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Nm23-H1 protein, DNA-ploidy and S-phase fraction in relation to overall survival and disease free survival in transitional cell carcinoma of the bladder.

OBJECTIVES: To explain the overall survival (OS) and disease free survival (DFS) in relation to nm23-H1 protein, DNA-ploidy and S-phase fraction (SPF) in transitional cell carcinoma of the bladder. PATIENTS AND METHODS: Ninety-four samples were obtained from patients with transitional cell carcinoma of the bladder examined between 1994 and 1996. The patients were underwent cistectomy or surgical biopsy and the material was histologically evaluated according to World Health Organization classification. Nm23-H1 protein expression in immunohistological staining and DNA ploidy, S-phase fraction by flow cytometric were performed. RESULTS: The correlation between OS and staging, grading, DNA-ploidy and S-phase was significant; whereas the overall survival and nm23-H1 protein, was not significant. The relationship between DFS and stage, DNA-ploidy and S-phase had a significant value. The correlation between DFS and age, sex, grading and nm23-H1 protein was not significant. There was no significant difference in age, sex, stage, grading, DNA-ploidy and SPF distribution between patients with nm23-H1 positive bladder cancer and those with nm23-H1 negative tumours. CONCLUSION: In our study, multivariate analysis showed that stage, ploidy and SPF were the strongest prognostic factors in predicting disease-free survival and prolonged survival, while nm23-H1 expression was not related to disease progression and/or prolonged survival. This expression, therefore, does not appear to be an independent prognostic factor in bladder cancer, although a still larger number of patients and a longer follow-up period are now needed for a definitive assessment of the prognostic significance of nm23-H1 expression.

Adult↗

Hepatobiliary transport governs overall elimination of peptidic endothelin antagonists in rats.

The overall disposition and hepatobiliary transport of BQ-123, an anionic cyclopentapeptide, and three analogs were examined in rats in vivo. Total body clearance (CLtotal) and biliary excretion clearance (CLbile, p) exhibited 4- to 8-fold differences between the compounds, with those for BQ-485 and compound A having the highest and lowest values, respectively. The CLbile, p values of BQ-485, BQ-123, and BQ-518 were almost equal to the CLtotal, suggesting that hepatobiliary transport is the major elimination pathway for these compounds. Hepatic uptake clearance (CLuptake, vivo) and biliary excretion clearance (CLbile, h/fT), which was defined for the hepatic unbound concentration, were separately determined to examine the hepatic uptake and excretion processes, respectively. Both the CLuptake, vivo and CLbile, h/fT of BQ-485 were higher than those of BQ-123, whereas the corresponding values for BQ-518 were similar to those for BQ-123. The CLuptake, vivo and CLbile, h/fT of compound A were, respectively, approximately two thirds and one half those of BQ-123, suggesting that the lower CLbile, p value is due to the low efficiency of both the uptake and excretion processes. The CLuptake, vivo of these four peptides in vivo was similar to the extrapolated values based on the carrier-mediated transport activity previously assessed in vitro in isolated rat hepatocytes. The primary active transport previously assessed in an in vitro study in canalicular membrane vesicles was also highest for BQ-485 and lowest for compound A, similar to CLbile, h/fT in vivo. Thus, the transporters on both the sinusoidal and canalicular membranes determine the efficiency of the peptide overall elimination from the circulation.

Animals↗

Antidepressants and the risk of suicide, attempted suicide, and overall mortality in a nationwide cohort.

BACKGROUND: It is unknown if antidepressant treatment is associated with either increased or decreased risk of suicide. OBJECTIVE: To estimate the risk of suicide, attempted suicide, and overall mortality during antidepressant treatments in a real-life setting with high statistical power. DESIGN AND SETTING: A cohort study in which all subjects without psychosis, hospitalized because of a suicide attempt from January 1, 1997, to December 31, 2003, in Finland, were followed up through a nationwide computerized database. PARTICIPANTS: A total of 15 390 patients with a mean follow-up of 3.4 years. MAIN OUTCOME MEASURES: The propensity score-adjusted relative risks (RRs) during monotherapy with the most frequently used antidepressants compared with no antidepressant treatment. RESULTS: In the entire cohort, fluoxetine use was associated with the lowest risk (RR, 0.52; 95% confidence interval [CI], 0.30-0.93), and venlafaxine hydrochloride use with the highest risk (RR, 1.61; 95% CI, 1.01-2.57), of suicide. A substantially lower mortality was observed during selective serotonin reuptake inhibitor use (RR, 0.59; 95% CI, 0.49-0.71; P<.001), and this was attributable to a decrease in cardiovascular- and cerebrovascular-related deaths (RR, 0.42; 95% CI, 0.24-0.71; P=.001). Among subjects who had ever used any antidepressant, the current use of medication was associated with a markedly increased risk of attempted suicide (39%, P<.001), but also with a markedly decreased risk of completed suicide (-32%, P=.002) and mortality (-49%, P<.001), when compared with no current use of medication. The results for subjects aged 10 to 19 years were basically the same as those in the total population, except for an increased risk of death with paroxetine hydrochloride use (RR, 5.44; 95% CI, 2.15-13.70; P<.001). CONCLUSIONS: Among suicidal subjects who had ever used antidepressants, the current use of any antidepressant was associated with a markedly increased risk of attempted suicide and, at the same time, with a markedly decreased risk of completed suicide and death. Lower mortality was attributable to a decrease in cardiovascular- and cerebrovascular-related deaths during selective serotonin reuptake inhibitor use.

Adolescent↗

Overall survival from breast cancer in women pregnant or lactating at or after diagnosis. Auckland Breast Cancer Study Group.

The effect of concurrent or subsequent pregnancy or lactation has been studied in women with breast cancer to determine if these variables influence prognosis. Information was collected from 382 women potentially capable of bearing children, aged less than 45 years, in the Auckland Breast Cancer Study Group data file, a consecutive series of women diagnosed with breast cancer from 1976 to 1985, with a median follow-up of 10.2 years. The prevalence of both pregnancy at diagnosis and lactation at diagnosis was 2.6%. The incidence of pregnancy subsequent to diagnosis was 3.9%. Women pregnant at the time of breast cancer diagnosis had significantly more advanced disease than non-pregnant patients, and there was a similar trend for women lactating at diagnosis. Overall survival in these women was poor compared with the non-pregnant and non-lactating groups; only 2 of 10 pregnant patients and 0 of 10 lactating patients survived more than 12 years. The adverse outcome for women lactating at diagnosis of their breast cancer persisted despite allowance for nodal status, tumour size and age. However, survival was similar between pregnant and non-pregnant patients when these variables were taken into account. No significant differences in survival were found between those women who had pregnancies subsequent to diagnosis of breast cancer and breast cancer patients who did not become pregnant.

Adult↗

Androgen receptor polymorphisms: association with prostate cancer risk, relapse and overall survival.

Several reports have suggested that one or both of the trinucleotide repeat polymorphisms in the human androgen receptor (hAR) gene, (CAG)n coding for polyglutamine and (GGC)n coding for polyglycine, may be associated with prostate cancer risk; but no study has investigated their association with disease progression. We present here a study of both hAR trinucleotide repeat polymorphisms not only as they relate to the initial diagnosis but also as they are associated with disease progression after therapy. Lymphocyte DNA samples from 178 British Caucasian prostate cancer patients and 195 control individuals were genotyped by PCR for the (CAG)n and (GGC)n polymorphisms in hAR. Univariate Cox proportional hazard analysis indicated that stage, grade and GGC repeat length were individually significant factors associated with disease-free survival (DFS) and overall survival (OS). The relative risk (RR) of relapse for men with more than 16 GGC repeats was 1.74 (95% CI 1. 08-2.79) and of dying from any cause, 1.98 (1.13-3.45). Adjusting for stage and grade, GGC effects remained but were not significant (RR(DFS)= 1.60, p = 0.052; RR(OS)= 1.65, p = 0.088). The greatest effects were in stage T1-T2 (RR(DFS)= 3.56, 95% CI 1.13-11.21) and grade 1 (RR(DFS)= 6.47, 95% CI 0.57-72.8) tumours. No differences between patient and control allele distributions were found by odds-ratio analysis, nor were trends with stage or grade evident in the proportion of short CAG alleles. Non-significant trends with stage and grade were found in the proportion of short GGC alleles. The (GGC)n polymorphism in this population is a significant predictor of disease outcome. Since the (GGC)(n) effect is strongest in early-stage tumours, this marker may help forecast aggressive behaviour and could be used to identify those patients meriting more radical treatment.

Aged↗

Parametric and non-parametric tests for the overall comparison of several treatments to a control when treatment is expected to increase variability.

We consider the problem of making an overall comparison of several treatments to a control where experimental units are randomly assigned to either the 'control' group which receives no treatment or to one of k-1 'treatment' groups. We assume that the effect of the treatments is, if anything, a location shift possibly accompanied by an increase in scale relative to that of the control group. The ANOVA F test loses considerable power in such circumstances. A modification of the ANOVA F test has been proposed which uses the variance estimate from the controls in place of the usual pooled variance estimate. However, this modification has shortcomings when k exceeds two and the variances of the treatment groups are not inflated. We develop a combination procedure to avoid the pitfalls of the modified and usual F tests. We then propose parametric and non-parametric implementations of a likelihood ratio test that more efficiently incorporates the assumptions of this problem, yielding a test with a high power profile over a large range of normal alternatives. We use simulations to compare the power of the competing tests against several alternatives for normal and non-normal data.

Analysis of Variance↗

(13)C cross-polarization/magic angle spinning NMR studies of alpha-elastin preparations show retention of overall structure and reduction of mobility with a decreased number of cross-links.

High-resolution solid-state (13)C NMR spectra are presented for samples of alpha-elastin prepared from the aorta of normal and copper-deficient pigs. Chemical shifts of the various peaks indicate that both the normal and undercross-linked peptides have similar overall structures. However, (13)C T(1), (13)C T(1 rho), and (1)H T(1 rho) measurements indicate that the alpha-elastin peptides obtained from the abnormal elastic fibers samples exhibit altered mobilities, particularly in their side chains. Results from spectra taken with a range of contact times and from dipolar dephasing experiments are consistent with conclusions reached with the relaxation measurements. Namely, the loss of function associated with the undercross-linked sample is correlated to a small but measurable difference in relative mobility.

Animals↗

Factors Impacting Overall Survival Post-Relapse in High-Risk Neuroblastoma: Children's Oncology Group Outcomes From 2000 to 2019.

PURPOSE: Prior studies of features impacting post-relapse survival in high-risk neuroblastoma (HRNB) evaluated patient cohorts that did not receive contemporary high-risk or relapse therapies. We describe overall survival (OS) after first progression or first relapse of HRNB in a modern cohort. METHODS: Patients with HRNB enrolled on COG ANBL00B1(NCT00904241) between 2000 and 2019, who had relapsed or progressive disease were eligible. Clinical and molecular risk factors at diagnosis, therapy era, clinical trial enrollment, and clinical features at relapse, including site of and time to relapse, were evaluated. OS post-relapse was compared between groups using log-rank tests and Cox models. RESULTS: Among 4253 eligible HRNB patients, 1616 had relapse or progression as a first event. Five-year OS post-relapse was 19.1&#xa0;&#xb1;&#xa0;1.1%. The risk group with the lowest post-relapse survival was observed in patients with INSS Stage 4 or 4S disease <&#xa0;18 months of age at diagnosis with MYCN amplified (MYCN-A) tumors. The other significant most unfavorable factors at diagnosis included diagnosis 2000-2004, tumor MYCN-A, 1p loss of heterozygosity (LOH), and elevated LDH or ferritin. Unfavorable factors at relapse included the time to relapse <&#xa0;36 months from diagnosis, and combined local and metastatic disease at relapse. Multivariable analysis indicated that those with tumors harboring 1p LOH, age &#x2264;&#xa0;5 years at diagnosis, or earlier treatment therapy era (2000-2004) had a higher risk of post-relapse death. CONCLUSIONS: While the 5-year OS rate was low in this cohort, there are subsets of patients with relapsed HRNB who demonstrate long-term survival. TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT00904241.

Humans↗

Prolonged overall survival with second on-demand autologous transplant in multiple myeloma.

Between August 1993 and March 2003, 130 consecutive multiple myeloma (MM) patients eligible for high-dose treatment were offered a program including up-front autologous stem cell transplantation (ASCT) after conditioning with 200 mg/m(2) melphalan followed by a second ASCT in case of relapse or progression. A total of 107 (82%) patients completed the first ASCT. The best response obtained after ASCT was complete response (CR) 23%, very good partial response (VGPR) 28%, partial response (PR) 42%, and minimal response (MR) 7%. Median overall survival (OS) and event-free survival (EFS) were 65.4 and 27.7 months, respectively. Relapse or progression occurred in 70 patients; 26 received a second ASCT (with a median time of 20.4 months from first ASCT). A major response (> or =PR) was obtained in 69% of these patients. Median OS and EFS after the second ASCT were 38.1 and 14.8 months. Treatment-related mortality was 1.9% after the first ASCT but no deaths occurred after the second. Our experience suggests that elective up-front single ASCT followed by second ASCT after relapse or progression is a safe and effective global strategy to treat MM patients.

Adult↗

The possible role of direct ingestion on the overall absorption of cadmium or arsenic in workers exposed to CdO or As2O3 dust.

Six volunteers (two office and four cadmium (Cd)-exposed workers, all nonsmokers) from an electric condenser factory participated in a study involving the measurement of cadmium in air and in dust, the evaluation of hand and mouth contamination by cadmium, and the determination of fecal cadmium. The mean levels of total airborne cadmium measured with static and personal samplers were for the exposed workers 9.5 and 16.7 microgram/m3, respectively, and for the office workers 0.3 and 0.5 microgram/m3, respectively. In the office workers, hand contamination by Cd hardly changes over the workday (less than 10 microgram/hand), whereas in the exposed workers important hand contamination by Cd was observed (up to 1,200 microgram/hand during the workday and up to 300 microgram/hand before lunch or before leaving the factory). Mouth contamination by Cd is rather similar in both groups on Monday morning, but increases 20- to 50-fold on Friday afternoon in the Cd workers against a slight increase for the office workers. The concentration of Cd in the feces was not much different between Sunday and Friday in the office workers, whereas in the exposed workers it was higher on Friday than on Sunday. There is suggestive evidence from a comparative study of fecal cadmium in two Cd-exposed volunteers who carried out their jobs with and without gloves that direct cadmium intake from hand contamination may contribute to the overall Cd absorption. A limited study in a glassware factory (As2O3 exposure) involving the measurement of total airborne arsenic, the determination of urinary arsenic, and the evaluation of hand and mouth contamination by arsenic before and after the workshift suggests that the high urinary arsenic levels (300 microgram/g creatinine) are likely to be more related to an increased oral intake from contaminated hands than to an increased absorption from the lungs.

Air↗

Team versus non-team outpatient care in rheumatoid arthritis. A comprehensive outcome evaluation including an overall health measure.

In a rheumatology department, 2 randomized groups of female outpatients with rheumatoid arthritis were studied prospectively for 1 year. The outcome of multidisciplinary team care (T group, 31 patients) was compared with that of regular outpatient clinic care (NT group, 28 patients). Pharmacologic treatment and orthopedic specialist consultations were similar in both groups, but use of paramedical care was higher in the T group. Outcome measures of disease activity, specific joint function, and self-rated physical discomfort disclosed no significant differences between the 2 groups. Mental well-being increased in the T group. Overall health, measured by the Sickness Impact Profile, improved significantly only in the T group. This improvement was also significant compared with the NT group.

Adult↗

The American College of Rheumatology response criteria for systemic lupus erythematosus clinical trials: measures of overall disease activity.

OBJECTIVE: Improved standards for the evaluation of therapeutic interventions in systemic lupus erythematosus (SLE) are needed. The purpose of this study by a committee of the American College of Rheumatology was to define clinically meaningful improvement, no change, or worsening in 6 existing clinical measures of SLE disease activity. This represents an important step in a disease in which some organ symptoms get better and others get worse. It is intended to help investigators develop sample size estimates based on meaningful effect sizes and to gauge the clinical relevance of any observed change in disease activity. METHODS: Medical records from 310 patients drawn from 3 sources were abstracted into a standard format. Each vignette included clinical and laboratory data obtained during 2-3 visits. Ratings on the following 6 instruments were obtained for the same patients during the visit or retrospectively: the British Isles Lupus Assessment Group (BILAG), the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the revised Systemic Lupus Activity Measure (SLAM-R), the European Consensus Lupus Activity Measure (ECLAM), the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA)-SLEDAI, and the Responder Index for Lupus Erythematosus (RIFLE). From this pool of vignettes, 5 common vignettes and 10 randomly selected vignettes were rated through a secure Web site by 88 international experts on SLE. The experts, who were blinded to the activity measure scores, were asked to rate each patient's clinical condition as worsened, improved, or unchanged relative to the previous visit. These ratings were transformed by statistical procedures into performance characteristic curves that related a change on a particular SLE activity measure to the physicians' agreement on whether that patient had worsened, improved, or remained the same clinically. These were discussed by the committee members, who were blinded to the actual instrument used. The committee then voted on what level of expert agreement would be used to determine clinically meaningful change. RESULTS: The physician ratings on the 5 common vignettes revealed considerable variation in their clinical appraisals. Overall, the 6 SLE activity measures showed excellent separation of clinical conditions as being worsened, improved, or the same. The committee voted to take 70% agreement by physicians as the point on the performance characteristic curves at which meaningful change in a score could be identified. For each instrument, we computed the units of change required to indicate improvement or worsening. CONCLUSION: To our knowledge, these are the first response criteria in any disease where a clinically relevant change has been determined a priori and mapped to standardized measures. This criterion should aid the clinical evaluation of new therapies, improve comparability between trials, and facilitate innovative trial designs.

Clinical Trials as Topic↗

Fundamental Escherichia coli biochemical pathways for biomass and energy production: creation of overall flux states.

We have previously shown that the metabolism for most efficient cell growth can be realized by a combination of two types of elementary modes. One mode produces biomass while the second mode generates only energy. The identity of the four most efficient biomass and energy pathway pairs changes, depending on the degree of oxygen limitation. The identification of such pathway pairs for different growth conditions offers a pathway-based explanation of maintenance energy generation. For a given growth rate, experimental aerobic glucose consumption rates can be used to estimate the contribution of each pathway type to the overall metabolic flux pattern. All metabolic fluxes are then completely determined by the stoichiometries of involved pathways defining all nutrient consumption and metabolite secretion rates. We present here equations that permit computation of network fluxes on the basis of unique pathways for the case of optimal, glucose-limited Escherichia coli growth under varying levels of oxygen stress. Predicted glucose and oxygen uptake rates and some metabolite secretion rates are in remarkable agreement with experimental observations supporting the validity of the presented approach. The entire most efficient, steady-state, metabolic rate structure is explicitly defined by the developed equations without need for additional computer simulations. The approach should be generally useful for analyzing and interpreting genomic data by predicting concise, pathway-based metabolic rate structures.

Cell Division↗

Characteristics of unbuffered gel-immobilized urease particles. II. Overall rate of reaction.

The overall rates of reaction of unbuffered gel-immobilized urease particles have been investigated with the aid of a packed-bed differential recycle reactor. Both substrate and enzyme concentrations have received attention. Cylindrical gel particles contained within impermeable tubelets were used to provide the physical strength necessary for the packed-bed arrangement and a one dimensional diffusion path to aid understanding of the complex interactions between substrate and product diffusion, and their effect on the reactions taking place. The experimental data have been interpreted with the aid of an enzyme rate equation (ERE) which relates the free solution characteristics of the enzyme to the conditions within a diffusion limited particle. The internal hydrogen ion profiles have been accommodated by a lumped parameter, the apparent pH (pHapp). Two methods have been suggested for the calculation of pHapp and the loss of activity on particle preparation, these methods are based on the use of the ERE in conjunction with experimental data.

Acrylamides↗

Preoperative probability model for predicting overall survival after resection of pulmonary metastases from colorectal cancer.

BACKGROUND: The aim of this study was identify readily available factors most helpful in predicting survival and to develop a prognostic nomogram for patients with pulmonary metastases from colorectal cancer who are candidates for thoracotomy. METHODS: Pretreatment data on 313 patients with metastases who underwent thoracotomy were analysed. Fourteen preoperative clinical and pathological variables were used to develop a probability model, in which their association with 3-year survival was tested. A nomogram to predict median, 1- and 3-year survival was constructed and validated internally using the concordance index (c-index). The nomogram was then validated with an external data set. RESULTS: Five variables were identified as independent predictors of 3-year survival: prethoracotomy carcinoembryonic antigen level, number of pulmonary tumours, presence of hilar or mediastinal tumour-infiltrated lymph nodes, histology of the primary tumour and presence of extrathoracic disease. The nomogram was well calibrated for predicting 3-year overall survival. The internal validated c-index of the nomogram was 0.72. Applied to another data set, the external validated c-index was 0.66. CONCLUSION: This model has moderate predictive ability to discriminate between patients who are likely to survive after thoracotomy for pulmonary metastases from colorectal cancer.

Adult↗

Inclusion of Multi-Omic Biomarkers Improves Prediction Accuracy of Response, Relapse, and Overall Survival in Acute Myeloid Leukemia Patients Receiving High-Intensity Induction Chemotherapy.

BACKGROUND: Despite advancements in genetic markers for acute myeloid leukemia (AML) risk stratification, outcome prediction remains challenging due to disease heterogeneity and dynamic genetic changes, highlighting the need for reliable biomarkers to improve AML treatment strategies and patient outcomes. To refine outcome predictions, we investigated the use of microbial-derived biomarkers to predict composite complete remission (CRc), relapse, and survival for patients on high- and low-intensity regimens, and to integrate those variables into the widely clinically utilized European Leukemia Network (ELN-2022) genetic risk classification model for high-intensity-treated patients. METHODS: We first developed machine learning models that integrate baseline fecal metabolomics, 16S rRNA-based stool microbiome features, and clinical metadata (sex, antibiotic administration, AML somatic mutations, and cytogenetics) from two cohorts of AML patients (n&#x2009;=&#x2009;83) undergoing remission induction chemotherapy. Univariate tests and sparse canonical correlation analysis were employed for variable selection and to explore fecal metabolite-microbe relationships. A robust machine learning approach using XGBoost was employed, with 100 stratified data splits (80% training, 20% testing) and coarse-to-fine hyperparameter optimization. Variable importance was aggregated across all models to select key predictors. RESULTS: For high-intensity-treated patients, XGBoost models achieved aggregated AUROC scores of 0.719, 0.729, and 0.65 for CRc, relapse, and overall survival, respectively. For low-intensity-treated patients, these models achieved aggregate AUROC scores of 0.945, 0.724, and 0.768 for these same outcomes, respectively. Integrating the biomarkers identified in the high-intensity machine-learning models with the current ELN-2022 AML risk stratification system effectively stratified patients into risk categories, which obtained higher concordance indices and likelihood ratios, demonstrating improved prognostic accuracy for each outcome compared to ELN-2022 alone. CONCLUSIONS: The inclusion of microbial-derived biomarkers serves as a robust prognostic tool to improve outcome prediction in AML patients, highlighting the potential of its integration into AML risk assessment and paving the way for personalized treatment strategies and improved patient outcomes.

Humans↗

Left atrial size is the major predictor of cardiac death and overall clinical outcome in patients with dilated cardiomyopathy: a long-term follow-up study.

HYPOTHESIS: This study was undertaken to determine whether echo-derived left atrial dimension and other echocardiographic, clinical, and hemodynamic parameters detected at the time of entry into the study may influence prognosis in patients with dilated cardiomyopathy during a long-term follow-up. METHODS: This was a prospective cohort analysis of 123 patients with dilated cardiomyopathy. Clinical evaluation, chest x-ray, M-mode and two-dimensional echocardiogram, exercise test, 72-h ambulatory electrocardiogram monitoring, and cardiac catheterization study were performed in all patients. The study was divided into two phases: in the first phase, patients were divided into two groups according to the left atrial size (> or = 45 mm; < 45 mm), with cardiac death as the end point. In the second phase, all patients were further divided into two groups according to their clinical course. A multivariate analysis was performed to determine independent correlated parameters of cardiac mortality and overall clinical outcome. RESULTS: Cardiac mortality rate was 47.9%: 29% in the group without left atrial dilation and 54.3% in the group with dilated left atrium. Multivariate analysis revealed that left atrium > or = 45 mm, New York Heart Association functional classes III/IV, and the presence of one or more episodes of ventricular tachycardia at Holter monitoring were independent predictors of cardiac mortality, while left atrium > or = 45 mm, left ventricular end-diastolic pressure > 17 mmHg, and exercise tolerance < or = 15 min were independent predictors of poor clinical outcome. CONCLUSIONS: Our results revealed that left atrial size is the principal independent predictor of prognosis in patients with dilated cardiomyopathy in that patients with left atrial dilation had an increase in mortality and a worse clinical outcome compared with those without left atrial dilation.

Adult↗

An elevated serum beta-2-microglobulin level is an adverse prognostic factor for overall survival in patients with early-stage Hodgkin disease.

BACKGROUND: The relative importance of prognostic factors in patients with early-stage Hodgkin disease remains controversial. The purpose of this study was to evaluate prognostic factors among patients who received chemotherapy before radiotherapy. METHODS: From 1987 to 1995, 217 consecutive patients ranging in age from 16 to 88 years (median, 28 years) with Ann Arbor Stage I (n = 55) or II (n = 162) Hodgkin disease underwent chemotherapy before radiotherapy at a single center. Most were treated on prospective studies. Patients received a median of three cycles of induction chemotherapy. Mitoxantrone, vincristine, vinblastine, and prednisone (NOVP), doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), cyclophosphamide, vinblastine, procarbazine, prednisone, doxorubicin, bleomycin, dacarbazine, and CCNU (CVPP/ABDIC), or other chemotherapeutic regimens were given to 160, 18, 15, 10, and 14 patients, respectively. The median radiotherapy dose was 40 Gy. Serum beta-2-microglobulin (beta-2M) levels ranged from 1.0 to 4.1 mg/L (median, 1.7 mg/L; upper limit of normal, 2.0 mg/L). We studied univariate and multivariate associations between survival and the following clinical features: serum beta-2M level above 1.25 times the upper limit of normal (n = 12), male gender (n = 113), hypoalbuminemia (n = 11), and bulky mediastinal disease (n = 94). RESULTS: Follow-up of surviving patients ranged from 0.9 to 13.4 years (median, 6.6 years) and 92% were observed for 3.0 or more years. Nineteen patients have died. Only elevation of the serum beta-2M level was an independent adverse prognostic factor for overall survival (P = 0.0009). CONCLUSIONS: The prognostic significance of a simple, widely available, and inexpensive blood test, beta-2M, has not been studied routinely in patients with Hodgkin disease and should be tested prospectively in large, cooperative group trials.

Adolescent↗