| 1. |
- Mårild, Karl, 1982, et al.
(författare)
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Histological remission in inflammatory bowel disease and female fertility : A nationwide study
- 2024
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Ingår i: Gastroenterology. - : American Gastroenterology Association Institute. - 0016-5085 .- 1528-0012. ; 166:5, s. 802-814.e18
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is linked to reduced female fertility, but it is unclear how fertility rates vary by histological disease activity.METHODS: Nationwide IBD cohort of Swedish women aged 15-44 years. We examined fertility rates during periods with vs. without histological inflammation (n=21,046; follow-up: 1990-2016) and during periods with vs. without clinical activity (IBD-related hospitalization, surgery, or treatment escalation) (n=24,995; follow-up: 2006-2020). Accounting for socio-demographics and comorbidities, we used Poisson regression to estimate adjusted fertility rate ratios (aFRRs) for live-births conceived during 12-month-periods of histological inflammation (vs. histological remission) and 3-month-periods of clinically active IBD (vs. quiescent IBD).RESULTS: During periods with vs. without histological inflammation, there were 6.35 (95%CI=5.98-6.73) and 7.09 (95%CI=6.48-7.70) live-births conceived per 100 person-years of follow-up, respectively, or one fewer child per fourteen women with 10 years of histological inflammation (aFRR=0.90; 95%CI=0.81-1.00). In women with histological inflammation fertility was similarly reduced in ulcerative colitis (UC, aFRR=0.89 [95%CI=0.78-1.02]) and Crohn's disease (CD, aFRR=0.86 [95%CI=0.72-1.04]). Clinical IBD activity was associated with an aFRR of 0.76 (95%CI=0.72-0.79) or one fewer child per six women with 10 years of clinical activity. Fertility was reduced in clinically active UC (aFRR=0.75 [95%CI=0.70-0.81]) and CD (aFRR=0.76 [95%CI=0.70-0.82]). Finally, also among women with clinically quiescent IBD, histological inflammation (vs. histological remission) was associated with reduced fertility (aFRR=0.85 [95%CI=0.73-0.98]).CONCLUSIONS: An association between histological and clinical activity and reduced female fertility in CD and UC was found. Notably, histological inflammation was linked to reduced fertility also in women with clinically quiescent IBD.
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| 2. |
- Choung, Rok Seon, et al.
(författare)
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Community-Based Study of Celiac Disease Autoimmunity Progression in Adults
- 2020
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Ingår i: Gastroenterology. - : Elsevier BV. - 1528-0012 .- 0016-5085. ; 158:1, s. 151-159
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Celiac disease can develop at any age, but outcomes of adults with positive results from serologic tests for tissue transglutaminase antibodies (tTGA) without endoscopic determination of celiac disease (called celiac autoimmunity) have not been thoroughly evaluated. We investigated the proportion of adults with celiac autoimmunity at a community medical center and their progression to celiac disease. Methods: We analyzed waste blood samples from a community clinic from 15,551 adults for tTGA and, if titer results were above 2 U/mL, for endomysial antibody. The blood samples had been collected at 2 time points (median interval, 8.8 years) from 2006 through 2017. We collected data from the clinic on diagnoses of celiac disease based on duodenal biopsy analysis. Results: Of the serum samples collected at the first time point, 15,398 had negative results for tTGA, and 153 had positive results for tTGA (>4 U/mL). Based on medical records, 6 individuals received a diagnosis of celiac disease, for a cumulative incidence of celiac disease diagnosis of 0.06% (95% confidence interval, 0.01–0.11). Forty-nine (0.32%) individuals with a negative result from the first serologic test for tTGA had a positive result from the second test. Among the 153 adults who were tTGA positive at the first time point, 31 (20%) had a subsequent diagnosis of celiac disease, 81 (53%) remained positive for tTGA without a clinical diagnosis of celiac disease, and 41 (27%) had negative test results for tTGA at the second time point. Higher initial tTGA titers, female sex, and a history of hypothyroidism and autoimmune disease were associated with increased risks of subsequent diagnosis of celiac disease. Interestingly, adults whose first blood sample had a positive test result but second blood sample had a negative result for tTGA were older, had lower-than-average initial tTGA titer results, and had a higher mean body mass index than adults whose blood samples were positive for tTGA at both time points and adults later diagnosed with celiac disease. Conclusions: In an analysis of serum samples collected from a community clinic an average of 8.8 years apart, we found that fewer than 1% of adults with negative results from an initial test for tTGA have a positive result on a second test. Of adults with positive results from the test for tTGA, only 20% are later diagnosed with celiac disease; the remaining individuals maintain persistent increases in tTGA without diagnoses of celiac disease or have negative results from second tests.
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| 3. |
- Olén, Ola, et al.
(författare)
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Increased Mortality of Patients With Childhood- Onset Inflammatory Bowel Diseases, Compared With the General Population
- 2019
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Ingår i: Gastroenterology. - : Saunders Elsevier. - 0016-5085 .- 1528-0012. ; 156:3, s. 614-622
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Childhood-onset inflammatory bowel disease (IBD) is believed to be a more severe disease than adultonset IBD, but there is little information on all-cause and causespecific mortality in patients with childhood-onset IBD. We performed a population-based cohort study, with 50 years of follow-up, to estimate absolute and relative risks for overall and cause-specific mortality in patients with childhood-onset IBD, during childhood and adulthood.METHODS: We identified children with a diagnosis of IBD (younger than 18 years) in the Swedish nationwide health registers (1964-2014; n = 9442) and individuals from the general population matched for sex, age, calendar year, and place of residence (reference group; n = 93,180). Hazard ratios (HR) for death were estimated using Cox regression separately in patients with ulcerative colitis (n = 4671), Crohn's disease (n = 3780), and IBD unclassified (n = 991). HRs were compared among calendar periods.RESULTS: During 138,690 person-years of follow-up, 294 deaths (2.1/1000 person-years) occurred among the patients with IBD compared with 940 deaths in the reference group (0.7/1000 person-years; adjusted HR, 3.2; 95% confidence interval [CI] 2.8-3.7). Mean age at end of follow-up was 30 years. HRs were increased for patients with ulcerative colitis 4.0, 95% CI 3.4-4.7; Crohn's disease 2.3, 95% CI 1.8-3.0; and IBD unclassified 2.0, 95% CI 1.2-3.4. Among patients younger than 18 years, there were 27 deaths from IBD 4.9, 95% CI 3.0-7.7. Among young adults with IBD, we found no evidence that HRs for death decreased from 1964 through 2014 (P = .90).CONCLUSIONS: Children with IBD have a 3-fold increase in risk of death when followed through adulthood. The relative risk for death has not decreased with development of new drugs for treatment of IBD.
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| 4. |
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| 5. |
- Aziz, Q, et al.
(författare)
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Identification of human brain loci processing esophageal sensation using positron emission tomography
- 1997
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Ingår i: Gastroenterology. - 0016-5085 .- 1528-0012. ; 113:1, s. 50-59
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS:Brain loci that process human esophageal sensation remain unidentified. The aim of this study was to identify the brain loci that process nonpainful and painful human esophageal sensation.METHODS:In 8 healthy subjects (7 men; age range, 24-47 years), distal esophageal stimulation was performed by repeatedly inflating a balloon at volumes that produced either no sensation, definite sensation, or pain. Two positron emission tomography scans were performed for each sensation using H2(15)O. Magnetic resonance brain scans were also performed in each subject, and the positron emission tomography data were coregistered with magnetic resonance scans. Analysis of covariance-corrected t images showing the contrasts definite sensation-baseline, pain-baseline, and pain-definite sensation were created.RESULTS:Nonpainful stimulation elicited bilateral activations along the central sulcus, insular cortex, and frontal/parietal operculum (P < 0.01). Painful stimulation produced more intense activations of the same areas and additional activation of the right anterior insular cortex and the anterior cingulate gyrus. Multiple areas of decreased activation were also observed; prominent among these was the right prefrontal cortex, which was inhibited during both nonpainful and painful stimulation.CONCLUSIONS:Esophageal sensation activates bilaterally the insula, primary somatosensory cortex, and operculum. The right anterior insular cortex and anterior cingulate gyrus process esophageal pain.
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| 6. |
- Halfvarson, Jonas, 1970-, et al.
(författare)
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Inflammatory bowel disease in a Swedish twin cohort : a long-term follow-up of concordance and clinical characteristics
- 2003
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 124:7, s. 1767-1773
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: In 1988, we reported the first twin study in inflammatory bowel disease. The aim of the current study was to follow up these twins regarding new cases of inflammatory bowel disease and Crohn's disease characteristics using the Vienna classification.METHODS: The official Swedish population register and the cause of death register were used to search for the twins. All living patients were interviewed.RESULTS: Three monozygotic twins earlier classified as healthy had been diagnosed with inflammatory bowel disease (ulcerative colitis, n = 2; Crohn's disease, n = 1). Retrospectively, all 3 were symptomatic at the original survey. This changed the pair concordance in monozygotic twins from 6.3% to 18.8% in ulcerative colitis and from 44.4% to 50.0% in Crohn's disease. A high degree of concordance regarding age at diagnosis, disease location at diagnosis and during the course, and disease behavior was found in concordant monozygotic twin pairs with Crohn's disease. Seven of 9 pairs were identical in 3 or more of these disease characteristics compared with an expected number of 1.5 (P = 0.000076).CONCLUSIONS: This study confirms that the genetic influence is stronger in Crohn's disease than in ulcerative colitis. A remarkable phenotype similarity within concordant pairs with Crohn's disease was found using the Vienna classification.
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| 7. |
- Keefer, Laurie, et al.
(författare)
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Centrally Mediated Disorders of Gastrointestinal Pain.
- 2016
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Ingår i: Gastroenterology. - : Elsevier BV. - 1528-0012 .- 0016-5085. ; 150:6, s. 1408-1419
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Tidskriftsartikel (refereegranskat)abstract
- Centrally Mediated Abdominal Pain Syndrome (CAPS), formerly known as Functional Abdominal Pain Syndrome, can be distinguished from other functional GI disorders by its strong central component and relative independence from motility disturbances. CAPS is a result of central sensitization with disinhibition of pain signals rather than increased peripheral afferent excitability. A newly described condition, Narcotic Bowel Syndrome (NBS)/Opioid-Induced GI Hyperalgesia, is characterized by the paradoxical development of or increases in abdominal pain associated with continuous or increasing dosages of opioids. Patients only have relief when opioids are withdrawn. We define both conditions in the context of epidemiology, pathophysiology, clinical evaluation and treatment, emphasizing the importance of a physician-patient relationship in all aspects of care.
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| 8. |
- Bonfiglio, F., et al.
(författare)
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Female-Specific Association Between Variants on Chromosome 9 and Self-Reported Diagnosis of Irritable Bowel Syndrome
- 2018
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 155:1, s. 168-179
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Genetic factors are believed to affect risk for irritable bowel syndrome (IBS), but there have been no sufficiently powered and adequately sized studies. To identify DNA variants associated with IBS risk, we performed a genome-wide association study (GWAS) of the large UK Biobank population-based cohort, which includes genotype and health data from 500,000 participants. METHODS: We studied 7,287,191 high-quality single nucleotide polymorphisms in individuals who self-reported a doctor's diagnosis of IBS (cases; n = 9576) compared to the remainder of the cohort (controls; n = 336,499) (mean age of study subjects, 40-69 years). Genome-wide significant findings were further investigated in 2045 patients with IBS from tertiary centers and 7955 population controls from Europe and the United States, and a small general population sample from Sweden (n = 249). Functional annotation of GWAS results was carried out by integrating data from multiple biorepositories to obtain biological insights from the observed associations. RESULTS: We identified a genome-wide significant association on chromosome 9q31.2 (single nucleotide polymorphism rs10512344; P = 3.57 x 10(-8)) in a region previously linked to age at menarche, and 13 additional loci of suggestive significance (P < 5.0 x 10(-6)). Sex-stratified analyses revealed that the variants at 9q31.2 affect risk of IBS in women only (P = 4.29 x 10(-10) in UK Biobank) and also associate with constipation-predominant IBS in women (P = .015 in the tertiary cohort) and harder stools in women (P = .0012 in the population-based sample). Functional annotation of the 9q31.2 locus identified 8 candidate genes, including the elongator complex protein 1 gene (ELP1 or IKB-KAP), which is mutated in patients with familial dysautonomia. CONCLUSIONS: In a sufficiently powered GWAS of IBS, we associated variants at the locus 9q31.2 with risk of IBS in women. This observation may provide additional rationale for investigating the role of sex hormones and autonomic dysfunction in IBS.
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| 9. |
- Archambault, Alexi N., et al.
(författare)
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Cumulative Burden of Colorectal Cancer Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer
- 2020
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 158:5, s. 1274-1286.e12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC.METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants.RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 x 10(-5)). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings.CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.
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