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Nuclear morphometry for improved prediction of the prognosis of human bladder carcinoma.

BACKGROUND: Histologic grade and clinical stage generally are used for estimating the prognosis of bladder carcinoma. However, both methods have been reported to have a rather low reproducibility and to be unsatisfactory for predicting the recurrence and progression of superficial bladder carcinoma. Recently, nuclear morphometry was used to quantitate the malignant potential of cancer cells in a more objective and reproducible manner. The authors quantitatively analyzed the malignant potential of bladder carcinoma at initial presentation using a combination of several nuclear morphometric variables. METHODS: The subjects were 156 patients with previously untreated bladder carcinoma. Three morphometric variables were measured in each subject: the mean nuclear volume (MNV), the nuclear roundness factor (NRF), and the variation of nuclear area (VNA). RESULTS: Univariate analysis showed that MNV and NRF were significant prognostic indicators for survival (MNV, P < 0.0001; NRF, P = 0.008). In addition, MNV was a prognostic indicator for tumor recurrence (P = 0.001), whereas MNV and NRF were prognostic indicators for invasive progression (MNV, P = 0.02; NRF, P = 0.009). For accurate prediction of the prognosis of patients with bladder carcinoma, a prognostic score, a recurrence score, and a progression score were designed using the coefficients of MNV and NRF in a proportional hazards model. The prognostic score clearly divided the patients into two different groups with 5-year survival rates of 88% and 64% (P = 0.0002). In addition, patients with superficial bladder carcinoma and a low recurrence score had a significantly higher 5-year recurrence free rate than those with a high recurrence score (40% vs. 23%, P = 0.0004), and the 5-year progression free rate of patients with a low progression score was significantly higher than that of those with a high progression score (98% vs. 73%, P = 0.0006). CONCLUSIONS: These findings suggest that nuclear morphometry is a reliable technique with which to identify prognostic indicators for human bladder carcinoma. A combination of several nuclear morphometric variables provides a more accurate indication of prognosis than any single parameter.

Adult↗

[Significance of clinical and laboratory chemical parameters for the course and prognosis of non-Hodgkin's lymphomas].

Using a regression model, the prognostic significance of clinical and biochemical parameters as well as of histology was analyzed in a group of 336 patients with Non-Hodgkin's lymphoma. A stochastic process model was used for evaluation of the course of disease. With respect to overall survival, serum-LDH-activity, performance status, and the histologically defined grade of malignancy were found to be the most important prognostic parameters, as well as age, though that to a lesser extent. In the course of disease, stage was the most relevant factor for achievement of a complete remission. In patients without remission, survival was determined mainly by histology and serum-LDH-activity; the latter was also of importance for duration of remission. Our study shows that histology is not the only prognostic factor in NHL but that other parameters, mainly serum-LDH-activity and performance status, also have to be considered in comparing different groups of patients.

Age Factors↗

Metabolism pathway-based subtyping in pancreatic adenocarcinoma: an integrated study by bulk RNA-sequence and machine learning algorithms.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is highly aggressive, and its tumor microenvironment has significant metabolic and immune microenvironment complexity and genomic instability. In this study, by integrating the metabolic pathway activity score and clinical data, we constructed a novel risk assessment model to reveal the unique biological behavior and clinical significance behind different PAAD subtypes. METHODS: In this study, the transcriptome and clinical data of TCGA and GSE57495 databases were integrated to explore the interaction between metabolic pathways. Based on unsupervised clustering analysis of pathway activity and survival prognosis, patients with PAAD were classified into metabolic subtypes with significant prognostic differences. Subsequently, we assessed the heterogeneity of these subtypes in terms of clinical outcomes, genomic characteristics, and immune microenvironment composition. Based on the differentially expressed genes (DEGs) among metabolic subtypes, a clinical prognostic risk model and nomogram were constructed, which were double-validated by GSE57495-independent cohort and GSE57495&#xa0;+&#xa0;TCGA-PAAD combined cohort. Finally, the correlations between risk scores (RSs) and signaling pathway activity and tumor immune microenvironment characteristics were evaluated. RESULTS: Based on metabolic pathway correlation and prognostic information, 240 patients in the TCGA-PAAD and GSE57495 datasets were divided into three subgroups. There were significant differences between subgroups in gene expression, pathway activity, clinical prognosis, and immune infiltration characteristics among the subtypes. Using machine learning algorithms, an RS model was constructed from DEGs among the subgroups, with the random forest method showing the best performance. A nomogram integrating the RS and clinical indicators demonstrated excellent predictive accuracy for 1-, 3-, and 5-year survival rates, confirming the RS as an independent prognostic factor. High- and low-risk groups exhibited significant differences in immune infiltration, pathway activity, and gene mutations. Drug sensitivity analysis showed that the high-risk group was more sensitive to AZD6244, ABT737, and other drugs. CONCLUSION: This study stratified patients with PAAD into three subgroups based on metabolic pathways and prognostic information, revealing significant differences in clinical outcomes, immune characteristics, and genetic mutations. The robust RS model developed from these findings demonstrated strong predictive power for patient survival and identified promising therapeutic strategies, providing valuable insights for advancing precision medicine in PAAD.

immune microenvironment↗

The urokinase system of plasminogen activation and prognosis in 2780 breast cancer patients.

The antigen levels of components of the urokinase-type plasminogen activator (uPA) system of plasminogen activation are correlated with prognosis in several types of cancers, including breast cancer. In the present study involving 2780 patients with primary invasive breast cancer, we have evaluated the prognostic importance of the four major components of the uPA system [uPA, the receptor uPAR (CD87), and the inhibitors PAI-1 and PAI-2]. The antigen levels were determined by ELISA in cytosols prepared from primary breast tumors. The levels of the four factors significantly correlated with each other; the Spearman rank correlation coefficients (r(s)) ranged from 0.32 (between PAI-2 and PAI-1 or uPAR) to 0.59 (between uPA and PAI-1). The median duration of follow-up of patients still alive was 88 months. In the multivariate analyses for relapse-free survival (RFS) and overall survival (OS), we defined a basic model including age, menopausal status, tumor size and grade, lymph node status, adjuvant therapy, and steroid hormone receptor status. uPA, uPAR, PAI-1, and PAI-2 were considered as categorical variables, each with two cut points that were established by isotonic regression analysis. Compared with tumors with low levels, those with intermediate and high levels showed a relative hazard rate (RHR) and 95% confidence interval (95% CI) of 1.22 (1.02-1.45) and 1.69 (1.39-2.05) for uPA, and 1.32 (1.14-1.54) and 2.17 (1.74-2.70) for PAI-1, respectively, in multivariate analysis for RFS in all patients. Compared with tumors with high PAI-2 levels, those with intermediate and low levels showed a poor RFS with a RHR (95% CI) of 1.30 (1.14-1.48) and 1.76 (1.38-2.24), respectively. Similar results were obtained in the multivariate analysis for OS in all patients. Furthermore, uPA and PAI-1 were independent predictive factors of a poor RFS and OS in node-negative and node-positive patients. PAI-2 also added to the multivariate models for RFS in node-negative and node-positive patients, and in the analysis for OS in node-negative patients. uPAR did not further contribute to any of the multivariate models. A prognostic score was calculated based on the estimates from the final multivariate model for RFS. Using this score, the difference between the highest and lowest 10% risk groups was 66% in the analysis for RFS at 10 years and 61% in the analysis for OS. Moreover, separate prognostic scores were calculated for node-negative and node-positive patients. In the 10% highest risk groups, the proportion of disease-free patients was only 27 +/- 6% and 9 +/- 3% at 10 years for node-negative and node-positive patients, respectively. These proportions were 86 +/- 4% and 61 +/- 6% for the corresponding 10% lowest risk groups of relapse. We conclude that several components of the uPA system are potential predictors of RFS and OS in patients with primary invasive breast cancer. Knowledge of these factors could be helpful to assess the individual risk of patients, to select various types of adjuvant treatment and to identify patients who may benefit from targeted therapies that are currently being developed.

Adult↗

Rapid and prognostically valid quantification of immunohistochemical reactions by immunohistometry of the most positive tumour focus. A prospective follow-up study on breast cancer using antibodies against MIB-1, PCNA, ER, and PR.

The prognostic significance of immunohistochemical markers for cell proliferation [MIB-1, proliferating cell nuclear antigen (PCNA)] and hormone receptor analysis [oestrogen receptor (ER), progesterone receptor (PR)] was tested by means of immunohistometry in a series of 103 breast cancer patients in comparison with the lymph node status N, the tumour size T, histomorphological grading, and the biochemical ER and PR status. Immunohistochemical reactions were performed on 2 microns sections from paraffin-embedded tissue, using an indirect peroxidase method. The proportion of immunostained tumour cell nuclei was determined using a TV-image analysis system. Measurements were performed using a 20 x objective on 40 viewing fields (1.94 mm2, MIB-1 and PCNA) or 20 viewing fields (0.97 mm2, ER and PR). The mean immunopositivity of all viewing fields and the value of the most immunopositive viewing field (MIB-1max, PCNAmax, PRmax, ERmax) were calculated. The mean values and the maximal values were highly correlated (r = 0.903, P < 0.001). After 1:2:1 quantilization, 84.2 per cent of the 412 single measurements revealed mean and maximal values in the same category (P < 0.0001). For each of the four immunohistochemical markers, the prognostic significance of the maximal values was higher than that of the mean values. The highest prognostic significance was found for MIC-1max (P = 0.0002), followed by PRmax (P = 0.0046), ERmax (P = 0.0154), and PCNAmax (P = 0.0161). From the results of a Cox model, a 'prognostic index (PI)' was developed, ranging from -1 to 8: PI = 2 x N + T + MIB-1max-PRmax. The four groups of patients with PI values of < 2, 2-3, 4-5, and > 5 revealed significantly different 7.5-year survival probabilities (P < 0.0001). The simplicity of the PI makes it a clinically useful, routinely applicable, and understandable parameter in the surgical pathology of breast carcinoma.

Adult↗

[An analysis of tumor status of stage 3 carcinoma of the uterine cervix according to Cox's theory].

Four hundred and eighty three cases of primary stage 3 carcinoma of the uterine cervix which were treated at the National Institute of Radiological Sciences were analyzed with reference to the tumor status at the first examination, using Cox's proportional hazard model. Five prognostic factors, i.e. growth type of tumor, size of tumor at portio, size of uterus (including cervix and body), degree of tumor infiltration of parametrium and degree of tumor infiltration of vaginal wall, were considered. A coefficient of correlation, parameters of a hazard model, relative risk and survival functions were calculated with a program developed by us. The coefficient of correlation between the size of the uterus and the size of the tumor at the portio or the parametrial infiltration was about -0.5. Other combinations of prognostic factors indicated only a small correlation. When five prognostic factors were analyzed independently, the size of the uterus was found to have the greatest influence on the patient's prognosis and infiltration of the vaginal wall had the least. A combination of prognostic factors was selected according to the criterion of small correlation with each other. And then, the combination was evaluated for prognosis and to find the level of parameters under the asymtotic normal distribution. The best combination consisted of a growth type of tumor, a size of tumor at portio and tumor infiltration into the parametrium. Parameters of each prognostic factor which were calculated simultaneously from marginal likelihood were 0.236, 0.534 and 0.151, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Prognostic significance of DNA damage response-related markers in esophageal squamous cell carcinoma using machine learning approaches.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) lacks reliable prognostic biomarkers. Homologous recombination deficiency (HRD) has been implicated in genomic instability across multiple cancers, but its prognostic significance in ESCC remains unexplored. This study aimed to evaluate HRD score as a prognostic biomarker and develop a machine learning-based predictive model for ESCC. METHODS: Transcriptomic and clinical data from 78 ESCC patients were obtained from The Cancer Genome Atlas (TCGA) and randomly split into training (70%) and test (30%) cohorts. Prognostic models were constructed using 112 machine learning algorithm combinations based on DNA damage response (DDR)-related genes. Gene set enrichment analysis (GSEA), somatic mutation profiling, and immune cell infiltration estimation via CIBERSORT were performed to characterize HRD-associated molecular features. RESULTS: High HRD scores were significantly associated with poorer overall survival (P<0.05). Among 112 algorithm combinations, the survival support vector machine (Survival-SVM) model demonstrated optimal performance [training concordance index (C-index): 0.741; test C-index: 0.708], identifying six hub genes: PARP1, MBD4, TELO2, NSMCE3, SMUG1, and BABAM1. A nomogram incorporating risk score (RS) and clinical variables achieved strong predictive accuracy for 1- to 3-year survival [area under the curve (AUC) >0.7]. High-HRD tumors exhibited distinct mutational patterns (TP53 and TTN) and enriched glutathione metabolism and cytochrome P450 pathways. Immune infiltration analysis revealed significant differences in plasma cell and neutrophil infiltration between risk groups (P<0.05), suggesting HRD-associated immune microenvironment remodeling. CONCLUSIONS: We developed a novel HRD-based prognostic model incorporating six DDR-related genes that demonstrates robust predictive performance in ESCC. HRD score is identified as an independent prognostic factor associated with genomic instability, immune microenvironment alterations, and clinical outcomes. These findings provide a theoretical basis for personalized treatment strategies, including potential applications of PARP inhibitors and immunotherapy in ESCC.

Esophageal squamous cell carcinoma (ESCC)↗

The effect of radiotherapy on the survival of non-small cell lung cancer patients.

PURPOSE: To determine if thoracic radiotherapy improves the survival of non-small cell lung cancer (NSCLC) patients. METHODS AND MATERIALS: A Cox proportional hazards model with prognostic and treatment covariates was estimated using prospective data for 129 NSCLC patients presenting at the Victoria Clinic (ViCC) of the British Columbia Cancer Agency (BCCA) 1990-1991. The estimated model was simulated to predict survival curves for groups of patients with and without treatment. The difference between the predicted median survival with treatment and without treatment is the gain in survival attributable to treatment. RESULTS: After adjusting for the effect of TNM staging, Karnofsky performance status, weight loss, tumor size, and tumor histology on survival, high-dose palliative radiotherapy (RT) (30-50 Gy in 10-20 fractions) increased median survival by 79 days (95% confidence interval: 31-106 days), and lowered the relative risk of death rate to 0.53 (95% confidence interval: 0.35-0.85). Radical RT (50 or more Gy, in 20 or more fractions) increased median survival by 424 days (95% confidence interval: 302-488 days), and lowered the relative risk of death to 0.24 (95% confidence interval: 0.14-0.43). CONCLUSION: Our results support the hypothesis that the increased survival of patients receiving aggressive palliative, or radical, RT is due not solely to patient selection, but also partly to a response to treatment.

Carcinoma, Non-Small-Cell Lung↗

An individualized nomogram for predicting progression-free survival in systemic anaplastic large cell lymphoma: a multicenter, retrospective, and internally validated study.

OBJECTIVES: To develop an individualized nomogram for predicting disease progression risk in systemic anaplastic large cell lymphoma (sALCL). METHODS: Independent predictors of progression-free survival (PFS) were identified using Cox regression in a multicenter retrospective cohort of 109 sALCL patients (2010-2022). These were incorporated into a three-factor nomogram, evaluated via bootstrapped internal validation (1000 resamples), ROC analysis, C-index, decision curve analysis (DCA), and clinical impact curve (CIC). RESULTS: A total of 29 PFS events occurred during a median follow-up of 31 months. Multivariable modelling selected serum &#x3b2;2-microglobulin elevation, extranodal disease, and front-line chemotherapy choice (CHOP versus CHOPE or BV+CHP) as autonomous progression drivers. Upon internal bootstrap validation, the nomogram yielded strong prognostic accuracy, achieving AUCs of 0.81, 0.85 and 0.87 for 1-, 3- and 5-year progression-free survival, alongside a corrected C-index of 0.779 (95% CI: 0.699 - 0.861). Calibration plots showed close agreement between predicted and observed outcomes, while DCA confirmed superior net clinical benefit versus conventional IPI or Ann Arbor stratification across multiple decision thresholds. CONCLUSION: This first sALCL-specific nomogram integrates clinical and treatment variables to provide personalized PFS risk estimation. While internally validated, this exploratory, observation-based tool requires external validation and recalibration in prospective cohorts before clinical implementation.

Humans↗

Application of the time-dependent ROC curves for prognostic accuracy with multiple biomarkers.

The rapid advancement in molecule technology has led to the discovery of many markers that have potential applications in disease diagnosis and prognosis. In a prospective cohort study, information on a panel of biomarkers as well as the disease status for a patient are routinely collected over time. Such information is useful to predict patients' prognosis and select patients for targeted therapy. In this article, we develop procedures for constructing a composite test with optimal discrimination power when there are multiple markers available to assist in prediction and characterize the accuracy of the resulting test by extending the time-dependent receiver operating characteristic (ROC) curve methodology. We employ a modified logistic regression model to derive optimal linear composite scores such that their corresponding ROC curves are maximized at every false positive rate. We provide theoretical justification for using such a model for prognostic accuracy. The proposed method allows for time-varying marker effects and accommodates censored failure time outcome. When the effects of markers are approximately constant over time, we propose a more efficient estimating procedure under such models. We conduct numerical studies to evaluate the performance of the proposed procedures. Our results indicate the proposed methods are both flexible and efficient. We contrast these methods with an application concerning the prognostic accuracies of expression levels of six genes.

Biomarkers↗

Prognostic factors of hepatocellular carcinoma in the west: a multivariate analysis in 206 patients.

To investigate the prognostic factors in Western patients with hepatocellular carcinoma, 206 patients with confirmed diagnoses of hepatocellular carcinoma were studied in terms of survival. All patients were diagnosed between 1983 and 1987. A multivariate survival analysis (Cox regression model) using clinical, biochemical, ultrasonographical and pathological data obtained at diagnosis disclosed that bilirubin (p = 0.0001), ascites (p = 0.0001), toxic syndrome (defined by the presence of weight loss greater than 10% premorbid weight, malaise and anorexia) (p = 0.009), blood urea nitrogen (p = 0.025), tumor size (p = 0.001), gamma-glutamyltranspeptidase (p = 0.0006), age (p = 0.0005), serum sodium (p = 0.003) and presence of metastases (p = 0.002) were independent predictors of survival. According to the contribution of each of these factors to the final model, a prognostic index was constructed allowing division of patients in different groups according to their relative risk of death: RRD = EXP (Age x 0.03 + Ascites x 0.8281 + BUN x 0.0137 + Serum sodium x (-0.0538) + gamma-Glutamyltranspeptidase x 0.0019 + Bilirubin x 0.0734 + Tumor size x 0.33 + Toxic syndrome x 0.4965 + Metastases x 0.55). These results facilitate the stratification of hepatocellular carcinoma patients to design and evaluate future controlled trials.

Adult↗

Simulating urban-scale air pollutants and their predicting capabilities over the Seoul metropolitan area.

Urban-scale air pollutants for sulfur dioxide, nitrogen dioxide, particulate matter with aerodynamic diameter > or = 10 microm, and ozone (O3) were simulated over the Seoul metropolitan area, Korea, during the period of July 2-11, 2002, and their predicting capabilities were discussed. The Air Pollution Model (TAPM) and the highly disaggregated anthropogenic and the biogenic gridded emissions (1 km x 1 km) recently prepared by the Korean Ministry of Environment were applied. Wind fields with observational nudging in the prognostic meteorological model TAPM are optionally adopted to comparatively examine the meteorological impact on the prediction capabilities of urban-scale air pollutants. The result shows that the simulated concentrations of secondary air pollutant largely agree with observed levels with an index of agreement (IOA) of >0.6, whereas IOAs of approximately 0.4 are found for most primary pollutants in the major cities, reflecting the quality of emission data in the urban area. The observationally nudged wind fields with higher IOAs have little effect on the prediction for both primary and secondary air pollutants, implying that the detailed wind field does not consistently improve the urban air pollution model performance if emissions are not well specified. However, the robust highest concentrations are better described toward observations by imposing observational nudging, suggesting the importance of wind fields for the predictions of extreme concentrations such as robust highest concentrations, maximum levels, and >90th percentiles of concentrations for both primary and secondary urban-scale air pollutants.

Air↗

Prognosis in acquired aplastic anaemia. A multivariate statistical analysis of 80 cases.

Prognostic factors were studied in a series of 80 patients with aplastic anaemia. The most important and easily obtainable individual variables, isolated in a previous univariate statistical analysis, were placed in a linear logistic regression model. A prognostic formula was derived containing the following 4 variables, in decreasing order of significance: (1) reticulocytes, (2) interval from onset of symptoms to first visit, (3) mean red cell volume, and (4) platelets. The prognostic formula permits an estimate of the probability of death within 3 months from the first visit. Its usefulness in several clinical situations, especially those related to bone marrow transplantation, is illustrated.

Adolescent↗

Prospectively validated prediction of physiologic variables and organ failure in septic patients: The Systemic Mediator Associated Response Test (SMART).

OBJECTIVE: Conventional outcomes research provides only percentage risk of such end points as mortality rate, utilization of resources, and/or broad groupings of multiple organ system dysfunction. These prognostications generally are not applicable to individual patients. The purpose of the present study was to determine whether the Systemic Mediator Associated Response Test (SMART) methodology could identify interactions among demographics, physiologic variables, standard hospital laboratory tests, and circulating cytokine concentrations that predicted continuous and dichotomous dependent clinical variables, in advance, in individual patients with severe sepsis and septic shock, and whether these independent variables could be integrated into prospectively validated predictive models. DESIGN: Data review and multivariate stepwise logistic regression. SETTING: University research laboratory. PATIENTS: Three hundred three patients with severe sepsis or septic shock who comprised the placebo arm of a multiple-institution clinical trial, who were randomly separated into a model building training cohort (n = 200) and a predictive cohort (n = 103). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From baseline data and baseline plus serial input, including patient demographics, hospital laboratory tests, and plasma concentrations of interleukin-6, interleukin-8, and granulocyte colony stimulating factor, multiple regression models were developed that predicted clinically important continuous dependent variables quantitatively, in individual patients. Multivariate stepwise logistic regression was used to develop models that prognosticated dichotomous dependent end points. Data from individual patients in the predictive cohort were inserted into each predictive model for each day, with prospective validation accomplished by simple linear regression of individual predicted vs. observed values for continuous dependent variables, and by establishing the receiver operator characteristics area under the curve for logistic regression models that predicted dichotomous end points. Of SMART models for continuous dependent variables, 100 of 143 (70%) were validated at r values >.7 through day 3, and 184 of 259 (71%) above r =.5 through day 5. SMART predictions of dichotomous end points achieved receiver operator characteristics areas under the curve >.7 for up to 84% of the equations in the first week. Many SMART models for both continuous and dichotomous dependent variables were validated at clinically useful levels of accuracy as far as 28 days after baseline. CONCLUSIONS: SMART integration of demographics, bedside physiology, hospital laboratory tests, and circulating cytokines predicts organ failure and physiologic function indicators in individual patients with severe sepsis and septic shock.

Clinical Laboratory Techniques↗

Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation. The National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: A prospective randomized trial was conducted to determine whether the addition of concurrent cisplatin to preoperative or definitive radiation therapy in patients with muscle-invasive bladder cancer improved local control or survival. PATIENTS AND METHODS: Ninety-nine eligible patients with T2 to T4b transitional cell bladder cancer participated, 64% with cT3b or cT4. Patients and their physicians selected either definitive radiotherapy or precystectomy radiotherapy; patients were then randomly allocated to receive intravenous cisplatin 100 mg/m2 at 2-week intervals for three cycles concurrent with pelvic radiation, or to receive radiation without chemotherapy. Patients were stratified by clinical tumor stage and by radiation plan. The median follow-up duration is 6.5 years. RESULTS: The occurrence of distant metastases was the same in both study arms. However, 25 of 48 control patients have had a first recurrence in the pelvis, compared with 15 of 51 cisplatin-treated patients (P = .036). The pelvic relapse rate in the two groups was significantly reduced by concurrent cisplatin (P = .038, log-rank test) and this effect was preserved in a stepwise Cox regression model of prognostic factors (hazards ratio, 0.50; 90% confidence interval [CI], 0.29 to 0.86; P = .036). The hazard reduction was similar for both radiation plans. Pretreatment leukocytosis and high clinical stage were independent adverse factors in a Cox model of overall survival, but the effect of cisplatin was not significant. CONCLUSION: Concurrent cisplatin may improve pelvic control of locally advanced bladder cancer with preoperative or definitive radiation, but has not been shown to improve overall survival. The use of concurrent cisplatin had no detectable effect on distant metastases.

Adult↗

Factors predictive of follow-up clinic attendance and developmental outcome in a regional cohort of very low birth weight infants.

This population-based, retrospective cohort study of very low birth weight infants was undertaken to: 1) identify factors associated with nonattendance for follow-up, 2) estimate the prevalence of cerebral palsy at age > or = 18 months, and 3) model the prognostic association between prenatal and perinatal risk markers and cerebral palsy. The sample included 496 surviving very low birth weight infants born in 32 hospitals in Southwest Ontario between January 1982 and December 1986. Multivariate analyses were performed using the proportional odds regression model. Loss to follow-up was more likely among those with mothers < 20 years of age, those with unmarried mothers, and those not born in a tertiary center. Loss to follow-up was less likely for those with neonatal anemia and those of lower birth weight. Motor development of the 369 children who were followed at least 18 months was classified into one of three categories: normal, suspect, or cerebral palsy. Multivariate analysis revealed that factors predictive of poorer outcome were intraventricular hemorrhage, unmarried mother, male sex, recurrent apnea, and hydrocephalus. The finding that unmarried status was associated with loss to follow-up and was also an important predictor of cerebral palsy suggests that it is important for follow-up clinics to identify ways of assisting this population to remain in contact with the clinic.

Adult↗

The risk of cardiovascular death in elderly patients with possible heart failure. Results from a 6-year follow-up of a Swedish primary care population.

UNLABELLED: Little is known about the prognosis and clinical variables influencing the prognosis among elderly patients in primary health care with mild to moderate heart failure. AIM: To evaluate the risk of cardiovascular mortality in elderly patients with symptoms of heart failure with respect to systolic and diastolic function, and functional impairment. To evaluate prognostic determinants and to risk-stratify the patients. METHODS: A cardiologist examined 510 patients, out of 548 invited, attending primary care for symptoms of dyspnoea, fatigue and/or peripheral oedema and assessed New York Heart Association (NYHA) functional class. Examination by Doppler echocardiography was done in 454 patients, 56 patients being excluded because of, e.g., atrial fibrillation. Abnormal systolic function was defined as ejection fraction<40%. The diastolic function was evaluated using the mitral inflow and pulmonary venous flow variables. Different clinical and echocardiographic variables were analysed using a Cox regression analysis to identify those most influencing the risk of cardiovascular mortality. CONCLUSION: Abnormal systolic and/or diastolic function was found in 219 patients (48% of the 454 patients who could be echocardiographically completely investigated). The follow-up period was 6 years. Total mortality was 20%, and cardiovascular mortality was 14% (70% of total mortality). Cardiovascular mortality was high in patients with severely impaired functional capacity and ejection fraction<40% at the start of the study. Risk variables identified were male gender, diabetes mellitus, impaired functional capacity and abnormal cardiac function by echocardiography. A prognostic score model using simple clinical variables (gender, NYHA class, cardiac function) was developed to assess the risk of cardiovascular death in order to identify patients with high, moderate or low risk. In a ROC curve analysis, the AUC for clinical variables was only 0.75, whereas the AUC for clinical variables and echocardiography was 0.78, indicating that the additional prognostic information obtained by Doppler echocardiography was rather small.

Aged↗

Long-term results of a randomized trial comparing cisplatin with cisplatin and cyclophosphamide with cisplatin, cyclophosphamide, and adriamycin in advanced ovarian cancer. GICOG (Gruppo Interregionale Cooperativo Oncologico Ginecologia), Italy.

We report the long-term results of a randomized trial comparing cisplatin (P) with cisplatin and cyclophosphamide (CP) with cisplatin, cyclophosphamide, and adriamycin (CAP) in advanced ovarian cancer. Overall, this update confirms previously published data on 529 cases. Median survival times for the three treatments--CAP, CP, and P--are, respectively, 23, 20, and 19 months. The differences among the three arms are still nonsignificant and the estimated percentage survival at 7 years and confidence limits are, respectively, 21.7 (14.9-28.4), 17.0 (11.0-22.9), and 12.2 (6.9-17.4). According to the results of the Cox regression model on prognostic factors, higher grading, a larger residual tumor size, and performance status less than 80 (Karnovsky) all were independently associated with a poorer outcome, while a serous histotype was related to a better prognosis. The other variables (age, stage, center, type of surgery) initially included in the model did not appear to be significantly related to prognosis. The implications of these long-terms results relative to the application of combination chemotherapy with CAP or CP are discussed.

Antineoplastic Combined Chemotherapy Protocols↗