Patients with long-standing UC have an increased risk for the development of colonic neoplastic l... more Patients with long-standing UC have an increased risk for the development of colonic neoplastic lesions. Chromoendoscopy (CE) has been proven to enhance neoplasia detection while the role of virtual chromoendoscopy (VC) is still to be defined. To compare the performance of CE to VC for the detection of neoplastic lesions in patients with long-standing UC. A multicentre prospective randomised controlled trial. 131 patients with long-standing UC were randomised between CE with methylene blue 0.1% (n=66) or VC with narrow band imaging (NBI) (n=65). Biopsies were taken from visible lesions and surrounding mucosa. No random biopsies were performed. The primary outcome was the difference in total number of neoplastic lesions detected in each group. There was no significant difference between NBI and CE for neoplasia detection. Mean number of neoplastic lesions per colonoscopy was 0.47 for CE and 0.32 for NBI (p=0.992). The neoplasia detection rate was not different between CE (21.2%) and ...
Although intestinal dysbiosis is well established in Crohn&am... more Although intestinal dysbiosis is well established in Crohn's disease (CD), little is known about the microbial metabolic activity of CD patients. In this study, we compared the metabolite patterns of the CD patients with profiles from healthy controls (HCs) and correlated them to disease activity and bacterial composition. In addition, the influence of the prebiotic oligofructose-enriched inulin (OF-IN) on the CD metabolites profile was evaluated. Sixty-seven inactive and moderately active CD patients were included in a double-blinded randomized placebo controlled trial (RCT). Patients consumed either 10 g OF-IN or 10 g placebo twice per day for 4 weeks. They collected a fecal sample before the start of the study (baseline) and after the treatment period. In addition, fecal samples were obtained from 40 HCs. The metabolite profile was assessed using gas chromatography-mass spectrometry. The number of fecal metabolites was significantly higher in HCs than in CD patients (P<0.001). Forty compounds differed between CD patients and HCs. When correlating the metabolite levels to disease activity, significantly lower levels of butyrate, pentanoate, hexanoate, heptanoate, and p-cresol were found in active patients as compared with HCs. In the RCT, no significant changes in the metabolite pattern were found in patients randomized to placebo. In patients receiving OF-IN (per protocol; n=21), the relative levels of acetaldehyde (P=0.0008) and butyrate (P=0.0011) were significantly increased as compared with baseline. We identified medium chain fatty acids and p-cresol as differentiating metabolites toward CD disease status and as compared with HCs. In addition, OF-IN intake primarily increased the carbohydrate fermentation metabolites butyrate and acetaldehyde.
European journal of gastroenterology & hepatology, Jan 28, 2015
Patients with inflammatory bowel disease (IBD) have a higher risk of developing thromboembolic ev... more Patients with inflammatory bowel disease (IBD) have a higher risk of developing thromboembolic events (TE) compared with the healthy population. This study aimed to describe a cohort of IBD patients with a history of TE focusing on recurrence of TE, disease activity and IBD medication at the time of TE and surgery before TE. In a retrospective monocentric cohort study, we included IBD patients in whom an arterial and/or venous TE occurred. Eighty-four IBD patients with a history of TE (63% Crohn's disease, 44% men) and a mean age of 45±15 years were included; 25/84 patients (30%) were identified to have recurrent TE. Seventy out of 84 (83%) developed a venous TE, with a deep vein thrombosis as the major manifestation (28/70, 40%), followed by a pulmonary embolism (16/70, 23%). At the time of TE, 60/84 (71%) patients were diagnosed with active disease. In all, 23% patients were on 5-aminosalicylic acids, 36% on steroids, 18% on azathioprine, 5% on methotrexate, 12% on biologicals...
OBJECTIVES: Although intestinal dysbiosis is well established in Crohn's disease (CD), little is ... more OBJECTIVES: Although intestinal dysbiosis is well established in Crohn's disease (CD), little is known about the microbial metabolic activity of CD patients. In this study, we compared the metabolite patterns of the CD patients with profiles from healthy controls (HCs) and correlated them to disease activity and bacterial composition. In addition, the influence of the prebiotic oligofructose-enriched inulin (OF-IN) on the CD metabolites profile was evaluated. METHODS: Sixty-seven inactive and moderately active CD patients were included in a double-blinded randomized placebo controlled trial (RCT). Patients consumed either 10 g OF-IN or 10 g placebo twice per day for 4 weeks. They collected a fecal sample before the start of the study (baseline) and after the treatment period. In addition, fecal samples were obtained from 40 HCs. The metabolite profile was assessed using gas chromatography-mass spectrometry. RESULTS: The number of fecal metabolites was significantly higher in HCs than in CD patients (Po0.001). Forty compounds differed between CD patients and HCs. When correlating the metabolite levels to disease activity, significantly lower levels of butyrate, pentanoate, hexanoate, heptanoate, and p-cresol were found in active patients as compared with HCs. In the RCT, no significant changes in the metabolite pattern were found in patients randomized to placebo. In patients receiving OF-IN (per protocol; n ¼ 21), the relative levels of acetaldehyde (P ¼ 0.0008) and butyrate (P ¼ 0.0011) were significantly increased as compared with baseline. CONCLUSIONS: We identified medium chain fatty acids and p-cresol as differentiating metabolites toward CD disease status and as compared with HCs. In addition, OF-IN intake primarily increased the carbohydrate fermentation metabolites butyrate and acetaldehyde.
Health Improvement Network primary care database was used to identify 2 cohorts of patients aged ... more Health Improvement Network primary care database was used to identify 2 cohorts of patients aged 1-17 years between 2000 and 2005; patients with a recorded diagnosis of gastroesophageal reflux disease (GERD) during the study period (n = 1809) and a cohort of patients without GERD (n = 5000). Non-GERD patients were frequency matched to GERD patients by age, sex and calendar year. Among GERD patients, 2 sub-cohorts of patients were identified according to whether they had been prescribed a PPI within 1 year of GERD diagnosis; there were 487 GERD PPI users and 1322 GERD PPI non-users. All patients (GERD and non-GERD) were followed-up for up to 1 year from the start date (date of first prescription for GERD PPI users, date of GERD diagnosis for GERD PPI non-users and a random date for non-GERD patients). A total of 118 patients with a recorded diagnosis of fracture were identified; their medical records were reviewed manually to ascertain incident cases. There were a total of 45 fracture cases among GERD patients; 11 among PPI users and 34 among PPI non-users. Adjusted incidence rate ratios (IRRs) for fracture risk associated with exposure to PPIs were calculated. We also conducted a nested case-control analysis, using all 118 cases of fracture identified in both GERD and non-GERD cohorts. All remaining patients without fracture at the end of follow-up in both cohorts served as controls (n = 6656). The index date was the date of diagnosis for fracture cases and a random date for controls. Data on PPI use were obtained and odds ratios (ORs) for fracture risk associated with PPI use were calculated by multivariate adjusted logistic regression models. Results. Among GERD patients, there was no association between fracture risk and current (IRR: 0.68; 95% CI: 0.24-1.94) or recent/past use (IRR: 0.90; 95% CI: 0.40-2.05) of PPIs compared with non-use of PPIs. Similarly, among all patients (with or without GERD), neither current (OR: 0.71; 95% CI: 0.25-2.04) nor recent/past use (OR: 0.95; 95% CI: 0.41-2.18) of PPIs was associated with an increased risk of fracture compared with non-use of PPIs. However, these estimates were based on only four currently exposed cases and seven recently/past exposed cases. Conclusion. The results of our study do not support an association between PPI use and risk of fracture in children and adolescents with or without a diagnosis of GERD. However, it should be noted that only a small number of cases were exposed to a PPI.
Although intestinal dysbiosis is well established in Crohn&am... more Although intestinal dysbiosis is well established in Crohn's disease (CD), little is known about the microbial metabolic activity of CD patients. In this study, we compared the metabolite patterns of the CD patients with profiles from healthy controls (HCs) and correlated them to disease activity and bacterial composition. In addition, the influence of the prebiotic oligofructose-enriched inulin (OF-IN) on the CD metabolites profile was evaluated. Sixty-seven inactive and moderately active CD patients were included in a double-blinded randomized placebo controlled trial (RCT). Patients consumed either 10 g OF-IN or 10 g placebo twice per day for 4 weeks. They collected a fecal sample before the start of the study (baseline) and after the treatment period. In addition, fecal samples were obtained from 40 HCs. The metabolite profile was assessed using gas chromatography-mass spectrometry. The number of fecal metabolites was significantly higher in HCs than in CD patients (P<0.001). Forty compounds differed between CD patients and HCs. When correlating the metabolite levels to disease activity, significantly lower levels of butyrate, pentanoate, hexanoate, heptanoate, and p-cresol were found in active patients as compared with HCs. In the RCT, no significant changes in the metabolite pattern were found in patients randomized to placebo. In patients receiving OF-IN (per protocol; n=21), the relative levels of acetaldehyde (P=0.0008) and butyrate (P=0.0011) were significantly increased as compared with baseline. We identified medium chain fatty acids and p-cresol as differentiating metabolites toward CD disease status and as compared with HCs. In addition, OF-IN intake primarily increased the carbohydrate fermentation metabolites butyrate and acetaldehyde.
Infliximab (IFX) and adalimumab (ADA) are attractive treatment options in patients with inflammat... more Infliximab (IFX) and adalimumab (ADA) are attractive treatment options in patients with inflammatory bowel disease (IBD) also during pregnancy but there is still limited data on the benefit/risk profile of IFX and ADA during pregnancy. This observational study assessed pregnancy outcomes in 212 women with IBD under antitumor necrosis factor alpha (TNF) treatment at our IBD unit. Pregnancy outcomes in 42 pregnancies with direct exposure to anti-TNF treatment (35 IFX, 7 ADA) were compared with that in 23 pregnancies prior to IBD diagnosis, 78 pregnancies before start of IFX, 53 pregnancies with indirect exposure to IFX, and 56 matched pregnancies in healthy women. Thirty-two of the 42 pregnancies ended in live births with a median gestational age of 38 weeks (interquartile range [IQR] 37-39). There were seven premature deliveries, six children had low birth weight, and there was one stillbirth. One boy weighed 1640 g delivered at week 33, died at age of 13 days because of necrotizing enterocolitis. A total of eight abortions (one patient wish) occurred in seven women. Trisomy 18 was diagnosed in one fetus of a mother with CD at age 37 under ADA treatment (40 mg weekly) and pregnancy was terminated. Pregnancy outcomes after direct exposure to anti-TNF treatment were not different from those in pregnancies before anti-TNF treatment or with indirect exposure to anti-TNF treatment but outcomes were worse than in pregnancies before IBD diagnosis. Direct exposure to anti-TNF treatment during pregnancy was not related to a higher incidence of adverse pregnancy outcomes than IBD overall.
Patients with inflammatory bowel disease (IBD) display immunoreactivity to self-antigens and micr... more Patients with inflammatory bowel disease (IBD) display immunoreactivity to self-antigens and microbial antigens. We used a protein microarray approach to identify novel autoantigens in IBD. ProtoArray Human Protein Microarray v4.0 containing 8268 human proteins from Invitrogen (La Jolla, CA) was used. Twenty-five IBD patients and five healthy controls were screened for candidate autoantigens. For 256 antigens, IBD patients had a higher seroreactivity than controls. Twenty antigens were selected for further evaluation in a larger cohort (60 ulcerative colitis [UC] patients, 60 Crohn's disease [CD] patients, 60 healthy controls, and 60 gastrointestinal-diseased controls) by means of a customized protein microarray. Out of these 20 antigens, one antigen, family with sequence similarity 84 member A (FAM84A), was identified as a target antigen in IBD. Antibodies to FAM84A were significantly more prevalent in IBD patients (19%) than in gastrointestinal-diseased controls (1.7%) (P = 0.0008) and healthy controls (5%) (P = 0.01). Anti-FAM84A antibodies were found in 26.6% of UC patients and in 11.7% of CD patients. FAM84A was confirmed as target antigen in IBD by means of Western blotting in a large independent cohort (100 UC patients, 106 CD patients, 102 healthy controls, and 100 gastrointestinal-diseased controls). Antibodies to FAM84A were significantly more prevalent in IBD patients (20%) than in gastrointestinal-diseased controls (5%) (P = 0.0004) and healthy controls (0%) (P < 0.0001). Anti-FAM84A antibodies were found in 18% of UC patients and in 22% of CD patients. We identified FAM84A as a novel autoantigen in IBD. (Inflamm Bowel Dis 2011;).
Patients with long-standing UC have an increased risk for the development of colonic neoplastic l... more Patients with long-standing UC have an increased risk for the development of colonic neoplastic lesions. Chromoendoscopy (CE) has been proven to enhance neoplasia detection while the role of virtual chromoendoscopy (VC) is still to be defined. To compare the performance of CE to VC for the detection of neoplastic lesions in patients with long-standing UC. A multicentre prospective randomised controlled trial. 131 patients with long-standing UC were randomised between CE with methylene blue 0.1% (n=66) or VC with narrow band imaging (NBI) (n=65). Biopsies were taken from visible lesions and surrounding mucosa. No random biopsies were performed. The primary outcome was the difference in total number of neoplastic lesions detected in each group. There was no significant difference between NBI and CE for neoplasia detection. Mean number of neoplastic lesions per colonoscopy was 0.47 for CE and 0.32 for NBI (p=0.992). The neoplasia detection rate was not different between CE (21.2%) and ...
Although intestinal dysbiosis is well established in Crohn&am... more Although intestinal dysbiosis is well established in Crohn's disease (CD), little is known about the microbial metabolic activity of CD patients. In this study, we compared the metabolite patterns of the CD patients with profiles from healthy controls (HCs) and correlated them to disease activity and bacterial composition. In addition, the influence of the prebiotic oligofructose-enriched inulin (OF-IN) on the CD metabolites profile was evaluated. Sixty-seven inactive and moderately active CD patients were included in a double-blinded randomized placebo controlled trial (RCT). Patients consumed either 10 g OF-IN or 10 g placebo twice per day for 4 weeks. They collected a fecal sample before the start of the study (baseline) and after the treatment period. In addition, fecal samples were obtained from 40 HCs. The metabolite profile was assessed using gas chromatography-mass spectrometry. The number of fecal metabolites was significantly higher in HCs than in CD patients (P<0.001). Forty compounds differed between CD patients and HCs. When correlating the metabolite levels to disease activity, significantly lower levels of butyrate, pentanoate, hexanoate, heptanoate, and p-cresol were found in active patients as compared with HCs. In the RCT, no significant changes in the metabolite pattern were found in patients randomized to placebo. In patients receiving OF-IN (per protocol; n=21), the relative levels of acetaldehyde (P=0.0008) and butyrate (P=0.0011) were significantly increased as compared with baseline. We identified medium chain fatty acids and p-cresol as differentiating metabolites toward CD disease status and as compared with HCs. In addition, OF-IN intake primarily increased the carbohydrate fermentation metabolites butyrate and acetaldehyde.
European journal of gastroenterology & hepatology, Jan 28, 2015
Patients with inflammatory bowel disease (IBD) have a higher risk of developing thromboembolic ev... more Patients with inflammatory bowel disease (IBD) have a higher risk of developing thromboembolic events (TE) compared with the healthy population. This study aimed to describe a cohort of IBD patients with a history of TE focusing on recurrence of TE, disease activity and IBD medication at the time of TE and surgery before TE. In a retrospective monocentric cohort study, we included IBD patients in whom an arterial and/or venous TE occurred. Eighty-four IBD patients with a history of TE (63% Crohn's disease, 44% men) and a mean age of 45±15 years were included; 25/84 patients (30%) were identified to have recurrent TE. Seventy out of 84 (83%) developed a venous TE, with a deep vein thrombosis as the major manifestation (28/70, 40%), followed by a pulmonary embolism (16/70, 23%). At the time of TE, 60/84 (71%) patients were diagnosed with active disease. In all, 23% patients were on 5-aminosalicylic acids, 36% on steroids, 18% on azathioprine, 5% on methotrexate, 12% on biologicals...
OBJECTIVES: Although intestinal dysbiosis is well established in Crohn's disease (CD), little is ... more OBJECTIVES: Although intestinal dysbiosis is well established in Crohn's disease (CD), little is known about the microbial metabolic activity of CD patients. In this study, we compared the metabolite patterns of the CD patients with profiles from healthy controls (HCs) and correlated them to disease activity and bacterial composition. In addition, the influence of the prebiotic oligofructose-enriched inulin (OF-IN) on the CD metabolites profile was evaluated. METHODS: Sixty-seven inactive and moderately active CD patients were included in a double-blinded randomized placebo controlled trial (RCT). Patients consumed either 10 g OF-IN or 10 g placebo twice per day for 4 weeks. They collected a fecal sample before the start of the study (baseline) and after the treatment period. In addition, fecal samples were obtained from 40 HCs. The metabolite profile was assessed using gas chromatography-mass spectrometry. RESULTS: The number of fecal metabolites was significantly higher in HCs than in CD patients (Po0.001). Forty compounds differed between CD patients and HCs. When correlating the metabolite levels to disease activity, significantly lower levels of butyrate, pentanoate, hexanoate, heptanoate, and p-cresol were found in active patients as compared with HCs. In the RCT, no significant changes in the metabolite pattern were found in patients randomized to placebo. In patients receiving OF-IN (per protocol; n ¼ 21), the relative levels of acetaldehyde (P ¼ 0.0008) and butyrate (P ¼ 0.0011) were significantly increased as compared with baseline. CONCLUSIONS: We identified medium chain fatty acids and p-cresol as differentiating metabolites toward CD disease status and as compared with HCs. In addition, OF-IN intake primarily increased the carbohydrate fermentation metabolites butyrate and acetaldehyde.
Health Improvement Network primary care database was used to identify 2 cohorts of patients aged ... more Health Improvement Network primary care database was used to identify 2 cohorts of patients aged 1-17 years between 2000 and 2005; patients with a recorded diagnosis of gastroesophageal reflux disease (GERD) during the study period (n = 1809) and a cohort of patients without GERD (n = 5000). Non-GERD patients were frequency matched to GERD patients by age, sex and calendar year. Among GERD patients, 2 sub-cohorts of patients were identified according to whether they had been prescribed a PPI within 1 year of GERD diagnosis; there were 487 GERD PPI users and 1322 GERD PPI non-users. All patients (GERD and non-GERD) were followed-up for up to 1 year from the start date (date of first prescription for GERD PPI users, date of GERD diagnosis for GERD PPI non-users and a random date for non-GERD patients). A total of 118 patients with a recorded diagnosis of fracture were identified; their medical records were reviewed manually to ascertain incident cases. There were a total of 45 fracture cases among GERD patients; 11 among PPI users and 34 among PPI non-users. Adjusted incidence rate ratios (IRRs) for fracture risk associated with exposure to PPIs were calculated. We also conducted a nested case-control analysis, using all 118 cases of fracture identified in both GERD and non-GERD cohorts. All remaining patients without fracture at the end of follow-up in both cohorts served as controls (n = 6656). The index date was the date of diagnosis for fracture cases and a random date for controls. Data on PPI use were obtained and odds ratios (ORs) for fracture risk associated with PPI use were calculated by multivariate adjusted logistic regression models. Results. Among GERD patients, there was no association between fracture risk and current (IRR: 0.68; 95% CI: 0.24-1.94) or recent/past use (IRR: 0.90; 95% CI: 0.40-2.05) of PPIs compared with non-use of PPIs. Similarly, among all patients (with or without GERD), neither current (OR: 0.71; 95% CI: 0.25-2.04) nor recent/past use (OR: 0.95; 95% CI: 0.41-2.18) of PPIs was associated with an increased risk of fracture compared with non-use of PPIs. However, these estimates were based on only four currently exposed cases and seven recently/past exposed cases. Conclusion. The results of our study do not support an association between PPI use and risk of fracture in children and adolescents with or without a diagnosis of GERD. However, it should be noted that only a small number of cases were exposed to a PPI.
Although intestinal dysbiosis is well established in Crohn&am... more Although intestinal dysbiosis is well established in Crohn's disease (CD), little is known about the microbial metabolic activity of CD patients. In this study, we compared the metabolite patterns of the CD patients with profiles from healthy controls (HCs) and correlated them to disease activity and bacterial composition. In addition, the influence of the prebiotic oligofructose-enriched inulin (OF-IN) on the CD metabolites profile was evaluated. Sixty-seven inactive and moderately active CD patients were included in a double-blinded randomized placebo controlled trial (RCT). Patients consumed either 10 g OF-IN or 10 g placebo twice per day for 4 weeks. They collected a fecal sample before the start of the study (baseline) and after the treatment period. In addition, fecal samples were obtained from 40 HCs. The metabolite profile was assessed using gas chromatography-mass spectrometry. The number of fecal metabolites was significantly higher in HCs than in CD patients (P<0.001). Forty compounds differed between CD patients and HCs. When correlating the metabolite levels to disease activity, significantly lower levels of butyrate, pentanoate, hexanoate, heptanoate, and p-cresol were found in active patients as compared with HCs. In the RCT, no significant changes in the metabolite pattern were found in patients randomized to placebo. In patients receiving OF-IN (per protocol; n=21), the relative levels of acetaldehyde (P=0.0008) and butyrate (P=0.0011) were significantly increased as compared with baseline. We identified medium chain fatty acids and p-cresol as differentiating metabolites toward CD disease status and as compared with HCs. In addition, OF-IN intake primarily increased the carbohydrate fermentation metabolites butyrate and acetaldehyde.
Infliximab (IFX) and adalimumab (ADA) are attractive treatment options in patients with inflammat... more Infliximab (IFX) and adalimumab (ADA) are attractive treatment options in patients with inflammatory bowel disease (IBD) also during pregnancy but there is still limited data on the benefit/risk profile of IFX and ADA during pregnancy. This observational study assessed pregnancy outcomes in 212 women with IBD under antitumor necrosis factor alpha (TNF) treatment at our IBD unit. Pregnancy outcomes in 42 pregnancies with direct exposure to anti-TNF treatment (35 IFX, 7 ADA) were compared with that in 23 pregnancies prior to IBD diagnosis, 78 pregnancies before start of IFX, 53 pregnancies with indirect exposure to IFX, and 56 matched pregnancies in healthy women. Thirty-two of the 42 pregnancies ended in live births with a median gestational age of 38 weeks (interquartile range [IQR] 37-39). There were seven premature deliveries, six children had low birth weight, and there was one stillbirth. One boy weighed 1640 g delivered at week 33, died at age of 13 days because of necrotizing enterocolitis. A total of eight abortions (one patient wish) occurred in seven women. Trisomy 18 was diagnosed in one fetus of a mother with CD at age 37 under ADA treatment (40 mg weekly) and pregnancy was terminated. Pregnancy outcomes after direct exposure to anti-TNF treatment were not different from those in pregnancies before anti-TNF treatment or with indirect exposure to anti-TNF treatment but outcomes were worse than in pregnancies before IBD diagnosis. Direct exposure to anti-TNF treatment during pregnancy was not related to a higher incidence of adverse pregnancy outcomes than IBD overall.
Patients with inflammatory bowel disease (IBD) display immunoreactivity to self-antigens and micr... more Patients with inflammatory bowel disease (IBD) display immunoreactivity to self-antigens and microbial antigens. We used a protein microarray approach to identify novel autoantigens in IBD. ProtoArray Human Protein Microarray v4.0 containing 8268 human proteins from Invitrogen (La Jolla, CA) was used. Twenty-five IBD patients and five healthy controls were screened for candidate autoantigens. For 256 antigens, IBD patients had a higher seroreactivity than controls. Twenty antigens were selected for further evaluation in a larger cohort (60 ulcerative colitis [UC] patients, 60 Crohn's disease [CD] patients, 60 healthy controls, and 60 gastrointestinal-diseased controls) by means of a customized protein microarray. Out of these 20 antigens, one antigen, family with sequence similarity 84 member A (FAM84A), was identified as a target antigen in IBD. Antibodies to FAM84A were significantly more prevalent in IBD patients (19%) than in gastrointestinal-diseased controls (1.7%) (P = 0.0008) and healthy controls (5%) (P = 0.01). Anti-FAM84A antibodies were found in 26.6% of UC patients and in 11.7% of CD patients. FAM84A was confirmed as target antigen in IBD by means of Western blotting in a large independent cohort (100 UC patients, 106 CD patients, 102 healthy controls, and 100 gastrointestinal-diseased controls). Antibodies to FAM84A were significantly more prevalent in IBD patients (20%) than in gastrointestinal-diseased controls (5%) (P = 0.0004) and healthy controls (0%) (P < 0.0001). Anti-FAM84A antibodies were found in 18% of UC patients and in 22% of CD patients. We identified FAM84A as a novel autoantigen in IBD. (Inflamm Bowel Dis 2011;).
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