| 1. |
- Gunaltay, Sezin, 1986-, et al.
(författare)
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Oligoclonal T-cell Receptor Repertoire in Colonic Biopsies of Patients with Microscopic Colitis and Ulcerative Colitis
- 2017
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Ingår i: Inflammatory Bowel Diseases. - : Lippincott Williams & Wilkins. - 1078-0998 .- 1536-4844. ; 23:6, s. 932-945
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Tidskriftsartikel (refereegranskat)abstract
- Background: Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a type of variation of inflammatory bowel diseases. Local T-cell infiltration in the mucosa plays a major role in MC immunopathology.Methods: To understand diversity and clonality of infiltrating T cells, we analyzed the T-cell receptor beta (TCR beta) chains in colonic biopsies of MC, ulcerative colitis (UC), and their remission counterparts (CC/LC-HR [histological remission] or UC-R [remission]) compared with patients with non-inflamed colons using next-generation sequencing.Results: Compared with controls and patients with CC, patients with LC had significantly lower diversity with significantly lower evenness and richness in TCRVb-Jb gene segments. Similarly, patients with LC-HR had lower diversity because of significantly lower TCRVb-Jb clone richness. Patients with UC and UC-R showed significantly higher diversity and richness. Univariate and multivariate analyses were performed to identify TCRVb-Jb gene segments differentiating disease types from controls or their remission counterparts. Patients with LC were discriminated from controls by 12 clones and from patients with CC by 8 clones. Neither univariate nor multivariate analyses showed significance for patients with CC or CC-HR compared with controls. Patients with UC and UC-R had 16 and 14 discriminating clones, respectively, compared with controls.Conclusions: Altogether, patients with MC and UC showed an oligoclonal TCRb distribution. TCRVb-Jb clone types and their diversity were distinctive between patients with CC and LC, as well as for patients with UC, suggesting different pathophysiological mechanisms according to disease type and stage. This study suggests that CC and LC are different entities because of differences in immunoregulatory responses, as mirrored by their T-cell repertoire.
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| 3. |
- Henriksson, Ida, 1980-, et al.
(författare)
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Clinical outcomes and sick leave in relation to UDCA treatment in Swedish patients with primary biliary cholangitis
- 2023
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 58:1, s. 70-75
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Primary biliary cholangitis (PBC) is an autoimmune liver disease that may progress into liver cirrhosis. Ursodeoxycholic acid (UDCA) is known to prevent or delay the disease progression, but little is known about work incapacity in PBC patients. We aimed to compare clinical outcomes (transplantation-free survival; cirrhosis development) and sick leave in patients with PBC with and without UDCA therapy. Methods The medical records of 526 patients with PBC diagnosed from 2004 to 2016 were reviewed retrospectively. Sick leave data retrieved from the Swedish Social Insurance Agency were analysed for a sub-cohort of patients and matched controls. Cox regression was used for analysis of clinical outcomes. Logistic and conditional logistic regressions were used for sick leave analysis. Results A total of 10.6% of patients died and 3.4% received liver transplantation over a median follow-up time of 5.7 years. UDCA-untreated patients (HR 3.62 (95%CI 2.02-6.49)) and UDCA non-responders (HR 3.78 (95% CI 1.87-7.66)) had higher mortality or transplantation rates than UDCA responders. Patients with PBC had higher odds of sick leave (OR 2.50; 95% CI 1.69-3.70) than matched controls. Untreated patients were more likely to be on sick leave (OR 3.22; 95% CI 1.12-9.25) two years after diagnosis than UDCA responders. Conclusion Both untreated patients and UDCA non-responders had lower liver transplantation-free survival rates than UDCA responders. Patients with PBC were more likely to be on sick leave compared to matched controls from the general population.
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| 4. |
- Wickbom, Anna, 1970-, et al.
(författare)
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Stable Incidence of Collagenous Colitis and Lymphocytic Colitis in Orebro, Sweden, 1999-2008 : A Continuous Epidemiologic Study
- 2013
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Ingår i: Inflammatory Bowel Diseases. - 1078-0998 .- 1536-4844. ; 19:11, s. 2387-2393
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Tidskriftsartikel (refereegranskat)abstract
- Background: The incidence of microscopic colitis (MC) has increased in several centers, but long-term epidemiologic data are missing. We report an epidemiologic study of collagenous colitis (CC) and lymphocytic colitis (LC) during 1999-2008, as a follow-up of our previous studies 1984-1998.Methods: Population-based study of residents of the catchment area of the hospital, with a new diagnosis of MC between 1999 and 2008. Patients were identified by diagnosis registers of the Departments of Medicine and Pathology. Medical files were reviewed, and colonic biopsies were reevaluated.Results: Collagenous colitis was diagnosed in 96 patients (75 females) and LC in 90 patients (74 females). The mean annual age-standardized incidence (per 100,000 inhabitants) was MC 10.2 (95% confidence interval: 8.7-11.7), CC 5.2 (4.2-6.3), and LC 5.0 (4.0-6.0). Age-specific incidence showed a peak in females older than 70 years. Prevalence (per 100,000 inhabitants) on December 31, 2008, was MC 123 (107.6-140.0), CC 67.7 (56.4-80.6), and LC 55.3 (45.2-67.1). A comparison of current study period with 1993-1998 showed unchanged mean incidence of MC, but a 2-fold increase in women older than 60 years with LC (standardized rate ratios 2.2, [1.2-3.7]) and increased female to male ratio (4.6:1 versus 2.1:1; P = 0.02) in LC.Conclusions: After an initial rise during 1980s and early 1990s, annual incidence of CC and LC has been stable during the last 15 years around 5/100,000 inhabitants for each disorder. The increasing incidence in older women with LC may be related to an increasing proportion of older individuals in the background population and increased colonoscopy frequency in elderly.
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| 5. |
- Zhulina, Yaroslava, 1973-, et al.
(författare)
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Subclinical Inflammation with Increased Neutrophil Activity in Healthy Twin Siblings Reflect Environmental Influence in the Pathogenesis of Inflammatory Bowel Disease
- 2013
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Ingår i: Inflammatory Bowel Diseases. - Philadelphia, USA : Lippincott Williams & Wilkins. - 1078-0998 .- 1536-4844. ; 19:8, s. 1725-1731
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Tidskriftsartikel (refereegranskat)abstract
- Background: The mechanisms behind increased fecal calprotectin (FC) in healthy relatives of patients with inflammatory bowel disease (IBD) are unknown. Our aims were to explore if there is a subclinical inflammation with increased neutrophil activity in healthy twin siblings in discordant twin pairs with IBD and to assess the influence of genetics in this context.Methods: Nuclear factor kappa B (NF-B) and neutrophil activity, based on myeloperoxidase (MPO) and FC, were analyzed in healthy twin siblings in discordant twin pairs with IBD and compared with healthy controls. NF-B and MPO were assessed by immunohistochemistry and FC by enzyme-linked immunosorbent assay.Results: In total, 33 of 34 healthy twin siblings were histologically normal. Increased NF-B was more often observed in healthy twin siblings in discordant twin pairs with Crohn's disease (13/18 [73%]) and with ulcerative colitis (12/16 [75%]) than in healthy controls (8/45 [18%]). MPO was more often increased in healthy twin siblings in discordant pairs with Crohn's disease (12/18 [67%]) than in healthy controls (11/45 [24%]) and FC more often in healthy twin siblings in discordant pairs with ulcerative colitis (14/21 [67%]) than in healthy controls (6/31 [19%]). Interestingly, the observed differences remained when healthy monozygotic and dizygotic twin siblings were analyzed separately.Conclusions:We observed increased NF-B, MPO, and FC in healthy twins in both monozygotic and dizygotic discordant pairs with IBD. These novel findings speak for an ongoing subclinical inflammation with increased neutrophil activity in healthy first-degree relatives.
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| 6. |
- Amcoff, Karin, 1975-, et al.
(författare)
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Concordance in Anti-OmpC and Anti-I2 Indicate the Influence of Genetic Predisposition : Results of a European Study of Twins with Crohn's Disease
- 2016
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Ingår i: Journal of Crohn's & Colitis. - Oxford, United Kingdom : Oxford University Press. - 1873-9946 .- 1876-4479. ; 10:6, s. 695-702
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: An adaptive immunological response to microbial antigens has been observed in Crohn's disease (CD). Intriguingly, this serological response precedes the diagnosis in some patients and has also been observed in healthy relatives. We aimed to determine whether genetic factors are implicated in this response in a CD twin cohort.Methods: In total, 82 twin pairs (Leuven n = 13, Maastricht n = 8, Örebro n = 61) took part: 81 pairs with CD (concordant monozygotic n = 16, discordant monozygotic n = 22, concordant dizygotic n = 3, discordant dizygotic n = 40) and 1 monozygotic pair with both CD and ulcerative colitis. Serology for Pseudomonas fluorescens-related protein (anti-I2), Escherichia coli outer membrane porin C (anti-OmpC), CBir1flagellin (anti-CBir1) and antibodies to oligomannan (anti-Saccharomyces cerevisiae antibody [ASCA]) was determined by standardized enzyme-linked immunoassay.Results: All markers were more often present in CD twins than in their healthy twin siblings. Using the intraclass correlation coefficient (ICC), agreements in concentrations of anti-OmpC and anti-I2 were observed in discordant monozygotic but not in discordant dizygotic twin pairs with CD (anti-OmpC, ICC 0.80 and -0.02, respectively) and (anti-I2, ICC 0.56 and 0.05, respectively). In contrast, no agreements were found in anti-CBir, immunoglobulin (Ig) G ASCA and ASCA IgA.Conclusions: We show that anti-I2 and anti-CBir1 statuses have specificity for CD and confirm previous reported specificities for anti-OmpC and ASCA. Based on quantitative analyses and observed ICCs, genetics seems to predispose to the anti-OmpC and anti-I2 response but less to ASCA and anti-CBir1 responses.
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| 7. |
- Andersson, Emilia, et al.
(författare)
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The effectiveness of the colorectal cancer referral pathway : identification of colorectal cancer in a Swedish region
- 2021
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 56:5, s. 552-558
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: To shorten the time for diagnosis of suspected colorectal cancer (CRC), a standardized colorectal cancer referral pathway (CCRP) was introduced in Sweden in September 2016. However, the effects of the CCRP are still uncertain, and CRC is also found in patients undergoing a routine colonoscopy.Objective: To identify all CRC-cases in the Region orebro County and to investigate via which diagnostic pathway they were diagnosed. Furthermore, to investigate the reasons for and possible effect of not being included in the CCRP for cases found via colonoscopy.Methods: Review of medical records of patients with CRC referred to the department of surgery in the Region orebro County in 2016-2018 (n = 459).Results: In CRC-cases found through colonoscopy (n = 347), 37.5% were diagnosed via a routine waiting list and 62.5% within the CCRP. No difference in tumor stage or tumor grade was found between the two groups. The non-CCRP showed a longer time to diagnosis than the CCRP group (21.5 days, IQR 7-43 vs. 13 days, IQR 8-17 (p < .001), respectively). Non-rectal cancer was more common in the non-CCRP group (81.5% vs. 57.6%, p < .001). The non-CCRP group had lower median Hb-value (106, IQR 87-129 vs. 117, IQR 101-136, p = .001). 85% of the non-CCRP group was found to meet one or more CCRP referral criteria, with bleeding anemia being the dominant criterion to meet.Conclusion: The CCRP did not appear to improve prognostic outcomes for CRC-patients.ClinicalTrials.gov Identifier: NCT04585516
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| 8. |
- Bednarska, Olga, et al.
(författare)
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The Effectiveness and Tolerability of a Very Low-Volume Bowel Preparation for Colonoscopy Compared to Low and High-Volume Polyethylene Glycol-Solutions in the Real-Life Setting
- 2022
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Ingår i: Diagnostics. - Basel, Switzerland : MDPI. - 2075-4418. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Adequate bowel cleansing is essential for high-quality colonoscopy. Recently, a new very low-volume 1 litre (1L) polyethylene glycol (PEG) plus ascorbate solution (ASC) has been introduced. Our aims were to assess the effectiveness and tolerability of this product compared to low-volume 2L PEG-ASC and high-volume 4L PEG solutions, in a real-life setting. In six endoscopy units in Sweden, outpatients undergoing colonoscopy were either prescribed solutions according to local routines, or the very low-volume solution in split dose regimen. Bowel cleansing effectiveness and patient experience was assessed using the Boston Bowel preparation scale (BBPS) and a patient questionnaire. A total of 1098 patients (mean age 58 years, 52% women) were included. All subsegment and the total BBPS scores were significantly greater for 1L PEG-ASC in comparison to other solutions (p < 0.05 for 1L PEG-ASC and 4L PEG for transverse and left colon, otherwise p < 0.001). Nausea was more frequent with 1L PEG-ASC compared to 2L PEG-ASC (p < 0.001) and vomiting were more often reported compared to both other solutions (p < 0.01 and p < 0.05 for 2L PEG-ASC and 4L PEG, respectively). Smell, taste, and total experience was better for 1L PEG-ASC compared to 4L PEG (p < 0.001), and similar compared to the 2L PEG-ASC. In conclusion, 1L PEG-ASC leads to better bowel cleansing compared to 2L PEG-ASC or 4L PEG products, with similar or greater patient satisfaction.
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| 9. |
- Bergquist, Annika, et al.
(författare)
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Impact on follow-up strategies in patients with primary sclerosing cholangitis
- 2023
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Ingår i: Liver international (Print). - Chichester, United Kingdom : Wiley-Blackwell Publishing Inc.. - 1478-3223 .- 1478-3231. ; 43:1, s. 127-138
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Evidence for the benefit of scheduled imaging for early detection of hepatobiliary malignancies in primary sclerosing cholangitis (PSC) is limited. We aimed to compare different follow-up strategies in PSC with the hypothesis that regular imaging improves survival.METHODS: We collected retrospective data from 2,975 PSC patients from 27 centers. Patients were followed from the start of scheduled imaging or in case of clinical follow-up from January 1, 2000, until death or last clinical follow-up alive. The primary endpoint was all-cause mortality.RESULTS: A broad variety of different follow-up strategies were reported. All except one center used regular imaging, ultrasound (US) and/or magnetic resonance imaging (MRI). Two centers used scheduled ERCP in addition to imaging for surveillance purposes. The overall HR (CI95%) for death, adjusted for sex, age and start year of follow-up, were 0.61 (0.47-0.80) for scheduled imaging with and without ERCP; 0.64 (0.48-0.86) for US/MRI and 0.53 (0.37-0.75) for follow-up strategies including scheduled ERCP. The lower risk of death remained for scheduled imaging with and without ERCP after adjustment for cholangiocarcinoma (CCA) or high-grade dysplasia as a time-dependent covariate, HR 0.57 (0.44-0.75). Hepatobiliary malignancy was diagnosed in 175 (5.9%) of the patients at 7.9 years follow-up. Asymptomatic patients (25%) with CCA had better survival if scheduled imaging had been performed.CONCLUSIONS: Follow-up strategies vary considerably across centers. Scheduled imaging was associated with improved survival. Multiple factors may contribute to this result including early tumor detection and increased endoscopic treatment of asymptomatic benign biliary strictures.
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| 10. |
- Bergquist, Annika M., et al.
(författare)
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Hepatobiliary malignancy surveillance strategies in primary sclerosing cholangitis associate with reduced mortality
- 2021
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 75:Suppl. 2, s. S227-S228
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: Patients with primary sclerosing cholangitis (PSC) are at increased risk for hepatobiliary malignancies, especially cholangiocarcinoma. Although many recommend surveillance for malignancy in PSC, different strategies are used by various centers and countries. We aimed to evaluate different surveillance strategies and their effectiveness in PSC with the hypothesis that surveillance imaging improves survival.Method: We queried centers about surveillance practices and retrospectively collected imaging surveillance data for hepatobiliary cancer in 2, 975 patients with PSC from 28 centers within the International PSC Study Group (IPSCSG). Surveillance strategies were grouped in (i) non-surveillance (no imaging in asymptomatic patients), (ii) magnetic resonance imaging (MRI) and/or ultrasound (US) surveillance (regular imaging regardless of symptoms/labs) and (iii) surveillance including endoscopic retrograde cholangiopancreatography (ERCP)-based (imaging and/or ERCP regardless of symptoms/labs). The primary end point was all-cause mortality. Cox-proportional hazard regression models were used to estimate hazard ratios (HRs).Results: 65.6% (1953/2975) of patients were male, mean age (SD) at diagnosis of PSC was 35.6 (14.2) years, with concomitant IBD in 71.5% (2127/2973). Hepatobiliary malignancy was found in 175 (5.9%) patients at 7.9 years of follow-up (Figure). Surveillance strategies differed significantly between centers. Of patients undergoing surveillance, 83% were subjected to MRI/MRCP, 49% to US and 28% to ERCP. Deaths were more frequent in the non-surveillance group 23.4% (82/350) than in the surveillance group 8.3% (218/2625). Mortality rate (95% CI) per 1000 person-years was 23.1 (18.1–28.1) inthe non-surveillance group (n = 350), 12.5 (10.6–14.5) in imaging surveillance with MRI and/or US (n = 1897) and 8.4 (6.3–10.5) in surveillance that included ERCP (n = 728). The risk of dying wasr educed in patients undergoing any type of surveillance (HR 0.53; 95% CI: 0.41–0.68) and the reduced risk remained after adjusting for sex, age and start year of follow-up (HR 0.61; 95% CI: 0.47–0.80).Conclusion: A broad variety of surveillance strategies across centers are used. Regular sur veillance for hepatobiliary malignancy in patients with PSC is associated with improved survival.
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