom the early subclinical metastasis exists and disclosing the intrinsic regulation of malignant metastasis. The presence of DTCs in LNs is an independent factor for prognosis. Molecular detection of DTCs in LNs is a supplement for current tumor staging in lung carcinoma.

Aged↗

PubMed2004

[Prognostic factors in severe head injury].

The knowledge of the so called prognostic factors or indicators involved in severe head injury (SHI) is an issue of great interest to make predictions about the future of patients with this pathology. Those indicators constitute the basic elements of the different prognostic formulas or models carried out in order to make predictions in SHI. The mentioned models, therefore, will be constructed by a group of variables (prognostic indicators or factors) and several scales (prognostic scales) that are useful for measuring the final outcome of these patients. In this paper we resume, after an exhaustive review of the literature, the knowledge about the prognostic factors related to SHI. These indicators have been classified as follows: clinical, radiological, physiological, and biochemical. Moreover, we have briefly described the prognostic scales more commonly used in SHI.

Age Factors↗