| 1. |
- Forss, Anders, et al.
(author)
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Patients With Microscopic Colitis Are at Higher Risk of Major Adverse Cardiovascular Events : A Matched Cohort Study
- 2023
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In: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 21:13
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Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: Inflammatory diseases are associated with an increased risk of incident major adverse cardiovascular events (MACE). However, data on MACE are lacking in large population-based histopathology cohorts of microscopic colitis (MC).METHODS: This study included all Swedish adults with MC without previous cardiovascular disease (1990- 2017; N = 11,018). MC and subtypes (collagenous colitis and lymphocytic colitis) were defined from prospectively recorded intestinal histopathology reports from all pathology departments (n = 28) in Sweden. MC patients were matched for age, sex, calendar year, and county with up to 5 reference individuals (N = 48,371) without MC or cardiovascular disease. Sensitivity analyses included full sibling comparisons, and adjustment for cardiovascular medication and healthcare utilization. Multivariable-adjusted hazard ratios for MACE (any of ischemic heart disease, congestive heart failure, stroke, and cardiovascular mortality) were calculated using Cox proportional hazards modelling. RESULTS: Over a median of 6.6 years of follow-up, 2181 (19.8%) incident cases of MACE were confirmed in MC patients and 6661 (13.8%) in reference individuals. MC patients had a higher overall risk of MACE outcomes compared with reference individuals (adjusted hazard ratio [aHR], 1.27; 95% confidence interval [CI], 1.21-1.33) and higher risk of its components: ischemic heart disease (aHR, 1.38; 95% CI, 1.28-1.48), congestive heart failure (aHR, 1.32; 95% CI, 1.22-1.43), and stroke (aHR, 1.12; 95% CI, 1.02-1.23) but not cardiovascular mortality (aHR, 1.07; 95% CI, 0.98-1.18). The results remained robust in the sensitivity analyses.CONCLUSIONS: Compared with reference individuals, MC patients had a 27% higher risk of incident MACE, equal to 1 extra case of MACE for every 13 MC patients followed for 10 years.
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| 2. |
- Sun, Jiangwei, et al.
(author)
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Normal gastrointestinal mucosa at biopsy and subsequent cancer risk : nationwide population-based, sibling-controlled cohort study
- 2022
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In: BMC Cancer. - : BioMed Central. - 1471-2407. ; 22:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: While individuals with normal gastrointestinal (GI) mucosa on endoscopy have a lower risk of colorectal cancer, risks of other cancers remain unexplored.METHODS: Through Sweden's 28 pathology departments, we identified 415,092 individuals with a first GI biopsy with histologically normal mucosa during 1965-2016 and no prior cancer. These individuals were compared to 1,939,215 matched reference individuals from the general population. Follow-up began 6 months after biopsy, and incident cancer data were retrieved from the Swedish Cancer Register. Flexible parametric model was applied to estimate cumulative incidences and hazard ratios (HRs) for cancers. We also used full siblings (n = 441,534) as a secondary comparison group.RESULTS: During a median follow-up of 10.9 years, 40,935 individuals with normal mucosa (incidence rate: 82.74 per 10,000 person-years) and 177,350 reference individuals (incidence rate: 75.26) developed cancer. Restricting the data to individuals where follow-up revealed no cancer in the first 6 months, we still observed an increased risk of any cancer in those with a histologically normal mucosa (average HR = 1.07; 95%CI = 1.06-1.09). Although the HR for any and specific cancers decreased shortly after biopsy, we observed a long-term excess risk of any cancer, with an HR of 1.08 (95%CI = 1.05-1.12) and a cumulative incidence difference of 0.93% (95%CI = 0.61%-1.25%) at 30 years after biopsy. An elevated risk of gastric cancer, lung cancer, and hematological malignancy (including lymphoproliferative malignancy) was also observed at 20 or 30 years since biopsy. Sibling analyses confirmed the above findings.CONCLUSION: Individuals with a histologically normal mucosa at biopsy and where follow-up revealed no cancer in the first 6 months, may still be at increased risk of cancer, although excess risks are small.
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| 3. |
- Wang, Kai, et al.
(author)
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Association of inflammatory bowel disease in first-degree relatives with risk of colorectal cancer : A nationwide case-control study in Sweden
- 2023
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In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 152:11, s. 2303-2313
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Journal article (peer-reviewed)abstract
- This study aims to assess the association between inflammatory bowel disease (IBD) history in first-degree relatives (FDRs) and colorectal cancer (CRC) risk. We conducted a nationwide case-control study in Sweden among 69,659 CRC cases and 343,032 non-CRC controls matched on age, sex, birth year, and residence county. Through linkage of multi-generation register and the nationwide ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) cohort, we ascertained IBD diagnoses among parents, full siblings, and offspring of the index individuals. Odds ratios (ORs) of CRC associated with IBD family history were calculated using conditional logistic regression. 2.2% of both CRC cases (1,566/69,659) and controls (7,676/343,027) had ≥1 FDR with IBD history. After adjusting for family history of CRC, we observed no increased risk of CRC in FDRs of IBD patients (OR, 0.96; 95%CI, 0.91-1.02). The null association was consistent according to IBD subtype (Crohn's disease or ulcerative colitis), number of FDRs with IBD (1 or ≥2), age at first IBD diagnosis in FDRs (<18, 18-39, 40-59, or ≥60 years), maximum location/extent of IBD, or FDR relation (parent, sibling, or offspring). The null association remained for early-onset CRC (diagnosed at age <50 years). In conclusion, IBD history in FDRs was not associated with an increased risk of CRC. Our findings suggest that extra screening for CRC may not be needed in the offspring, siblings, or parents of IBD patients, and strengthen the theory that it is the actual inflammation or atypia of the colon in IBD patients that confers the increased CRC risk.
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| 4. |
- Axelrad, Jordan E., et al.
(author)
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Gastrointestinal Infection Increases Odds of Inflammatory Bowel Disease in a Nationwide Case-Control Study
- 2019
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In: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 17:7, s. 1311-1322
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: Gastrointestinal infections have been associated with later development of inflammatory bowel diseases (IBD). However, studies have produced conflicting results. We performed a nationwide case-control study in Sweden to determine whether gastroenteritis is associated with the development of Crohn's disease (CD) or ulcerative colitis (UC).METHODS: Using the Swedish National Patient Register, we identified 44,214 patients with IBD (26,450 with UC; 13,387 with CD; and 4377 with IBD-unclassified) from 2002 to 2014 and matched them with 436,507 individuals in the general population (control subjects). We then identified patients and control subjects with reported episodes of gastroenteritis (from 1964 to 2014) and type of pathogen associated. We collected medical and demographic data and used logistic regression to estimate odds ratios (ORs) for IBD associated with enteric infection.RESULTS: Of the patients with IBD, 3105 (7.0%) (1672 with UC, 1050 with CD, and 383 with IBD-unclassified) had a record of previous gastroenteritis compared with 17,685 control subjects (4.1%). IBD cases had higher odds for an antecedent episode of gastrointestinal infection (aOR, 1.64; 1.57-1.71), bacterial gastrointestinal infection (aOR, 2.02; 1.82-2.24), parasitic gastrointestinal infection (aOR, 1.55; 1.03-2.33), and viral gastrointestinal infection (aOR, 1.55; 1.34-1.79). Patients with UC had higher odds of previous infection with Salmonella, Escherichia coli, Campylobacter, or Clostridium difficile compared to control subjects. Patients with CD had higher odds of previous infection with Salmonella, Campylobacter, Yersinia enterocolitica, C difficile, amoeba, or norovirus compared to control subjects. Increasing numbers of gastroenteritis episodes were associated with increased odds of IBD, and a previous episode of gastroenteritis remained associated with odds for IBD more than 10 years later (aOR, 1.26; 1.19-1.33).CONCLUSIONS: In an analysis of the Swedish National Patient Register, we found previous episodes of gastroenteritis to increase odds of later development of IBD. Although we cannot formally exclude misclassification bias, enteric infections might induce microbial dysbiosis that contributes to the development of IBD in susceptible individuals.
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| 5. |
- Axelrad, Jordan, et al.
(author)
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Inflammatory Bowel Disease and Risk of Colorectal Polyps : A nationwide population-based cohort study from Sweden
- 2023
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In: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 17:9, s. 1395-1409
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Journal article (peer-reviewed)abstract
- BACKGROUND: Inflammatory bowel disease (IBD) has been linked to an increased risk of colorectal neoplasia. However, the types and risks of specific polyp types in IBD are less clear.METHODS: We identified 41,880 individuals with IBD [Crohn's disease (CD: n=12,850); Ulcerative colitis (UC): n=29,030)] from Sweden matched with 41,880 reference individuals. Using Cox regression, we calculated adjusted hazard ratios (aHRs) for neoplastic colorectal polyps (Tubular, Serrated/Sessile, Advanced and Villous) defined by histopathology codes.RESULTS: During follow-up, 1648 (3.9%) IBD patients and 1143 (2.7%) reference individuals had an incident neoplastic colorectal polyp, corresponding to an incidence rate of 46.1 and 34.2 per 10,000 person-years, respectively. This correlated to an aHR of 1.23 (95% CI 1.12-1.35) with the highest HRs seen for sessile serrated polyps (8.50, 95% CI 1.10-65.90) and traditional serrated adenomas (1.72, 95% CI 1.02-2.91). aHRs for colorectal polyps were particularly elevated in those diagnosed with IBD at a young age and after 10 years after diagnosis. Both absolute and relative risks of colorectal polyps were higher in UC than in CD (aHRs 1.31 vs. 1.06, respectively), with a 20-year cumulative risk differences of 4.4% in UC and 1.5% in CD, corresponding to one extra polyp in 23 patients with UC and one in 67 CD patients during the first 20 years after IBD diagnosis.CONCLUSIONS: In this nationwide population-based study, there was an increased risk of neoplastic colorectal polyps in IBD patients. Colonoscopic surveillance in IBD appears important, especially in UC and after 10 years of disease.
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| 6. |
- Bergman, David, et al.
(author)
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Microscopic Colitis and Risk Of Cancer-AA Population-Based Cohort Study
- 2021
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In: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 15:2, s. 212-221
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Journal article (peer-reviewed)abstract
- Background and Aims: The association between microscopic colitis [MC] and cancer risk is unclear. Large, population-based studies are lacking.Methods: We conducted a nationwide cohort study of 11 758 patients with incident MC [diagnosed 1990-2016 in Sweden], 50 828 matched reference individuals, and 11 614 siblings to MC patients. Data were obtained through Sweden's pathology departments and from the Swedish Cancer Register. Adjusted hazard ratios [aHRs] were calculated using Cox proportional hazards models.Results: At the end of follow-up [mean: 6.7 years], 1239 [10.5%] of MC patients had received a cancer diagnosis, compared with 4815 [9.5%] of reference individuals (aHR 1.08 [95% confidence interval1.02-1.16]). The risk of cancer was highest during the first year of follow up. The absolute excess risks for cancer at 5, 10, and 20 years after MC diagnosis were + 1.0% (95% confidence interval [C1]0.4%-1.6%), +1.5% [0.4%-2.6%], and + 3.7% [-2.3-9.6%], respectively, equivalent to one extra cancer event in every 55 individuals with MC followed for 10 years. MC was associated with an increased risk of lymphoma (aHR 1.43 [1.06-1.92]) and lung cancer (aHR 1.32 [1.04-1.68]) but with decreased risks of colorectal (aHR 0.52 [0.40-0.66]) and gastrointestinal cancers (aHR 0.72 [0.60-0.85]). We found no association with breast or bladder cancer. Using siblings as reference group to minimise the impact of shared genetic and early environmental factors, patients with MC were still at an increased risk of cancer (HR 1.20 [1.06-1.36]).Conclusions: This nationwide cohort study demonstrated an 8% increased risk of cancer in MC patients. The risk was highest during the first year of follow-up.
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| 7. |
- Burke, Kristin E., et al.
(author)
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Identification of Menopausal and Reproductive Risk Factors for Microscopic Colitis-Results From the Nurses' Health Study
- 2018
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In: Gastroenterology. - : Saunders Elsevier. - 0016-5085 .- 1528-0012. ; 155:6, s. 1764-1775
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: Microscopic colitis is a chronic inflammatory disorder of the colon primarily affecting postmenopausal women. However, the relation between hormonal determinants, including reproductive and menopausal factors, and risk of microscopic colitis has yet to be characterized.METHODS: We collected data from 227,766 women who participated in the Nurses' Health Study (NHS) and the NHSII without a baseline history of microscopic colitis. Reproductive and menopausal factors were assessed in 1988 in the NHS and 1989 in the NHSII and updated biennially. Cases of microscopic colitis were confirmed through review of pathology records. We used Cox proportional hazards modeling to estimate hazard ratios and 95% confidence intervals.RESULTS: Through 2014 in the NHS and 2015 in the NHSII, we confirmed 275 incident cases of microscopic colitis over 5,147,282 person-years. Compared with never use, current use of menopausal hormone therapy was associated with increased risk of microscopic colitis (multivariable-adjusted hazard ratio 2.64; 95% confidence interval 1.78-3.90). The risk increased with longer duration of use (P for trend < .0001) and decreased after discontinuation (P for trend = .002). The association did not differ according to disease subtype (P for heterogeneity = .34). Similarly, ever use of oral contraceptives was associated with increased risk of microscopic colitis (multivariable-adjusted hazard ratio 1.57; 95% confidence interval 1.16-2.13). There were no associations between age at menarche, parity, age at first birth, age at menopause, or menopause type and incident microscopic colitis.CONCLUSIONS: In 2 large prospective cohort studies, we observed an association between exogenous hormone use and incident microscopic colitis. Further studies are needed to determine the mechanisms underlying these associations.
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| 8. |
- Burke, Kristin E., et al.
(author)
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Microscopic colitis
- 2021
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In: Nature reviews. Disease primers. - : Nature Publishing Group. - 2056-676X. ; 7:1
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Research review (peer-reviewed)abstract
- Microscopic colitis (MC) is an inflammatory disease of the large intestine associated with urgent watery diarrhoea. MC may occur in people of all ages, although the disease primarily affects older women. Once believed to be rare, MC is now known to be a common cause of chronic watery diarrhoea in high-income countries, affecting 1 in 115 women and 1 in 286 men during their lifetime in Swedish population-based estimates. An inappropriate immune response to disturbances in the gut microenvironment is implicated in the pathogenesis of MC. Evidence also supports an underlying genetic basis for disease. The diagnosis of MC relies on clinical symptoms and microscopic assessment of colonic biopsy samples. MC is categorized histologically into collagenous colitis, lymphocytic colitis and their incomplete forms. The mainstay of treatment includes the use of budesonide, with or without adjunctive therapies, and withdrawal of offending drugs. Emerging studies suggest a role for biologicals and immunosuppressive therapies for the management of budesonide-refractory or budesonide-dependent disease. MC can have a substantial negative effect on patient quality of life. The outlook for MC includes a better understanding of the immune response, genetics and the microbiome in disease pathogenesis along with progress in disease management through robust clinical trials.
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| 9. |
- Burke, Kristin E., et al.
(author)
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Smoking is Associated with an Increased Risk of Microscopic Colitis : Results From Two Large Prospective Cohort Studies of US Women
- 2018
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In: Journal of Crohn's & Colitis. - : Crohn's & Colitis Foundation of Canada. - 1873-9946 .- 1876-4479. ; 12:5, s. 559-567
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Journal article (peer-reviewed)abstract
- Introduction: Long-term data on the influence of smoking on risk of microscopic colitis are limited. We therefore sought to examine and characterize the association between smoking and risk of incident microscopic colitis in two large prospective cohorts of women.Methods: We conducted a prospective study of 231,015 women enrolled in the Nurses' Health Study (NHS) and NHSII. Information regarding smoking, other lifestyle factors, and medications were collected biennially from 1976 to 2012 in NHS and 1989 to 2013 in NHSII. Incident cases of microscopic colitis were confirmed through physician medical record review. We used Cox proportional hazards modeling to examine the association between smoking and risk of microscopic colitis.Results: We documented 166 incident cases of microscopic colitis over 6,122,779 person-years of follow up. Compared to non-smokers, the multivariable-adjusted hazard ratio (HR) for microscopic colitis was 2.52 (95% CI 1.59 - 4.00) amongst current smokers and 1.54 (95% CI 1.09 - 2.17) amongst past smokers. The risk increased with higher pack-years of smoking (Ptrend = 0.001) and diminished following smoking cessation (Ptrend = 0.017). Current smoking appeared to be more strongly associated with risk of collagenous colitis (3.68; 95% CI 1.94 - 6.97) than lymphocytic colitis (HR 1.71; 95% CI 0.83 - 3.53).Conclusion: In two large prospective cohort studies, we observed an association between current smoking and risk of microscopic colitis. Risk of microscopic colitis appeared to increase with higher pack-years and diminish following smoking cessation. Future studies focused on characterizing the biologic mechanisms underlying these associations are warranted.
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| 10. |
- Chan, Simon S. M., et al.
(author)
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Obesity is Associated With Increased Risk of Crohn's disease, but not Ulcerative Colitis : A Pooled Analysis of Five Prospective Cohort Studies
- 2022
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In: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 20:5, s. 1048-1058
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Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: It is unclear whether obesity is associated with the development of inflammatory bowel disease despite compelling data from basic science studies. We therefore examined the association between obesity and risk of Crohn's disease (CD) and ulcerative colitis (UC).METHODS: We conducted pooled analyses of 5 prospective cohorts with validated anthropometric measurements for body mass index (BMI) and waist-hip ratio and other lifestyle factors. Diagnoses of CD and UC were confirmed through medical records or ascertained using validated definitions. We used Cox proportional hazards modeling to calculate pooled multivariable-adjusted HRs (aHRs) and 95% confidence intervals (CIs).RESULTS: Among 601,009 participants (age range, 18-98 years) with 10,110,018 person-years of follow-up, we confirmed 563 incident cases of CD and 1047 incident cases of UC. Obesity (baseline BMI >= 30 kg/m(2)) was associated with an increased risk of CD (pooled aHR, 1.34; 95% CI, 1.05-1.71, I-2 = 0%) compared with normal BMI (18.5 to <25 kg/m(2)). Each 5 kg/m(2) increment in baseline BMI was associated with a 16% increase in risk of CD (pooled aHR, 1.16; 95% CI, 1.05-1.22; I-2 = 0%). Similarly, with each 5 kg/m(2) increment in early adulthood BMI (age, 18-20 years), there was a 22% increase in risk of CD (pooled aHR, 1.22; 95% CI, 1.05-1.40; I-2 = 13.6%). An increase in waist-hip ratio was associated with an increased risk of CD that did not reach statistical significance (pooled aHR across quartiles, 1.08; 95% CI, 0.97-1.19; I-2 = 0%). No associations were observed between measures of obesity and risk of UC.CONCLUSIONS: In an adult population, obesity as measured by BMI was associated with an increased risk of older-onset CD but not UC.
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