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Results for “Prognostic model”

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At least 595 records · Page 33Linked to original sources

PubMed1998

Prediction of sentinel lymph node micrometastasis by histological features in primary cutaneous malignant melanoma.

OBJECTIVE: To develop a prognostic model, based on clinical and pathological data, to estimate the probability of micrometastasis in the sentinel lymph node in patients with malignant melanoma. DESIGN: Retrospective analytical study. SETTING: University medical center. PATIENTS: Two hundred fifteen patients with American Joint Committee on Cancer stages I and II cutaneous malignant melanoma underwent sentinel lymph node biopsy. MEASUREMENTS: Presence of microscopic melanoma in the sentinel lymph node(s). Clinical attributes recorded included age, sex, and location of the primary melanoma. Pathological attributes recorded before lymph node evaluation included ulceration, microsatellites, angiolymphatic invasion, mitotic rate, tumor infiltrating lymphocytes, and regression. RESULTS: Forty-six patients (21.4%) overall had a positive sentinel lymph node. Patients with tumor thickness ranging from 3.0 to 3.9 mm had the highest incidence (50%) of nodal involvement, followed by those with tumors 4.0 to 4.9 mm thick (41%). Patients with melanomas measuring greater than 4.9 mm thick and those between 1.0 and 2.9 mm had a similar rate of nodal involvement (16%-17%). Clinical characteristics had minimal correlation with nodal status in multivariate analysis. The total number of histological high-risk features was significantly correlated with sentinel lymph node involvement. Important pathological risk factors included ulceration, high mitotic rate, angiolymphatic invasion, and microsatellites. Patients with tumor thickness greater than 1.0 mm but lacking these features had a 14% risk of occult metastases. CONCLUSION: Among patients with clinically node-negative primary melanoma, the presence of 1 or more high-risk histological features significantly increases the incidence of microscopic nodal involvement and can be used to predict the likelihood of a positive sentinel lymph node biopsy.

Adolescent↗

PubMed2005

Prediction of survival for patients with bullous pemphigoid: a prospective study.

OBJECTIVE: To identify the prognostic factors of bullous pemphigoid (BP). DESIGN: Prospective study of patients with BP included in a randomized, controlled trial. SETTING: Twenty dermatology departments in France. Patients One hundred seventy patients with BP initially treated with a 40-g/d dosage of clobetasol propionate cream (testing sample) and 171 patients initially treated with oral corticosteroids at a dosage of 0.5 or of 1.0 mg/kg per day, depending on the extent of BP (validation samples). MAIN OUTCOME MEASURES: The end point was overall survival during the first year after BP diagnosis. From the testing sample, associations of clinical and biological variables with overall survival were assessed using univariate and multivariate analyses. Selected predictors were included in a prognostic model. To verify that these predictors were not dependent on the treatment used, the model was then validated independently on the 2 series of BP patients treated with oral corticosteroids. RESULTS: Median age of the BP patients included in the testing sample was 83 years. The 1-year Kaplan-Meier survival rate was 74%. From univariate analysis, the main deleterious predictors were demographic factors (ie, older age and female sex), associated medical conditions (ie, cardiac insufficiency, history of stroke, and dementia), and low Karnofsky score, which is a measure of the patient's general condition. No factors directly related to BP, in particular extent of cutaneous lesions, were shown to be related to the patients' prognosis. From multivariate analysis, only older age (P = .02) and low Karnofsky score (P<.001) appeared independently predictive of death. From the Cox model including these 2 predictors, the predicted 1-year survival rates were 90% (95% confidence interval [CI], 85%-96%) for patients 83 years or younger with Karnofsky score greater than 40, 79% (95% CI, 69%-90%) for patients older than 83 years with Karnofsky score greater than 40, 65% (95% CI, 50%-86%) for patients 83 years or younger with Karnofsky score of 40 or less, and 38% (95% CI, 26%-57%) for patients older than 83 years with Karnofsky score of 40 or less. Kaplan-Meier survival distributions of patients from the validation samples appeared clearly separated according to these 4 categories and were in close agreement with corresponding predicted 1-year survival rates obtained from the testing sample. CONCLUSIONS: The prognosis of patients with BP is influenced by age and Karnofsky score. These predictors are easy to use and should facilitate the management of BP.

Administration, Oral↗

PubMed2006

A prediction rule to identify low-risk patients with pulmonary embolism.

BACKGROUND: A simple prognostic model could help identify patients with pulmonary embolism who are at low risk of death and are candidates for outpatient treatment. METHODS: We randomly allocated 15,531 retrospectively identified inpatients who had a discharge diagnosis of pulmonary embolism from 186 Pennsylvania hospitals to derivation (67%) and internal validation (33%) samples. We derived our rule to predict 30-day mortality using classification tree analysis and patient data routinely available at initial examination as potential predictor variables. We used data from a European prospective study to externally validate the rule among 221 inpatients with pulmonary embolism. We determined mortality and nonfatal adverse medical outcomes across derivation and validation samples. RESULTS: Our final model consisted of 10 patient factors (age > or = 70 years; history of cancer, heart failure, chronic lung disease, chronic renal disease, and cerebrovascular disease; and clinical variables of pulse rate > or = 110 beats/min, systolic blood pressure < 100 mm Hg, altered mental status, and arterial oxygen saturation < 90%). Patients with none of these factors were defined as low risk. The 30-day mortality rates for low-risk patients were 0.6%, 1.5%, and 0% in the derivation, internal validation, and external validation samples, respectively. The rates of nonfatal adverse medical outcomes were less than 1% among low-risk patients across all study samples. CONCLUSIONS: This simple prediction rule accurately identifies patients with pulmonary embolism who are at low risk of short-term mortality and other adverse medical outcomes. Prospective validation of this rule is important before its implementation as a decision aid for outpatient treatment.

Age Factors↗

PubMed2026

Prognostic Value of Blood-Based P-Tau217 Levels for Progression to Cognitive Impairment.

IMPORTANCE: Blood-based biomarkers for Alzheimer disease, particularly plasma phosphorylated tau 217 (p-tau217), accurately reflect early Alzheimer disease brain pathology in cognitively unimpaired individuals, but estimates of absolute risk of progression to cognitive impairment across multiple cohorts are needed. OBJECTIVE: To estimate absolute risk of progression to cognitive impairment and rates of cognitive decline based on plasma p-tau217 across cognitively unimpaired older adults. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal cohort study using harmonized data from 2684 cognitively unimpaired older adults (defined within cohort) across 6 observational and clinical trial cohorts based in North America, Japan, and Australia. The earliest enrollment was in 2004, with most recent follow-up in 2025. EXPOSURE: Baseline plasma p-tau217. MAIN OUTCOMES AND MEASURES: The primary outcome was time to progression to cognitive impairment (mild cognitive impairment, dementia, or 2 consecutive global Clinical Dementia Rating scores ≥0.5). The secondary outcome was longitudinal change on the latent Preclinical Alzheimer Cognitive Composite (PACC; higher values indicate better performance). RESULTS: Among the 2684 participants (median [IQR] age, 69.6 [66.2-74.2] years; 1697 [63%] female), there were 478 events of progression to cognitive impairment over a median follow-up of 5.4 years (maximum follow-up of 13.5 years). Each 1-SD increase in baseline p-tau217 level was associated with an increased risk of progression to cognitive impairment (hazard ratio, 1.38 [95% CI, 1.30-1.46]), and the association remained significant after adjustment, including β-amyloid positron emission tomography scan Centiloids (hazard ratio, 1.32 [95% CI, 1.24-1.41]). Participants with high (1.1-2.4 SD) and very high (>2.5 SD) baseline p-tau217 had 24% (95% CI, 20%-28%) and 38% (95% CI, 33%-43%) absolute risk of progression over 5 years, respectively, and risk was markedly higher over 10 years, although longer-term estimates were constrained by limited data. Elevated p-tau217 was also associated with faster cognitive decline based on change in latent PACC score. Among the overall sample, baseline latent PACC scores ranged from -0.8 to 2.7. The 5-year annualized decline for the very high p-tau217 group was -0.07 latent PACC units/y (95% CI, -0.10 to -0.05), relative to 0.03 units/y (95% CI, 0.02-0.04) in the low p-tau217 group. CONCLUSIONS AND RELEVANCE: In a pooled sample of multiple selected cohorts of cognitively unimpaired older adults, higher plasma p-tau217 levels were consistently associated with increased risk of clinical progression and accelerated cognitive decline. By providing time-specific absolute risk estimates, these findings support the potential of p-tau217 for prognostic model development, with direct implications for future trial design. Further validation in unselected populations is needed to inform individual prognosis and clinical decision-making in cognitively unimpaired individuals.

Aged↗

PubMed2002

Patient and caregiver characteristics and nursing home placement in patients with dementia.

CONTEXT: The decision to institutionalize a patient with dementia is complex and is based on patient and caregiver characteristics and the sociocultural context of patients and caregivers. Most studies have determined predictors of nursing home placement primarily according to patient or caregiver characteristics alone. OBJECTIVE: To develop and validate a prognostic model to determine the comprehensive predictors of placement among an ethnically diverse population of patients with dementia. DESIGN, SETTING, AND PARTICIPANTS: The Medicare Alzheimer's Disease Demonstration and Evaluation study, a prospective study at 8 sites in the United States, with enrollment between December 1989 and December 1994 of 5788 community-living persons with advanced dementia. MAIN OUTCOME MEASURES: Time to nursing home placement throughout a 36-month follow-up period, assessed by interview and review of Medicare records, and its association with patient and caregiver characteristics, obtained by interview at enrollment. RESULTS: Patients were divided into a development (n = 3859) and validation (n = 1929) cohort. In the development cohort, the Kaplan-Meier estimates of nursing home placement throughout 1, 2, and 3 years were 22%, 40%, and 52%, respectively. After multivariate adjustment, patient characteristics that were associated with nursing home placement were as follows: black ethnicity (hazard ratio, 0.60; 95% confidence interval [CI], 0.48-0.74), Hispanic ethnicity (HR, 0.40; 95% CI, 0.28-0.56) (both ethnicities were inversely associated with placement), living alone (HR, 1.74; 95% CI, 1.49-2.02), 1 or more dependencies in activities of daily living (HR, 1.38; 95% CI, 1.20-1.60), high cognitive impairment (for Mini-Mental Status Examination score < or =20: HR, 1.52; 95% CI, 1.33-1.73), and 1 or more difficult behaviors (HR, 1.30; 95% CI, 1.11-1.52). Caregiver characteristics associated with patient placement were age 65 to 74 years (HR, 1.17; 95% CI, 1.01-1.37), age 75 years or older (HR, 1.55; 95% CI, 1.31-1.84), and high Zarit Burden Scale score (for highest quartile: HR, 1.73; 95% CI, 1.49-2.00). Patients were assigned to quartiles of risk based on this model. In the development cohort, patients in the first, second, third, and fourth quartile had a 25%, 42%, 64%, and 91% rate of nursing home placement at 3 years, respectively. In the validation cohort, the respective rates were 21%, 50%, 64%, and 89%. The C statistic for 3-year nursing home placement was 0.66 in the development cohort and 0.63 in the validation cohort. CONCLUSIONS: Patient and caregiver characteristics are both important determinants of long-term care placement for patients with dementia. Interventions directed at delaying placement, such as reduction of caregiver burden or difficult patient behaviors, need to take into account the patient and caregiver as a unit.

Aged↗

PubMed1998

A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995 [see commetns].

BACKGROUND: The National Cancer Data Base (NCDB) represents a national electronic registry system now capturing nearly 60% of incident cancers in the U. S. In combination with other Commission on Cancer programs, the NCDB offers a working example of voluntary, accurate, cost-effective "outcomes management" on a both a local and national scale. In addition, it is of particular value in capturing clinical information concerning rare cancers, such as those of the thyroid. METHODS: For the accession years 1985-1995, NCDB captured demographic, patterns-of-care, stage, treatment, and outcome information for a convenience sample of 53,856 thyroid carcinoma cases (1% of total NCDB cases). This article focuses on overall 10-year relative survival and American Joint Committee on Cancer (AJCC) (3rd/4th edition) stage-stratified 5-year relative survival for each histologic type of thyroid carcinoma. Care patterns also are discussed. RESULTS: The 10-year overall relative survival rates for U. S. patients with papillary, follicular, Hürthle cell, medullary, and undifferentiated/anaplastic carcinoma was 93%, 85%, 76%, 75%, and 14%, respectively. For papillary and follicular neoplasms, current AJCC staging failed to discriminate between patients with Stage I and II disease at 5 years. Total thyroidectomy +/- lymph node sampling/dissection represented the dominant method of surgical treatment rendered to patients with papillary and follicular neoplasms. Approximately 38% of such patients receive adjuvant iodine-131 ablation/therapy. At 5 years, variation in surgical treatment (i.e., lobectomy vs. more extensive surgery) failed to translate into compelling differences in survival for any subgroup with papillary or follicular carcinoma, but longer follow-up is required to evaluate this. NCDB data appeared to validate the AMES prognostic system, as applied to papillary cases. Younger age appeared to influence prognosis favorably for all thyroid neoplasms, including medullary and undifferentiated/anaplastic carcinoma. NCDB data also revealed that unusual patients diagnosed with undifferentiated/anaplastic carcinoma before age of 45 years have better survival. CONCLUSIONS: The NCDB system permits analysis of care patterns and survival for large numbers of contemporaneous U. S. patients with relatively rare neoplasms, such as thyroid carcinoma. In this context, it represents an unsurpassed clinical tool for analyzing care, evaluating prognostic models, generating new hypotheses, and overcoming the volume-related drawbacks inherent in the study of such neoplasms. [See editorial on pages 2434-6, this issue.]

Adenocarcinoma↗

PubMed1990

Value of serum acute-phase reactant proteins and carcinoembryonic antigen in the preoperative staging of colorectal cancer. A multivariate analysis.

In 55 patients with benign or malignant neoplasias of the large bowel, serum carcinoembryonic antigen (CEA), C-reactive protein (CRP), alpha 1-antitrypsin (AAT), alpha 1-acid glycoprotein (AAG) levels, and the percentage of serum protein electrophoretic components were measured. Statistical analysis showed significant correlations between serum CEA, CRP, AAG, and AAT levels and the percentage of serum beta-globulins with the stage of the disease. Multivariate discriminant analysis gave a final prognostic model that included serum CEA, CRP, and AAT levels and the percentage of the serum beta-globulins with a significance of P less than 0.000001. The authors conclude that the serum acute-phase protein levels, in combination with serum CEA concentrations, have a definite role in the preoperative staging of large bowel cancer.

Acute-Phase Proteins↗

PubMed1991

DNA and RNA flow cytometric study in multiple myeloma. Clinical correlations.

Flow cytometric studies of cellular DNA and RNA content using the acridine-orange technique were conducted in 81 patients with multiple myeloma (MM). All patients were treated with the M-2 protocol and clinical response was evaluated according to the criteria of the Chronic Leukemia-Myeloma Task Force. Aneuploid DNA stemlines were found in 38.2% of untreated patients with a median DNA index (DNA-I) of 1.15 in marrow aspirates and 1.22 in biopsy specimens. The median percentage of cells with abnormal DNA content was 31.5 (aspirates) and 35 (biopsy specimens) and a positive correlation with the percentage of bone marrow plasma cells was observed. Significantly higher proliferation (S-phase) was found in marrow biopsy specimens as compared with marrow aspirates. Significantly higher RNA content (RNA index [RNA-I]) was observed in aneuploid versus diploid patients in biopsy material. There was no difference in response to the Memorial Hospital M-2 protocol between diploid and aneuploid patients. In patients with DNA-I greater than 1.15 remission duration was shorter as compared with DNA-I less than or equal to 1.15. Furthermore, no difference in cellular RNA content was noted between responders and nonresponders. This study demonstrates no correlation between cellular RNA content and response, as previously described for patients treated with vincristine, Adriamycin, and dexamethasone (VAD), but DNA aneuploidy appears to be an adverse prognostic factor in MM patients treated with the M-2 protocol. It also demonstrates that prognostic models for MM are not universal but depend on the chemotherapeutic regimen used.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1993

Presymptomatic DNA testing for Huntington disease: identifying the need for psychological intervention.

UNLABELLED: In the Dutch presymptomatic DNA-testing program for Huntington disease (HD), 29 individuals with increased risk and 44 with decreased risk were followed-up 6 months after test results. A prognostic model was built aimed at identifying individuals at risk for psychological maladjustment, as measured by the Impact of Event Scale, the Beck Hopelessness Scale, the General Health Questionnaire, and the Social Support Questionnaire. RESULTS: 1) The more that applicants suffered from intrusive feelings about HD and tried to avoid HD-related situations, prior to the test, the greater the chance that they will experience this 6 months after the test if they proved to be at increased risk; 2) the more that both individuals with increased risk and those with decreased risk who suffered from the threat of having HD tried to avoid HD-related situations prior to the test and the less satisfied they were with available support, the greater the probability that they will show avoidance behavior after the test; 3) the more pessimistic that individuals with increased risk as well as those with decreased risk were about their future prior to the test, the more they avoided HD-related situations and the more dissatisfied they were about their available support (pretest), the greater the probability that they will become depressive and suicidal. Psychological adjustment was also studied as a function of a) intrusion/denial-avoidance pattern over time and b) healthy mental functioning/future expectancies. Most individuals with increased risk (86%) seem to cope well thus far, although this was based largely on strong psychological defenses and dependent on satisfactory relationships.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2004

Circulating D-dimer levels are better predictors of overall survival and disease progression than carcinoembryonic antigen levels in patients with metastatic colorectal carcinoma.

BACKGROUND: Fibrin formation is required for tumor angiogenesis, metastasis, and invasion. D-dimer, a fibrin degradation product, is produced when crosslinked fibrin is degraded by plasmin. The current study prospectively examined D-dimer levels in patients with metastatic colorectal carcinoma treated in a Phase II randomized trial comparing bevacizumab (Avastin, Genentech, South San Francisco, CA) plus 5-fluorouracil/leucovorin (5-FU/LV) with 5-FU/LV alone. METHODS: At least one circulating D-dimer level was evaluable in 98 of the 104 previously untreated patients with metastatic colorectal carcinoma in the current trial. Plasma D-dimer levels were determined using a quantitative immunoassay kit at enrollment, before each treatment, and at the time of trial completion or disease progression. RESULTS: At trial enrollment, 86 of 104 patients (88%) had elevated D-dimer levels (> 20 ng/mL), and 86 of 102 patients (84%) had elevated carcinoembryonic antigen (CEA) levels (> 3 ng/mL). Baseline D-dimer levels were correlated with the following baseline characteristics: CEA (Pearson coefficient, 0.31; P = 0.002), albumin levels (Pearson coefficient, -0.32; P = 0.002), tumor burden (Pearson coefficient, 0.30; P = 0.003), and number of metastatic sites (Pearson coefficient, 0.21; P = 0.04). At the time of progression, plasma D-dimer levels reached a maximum postbaseline value in 51 of 61 patients (84%), whereas the CEA level was at its maximum postbaseline value in 39 of 55 patients (71%). Baseline D-dimer levels were a strong predictor of overall survival on univariate analysis (P = 0.008) and multivariate analysis (P = 0.03). Overall, treatment with bevacizumab (5 mg/kg) and baseline D-dimer levels were the only predictors of overall survival (P < 0.05). CONCLUSIONS: The current study indicates that fibrin remodeling is an important prognostic feature in metastatic colorectal carcinoma. D-dimer levels should be incorporated into prognostic models, and D-dimer may represent a useful biomarker for patients treated with antiangiogenic agents.

Adult↗

PubMed1989

The Multivariate Prognostic Index and nuclear DNA content are independent prognostic factors in primary breast cancer patients.

The predictive value of a previously described Multivariate Prognostic Index (which incorporates weighted values of the mitotic activity index, tumor size, and the axillary lymph node status), and the nuclear DNA content (DNA) was evaluated in 156 patients with primary invasive ductal breast cancer, diagnosed between 1980 and 1983. The results were analysed with respect to the occurrence of distant recurrence and survival of the patients after at least 3 yr of follow-up (range 36-73 months; median 44 months). Known prognostic factors such as lymph node status, tumor size, and the mitotic activity index correlated independently with distant recurrence. Furthermore, in respect to survival, the investigated prognostic factors (except DNA content) were significantly correlated. The results indicate that the predictive value of the Multivariate Prognostic Index (MPI) is stronger (P less than 0.001) than of the nuclear DNA content (P less than 0.005) with respect to distant recurrence. In a Cox multivariate regression analysis DNA ploidy turned out to be an independent prognostic factor once the MPI was selected. Furthermore, in Cox's analysis, DNA ploidy was the fourth selected variable after lymph node status, mitotic activity index, and tumor size in individual parameter analysis. The results of this study indicate that, with respect to breast cancer screening programs, it seems worthwhile to integrate morphometric features, the MPI, and DNA ploidy in a new prognostic model.

Adult↗

PubMed2026

Dietary Polyphenol Acteoside-Related Molecular Signatures in Clear Cell Renal Cell Carcinoma: Multi-Omics Profiling and Functional Validation of IMPDH1.

Clear cell renal cell carcinoma (ccRCC) is characterized by substantial metabolic and molecular heterogeneity, but the disease-relevant programs associated with acteoside, a dietary polyphenol, remain poorly understood. We integrated predicted acteoside targets with bulk, single-cell, and spatial transcriptomic data from ccRCC and combined molecular subtyping with cross-cohort machine-learning analysis. Acteoside-related signatures were preferentially enriched in malignant compartments and increased with tumor grade and stage. Consensus clustering identified two molecular subtypes with distinct biological and clinical features. C1 was associated with immune activation, metabolic activity, and more favorable survival, whereas C2 showed greater genomic instability, reduced renal epithelial differentiation, and poorer outcomes. We further benchmarked multiple machine-learning strategies and established a 10-gene prognostic model that retained predictive performance across independent cohorts, with IMPDH1 emerging as the strongest risk-associated feature. Functional experiments confirmed the biological relevance of IMPDH1: its knockdown suppressed ccRCC cell proliferation, DNA synthesis, colony formation, and migration, whereas overexpression produced the opposite effects. Together, these findings indicate that acteoside-related molecular signatures capture clinically relevant heterogeneity in ccRCC and provide a framework for linking dietary-polyphenol-related molecular space with tumor biology. The identification and functional validation of IMPDH1 further highlight its potential importance in ccRCC progression.

IMPDH1↗

PubMed2005

MELD accurately predicts mortality in patients with alcoholic hepatitis.

Assessing severity of disease in patients with alcoholic hepatitis (AH) is useful for predicting mortality, guiding treatment decisions, and stratifying patients for therapeutic trials. The traditional disease-specific prognostic model used for this purpose is the Maddrey discriminant function (DF). The model for end-stage liver disease (MELD) is a more recently developed scoring system that has been validated as an independent predictor of patient survival in candidates for liver transplantation. The aim of the present study was to examine the ability of MELD to predict mortality in patients with AH. A retrospective cohort study of 73 patients diagnosed with AH between 1995 and 2001 was performed at the Mayo Clinic in Rochester, Minnesota. MELD was the only independent predictor of mortality in patients with AH. MELD was comparable to DF in predicting 30-day mortality (c-statistic and 95% CI: 0.83 [0.71-0.96] and 0.74 [0.62-0.87] for MELD and DF, respectively, not significant) and 90-day mortality (c-statistic and 95% CI: 0.86 [0.77-0.96] and 0.83 [0.74-0.92] for MELD and DF, respectively, not significant). A MELD score of 21 had a sensitivity of 75% and a specificity of 75% in predicting 90-day mortality in AH. In conclusion, MELD is useful for predicting 30-day and 90-day mortality in patients with AH and maintains some practical and statistical advantages over DF in predicting mortality rate in these patients. MELD is a useful clinical tool for gauging mortality and guiding treatment decisions in patients with AH, particularly those complicated by ascites and/or encephalopathy.

Adult↗

PubMed1996

Fulminant hepatitis in a tropical population: clinical course, cause, and early predictors of outcome.

The profiles of patients with fulminant hepatic failure (FHF) from developing countries have not been reported earlier. The current study was conducted prospectively, at a single tertiary care center in India, to document the demographic and clinical characteristics, natural course, and causative profile of patients with FHF as well as to define simple prognostic markers in these patients. Four hundred twenty-three consecutive patients with FHF admitted from January 1987 to June 1993 were included in the study. Each patient's serum was tested for various hepatotropic viruses. Univariate Cox's regression for 28 variables, multivariate Cox's proportional hazard regression, stepwise logistic regression, and Kaplan-Meier survival analysis were done to identify independent predictors of outcome at admission. All patients presented with encephalopathy within 4 weeks of onset of symptoms. Hepatotropic viruses were the likely cause in most of these patients. Hepatitis A (HAV), hepatitis B (HBV), hepatitis D (HDV) viruses, and antitubercular drugs could be implicated as the cause of FHF in 1.7% (n= 7), 28% (n= 117), 3.8% (n= 16), and 4.5% (n= 19) patients, respectively. In the remaining 62% (n= 264) of patients the serological evidence of HAV, HBV, or HDV infection was lacking, and none of them had ingested hepatotoxins. FHF was presumed to be caused by non-A, non-B virus(es) infection. Sera of 50 patients from the latter group were tested for hepatitis E virus (HEV) RNA and HCV RNA. In 31 (62%), HEV could be implicated as the causative agent, and isolated HCV RNA could be detected in 7 (19%). Two hundred eighty eight (66%) patients died. Approximately 75% of those who died did so within 72 hours of hospitalisation. One quarter of the female patients with FHF were pregnant. Mortality among pregnant females, nonpregnant females, and male patients with FHF was similar (P > .1). Univariate analysis showed that age, size of the liver assessed by percussion, grade of coma, presence of clinical features of cerebral edema, presence of infection, serum bilirubin, and prothrombin time prolongation over controls at admission were related to survival (P < .01). The rapidity of onset of encephalopathy and cause of FHF did not influence the outcome. Cox's proportional hazard regression showed age > or = 40 years, presence of cerebral edema, serum bilirubin > or = 15 mg/dL, and prothrombin time prolongation of 25 seconds or more over controls were independent predictors of outcome. Ninety-three percent of the patients with three or more of the above prognostic markers died. The sensitivity, specificity, positive predictive value, and the negative predictive value of the presence of three or more of these prognostic factors for mortality was 93%, 80%, 86%, and 89.5%, respectively, with a diagnostic accuracy of 87.3%. We conclude that most of our patients with FHF might have been caused by hepatotropic viral infection, and non-A, non-B virus(es) seems to be the dominant hepatotropic viral infection among these patients. They presented with encephalopathy within 4 weeks of the onset of symptoms. Pregnancy, cause, and rapidity of onset of encephalopathy did not influence survival. The prognostic model developed in the current study is simple and can be performed at admission.

Adolescent↗

PubMed2005

Is alcoholic hepatitis an indication for transplantation? Current management and outcomes.

1. In the absence of treatment, 50% of patients with severe alcoholic hepatitis (AH) [Maddrey function (DF) >or= 32] die 2 months later. Among patients with severe AH treated by corticosteroids, 80% had 2-month survival. Pentoxifylline is considered by some investigators to be an alternative option to corticosteroids. 2. Non-responders to corticosteroids (NRCs) have poor survival and require new strategies. Liver transplantation should be considered in order to improve survival of non-responders to therapeutic agents. 3. Prognostic models such as the Model for End-Stage Liver Disease (MELD) and DF are useful tools for predicting short-term mortality of patients with severe AH. Specific models taking into account the particular settings of treated patients are warranted. 4. In an era of organ shortage, use of liver transplants in patients with severe AH may negatively affect the public attitude on transplantation and organ donation, and may cause reluctance on the part of clinicians to modify guidelines for alcoholic patients. 5. Therefore, a reasonable approach would be to carry out only pilot studies on only a small cohort of patients to determine whether transplantation improves survival in patients with severe AH.

Glucocorticoids↗

PubMedDate not supplied

Role of multimodal treatment in oropharynx, larynx, and hypopharynx cancer.

Due to recent advances in radiation fractionation, radiochemotherapy, and conservative surgical techniques, the concept of multimodal therapy in head and neck cancer is currently changing. The recently published RTOG Phase III trial 9003, with 1,113 patients accrued, showed that hyperfractionation and accelerated fractionation with concomitant boost are more efficacious than standard fractionation for locally-advanced head and neck cancer. Acute, but not late, toxicity was also increased. Three meta-analyses have suggested that the impact of chemotherapy in head and neck cancer is small but is highly associated with the timing of therapy. Concomitant administration of radiation therapy and chemotherapy led to an absolute benefit in 5-year survival of about 10%. This finding has been further supported by recently published randomized prospective trials comparing concomitant radiochemotherapy with radiotherapy alone in advanced head and neck cancer. There is now clear evidence that radiochemotherapy provides a substantial and statistically significant improvement in survival and local-regional control, as compared to radiotherapy alone. Radiochemotherapy should be considered an accepted standard of care in cancers of the oropharynx, particularly for patients with locally-advanced disease who have a good performance status. Two randomized studies conducted by the Department of Veterans' Affairs and the EORTC, with a total of 534 patients accrued, showed that induction chemotherapy followed by radiotherapy of responders yields survival rates equal to those of total laryngectomy with postoperative radiotherapy. After 4 years, one-half to two-thirds of survivors of the chemotherapy arm retained a functional larynx. Larynx preservation using induction chemotherapy can now be regarded as feasible but still investigational. Current phase II studies show excellent larynx preservation rates using a primary concomitant radiochemotherapy with an altered fractionation regimen. More clinical and laboratory research is required to further evaluate the different treatment options of the multimodality concept, and to develop prognostic models that will allow individualization of the therapy.

Combined Modality Therapy↗

PubMed2005

Mortality from traumatic brain injury.

It is the general sense that mortality has been decreasing in recent years compared to earlier studies described by the NIH traumatic coma data bank. We studied mortality during the period of 1984 to 1996 to determine if indeed mortality from severe traumatic brain injury was decreasing and to identify factors which might account for the reduction. The study population (N = 1839) consisted of severely head injured patients extracted retrospectively from the TCDB (635), MCV (382), and 822 patients from clinical trial databases conducted in the United States. Mortality was obtained from each of the databases for the age range form 16 to 65. Penetrating injury and treatment groups in the clinical trial databases were excluded. Mortality in the year 1984 equaled 39% and gradually decreased to a level of 27% in 1996. When adjusting for age, motor score and pupil reaction, the mortality of the period from 1984 to 1987 was significantly higher (p < 0.05) than that of the period 1988 to 1996. During the period 1984 through 1996, mortality from severe brain injury steadily declined. Factors other than age, motor score and pupil reactivity over time are responsible for this reduction. This reduction over time is an important factor for prognostic modeling of TBI.

Adolescent↗

PubMed1990

Colony-stimulating factors (rhG-CSF, rhGM-CSF, rhIL-3, and BCGF) recruit myeloblastic and lymphoblastic leukemic cells and enhance the cytotoxic effects of cytosine-arabinoside.

Prognostic models for acute myeloid and lymphoid leukemias are presented that demonstrate that cell kinetic quiescence in acute leukemia is associated with poor response to chemotherapy, short remission duration, and survival. Recruitment of cells into the cell cycle should therefore enhance cytotoxic effects of cell cycle - specific chemotherapeutic agents. We previously demonstrated recruitment of myeloid leukemic cells by cytokines. We have now investigated whether recruitment can be used to increase cell killing by cytosine arabinoside (Ara-C). Blast cells from 16 acute leukemias were stimulated with cytokines as follows: 13 acute myeloid leukemias (AML) and 3 chronic myeloid leukemia (CML) in blastic phase (1 lymphoid, 2 myeloid) were treated with recombinant human granulocyte colony stimulating factor (rhG-CSF), recombinant human granulocyte-macrophage colony stimulating factor (rhG-CSF, AMGEN, 500 U/ml each), and recombinant human interleukin-3 (rhIL-3, IMMUNEX, 20 ng/ml), alone and in combination. After 48 h, at the time of maximal DNA synthesis, Ara-C (10(-3) M) was added and cell counts, cytokinetics (DNA/RNA, DNA/bromodeoxyuridine and DNA/Ki67 flow cytometry), and cell viability/clonogenicity (fluorescein diacetate/propidium iodide exclusion flow cytometry) were investigated. In all 13 cases of AML recruitment was found; in 6 of these cases over a three fold increase in S phase (P = 0.008) and a significant (P = 0.004) depletion of G0 was demonstrated. In 9 of 13 patients with AML, the effect of Ara-C was investigated, and in 3 of 5 patients with over three fold increase in S phase, Ara-C toxicity was enhanced. None of the patients with less than a three fold increase in S phase and no demonstrable recruitment from G0 had increased Ara-C cytotoxicity. Ara-C cytoreduction was paralled by reduction in clonogenicity as demonstrated by fluorescein diacetate/propidium iodide (FDA/PI) flow cytometry. Four samples of acute lymphoblastic leukemia (ALL) were treated with low molecular weight B-cell growth factor (15 kDa) and recruitment of aneuploid cells from G0 to G1 was found in all patients (from 19.3% to 84.9%). These results indicate that recruitment of leukemic cells is inducible by cytokines and that the cytotoxicity of cell cycle-specific drugs such as Ara-C can be increased. This concept is presently being tested in vivo.

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