Anti-tumor necrosis factor(TNF) antibodies are successfully used in the therapy of inflammatory bowel diseases(IBD). However, the molecular mechanism of action of these agents is still a matter of debate. Apart from n...Anti-tumor necrosis factor(TNF) antibodies are successfully used in the therapy of inflammatory bowel diseases(IBD). However, the molecular mechanism of action of these agents is still a matter of debate. Apart from neutralization of TNF, influence on the intestinal barrier function, induction of apoptosis in mucosal immune cells, formation of regulatory macrophages as well as other immune modulating properties have been discussed as central features. Nevertheless, clinically effective anti-TNF antibodies were shown to differ in their mode-of-action in vivo and in vitro. Furthermore, the anti-TNF agent etanercept is effective in the treatment of rheumatoid arthritis but failed to induce clinical response in Crohn's disease patients, suggesting different contributions of TNF in the pathogenesis of these inflammatory diseases. In the following, we will review different aspects regarding the mechanism of action of anti-TNF agents in general and analyze comparatively different effects of each antiTNF agent such as TNF neutralization, modulation of the immune system, reverse signaling and induction of apoptosis. We discuss the relevance of the membranebound form of TNF compared to the soluble form for the immunopathogenesis of IBD. Furthermore, we review reports that could lead to personalized medicine approaches regarding treatment with antiTNF antibodies in chronic intestinal inflammation, by predicting response to therapy.展开更多
AIM To report adalimumab(Ada) efficacy on articulargastrointestinal disease and health-related quality of life(HRQo L) in patients with enteropathic spondyloarthritis(ES).METHODS A cohort of 52 patients with ES was ev...AIM To report adalimumab(Ada) efficacy on articulargastrointestinal disease and health-related quality of life(HRQo L) in patients with enteropathic spondyloarthritis(ES).METHODS A cohort of 52 patients with ES was evaluated in the departments of gastroenterology and internal medicine. At baseline, all patients underwent assessment by an integrated gastro-rheumatologic evaluation of articular and gastrointestinal activity, as well patient reported outcomes(PROs) of the HRQo L questionnaires. After this integrated evaluation and following a specific working flowchart, the Ada anti-tumor necrosis factor(TNF)-inhibitor was assigned to a cohort of 30 patients and its clinical efficacy was evaluated at baseline and after 6-mo and 12-mo treatment by the following tests:(1) Ankylosing Spondylitis Disease Activity ScoreC-Reactive Protein(ASDAS-CRP); Bath Ankylosing Spondylitis Disease Activity Index(BASDAI), Bath Ankylosing Spondylitis Functional Index(BASFI) and Bath Ankylosing Spondylitis Metrology Index(BASMI) for articular activity;(2) Inflammatory Bowel Disease Questionnaire(IBDQ), Crohn's Disease Activity Index(CDAI) and partial Mayo(p Mayo) score for gastrointestinal symptoms and activity; and(3) Health Assessment Questionnaire(HAQ), Patient Global Assessment(PGA) and Short Form-36 health survey(SF-36) questionnaires for PROs of the HRQo L.RESULTS Integrated evaluation and management of the patients affected by ES, carried out simultaneously by a gastroenterologist and a rheumatologist, allowed clinicians to choose the optimal therapeutic strategy. In a cohort of 30 ES patients affected by active articular and gastrointestinal disease, or axial active articular inflammation, Ada led to fast and sustained improvement of both articular and gastrointestinal disease activities. In fact, all the clinimetric evaluation tests exploring articular or gastrointestinal activity, as well as all the HRQo L scores, showed a significant improvement having been achieved at the earliest(6-mo) assessment. This important clinical improvement was maintained at the 12-mo follow-up. Importantly, global and gastrointestinal quality of life significantly correlated with articular disease activity, providing evidence to support that the integrated evaluation is the best option to manage patients with ES.CONCLUSION Ada treatment, upon multidisciplinary(gastrorheumatologic) evaluation, significantly improves both articular and gastrointestinal inflammation, thereby improving the HRQo L in patients affected by ES.展开更多
Calcific aorta is a disease of old age and is an independent risk factor for morbidity and mortality. Here, we present two patients with calcific aorta at different levels. One with a descending porcelain aorta, and m...Calcific aorta is a disease of old age and is an independent risk factor for morbidity and mortality. Here, we present two patients with calcific aorta at different levels. One with a descending porcelain aorta, and modified Bentall＇s procedure was done. Second is a patient who is having a calcific ascending aorta and coronary artery. Coronary artery bypass grafting from left internal mammary artery to left anterior descending was done for the patient. The calcification and its morbidity had been discussed briefly.展开更多
AIM： To evaluate whether diabetic patients had a higher risk of colon cancer mortality and its associated risk factors. METHODS： The sex-specific crude and age-standard- ized （to the 2000 World Health Organization ...AIM： To evaluate whether diabetic patients had a higher risk of colon cancer mortality and its associated risk factors. METHODS： The sex-specific crude and age-standard- ized （to the 2000 World Health Organization popula- tion） mortality rates of colon cancer in the Taiwan Residents general population were first calculated from 1995 to 2006. The trends were evaluated by linear regression. A total of 113 347 diabetic men and 131 573 diabetic women aged ~〉 25 years at recruitment from 1995 to 1998 were followed up until the end of 2006. Age/sex- specific colon cancer mortality rate ratios were cal- culated comparing the mortality rates of the diabetic patients with the average mortality rates of the general population within 12 years （1995-2006）. A sub-cohort of diabetic patients （42 260 men and 49 405 women） was interviewed using a baseline questionnaire and Cox＇s regression was used to evaluate the risk factors for colon cancer mortality in these diabetic patients.RESULTS： The crude and age-standardized trends of colon cancer mortality from 1995 to 2006 increased significantly for both sexes in the general population. A total of 641 diabetic men and 573 diabetic women died of colon cancer, with a mortality rate of 74.4 and 54.3 per 100 000 person-years, respectively. Mortality rate ratios [95% confidence intervals （CIs）] showed a significantly higher risk of mortality from colon can- cer for the diabetic patients compared to the general population, with the magnitude increasing with de- creasing age： 1.65 （1.40-1.95）, 2.01 （1.78-2.27）, 2.75 （2.36-3.21） and 5.69 （4.65-6.96） for /〉 75, 65-74, 55-64 and 25-54 years old, respectively, for men; and 1.46 （1.24-1.72）, 2.09 （1.84-2.38）, 2.67 （2.27-3.14） and 3.05 （2.29-4.06）, respectively, for women. Among the sub-cohort of diabetic patients who had been in- terviewed with the baseline questionnaire, including information on age, sex, diabetes duration, diabe- tes type, body mass index, smoking, insulin use and area of residence, age and smoking were significantly predictive for colon cancer mortality, with respec- tive adjusted hazard ratios （HRs） （95% CIs） of 1.077 （1.066-1.088） and 1.384 （1.068-1.792）. Diabetes dura- tion became a significant factor when those who died of colon cancer within 5 years of diabetes diagnosis were excluded to minimize the possible contamination of diabetes caused by incipient colon cancer, with an adjusted hazard ratio of 1.021 （1.007-1.034）. Sex, dia- betes type, insulin use, body mass index and area of residence were not significant predictors for colon can- cer mortality in the diabetic patients. Although insulin use was categorized into subgroups of duration of use （non-users and users 〈 5 years, 5-9 years and i〉 10 years）, none of the HRs for colon cancer mortality was significant with regards to different durations of insulin use. CONCLUSION： Colon cancer mortality is increasing in Taiwan. A higher risk is observed in diabetic patients. Smoking, but not insulin use, is a modifiable risk factor.展开更多
A 46-year-old female patient with terminal ileum Crohn’s disease and ankylosing spondylitis presented with recurrent angioedema and urticaria. Investigations ruled out hereditary angioedema, and environmental or food...A 46-year-old female patient with terminal ileum Crohn’s disease and ankylosing spondylitis presented with recurrent angioedema and urticaria. Investigations ruled out hereditary angioedema, and environmental or food allergen triggers. She was diagnosed with chronic idiopathic urticaria with angioedema, and was treated with a trial of intravenous immunoglobulin immunotherapy, danazol, prednisone and hydroxyzine. Due to ongoing bowel and arthritic complaints, she was started on infliximab infusions and within 2 treatments, she had complete resolution of the angioedema and urticaria, as well as of the bowel and arthritic symptoms. Unfortunately she developed allergic reactions to the infliximab and was switched to another anti-tumor necrosis factor （TNF）-a agent, adalimumab. Since then, she has had no further angioedema or urticaria, and her Crohn’s disease has been quiescent. This is the first known case report of chronic idiopathic urticaria with angioedema coexistent with Crohn’s disease that was successfully treated with anti-TNF-α agents.展开更多
基金Supported by DFG-CRC1181-Project number(C02)a research operating grant from the International Organization for the Study of Inflammatory Bowel Diseases
文摘Anti-tumor necrosis factor(TNF) antibodies are successfully used in the therapy of inflammatory bowel diseases(IBD). However, the molecular mechanism of action of these agents is still a matter of debate. Apart from neutralization of TNF, influence on the intestinal barrier function, induction of apoptosis in mucosal immune cells, formation of regulatory macrophages as well as other immune modulating properties have been discussed as central features. Nevertheless, clinically effective anti-TNF antibodies were shown to differ in their mode-of-action in vivo and in vitro. Furthermore, the anti-TNF agent etanercept is effective in the treatment of rheumatoid arthritis but failed to induce clinical response in Crohn's disease patients, suggesting different contributions of TNF in the pathogenesis of these inflammatory diseases. In the following, we will review different aspects regarding the mechanism of action of anti-TNF agents in general and analyze comparatively different effects of each antiTNF agent such as TNF neutralization, modulation of the immune system, reverse signaling and induction of apoptosis. We discuss the relevance of the membranebound form of TNF compared to the soluble form for the immunopathogenesis of IBD. Furthermore, we review reports that could lead to personalized medicine approaches regarding treatment with antiTNF antibodies in chronic intestinal inflammation, by predicting response to therapy.
文摘AIM To report adalimumab(Ada) efficacy on articulargastrointestinal disease and health-related quality of life(HRQo L) in patients with enteropathic spondyloarthritis(ES).METHODS A cohort of 52 patients with ES was evaluated in the departments of gastroenterology and internal medicine. At baseline, all patients underwent assessment by an integrated gastro-rheumatologic evaluation of articular and gastrointestinal activity, as well patient reported outcomes(PROs) of the HRQo L questionnaires. After this integrated evaluation and following a specific working flowchart, the Ada anti-tumor necrosis factor(TNF)-inhibitor was assigned to a cohort of 30 patients and its clinical efficacy was evaluated at baseline and after 6-mo and 12-mo treatment by the following tests:(1) Ankylosing Spondylitis Disease Activity ScoreC-Reactive Protein(ASDAS-CRP); Bath Ankylosing Spondylitis Disease Activity Index(BASDAI), Bath Ankylosing Spondylitis Functional Index(BASFI) and Bath Ankylosing Spondylitis Metrology Index(BASMI) for articular activity;(2) Inflammatory Bowel Disease Questionnaire(IBDQ), Crohn's Disease Activity Index(CDAI) and partial Mayo(p Mayo) score for gastrointestinal symptoms and activity; and(3) Health Assessment Questionnaire(HAQ), Patient Global Assessment(PGA) and Short Form-36 health survey(SF-36) questionnaires for PROs of the HRQo L.RESULTS Integrated evaluation and management of the patients affected by ES, carried out simultaneously by a gastroenterologist and a rheumatologist, allowed clinicians to choose the optimal therapeutic strategy. In a cohort of 30 ES patients affected by active articular and gastrointestinal disease, or axial active articular inflammation, Ada led to fast and sustained improvement of both articular and gastrointestinal disease activities. In fact, all the clinimetric evaluation tests exploring articular or gastrointestinal activity, as well as all the HRQo L scores, showed a significant improvement having been achieved at the earliest(6-mo) assessment. This important clinical improvement was maintained at the 12-mo follow-up. Importantly, global and gastrointestinal quality of life significantly correlated with articular disease activity, providing evidence to support that the integrated evaluation is the best option to manage patients with ES.CONCLUSION Ada treatment, upon multidisciplinary(gastrorheumatologic) evaluation, significantly improves both articular and gastrointestinal inflammation, thereby improving the HRQo L in patients affected by ES.
文摘Calcific aorta is a disease of old age and is an independent risk factor for morbidity and mortality. Here, we present two patients with calcific aorta at different levels. One with a descending porcelain aorta, and modified Bentall＇s procedure was done. Second is a patient who is having a calcific ascending aorta and coronary artery. Coronary artery bypass grafting from left internal mammary artery to left anterior descending was done for the patient. The calcification and its morbidity had been discussed briefly.
基金Supported by The Department of Health of Taiwan,No. DOH97-TD-D-113-97009
文摘AIM： To evaluate whether diabetic patients had a higher risk of colon cancer mortality and its associated risk factors. METHODS： The sex-specific crude and age-standard- ized （to the 2000 World Health Organization popula- tion） mortality rates of colon cancer in the Taiwan Residents general population were first calculated from 1995 to 2006. The trends were evaluated by linear regression. A total of 113 347 diabetic men and 131 573 diabetic women aged ~〉 25 years at recruitment from 1995 to 1998 were followed up until the end of 2006. Age/sex- specific colon cancer mortality rate ratios were cal- culated comparing the mortality rates of the diabetic patients with the average mortality rates of the general population within 12 years （1995-2006）. A sub-cohort of diabetic patients （42 260 men and 49 405 women） was interviewed using a baseline questionnaire and Cox＇s regression was used to evaluate the risk factors for colon cancer mortality in these diabetic patients.RESULTS： The crude and age-standardized trends of colon cancer mortality from 1995 to 2006 increased significantly for both sexes in the general population. A total of 641 diabetic men and 573 diabetic women died of colon cancer, with a mortality rate of 74.4 and 54.3 per 100 000 person-years, respectively. Mortality rate ratios [95% confidence intervals （CIs）] showed a significantly higher risk of mortality from colon can- cer for the diabetic patients compared to the general population, with the magnitude increasing with de- creasing age： 1.65 （1.40-1.95）, 2.01 （1.78-2.27）, 2.75 （2.36-3.21） and 5.69 （4.65-6.96） for /〉 75, 65-74, 55-64 and 25-54 years old, respectively, for men; and 1.46 （1.24-1.72）, 2.09 （1.84-2.38）, 2.67 （2.27-3.14） and 3.05 （2.29-4.06）, respectively, for women. Among the sub-cohort of diabetic patients who had been in- terviewed with the baseline questionnaire, including information on age, sex, diabetes duration, diabe- tes type, body mass index, smoking, insulin use and area of residence, age and smoking were significantly predictive for colon cancer mortality, with respec- tive adjusted hazard ratios （HRs） （95% CIs） of 1.077 （1.066-1.088） and 1.384 （1.068-1.792）. Diabetes dura- tion became a significant factor when those who died of colon cancer within 5 years of diabetes diagnosis were excluded to minimize the possible contamination of diabetes caused by incipient colon cancer, with an adjusted hazard ratio of 1.021 （1.007-1.034）. Sex, dia- betes type, insulin use, body mass index and area of residence were not significant predictors for colon can- cer mortality in the diabetic patients. Although insulin use was categorized into subgroups of duration of use （non-users and users 〈 5 years, 5-9 years and i〉 10 years）, none of the HRs for colon cancer mortality was significant with regards to different durations of insulin use. CONCLUSION： Colon cancer mortality is increasing in Taiwan. A higher risk is observed in diabetic patients. Smoking, but not insulin use, is a modifiable risk factor.
文摘A 46-year-old female patient with terminal ileum Crohn’s disease and ankylosing spondylitis presented with recurrent angioedema and urticaria. Investigations ruled out hereditary angioedema, and environmental or food allergen triggers. She was diagnosed with chronic idiopathic urticaria with angioedema, and was treated with a trial of intravenous immunoglobulin immunotherapy, danazol, prednisone and hydroxyzine. Due to ongoing bowel and arthritic complaints, she was started on infliximab infusions and within 2 treatments, she had complete resolution of the angioedema and urticaria, as well as of the bowel and arthritic symptoms. Unfortunately she developed allergic reactions to the infliximab and was switched to another anti-tumor necrosis factor （TNF）-a agent, adalimumab. Since then, she has had no further angioedema or urticaria, and her Crohn’s disease has been quiescent. This is the first known case report of chronic idiopathic urticaria with angioedema coexistent with Crohn’s disease that was successfully treated with anti-TNF-α agents.
