Background: Recent reports have shown that physical activity improves the outcome of patients with colorectal cancer as well as breast and prostate cancer. However, the mechanisms whereby physical activity reduces can...Background: Recent reports have shown that physical activity improves the outcome of patients with colorectal cancer as well as breast and prostate cancer. However, the mechanisms whereby physical activity reduces cancer mortality are not well established. Methods: Incident cases of colorectal cancer were identified among participants of the Melbourne Collaborative Cohort Study, a prospective cohort study of 41 528 Australians recruited from 1990 to 1994. Information on tumour site and stage, treatments given, recurrences, and deaths were obtained from systematic review of the medical records. Baseline assessments of physical activity and body size were made, and cases with available plasma had pre-diagnosis insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) levels measured. We assessed associations between these hormones and colorectal cancer specific deaths with respect to physical activity. Results: A total of 526 cases of colorectal cancer were identified, of which 443 had IGF-1/IGFBP-3 levels measured. Median follow up among survivors was 5.6 years. For the physically active, increasing IGFBP-3 by 26.2 nmol/l was associated with a 48%reduction in colorectal cancer specific deaths (adjusted hazard ratio (HR) 0.52 (0.33-0.83); p = 0.006). No association was seen for IGF-1 (adjusted HR 0.90 (0.55-1.45); p = 0.65). For the physically inactive, neither IGF-1 nor IGFBP-3 was associated with disease specific survival. Conclusions: This study supports the hypothesis that the beneficial effects of physical activity in reducing colorectal cancer mortality may occur through interactions with the insulin-like growth factor axis and in particular IGFBP-3.展开更多
Background: Previous meta analyses demonstrated that high dose glucoc orticoi ds were not beneficial in sepsis.Recently, lower dose glucocorticoids have been studied. Purpose: To compare recent trials of glucocorticoi...Background: Previous meta analyses demonstrated that high dose glucoc orticoi ds were not beneficial in sepsis.Recently, lower dose glucocorticoids have been studied. Purpose: To compare recent trials of glucocorticoids for sepsis with p revious glucocorticoid trials. Data Sources: Systematic MEDLINE search for studi es published between 1988 and 2003. Study Selection: Randomized,controlled trial s of sepsis that examined the effects of glucocorticoids on survival or vasopres sor requirements. Data Extraction: Two investigators independently collected dat a on patient and study characteristics, treatment interventions, and outcomes. D ata Synthesis: The 5 included trials revealed a consistent and beneficial effect of glucocorticoids on survival (12=0%; relative benefit, 1.23, <<95%CI, 1.01 t o 1.50>>; P=0.036) and shock reversal (12=0%; relative benefit, 1.71 <<CI, 1.29 t o 2.26>>; P< 0.001). These effects were the same regardless of adrenal function. In contrast, 8 trials published before 1989 demonstrated a survival disadvantage with steroid treatment (12=14%; relative benefit, 0.89 <<CI, 0.82 to 0.97>>; P=0 .008). In comparison with the earlier trials, the more recent trials administere d steroids later after patients met enrollment criteria (median, 23 hours vs. < 2 hours; P=0.02), for longer courses (6 days vs. 1 day; P=0.01), and in lower to tal dosages (hydrocort isone equivalents,1209 mg vs. 23 975 mg; P=0.01) to patie nts with higher control group mortality rates (mean, 57%vs. 34%; P=0.06) who w ere more likely to be vasopressor dependent (100%vs. 65%; P=0.03). The relati onship between steroid dose and survival was linear, characterized by benefit at low doses and increasing harm at higher doses (P=0.02). Limitations: We could n ot analyze time related improvements in medical care and potential bias seconda ry to nonreporting of negative study results. Conclusions: Although short course s of high dose glucocorticoids decreased survival during sepsis, a 5-to 7-day course of physiologic hydrocortisone doses with subsequent tapering increases s urvival rate and shock reversal in patients with vasopressor dependent septic shock.展开更多
A collaborative study of human transmissible spongiform encephalopathies has b een carried out from 1993 to 2000 and includes data from 10 national registries, the majority in Western Europe. In this study, we present...A collaborative study of human transmissible spongiform encephalopathies has b een carried out from 1993 to 2000 and includes data from 10 national registries, the majority in Western Europe. In this study, we present analyses of predictor s of survival in sporadic (n = 2304), iatrogenic (n = 106) and variant Creutzfel dt Jakob disease (n = 86) and in cases associated with mutations of the prion p rotein gene (n=278), including Gerstmann Strussler Scheinker syndrome (n = 24) and fat al familial insomnia (n = 41). Overall survival for each disease type was assess ed by the .Kaplan Meier method and the multivariate analyses by the Cox proport ional hazards model. In sporadic disease, longer survival was correlated with yo unger age at onset of illness, female gender, codon 129 heterozygosity, presence of CSF 14-3-3 protein and type 2a prion protein type. The ability to predict survival based on patient covariates is important for diagnosis and counselling, and the characterization of the survival distributions, in the absence of thera py, will be an important starting point for the assessment of potential therapeu tic agents in the future.展开更多
Measurements of portal pressure, usually obtained via the hepatic venous pressure gradient (HVPG) may be a prognostic marker in cirrhosis. The aim of this study was to evaluate the impact of HVPG on survival in patien...Measurements of portal pressure, usually obtained via the hepatic venous pressure gradient (HVPG) may be a prognostic marker in cirrhosis. The aim of this study was to evaluate the impact of HVPG on survival in patients with cirrhosis in addition to the Model for End-Stage Liver Disease (MELD) score. We also examined whether inclusion of HVPG in a model with MELD variables improves its prognostic ability. Retrospective analyses of all patients who had HVPG measurements between January 1998 and December 2002 were considered. Proportional hazards Cox models were developed. Prognostic calibrative and discriminative ability of the model was evaluated. In this period, 693 patients had a hepatic hemodynamic study, and 393 patients were included. Survival was significantly worse in those patients with greater HVPG value (univariate HR, 1.05; 95%CI, 1.02-1.08; P = .001). HVPG remained as an independent variable in a model adjusted by MELD, ascites, encephalopathy, and age (multivariate HR, 1.03; 95%CI, 1.00-1.06; P = .05) so that each 1 mmHg increase in HVPG had a 3%increase in death risk. In addition, HVPG as well as MELD score variables and age, significantly contributes to the calibrative predictive capacity of the prognostic model; however, discriminative ability improved only slightly (overall C statistic [95%CI]; MELD score variables: 0.71 [0.62-0.80], MELD score variables, age, and HVPG 0.76: [0.69-0.83]). In conclusion, HVPG has an independent effect on survival in addition to the MELD score. Although inclusion of HVPG and age in a survival predicting model would improve the calibrative ability of MELD, its discriminative ability is not significantly improved.展开更多
To assess the roles of the extent of gastric resection and duodenal food passage reconstruction in gastric cancer, we examined a consecutive series of 1,061 patients who underwent total or partial (proximal and distal...To assess the roles of the extent of gastric resection and duodenal food passage reconstruction in gastric cancer, we examined a consecutive series of 1,061 patients who underwent total or partial (proximal and distal) gastrectomies with or without duodenal food passage reconstruction between August of 1974 and January of 2002, and received gastrectomies with D2- 3 lymph node dissection. Patients who underwent distal or proximal gastrectomy were found to have significantly better survival rates than those who underwent total gastrectomy in stages 1A (10- year survival: 86.6 and 78.9 vs. 61.6% ), 2 (56.5 and 65.6 vs. 34.4% ), 3A (45.9 and 33.3 vs. 15.2% ), and 4 (5- year survival rates: 23.7 and 50.0 vs. 7.1% ). Additionally, patients with duodenal food passage reconstruction or double tract reconstruction also showed significantly better survival rates than those without duodenal food reconstruction in stages 1A (10- year survival: 86.4 and 82.5 vs. 61.7% ), 1B (69.9 and 90.6 vs. 54.1% ), 2 (60.5 and 63.3 vs. 16.5% ), and 3A (39.9 and 47.4 vs. 23.1% ). In multivariate analysis, the independent prognostic factors were age at operation, depth of tumor, duodenal food passage reconstruction, and lymph node metastasis. Our results indicate that both the extent of gastric resection and duodenal food passage reconstruction were important factors in the outcome of gastric cancer patients, and that surgeons should perform minimal gastric resection with preservation of the duodenal food passage when the gastric stump is tumor- free.展开更多
文摘Background: Recent reports have shown that physical activity improves the outcome of patients with colorectal cancer as well as breast and prostate cancer. However, the mechanisms whereby physical activity reduces cancer mortality are not well established. Methods: Incident cases of colorectal cancer were identified among participants of the Melbourne Collaborative Cohort Study, a prospective cohort study of 41 528 Australians recruited from 1990 to 1994. Information on tumour site and stage, treatments given, recurrences, and deaths were obtained from systematic review of the medical records. Baseline assessments of physical activity and body size were made, and cases with available plasma had pre-diagnosis insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) levels measured. We assessed associations between these hormones and colorectal cancer specific deaths with respect to physical activity. Results: A total of 526 cases of colorectal cancer were identified, of which 443 had IGF-1/IGFBP-3 levels measured. Median follow up among survivors was 5.6 years. For the physically active, increasing IGFBP-3 by 26.2 nmol/l was associated with a 48%reduction in colorectal cancer specific deaths (adjusted hazard ratio (HR) 0.52 (0.33-0.83); p = 0.006). No association was seen for IGF-1 (adjusted HR 0.90 (0.55-1.45); p = 0.65). For the physically inactive, neither IGF-1 nor IGFBP-3 was associated with disease specific survival. Conclusions: This study supports the hypothesis that the beneficial effects of physical activity in reducing colorectal cancer mortality may occur through interactions with the insulin-like growth factor axis and in particular IGFBP-3.
文摘Background: Previous meta analyses demonstrated that high dose glucoc orticoi ds were not beneficial in sepsis.Recently, lower dose glucocorticoids have been studied. Purpose: To compare recent trials of glucocorticoids for sepsis with p revious glucocorticoid trials. Data Sources: Systematic MEDLINE search for studi es published between 1988 and 2003. Study Selection: Randomized,controlled trial s of sepsis that examined the effects of glucocorticoids on survival or vasopres sor requirements. Data Extraction: Two investigators independently collected dat a on patient and study characteristics, treatment interventions, and outcomes. D ata Synthesis: The 5 included trials revealed a consistent and beneficial effect of glucocorticoids on survival (12=0%; relative benefit, 1.23, <<95%CI, 1.01 t o 1.50>>; P=0.036) and shock reversal (12=0%; relative benefit, 1.71 <<CI, 1.29 t o 2.26>>; P< 0.001). These effects were the same regardless of adrenal function. In contrast, 8 trials published before 1989 demonstrated a survival disadvantage with steroid treatment (12=14%; relative benefit, 0.89 <<CI, 0.82 to 0.97>>; P=0 .008). In comparison with the earlier trials, the more recent trials administere d steroids later after patients met enrollment criteria (median, 23 hours vs. < 2 hours; P=0.02), for longer courses (6 days vs. 1 day; P=0.01), and in lower to tal dosages (hydrocort isone equivalents,1209 mg vs. 23 975 mg; P=0.01) to patie nts with higher control group mortality rates (mean, 57%vs. 34%; P=0.06) who w ere more likely to be vasopressor dependent (100%vs. 65%; P=0.03). The relati onship between steroid dose and survival was linear, characterized by benefit at low doses and increasing harm at higher doses (P=0.02). Limitations: We could n ot analyze time related improvements in medical care and potential bias seconda ry to nonreporting of negative study results. Conclusions: Although short course s of high dose glucocorticoids decreased survival during sepsis, a 5-to 7-day course of physiologic hydrocortisone doses with subsequent tapering increases s urvival rate and shock reversal in patients with vasopressor dependent septic shock.
文摘A collaborative study of human transmissible spongiform encephalopathies has b een carried out from 1993 to 2000 and includes data from 10 national registries, the majority in Western Europe. In this study, we present analyses of predictor s of survival in sporadic (n = 2304), iatrogenic (n = 106) and variant Creutzfel dt Jakob disease (n = 86) and in cases associated with mutations of the prion p rotein gene (n=278), including Gerstmann Strussler Scheinker syndrome (n = 24) and fat al familial insomnia (n = 41). Overall survival for each disease type was assess ed by the .Kaplan Meier method and the multivariate analyses by the Cox proport ional hazards model. In sporadic disease, longer survival was correlated with yo unger age at onset of illness, female gender, codon 129 heterozygosity, presence of CSF 14-3-3 protein and type 2a prion protein type. The ability to predict survival based on patient covariates is important for diagnosis and counselling, and the characterization of the survival distributions, in the absence of thera py, will be an important starting point for the assessment of potential therapeu tic agents in the future.
文摘Measurements of portal pressure, usually obtained via the hepatic venous pressure gradient (HVPG) may be a prognostic marker in cirrhosis. The aim of this study was to evaluate the impact of HVPG on survival in patients with cirrhosis in addition to the Model for End-Stage Liver Disease (MELD) score. We also examined whether inclusion of HVPG in a model with MELD variables improves its prognostic ability. Retrospective analyses of all patients who had HVPG measurements between January 1998 and December 2002 were considered. Proportional hazards Cox models were developed. Prognostic calibrative and discriminative ability of the model was evaluated. In this period, 693 patients had a hepatic hemodynamic study, and 393 patients were included. Survival was significantly worse in those patients with greater HVPG value (univariate HR, 1.05; 95%CI, 1.02-1.08; P = .001). HVPG remained as an independent variable in a model adjusted by MELD, ascites, encephalopathy, and age (multivariate HR, 1.03; 95%CI, 1.00-1.06; P = .05) so that each 1 mmHg increase in HVPG had a 3%increase in death risk. In addition, HVPG as well as MELD score variables and age, significantly contributes to the calibrative predictive capacity of the prognostic model; however, discriminative ability improved only slightly (overall C statistic [95%CI]; MELD score variables: 0.71 [0.62-0.80], MELD score variables, age, and HVPG 0.76: [0.69-0.83]). In conclusion, HVPG has an independent effect on survival in addition to the MELD score. Although inclusion of HVPG and age in a survival predicting model would improve the calibrative ability of MELD, its discriminative ability is not significantly improved.
文摘To assess the roles of the extent of gastric resection and duodenal food passage reconstruction in gastric cancer, we examined a consecutive series of 1,061 patients who underwent total or partial (proximal and distal) gastrectomies with or without duodenal food passage reconstruction between August of 1974 and January of 2002, and received gastrectomies with D2- 3 lymph node dissection. Patients who underwent distal or proximal gastrectomy were found to have significantly better survival rates than those who underwent total gastrectomy in stages 1A (10- year survival: 86.6 and 78.9 vs. 61.6% ), 2 (56.5 and 65.6 vs. 34.4% ), 3A (45.9 and 33.3 vs. 15.2% ), and 4 (5- year survival rates: 23.7 and 50.0 vs. 7.1% ). Additionally, patients with duodenal food passage reconstruction or double tract reconstruction also showed significantly better survival rates than those without duodenal food reconstruction in stages 1A (10- year survival: 86.4 and 82.5 vs. 61.7% ), 1B (69.9 and 90.6 vs. 54.1% ), 2 (60.5 and 63.3 vs. 16.5% ), and 3A (39.9 and 47.4 vs. 23.1% ). In multivariate analysis, the independent prognostic factors were age at operation, depth of tumor, duodenal food passage reconstruction, and lymph node metastasis. Our results indicate that both the extent of gastric resection and duodenal food passage reconstruction were important factors in the outcome of gastric cancer patients, and that surgeons should perform minimal gastric resection with preservation of the duodenal food passage when the gastric stump is tumor- free.
