Background & Aims: The natural history of nonalcoholic fatty liver disease (NAFLD) in the community remains unknown. We sought to determine survival and liver- related morbidity among community- based NAFLD patien...Background & Aims: The natural history of nonalcoholic fatty liver disease (NAFLD) in the community remains unknown. We sought to determine survival and liver- related morbidity among community- based NAFLD patients. Methods: Four hundred twenty patients diagnosed with NAFLD in Olmsted County, Minnesota, between 1980 and 2000 were identified using the resources of the Rochester Epidemiology Project. Medical records were reviewed to confirm diagnosis and determine outcomes up to 2003. Overall survival was compared with the general Minnesota population of the same age and sex. Results: Mean (SD) age at diagnosis was 49 (15) years; 231 (49% ) were male. Mean follow- up was 7.6 (4.0) years (range, 0.1- 23.5) culminating in 3192 person- years follow- up. Overall, 53 of 420 (12.6% ) patients died. Survival was lower than the expected survival for the general population (standardized mortality ratio, 1.34; 95% CI, 1.003- 1.76; P = .03). Higher mortality was associated with age (hazard ratio per decade, 2.2; 95% CI, 1.7- 2.7), impaired fasting glucose (hazard ratio, 2.6; 95% CI, 1.3- 5.2), and cirrhosis (hazard ratio, 3.1, 95% CI, 1.2- 7.8). Liver disease was the third leading cause of death (as compared with the thirteenth leading cause of death in the general Minnesota population), occurring in 7 (1.7% ) subjects. Twenty- one (5% ) patients were diagnosed with cirrhosis, and 13 (3.1% ) developed liver- related complications, including 1 requiring transplantation and 2 developing hepatocellular carcinoma. Conclusions: Mortality among community- diagnosed NA- FLD patients is higher than the general population and is associated with older age, impaired fasting glucose, and cirrhosis. Liver- related death is a leading cause of mortality, although the absolute risk is low.展开更多
Background & Aims: Although diabetes occurs frequently in pancreatic cancer, the value of new-onset diabetes as a marker of underlying pancreatic cancer is unknown. Methods: We assembled a population-based cohort ...Background & Aims: Although diabetes occurs frequently in pancreatic cancer, the value of new-onset diabetes as a marker of underlying pancreatic cancer is unknown. Methods: We assembled a population-based cohort of 2122 Rochester, Minnesota, residents age ≥ 50 years who first met standardized criteria for diabetes between January 1, 1950, and December 31, 1994, and identified those who developed pancreatic cancer within 3 years of meeting criteria for diabetes. We compared observed rates of pancreatic cancer with expected rates based on the Iowa Surveillance Epidemiology and End Results registry. In a nested case control study, we compared body mass index (BMI) and smoking status in diabetes subjects with and without pancreatic cancer. Results: Of 2122 diabetic subjects, 18 (0.85% ) were diagnosed with pancreatic cancer within 3 years of meeting criteria for diabetes; 10 of 18 (56% ) were diagnosed < 6 months after first meeting criteria for diabetes, and 3 were resected. The observed-to-expected ratio of pancreatic cancer in the cohort was 7.94 (95% CI, 4.70- 12.55). Compared with subjects without pancreatic cancer, diabetic subjects with pancreatic cancer were more likely to have met diabetes criteria after age 69 (OR = 4.52, 95% CI, 1.61- 12.74) years but did not differ significantly with respect to BMI values (29.2 ± 6.8 vs 26.5 ± 5.0, respectively). A larger proportion of those who developed pancreatic cancer were ever smokers (92% vs 69% , respectively), but this did not reach statistical significance. Conclusions: Approximately 1% of diabetes subjects aged < 50 yearswill be diagnosed with pancreatic cancer within 3 years of first meeting criteria for diabetes. The usefulness of new-onset diabetes as marker of early pancreatic cancer needs further evaluation.展开更多
Objective. The prevalence and main determinants of exocrine pancreatic insufficiency were investigated in a large population based sample of older adults by measuring pancreatic elastase- 1 in stool. Material and meth...Objective. The prevalence and main determinants of exocrine pancreatic insufficiency were investigated in a large population based sample of older adults by measuring pancreatic elastase- 1 in stool. Material and methods. The study comprised 914 participants aged 50 to 75 years recruited by their general practitioner during a general health examination. All participants and their physicians were asked to fill out a standardized questionnaire which contained information on socio- demographic and lifestyle factors as well as medical history. Native stool was examined for pancreatic elastase- 1 with a commercially available ELISA (ScheBo(r) Tech, Giessen, Germany). Results. Overall, 524 women and 390 men aged 50 to 75 years (mean age 61.9 years) were included in the analysis. In total, 105 (11.5% ) of the 914 subjects showed signs of exocrine pancreatic insufficiency (EPI) with ≤ 200μ g elastase- 1/g stool, and 47 (5.1% ) subjects showed signs of a severe exocrine pancreatic insufficiency (SEPI, < 100μ g elastase- 1/g stool). There was a clear increase in EPI with age. Patients taking angiotensin- converting enzyme (ACE) inhibitors had a lower prevalence than subjects without this medication; these associations persisted after adjustment for covariates. Conclusions. Prevalence of EPI increases with age and seems to be tentatively higher in men than in women. However, smoking seems to be an independent risk factor for EPI and SEPI whereas ACE- inhibitor intake might be a protective factor. The latter finding may even point to new options in the treatment of chronic pancreatitis.展开更多
Objective. There are few data on the epidemiology of gastroesophageal reflux disease (GERD) in South China. The aim of this study was to assess the prevalence of GERD symptoms in South China and to evaluate the impact...Objective. There are few data on the epidemiology of gastroesophageal reflux disease (GERD) in South China. The aim of this study was to assess the prevalence of GERD symptoms in South China and to evaluate the impact on health- related quality of life. Material andmethods. A face- to- face interview was carried out in South China using a validated Chinese version of the Reflux Disease Questionnaire to assess the prevalence of GERD symptoms. A randomly clustered sampling of permanent inhabitants aged 18 to 90 years was carried out under stratification of urban and suburban areas. The impact of GERD symptoms on health- related quality of life was evaluated using the Chinese version of SF- 36. Results. A total of 3338 residents (1468 M, 1870 F) were investigated. Mean age of the responders was 42.6 ± 16.4 years; response rate was 95% . The prevalence of heartburn and/or acid eructation occurring at least weekly was 6.2% . The age- and gender- adjusted point prevalence of GERD symptoms in South China is 2.3% (95% CI, 1.8% , 2.8% ) according to the definition in this study. There was no difference in prevalence between male (2.6% ) and female (2.4% ) subjects and there was no significant association between age and prevalence of GERD symptoms. Divorced/ widowed/ separated subjects (OR 4.61; 95% CI, 2.15% , 9.89% ) and subjects with a heavy burden of work (OR 3.43, 95% CI, 1.72% , 6.84% ) were significantly more likely to report GERD symptoms. As compared with the general population, subjects with GERD symptoms experienced considerable impairment in quality of life. Conclusions. The prevalence of GERD symptoms in South China was much lower than that reported in Western countries. GERD had a negative impact on quality of life.展开更多
PURPOSE: Elderly patients with colorectal cancer undergo surgery with curative intent less frequently than younger patients, and survival declines with increasing age. We compared relative survival of colorectal cance...PURPOSE: Elderly patients with colorectal cancer undergo surgery with curative intent less frequently than younger patients, and survival declines with increasing age. We compared relative survival of colorectal cancer among patients older than 75 years with that of younger patients in Denmark during the period 1977 to 1999. We also examined trends in choice of initial treatment. METHODS: From the files of the nationwide population- based Danish Cancer Registry, we identified all cases of colorectal cancer diagnosed between 1977 and 1999. We then linked this data to information on survival obtained from the Danish Register of Causes of Death and from the Central Population Register. RESULTS: During the entire study period, short- term and long- term relative survival improved for patients of all ages, but the improvement was more pronounced among elderly patients ( > 75 years). Radical resection was increasingly chosen as the initial treatment for elderly patients; during the 1995 to 1999 period it was performed on approximately 50 percent of such patients, almost as frequently as among younger patients. CONCLUSIONS: Relative survival of elderly colorectal cancer patients ( > 75 years) improved in Denmark between 1977 and 1999. In the most recent period studied, 1995 to 1997, only minor differences in five- year relative survival were observed among younger, middle- aged, and elderly patients. A simultaneous increase in the rate of radical resection among elderly patients, reflecting more effective treatment, may underlie this finding.展开更多
Objective. Endoscopy is the gold standard for diagnostic evaluation of upper gastrointestinal symptoms. The relation between endoscopy and use of antisecretory medication on a population level is unknown. The aim of t...Objective. Endoscopy is the gold standard for diagnostic evaluation of upper gastrointestinal symptoms. The relation between endoscopy and use of antisecretory medication on a population level is unknown. The aim of this study was to describe development in the number of patients undergoing first- time endoscopies and their use of antisecretory medication. Material and methods. Data on the use of endoscopies and antisecretory medication (H2 blockers and proton- pump inhibitors) were extracted from five population- based databases and included all citizens in Funen County (population 470,000) who had first time endoscopies between 1993 and 2002. Results. A total of 7,829 first- time endoscopy patients were identified. In 2002 the number of first- time endoscopies as 5.6/1000 persons. The proportion that had redeemed prescription(s) on antisecretory medication the last year before endoscopy increased from 33% (1095/3286) in 1993 to 41% (1012/2445) in 2002 (p = 0.000). Following endoscopy, average use of antisecretory medication increased by 90 defined daily doses (DDD)/patient/year (95% CI 84- 96) in patients with oesophagitis (N = 4850), by 59 DDD/patient/year (95% CI 54- 64) in peptic ulcer patients (N = 4373) and by 18 DDD/patient/year (95% CI 16- 20) in patients with normal endoscopies (N = 16,400). Conclusions. An increasing proportion of patients are treated with antisecretory medication before endoscopy. Following endoscopy, use of antisecretory medication increases irrespective of the diagnostic findings.展开更多
Background & Aims: The concept of a CpG island methylator phenotype (CIMP), especially inmicrosatellite stable colon cancer, is not accepted universally. We therefore evaluated a large population-based sample of i...Background & Aims: The concept of a CpG island methylator phenotype (CIMP), especially inmicrosatellite stable colon cancer, is not accepted universally. We therefore evaluated a large population-based sample of individuals with colon cancer and used univariate and multivariate analyses of CIMP with clinicopathologic variables and tumor mutations to determine the biologic relevance of this phenotype. Methods: A total of 864 tumors from individuals with colon cancer from Utah and Northern California were evaluated by methylation-specific polymerase chain reaction of CpG islands in hMLH1, methylated in tumors (MINT) 1, MINT 2, MINT 31, and CDKN2A (p16). CIMP high was defined as methylation at 2 or more of these loci. The BRAF V600E mutation was determined by sequencing. Microsatellite instability had been determined previously. Results: In a multivariate analysis of microsatellite stable tumors, CIMP high was related significantly to the V600E BRAF mutation (odds ratio, 39.52; 95% confidence interval, 11.44- 136.56), KRAS2 mutations (odds ratio, 2.22; 95% confidence interval, 1.48- 3.34), older age (P trend = .03), and increased stage (P trend = .03), and these tumors were less likely to be located in the distal colon (odds ratio, .42; 95% confidence interval, .27- .65). CIMP-high unstable tumors also were more likely to have the V600E BRAF mutation, be located proximally, and occur in older individuals (in univariate analyses). However, CIMP-high unstable tumors were significantly more likely than their stable counterparts to be KRAS2 wild type, TP53 wild type, poorly differentiated, proximally located, occur at lower stages, and have the BRAF V600E mutation (64.1% vs 17.6% ). Conclusions: The evaluation of a large, population-based sample strongly supports the biologic relevance of CIMP in colon cancer. However, the presence or absence of microsatellite instability has a major effect on the expression of this phenotype.展开更多
Background & Aims: We aimed to discern the relative risk for several chronic inflammatory conditions in patients with ulcerative colitis (UC) and Crohn s disease. Methods: We used the population- based Universit...Background & Aims: We aimed to discern the relative risk for several chronic inflammatory conditions in patients with ulcerative colitis (UC) and Crohn s disease. Methods: We used the population- based University of Manitoba IBD- Database that includes longitudinal files on all patients from all health system contacts identified by International Classification of Diseases, 9th revision, Clinical Modification codes for visit diagnosis. From the provincial database we extracted a control cohort matching the IBD patients 10 ∶ 1 by age, sex, and geography. We considered a potential comorbid disease to be present if the patient had 5 or more health system contacts for that diagnosis. The comorbid disease period prevalence was analyzed separately for patients with UC and Crohn s disease and a prevalence ratio was calculated comparing the IBD populations with the matched cohort. Results: There were 8072 cases of IBD from 1984 to 2003, including UC (n = 3879) and Crohn s disease (n = 4193). There was a mean of approximately 16 person- years of coverage for both patients and control patients. Both UC and Crohn s disease patients had a significantly greater likelihood of having arthritis, asthma, bronchitis, psoriasis, and pericarditis than population controls. An increased risk for chronic renal disease and multiple sclerosis was noted in UC but not Crohn s disease patients. The most common nonintestinal comorbidities identified were arthritis and asthma. Conclusions: The finding of asthma as the most common comorbidity increased in Crohn s disease patients compared with the general population is novel. These may be diseases with common causes or complications of one disease that lead to the presentation with another. Studies such as this should encourage further research into the common triggers in the organ systems that lead to autoimmune diseases.展开更多
OBJECTIVES:We sought to determine the association between patent foramen ovale(PFO), atrial septal aneurysm(ASA), and stroke prospectively in a unselected population sample. BACKGROUND: The disputed relationship betwe...OBJECTIVES:We sought to determine the association between patent foramen ovale(PFO), atrial septal aneurysm(ASA), and stroke prospectively in a unselected population sample. BACKGROUND: The disputed relationship between PFO and stroke reflects methodologic weaknesses in studies using invalid controls, unblinded transesophageal echocardiography examinations, and data that are unadjusted for age or comorbidity. METHODS: The use of transesophageal echocardiography to identify PFO was performed by a single echocardiographer using standardized definitions in 585 randomly sampled, Olmsted County(Minnesota) subjects age 45 years or older participating in the Stroke Prevention: Assessment of Risk in a Community(SPARC) study. RESULTS: A PFO was identified in 140(24.3% ) subjects and ASA in 11(1.9% ) subjects. Of the 140 subjects with PFO, 6(4.3% ) had an ASA; of the 437 subjects without PFO, 5 had an ASA(1.1% , two-sided Fisher exact test, p=0.028). During a median follow-up of 5.1 years, cerebrovascular events(cerebrovascular disease-related death, ischemic stroke, transient ischemic attack) occurred in 41 subjects. After adjustment for age and comorbidity, PFO was not a significant independent predictor of stroke(hazard ratio 1.46, 95% confidence interval 0.74 to 2.88, p=0.28). The risk of a cerebrovascular event among subjects with ASA was nearly four times higher than that in those without ASA(hazard ratio 3.72, 95% confidence interval 0.88 to 15.71, p=0.074). CONCLUSIONS: These prospective population-based data suggest that, after correction for age and comorbidity, PFO is not an independent risk factor for future cerebrovascular events in the general population. A larger study is required to test the putative stroke risk associated with ASA.展开更多
现代医学发展日新月益,2015年初美国国情咨文宣布了一项名为精准医学计划（precision medicine initiative）的项目,精准医学（precision medicine）这一概念迅速受到全球医疗界的关注。一般来讲,精准医学是以个性化医疗为核心指导、在...现代医学发展日新月益,2015年初美国国情咨文宣布了一项名为精准医学计划（precision medicine initiative）的项目,精准医学（precision medicine）这一概念迅速受到全球医疗界的关注。一般来讲,精准医学是以个性化医疗为核心指导、在基因组学、蛋白质组学等大数据为支撑的医学概念与模式。其本质是通过对于大样本人群与特定疾病类型进行生物标志物的分析、鉴定及验证,从而精确寻找到疾病的原因和治疗的靶点。然后针对特定疾病的不同疾病阶段,设计个性化治疗方案,提高疾病诊治水平。展开更多
文摘Background & Aims: The natural history of nonalcoholic fatty liver disease (NAFLD) in the community remains unknown. We sought to determine survival and liver- related morbidity among community- based NAFLD patients. Methods: Four hundred twenty patients diagnosed with NAFLD in Olmsted County, Minnesota, between 1980 and 2000 were identified using the resources of the Rochester Epidemiology Project. Medical records were reviewed to confirm diagnosis and determine outcomes up to 2003. Overall survival was compared with the general Minnesota population of the same age and sex. Results: Mean (SD) age at diagnosis was 49 (15) years; 231 (49% ) were male. Mean follow- up was 7.6 (4.0) years (range, 0.1- 23.5) culminating in 3192 person- years follow- up. Overall, 53 of 420 (12.6% ) patients died. Survival was lower than the expected survival for the general population (standardized mortality ratio, 1.34; 95% CI, 1.003- 1.76; P = .03). Higher mortality was associated with age (hazard ratio per decade, 2.2; 95% CI, 1.7- 2.7), impaired fasting glucose (hazard ratio, 2.6; 95% CI, 1.3- 5.2), and cirrhosis (hazard ratio, 3.1, 95% CI, 1.2- 7.8). Liver disease was the third leading cause of death (as compared with the thirteenth leading cause of death in the general Minnesota population), occurring in 7 (1.7% ) subjects. Twenty- one (5% ) patients were diagnosed with cirrhosis, and 13 (3.1% ) developed liver- related complications, including 1 requiring transplantation and 2 developing hepatocellular carcinoma. Conclusions: Mortality among community- diagnosed NA- FLD patients is higher than the general population and is associated with older age, impaired fasting glucose, and cirrhosis. Liver- related death is a leading cause of mortality, although the absolute risk is low.
文摘Background & Aims: Although diabetes occurs frequently in pancreatic cancer, the value of new-onset diabetes as a marker of underlying pancreatic cancer is unknown. Methods: We assembled a population-based cohort of 2122 Rochester, Minnesota, residents age ≥ 50 years who first met standardized criteria for diabetes between January 1, 1950, and December 31, 1994, and identified those who developed pancreatic cancer within 3 years of meeting criteria for diabetes. We compared observed rates of pancreatic cancer with expected rates based on the Iowa Surveillance Epidemiology and End Results registry. In a nested case control study, we compared body mass index (BMI) and smoking status in diabetes subjects with and without pancreatic cancer. Results: Of 2122 diabetic subjects, 18 (0.85% ) were diagnosed with pancreatic cancer within 3 years of meeting criteria for diabetes; 10 of 18 (56% ) were diagnosed < 6 months after first meeting criteria for diabetes, and 3 were resected. The observed-to-expected ratio of pancreatic cancer in the cohort was 7.94 (95% CI, 4.70- 12.55). Compared with subjects without pancreatic cancer, diabetic subjects with pancreatic cancer were more likely to have met diabetes criteria after age 69 (OR = 4.52, 95% CI, 1.61- 12.74) years but did not differ significantly with respect to BMI values (29.2 ± 6.8 vs 26.5 ± 5.0, respectively). A larger proportion of those who developed pancreatic cancer were ever smokers (92% vs 69% , respectively), but this did not reach statistical significance. Conclusions: Approximately 1% of diabetes subjects aged < 50 yearswill be diagnosed with pancreatic cancer within 3 years of first meeting criteria for diabetes. The usefulness of new-onset diabetes as marker of early pancreatic cancer needs further evaluation.
文摘Objective. The prevalence and main determinants of exocrine pancreatic insufficiency were investigated in a large population based sample of older adults by measuring pancreatic elastase- 1 in stool. Material and methods. The study comprised 914 participants aged 50 to 75 years recruited by their general practitioner during a general health examination. All participants and their physicians were asked to fill out a standardized questionnaire which contained information on socio- demographic and lifestyle factors as well as medical history. Native stool was examined for pancreatic elastase- 1 with a commercially available ELISA (ScheBo(r) Tech, Giessen, Germany). Results. Overall, 524 women and 390 men aged 50 to 75 years (mean age 61.9 years) were included in the analysis. In total, 105 (11.5% ) of the 914 subjects showed signs of exocrine pancreatic insufficiency (EPI) with ≤ 200μ g elastase- 1/g stool, and 47 (5.1% ) subjects showed signs of a severe exocrine pancreatic insufficiency (SEPI, < 100μ g elastase- 1/g stool). There was a clear increase in EPI with age. Patients taking angiotensin- converting enzyme (ACE) inhibitors had a lower prevalence than subjects without this medication; these associations persisted after adjustment for covariates. Conclusions. Prevalence of EPI increases with age and seems to be tentatively higher in men than in women. However, smoking seems to be an independent risk factor for EPI and SEPI whereas ACE- inhibitor intake might be a protective factor. The latter finding may even point to new options in the treatment of chronic pancreatitis.
文摘Objective. There are few data on the epidemiology of gastroesophageal reflux disease (GERD) in South China. The aim of this study was to assess the prevalence of GERD symptoms in South China and to evaluate the impact on health- related quality of life. Material andmethods. A face- to- face interview was carried out in South China using a validated Chinese version of the Reflux Disease Questionnaire to assess the prevalence of GERD symptoms. A randomly clustered sampling of permanent inhabitants aged 18 to 90 years was carried out under stratification of urban and suburban areas. The impact of GERD symptoms on health- related quality of life was evaluated using the Chinese version of SF- 36. Results. A total of 3338 residents (1468 M, 1870 F) were investigated. Mean age of the responders was 42.6 ± 16.4 years; response rate was 95% . The prevalence of heartburn and/or acid eructation occurring at least weekly was 6.2% . The age- and gender- adjusted point prevalence of GERD symptoms in South China is 2.3% (95% CI, 1.8% , 2.8% ) according to the definition in this study. There was no difference in prevalence between male (2.6% ) and female (2.4% ) subjects and there was no significant association between age and prevalence of GERD symptoms. Divorced/ widowed/ separated subjects (OR 4.61; 95% CI, 2.15% , 9.89% ) and subjects with a heavy burden of work (OR 3.43, 95% CI, 1.72% , 6.84% ) were significantly more likely to report GERD symptoms. As compared with the general population, subjects with GERD symptoms experienced considerable impairment in quality of life. Conclusions. The prevalence of GERD symptoms in South China was much lower than that reported in Western countries. GERD had a negative impact on quality of life.
文摘PURPOSE: Elderly patients with colorectal cancer undergo surgery with curative intent less frequently than younger patients, and survival declines with increasing age. We compared relative survival of colorectal cancer among patients older than 75 years with that of younger patients in Denmark during the period 1977 to 1999. We also examined trends in choice of initial treatment. METHODS: From the files of the nationwide population- based Danish Cancer Registry, we identified all cases of colorectal cancer diagnosed between 1977 and 1999. We then linked this data to information on survival obtained from the Danish Register of Causes of Death and from the Central Population Register. RESULTS: During the entire study period, short- term and long- term relative survival improved for patients of all ages, but the improvement was more pronounced among elderly patients ( > 75 years). Radical resection was increasingly chosen as the initial treatment for elderly patients; during the 1995 to 1999 period it was performed on approximately 50 percent of such patients, almost as frequently as among younger patients. CONCLUSIONS: Relative survival of elderly colorectal cancer patients ( > 75 years) improved in Denmark between 1977 and 1999. In the most recent period studied, 1995 to 1997, only minor differences in five- year relative survival were observed among younger, middle- aged, and elderly patients. A simultaneous increase in the rate of radical resection among elderly patients, reflecting more effective treatment, may underlie this finding.
文摘Objective. Endoscopy is the gold standard for diagnostic evaluation of upper gastrointestinal symptoms. The relation between endoscopy and use of antisecretory medication on a population level is unknown. The aim of this study was to describe development in the number of patients undergoing first- time endoscopies and their use of antisecretory medication. Material and methods. Data on the use of endoscopies and antisecretory medication (H2 blockers and proton- pump inhibitors) were extracted from five population- based databases and included all citizens in Funen County (population 470,000) who had first time endoscopies between 1993 and 2002. Results. A total of 7,829 first- time endoscopy patients were identified. In 2002 the number of first- time endoscopies as 5.6/1000 persons. The proportion that had redeemed prescription(s) on antisecretory medication the last year before endoscopy increased from 33% (1095/3286) in 1993 to 41% (1012/2445) in 2002 (p = 0.000). Following endoscopy, average use of antisecretory medication increased by 90 defined daily doses (DDD)/patient/year (95% CI 84- 96) in patients with oesophagitis (N = 4850), by 59 DDD/patient/year (95% CI 54- 64) in peptic ulcer patients (N = 4373) and by 18 DDD/patient/year (95% CI 16- 20) in patients with normal endoscopies (N = 16,400). Conclusions. An increasing proportion of patients are treated with antisecretory medication before endoscopy. Following endoscopy, use of antisecretory medication increases irrespective of the diagnostic findings.
文摘Background & Aims: The concept of a CpG island methylator phenotype (CIMP), especially inmicrosatellite stable colon cancer, is not accepted universally. We therefore evaluated a large population-based sample of individuals with colon cancer and used univariate and multivariate analyses of CIMP with clinicopathologic variables and tumor mutations to determine the biologic relevance of this phenotype. Methods: A total of 864 tumors from individuals with colon cancer from Utah and Northern California were evaluated by methylation-specific polymerase chain reaction of CpG islands in hMLH1, methylated in tumors (MINT) 1, MINT 2, MINT 31, and CDKN2A (p16). CIMP high was defined as methylation at 2 or more of these loci. The BRAF V600E mutation was determined by sequencing. Microsatellite instability had been determined previously. Results: In a multivariate analysis of microsatellite stable tumors, CIMP high was related significantly to the V600E BRAF mutation (odds ratio, 39.52; 95% confidence interval, 11.44- 136.56), KRAS2 mutations (odds ratio, 2.22; 95% confidence interval, 1.48- 3.34), older age (P trend = .03), and increased stage (P trend = .03), and these tumors were less likely to be located in the distal colon (odds ratio, .42; 95% confidence interval, .27- .65). CIMP-high unstable tumors also were more likely to have the V600E BRAF mutation, be located proximally, and occur in older individuals (in univariate analyses). However, CIMP-high unstable tumors were significantly more likely than their stable counterparts to be KRAS2 wild type, TP53 wild type, poorly differentiated, proximally located, occur at lower stages, and have the BRAF V600E mutation (64.1% vs 17.6% ). Conclusions: The evaluation of a large, population-based sample strongly supports the biologic relevance of CIMP in colon cancer. However, the presence or absence of microsatellite instability has a major effect on the expression of this phenotype.
文摘Background & Aims: We aimed to discern the relative risk for several chronic inflammatory conditions in patients with ulcerative colitis (UC) and Crohn s disease. Methods: We used the population- based University of Manitoba IBD- Database that includes longitudinal files on all patients from all health system contacts identified by International Classification of Diseases, 9th revision, Clinical Modification codes for visit diagnosis. From the provincial database we extracted a control cohort matching the IBD patients 10 ∶ 1 by age, sex, and geography. We considered a potential comorbid disease to be present if the patient had 5 or more health system contacts for that diagnosis. The comorbid disease period prevalence was analyzed separately for patients with UC and Crohn s disease and a prevalence ratio was calculated comparing the IBD populations with the matched cohort. Results: There were 8072 cases of IBD from 1984 to 2003, including UC (n = 3879) and Crohn s disease (n = 4193). There was a mean of approximately 16 person- years of coverage for both patients and control patients. Both UC and Crohn s disease patients had a significantly greater likelihood of having arthritis, asthma, bronchitis, psoriasis, and pericarditis than population controls. An increased risk for chronic renal disease and multiple sclerosis was noted in UC but not Crohn s disease patients. The most common nonintestinal comorbidities identified were arthritis and asthma. Conclusions: The finding of asthma as the most common comorbidity increased in Crohn s disease patients compared with the general population is novel. These may be diseases with common causes or complications of one disease that lead to the presentation with another. Studies such as this should encourage further research into the common triggers in the organ systems that lead to autoimmune diseases.
文摘OBJECTIVES:We sought to determine the association between patent foramen ovale(PFO), atrial septal aneurysm(ASA), and stroke prospectively in a unselected population sample. BACKGROUND: The disputed relationship between PFO and stroke reflects methodologic weaknesses in studies using invalid controls, unblinded transesophageal echocardiography examinations, and data that are unadjusted for age or comorbidity. METHODS: The use of transesophageal echocardiography to identify PFO was performed by a single echocardiographer using standardized definitions in 585 randomly sampled, Olmsted County(Minnesota) subjects age 45 years or older participating in the Stroke Prevention: Assessment of Risk in a Community(SPARC) study. RESULTS: A PFO was identified in 140(24.3% ) subjects and ASA in 11(1.9% ) subjects. Of the 140 subjects with PFO, 6(4.3% ) had an ASA; of the 437 subjects without PFO, 5 had an ASA(1.1% , two-sided Fisher exact test, p=0.028). During a median follow-up of 5.1 years, cerebrovascular events(cerebrovascular disease-related death, ischemic stroke, transient ischemic attack) occurred in 41 subjects. After adjustment for age and comorbidity, PFO was not a significant independent predictor of stroke(hazard ratio 1.46, 95% confidence interval 0.74 to 2.88, p=0.28). The risk of a cerebrovascular event among subjects with ASA was nearly four times higher than that in those without ASA(hazard ratio 3.72, 95% confidence interval 0.88 to 15.71, p=0.074). CONCLUSIONS: These prospective population-based data suggest that, after correction for age and comorbidity, PFO is not an independent risk factor for future cerebrovascular events in the general population. A larger study is required to test the putative stroke risk associated with ASA.
文摘现代医学发展日新月益,2015年初美国国情咨文宣布了一项名为精准医学计划（precision medicine initiative）的项目,精准医学（precision medicine）这一概念迅速受到全球医疗界的关注。一般来讲,精准医学是以个性化医疗为核心指导、在基因组学、蛋白质组学等大数据为支撑的医学概念与模式。其本质是通过对于大样本人群与特定疾病类型进行生物标志物的分析、鉴定及验证,从而精确寻找到疾病的原因和治疗的靶点。然后针对特定疾病的不同疾病阶段,设计个性化治疗方案,提高疾病诊治水平。
