| 1. |
- Brusselaers, Nele, et al.
(författare)
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Hospital and surgical volume in relation to long-term survival after oesophagectomy : systematic review and meta-analysis
- 2014
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Ingår i: Gut. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1468-3288 .- 0017-5749.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Centralisation of healthcare, especially for advanced cancer surgery, has been a matter of debate. Clear short-term mortality benefits have been described for oesophageal cancer surgery conducted at high-volume hospitals and by high-volume surgeons. OBJECTIVE: To clarify the association between hospital volume, surgeon volume and hospital type in relation to long-term survival after oesophagectomy for cancer, by a meta-analysis. DESIGN: The systematic literature search included PubMed, Web of Science, Cochrane library, EMBASE and Science Citation Index, for the period 1990-2013. Eligible articles were those which reported survival (time to death) as HRs after oesophagectomy for cancer by hospital volume, surgeon volume or hospital type. Fully adjusted HRs for the longest follow-up were the main outcomes. Results were pooled by a meta-analysis, and reported as HRs and 95% CIs. RESULTS: Sixteen studies from seven countries met the inclusion criteria. These studies reported hospital volume (N=13), surgeon volume (N=4) or hospital type (N=4). A survival benefit was found for high-volume hospitals (HR=0.82, 95% CI 0.75 to 0.90), and possibly also, for high-volume surgeons (HR=0.87, 95% CI 0.74 to 1.02) compared with their low-volume counterparts. No association with survival remained for hospital volume after adjustment for surgeon volume (HR=1.01, 95% CI 0.97 to 1.06; N=2), while a survival benefit was found in favour of high-volume surgeons after adjustment for hospital volume (HR=0.91, 95% CI 0.85 to 0.98; N=2). CONCLUSIONS: This meta-analysis demonstrated better long-term survival (even after excluding early deaths) after oesophagectomy with high-volume surgery, and surgeon volume might be more important than hospital volume. These findings support centralisation with fewer surgeons working at large centres. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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| 2. |
- Doorakkers, Eva, et al.
(författare)
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Helicobacter pylori eradication treatment and the risk of gastric adenocarcinoma in a Western population
- 2018
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Ingår i: Gut. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0017-5749 .- 1468-3288.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- OBJECTIVE: Gastric infection with Helicobacter pylori is a strong risk factor for non-cardia gastric adenocarcinoma. The aim of this study was to assess whether the risk of gastric adenocarcinoma and non-cardia gastric adenocarcinoma decreases after eradication treatment for H. pylori in a Western population. DESIGN: This was a nationwide, population-based cohort study in Sweden in 2005-2012. Data from the Swedish Prescribed Drug Registry provided information on H. pylori eradication treatment, whereas information concerning newly developed gastric adenocarcinoma was retrieved from the Swedish Cancer Registry. The risk of gastric adenocarcinoma and non-cardia gastric adenocarcinoma in individuals who had received H. pylori eradication treatment was compared with the background population of the corresponding age, sex and calendar year distribution, yielding standardised incidence ratios (SIRs) with 95% CIs. RESULTS: During the follow-up of 95 176 individuals who had received eradication treatment (351 018 person-years at risk), 75 (0.1%) developed gastric adenocarcinoma and 69 (0.1%) developed non-cardia gastric adenocarcinoma. The risk of gastric adenocarcinoma decreased over time after eradication treatment to levels below that of the corresponding background population. The SIRs were 8.65 (95% CI 6.37 to 11.46) for 1-3 years, 2.02 (95% CI 1.25 to 3.09) for 3-5 years and 0.31 (95% CI 0.11 to 0.67) for 5-7.5 years after eradication treatment. When restricted to non-cardia adenocarcinoma, the corresponding SIRs were 10.74 (95% CI 7.77 to 14.46), 2.67 (95% CI 1.63 to 4.13) and 0.43 (95% CI 0.16 to 0.93). CONCLUSION: Eradication treatment for H. pylori seems to counteract the development of gastric adenocarcinoma and non-cardia gastric adenocarcinoma in this Western population.
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| 3. |
- Dunlop, Malcolm G, et al.
(författare)
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Cumulative impact of 10 common genetic variants on colorectal cancer risk in 42,333 individuals from eight populations
- 2012
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Ingår i: Gut. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1468-3288 .- 0017-5749.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Colorectal cancer (CRC) has a substantial heritable component. Common genetic variation has been shown to contribute to CRC risk. A study was conducted in a large multi-population study to assess the feasibility of CRC risk prediction using common genetic variant data combined with other risk factors. A risk prediction model was built and applied to the Scottish population using available data. DESIGN: Nine populations of European descent were studied to develop and validate CRC risk prediction models. Binary logistic regression was used to assess the combined effect of age, gender, family history (FH) and genotypes at 10 susceptibility loci that individually only modestly influence CRC risk. Risk models were generated from case-control data incorporating genotypes alone (n=39 266) and in combination with gender, age and FH (n=11 324). Model discriminatory performance was assessed using 10-fold internal cross-validation and externally using 4187 independent samples. The 10-year absolute risk was estimated by modelling genotype and FH with age- and gender-specific population risks. RESULTS: The median number of risk alleles was greater in cases than controls (10 vs 9, p<2.2×10(-16)), confirmed in external validation sets (Sweden p=1.2×10(-6), Finland p=2×10(-5)). The mean per-allele increase in risk was 9% (OR 1.09; 95% CI 1.05 to 1.13). Discriminative performance was poor across the risk spectrum (area under curve for genotypes alone 0.57; area under curve for genotype/age/gender/FH 0.59). However, modelling genotype data, FH, age and gender with Scottish population data shows the practicalities of identifying a subgroup with >5% predicted 10-year absolute risk. CONCLUSION: Genotype data provide additional information that complements age, gender and FH as risk factors, but individualised genetic risk prediction is not currently feasible. Nonetheless, the modelling exercise suggests public health potential since it is possible to stratify the population into CRC risk categories, thereby informing targeted prevention and surveillance.
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| 4. |
- Ness-Jensen, Eivind, et al.
(författare)
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All-cause and cancer-specific mortality in GORD in a population-based cohort study (the HUNT study)
- 2018
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Ingår i: Gut. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0017-5749 .- 1468-3288.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Gastro-oesophageal reflux is a public health concern which could have associated oesophageal complications, including adenocarcinoma, and possibly also head-and-neck and lung cancers. The aim of this study was to test the hypothesis that reflux increases all-cause and cancer-specific mortalities in an unselected cohort. DESIGN: The Nord-Trondelag health study (HUNT), a Norwegian population-based cohort study, was used to identify individuals with and without reflux in 1995-1997 and 2006-2008, with follow-up until 2014. All-cause mortality and cancer-specific mortality were assessed from the Norwegian Cause of Death Registry and Cancer Registry. Multivariable Cox regression was used to calculate HRs with 95% CIs for mortality with adjustments for potential confounders. RESULTS: We included 4758 participants with severe reflux symptoms and 51 381 participants without reflux symptoms, contributing 60 323 and 747 239 person-years at risk, respectively. Severe reflux was not associated with all-cause mortality, overall cancer-specific mortality or mortality in cancer of the head-and-neck or lung. However, for men with severe reflux a sixfold increase in oesophageal adenocarcinoma-specific mortality was found (HR 6.09, 95% CI 2.33 to 15.93) and the mortality rate was 0.27 per 1000 person-years. For women, the corresponding mortality was not significantly increased (HR 3.68, 95% CI 0.88 to 15.27) and the mortality rate was 0.05 per 1000 person-years. CONCLUSIONS: Individuals with severe reflux symptoms do not seem to have increased all-cause mortality or overall cancer-specific mortality. Although the absolute risk is small, individuals with severe reflux symptoms have a clearly increased oesophageal adenocarcinoma-specific mortality.
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| 5. |
- Ness-Jensen, Eivind, et al.
(författare)
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Changes in prevalence, incidence and spontaneous loss of gastro-oesophagealreflux symptoms : a prospective population-based cohort study, the HUNT study
- 2012
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Ingår i: Gut. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0017-5749 .- 1468-3288.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Changes in the occurrence of gastro-oesophageal reflux symptoms (GORS) in the population remain uncertain. This study aimed to determine the prevalence changes, the incidence and the spontaneous loss of GORS. DESIGN: This population-based cohort study was conducted within the Nord-Trondelag Health Study (the HUNT study), a longitudinal series of population-based health surveys in Nord-Trondelag County, Norway. The study base encompassed all adult residents in the county, and the participants reported the degree of GORS during the previous 12 months. The number of participants included were 58,869 (64% response rate) in 1995-7 and 44,997 (49%) in 2006-9. Of these, 29,610 persons (61%) were prospectively followed up for an average of 11 years. RESULTS: Between 1995-7 and 2006-9, the prevalence of any, severe and at least weekly GORS increased by 30% (from 31.4% to 40.9%), 24% (from 5.4% to 6.7%) and 47% (from 11.6% to 17.1%), respectively. The average annual incidence of any and severe GORS was 3.07% and 0.23%, respectively. In women, but not men, the incidence of GORS increased with increasing age. The average annual spontaneous loss (not due to antireflux medication) of any and severe GORS was 2.32% and 1.22%, respectively. The spontaneous loss of GORS decreased with increasing age. CONCLUSION: Between 1995-7 and 2006-9 the prevalence of GORS increased substantially. At least weekly GORS increased by 47%. The average annual incidence of severe GORS was 0.23%, and the corresponding spontaneous loss was 1.22%. The incidence and spontaneous loss of GORS were influenced by sex and age.
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| 6. |
- Örtqvist, Anne K., et al.
(författare)
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Fetal and early life antibiotics exposure and very early onset inflammatory bowel disease : a population-based study
- 2019
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Ingår i: Gut. - Stockholm : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 68:2, s. 218-225
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Earlier studies on antibiotics exposure and development of IBD (Crohn's disease (CD) and ulcerative colitis (UC)) may have been biased by familial factors and gastroenteritis. We aimed to estimate the association between antibiotics during pregnancy or infantile age and very early onset (VEO) IBD.DESIGN: In this cohort study of 827 239 children born in Sweden between 2006 and 2013, we examined the link between exposure to systemic antibiotics and VEO-IBD (diagnosis <6 years of age), using Cox proportional hazard regression models. Information on antibiotics and IBD was retrieved from the nationwide population-based Swedish Prescribed Drug Register and the National Patient Register. We specifically examined potential confounding from parental IBD and gastroenteritis.RESULTS: Children exposed to antibiotics during pregnancy were at increased risk of IBD compared with general population controls (adjusted HR (aHR) 1.93; 95% CI 1.06 to 3.50). Corresponding aHRs were 2.48 (95% CI 1.01 to 6.08) for CD and 1.25 (95% CI 0.47 to 3.26) for UC, respectively. For antibiotics in infantile age, the aHR for IBD was 1.11 (95% CI 0.57 to 2.15); for CD 0.72 (95% CI 0.27 to 1.92) and 1.23 (95% CI 0.45 to 3.39) for UC. Excluding children with gastroenteritis 12 months prior to the first IBD diagnosis retained similar aHR for antibiotics during pregnancy and CD, while the association no longer remained significant for IBD.CONCLUSION: We found that exposure to antibiotics during pregnancy, but not in infantile age, is associated with an increased risk of VEO-IBD regardless of gastroenteritis. The risk increase for exposure in pregnancy may be due to changes in the microbiota.
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| 7. |
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| 8. |
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| 9. |
- Agrawal, Manasi, et al.
(författare)
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Inflammatory bowel diseases among first-generation and second-generation immigrants in Denmark : a population-based cohort study
- 2021
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:6, s. 1037-1043
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Our objective was to estimate the relative risk of IBD among first-generation and second-generation immigrants in Denmark compared with native Danes.DESIGN: Using national registries, we established a cohort of Danish residents between 1977 and 2018. Cohort members with known country of birth were followed for Crohn's disease (CD) and ulcerative colitis (UC) diagnoses. Incidence rate ratios (IRRs) served as measures of relative risk and were calculated by log-linear Poisson regression, using rates among native Danes as reference, stratified by IBD risk in parental country of birth, and among first-generation immigrants by age at immigration and duration of stay in Denmark.RESULTS: Among 8.7 million Danes, 4156 first-generation and 898 second-generation immigrants were diagnosed with CD or UC. Overall, comparing first-generation immigrants with native Danes, the IRR was 0.80 (95% CI 0.76 to 0.84) for CD and 0.74 (95% CI 0.71 to 0.77) for UC. The IRR of IBD increased with ≥20 years stay in Denmark. The IRR of CD increased with immigration at ≥40 years of age. Comparing second-generation immigrants with native Danes, the IRR of IBD was 0.97 (95% CI 0.91 to 1.04). There was significant interaction with sex, with higher IRR of IBD in male than in female immigrants.CONCLUSION: Relative to native Danish men and women, IBD risk among first-generation immigrants was lower, reflected the risk in their parental country of birth and increased with ≥20 years stay in Denmark. For second-generation immigrants, relative risk of IBD was lower only among women. These complex patterns suggest the role of environmental IBD risk factors.
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| 10. |
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| 11. |
- Alberts, R, et al.
(författare)
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Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis
- 2018
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 67:8, s. 1517-1524
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Tidskriftsartikel (refereegranskat)abstract
- Primary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications.DesignWe collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients—obtained using the Illumina immunochip—with their disease subphenotypes. Using logistic regression and Cox proportional hazards models, we identified genetic variants associated with binary and time-to-event PSC subphenotypes.ResultsWe identified genetic variant rs853974 to be associated with liver transplant-free survival (p=6.07×10–9). Kaplan-Meier survival analysis showed a 50.9% (95% CI 41.5% to 59.5%) transplant-free survival for homozygous AA allele carriers of rs853974 compared with 72.8% (95% CI 69.6% to 75.7%) for GG carriers at 10 years after PSC diagnosis. For the candidate gene in the region, RSPO3, we demonstrated expression in key liver-resident effector cells, such as human and murine cholangiocytes and human hepatic stellate cells.ConclusionWe present a large international PSC cohort, and report genetic loci associated with PSC disease progression. For liver transplant-free survival, we identified a genome-wide significant signal and demonstrated expression of the candidate gene RSPO3 in key liver-resident effector cells. This warrants further assessments of the role of this potential key PSC modifier gene.
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| 12. |
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| 13. |
- Angelini, Giulia, et al.
(författare)
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Small intestinal metabolism is central to whole-body insulin resistance
- 2021
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 70:6, s. 1098-1109
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Tidskriftsartikel (refereegranskat)abstract
- Objective To assess the role of jejunum in insulin resistance in humans and in experimental animals. Design Twenty-four subjects undergoing biliopancreatic diversion (BPD) or Roux-en-Y gastric bypass (RYGB) were enrolled. Insulin sensitivity was measured at baseline and at 1week after surgery using oral glucose minimal model. We excluded the jejunum from intestinal continuity in pigs and created a jejunal loop with its vascular and nerve supply intact accessible from two cutaneous stomas, and reconnected the bowel with an end-to-end anastomosis. Glucose stable isotopes were given in the stomach or in the jejunal loop. In vitro studies using primary porcine and human hepatocytes or myoblasts tested the effects of plasma on gluconeogenesis or glucose uptake and insulin signalling. Results Whole-body insulin sensitivity (SI∙104: 0.54±0.12 before vs 0.82±0.11 after BPD, p=0.024and 0.41±0.09 before vs 0.65±0.09/pM/min after RYGB, p=not significant) and Glucose Disposition Index increased only after BPD. In pigs, insulin sensitivity was significantly lower when glucose was administered in the jejunal loop than in the stomach (glucose rate of disappearance (Rd) area under the curve (AUC)/insulin AUC∙10: 1.82±0.31 vs 2.96±0.33mmol/pM/min, p=0.0017). Metabolomics showed a similar pattern before surgery and during jejunal-loop stimulation, pointing to a higher expression of gluconeogenetic substrates, a metabolic signature of impaired insulin sensitivity. A greater hepatocyte phosphoenolpyruvate-carboxykinase and glucose-6-phosphatase gene expression was elicited with plasma from porcine jejunal loop or before surgery compared with plasma from jejunectomy in pigs or jejunal bypass in humans. Stimulation of myoblasts with plasma from porcine jejunal loop or before surgery reduced glucose uptake, Ser473-Akt phosphorylation and GLUT4 expression compared with plasma obtained during gastric glucose administration after jejunectomy in pigs or after jejunal bypass in humans. Conclusion Proximal gut plays a crucial role in controlling insulin sensitivity through a distinctive metabolic signature involving hepatic gluconeogenesis and muscle insulin resistance. Bypassing the jejunum is beneficial in terms of insulin-mediated glucose disposal in obesity.
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| 14. |
- Anlauf, M, et al.
(författare)
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Allelic deletion of the MEN1 gene in duodenal gastrin and somatostatin cell neoplasms and their precursor lesions.
- 2007
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 56:5, s. 637-44
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with a multiple endocrine neoplasia type 1 (MEN1)-associated Zollinger-Ellison syndrome (ZES) show multifocal duodenal gastrinomas and precursor lesions.AIMS: To test these lesions for loss of heterozygosity (LOH) of the MEN1 gene locus on chromosome 11q13, and to investigate whether the MEN1-related endocrine cell changes also involved somatostatin cells.MATERIAL AND METHODS: Tissue specimens from six patients with MEN1 and ZES were analysed by immunohistochemistry and immunofluorescence. LOH analysis was performed by fluorescence in situ hybridisation (FISH), using probes containing the MEN1 gene locus and the centromere 11 (C11) region. For simultaneous analysis of hormones and allelic deletions, a combined FISH/immunofluorescence protocol was established.RESULTS: 28 of a total of 33 duodenal neuroendocrine tumours (NETs) were gastrin-producing tumours; 13/28 (46.4%) revealed LOH on 11q13 and/or C11. Five of the NETs were somatostatin-expressing tumours, two revealing LOH. Allelic loss was detected in tumours as small as 300 microm (gastrin) and 400 microm (somatostatin) in diameter. The gastrin-producing tumours showed different deletion/retention patterns. Hyperplastic somatostatin cell lesions, similar to those of the gastrin cells, were present in all patients. The hyperplastic lesions of both cell lines consistently retained both 11q13 alleles.CONCLUSIONS: Allelic deletion of the MEN1 gene may reflect a pivotal event in the development of multifocal gastrin and somatostatin cell neoplasms in the duodenum of patients with MEN1. The observation of distinct deletion patterns in small synchronous tumours supports the concept that each gastrin-producing tumour in an individual MEN1 patient arises from an independent cell clone.
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| 15. |
- Appelros, Stefan, et al.
(författare)
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Activation peptide of carboxypeptidase B in serum and urine in acute pancreatitis
- 1998
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 42:1, s. 97-102
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Tidskriftsartikel (refereegranskat)abstract
- The pathophysiology of acute pancreatitis involves activation of the pancreatic proenzymes. Levels of the trypsinogen activation peptide in urine in acute pancreatitis has been shown to correlate with the severity of disease. However, this peptide is unstable in urine and, because of its low molecular mass, difficult to measure. Procarboxypeptidase B has a larger activation peptide which could be more suitable for analysis in serum and urine.
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| 16. |
- Arber, N, et al.
(författare)
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Sporadic adenomatous polyp regression with exisulind is effective but toxic : A randomised, double blind, placebo controlled, dose-response study
- 2006
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 55:3, s. 367-373
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Tidskriftsartikel (refereegranskat)abstract
- Background and aim: A 12 month, multicentre, randomised, double blind, placebo controlled, phase 3, dose-response study was carried out. Exisulind inhibits tumour growth by induction of apoptosis. The aim of our study was to investigate if exisulind induces regression of sporadic colonic adenomas. Patients and methods: A 12 month multicentre randomised double blind placebo controlled phase 3 dose response study was carried out. At baseline colonoscopy, left sided polyps (3-10 mm) were tattooed, measured, and left in place. Subjects received exisulind 200 or 400 mg, or placebo daily. Follow up sigmoidoscopy was performed after six months, and removal of any remaining polyps at the 12 month colonoscopy. The primary efficacy variable was change in polyp size from baseline. Results: A total of 281 patients were enrolled and randomised, 155 (55%) fulfilled the criteria for the intention to treat (ITT) analysis and 114 (41%) fulfilled the criteria for the efficacy evaluation analysis (patients who underwent the 12 month colonoscopy). The decrease in median polyp size was significantly greater (p = 0.03) in patients who received exisulind 400 mg (-10 mm2) compared with those who received placebo (-4 mm2). Complete or partial response was significantly higher in the exisulind 400 mg group (54.6%) compared with the placebo group (30.2%), and disease progression was significantly lower (6.1% v 27.9%) (p = 0.04 and 0.02, respectively). Increased liver enzymes (8.4%) and abdominal pain (14.7%) were also reported at a greater frequency in the exisulind 400 mg group. Conclusion: Exisulind caused significant regression of sporadic adenomatous polyps but was associated with more toxicity. This model of polyp regression, short in its term and involving a comparatively small patient sample size, may be the best available tool to assess a therapeutic regimen before launching into large preventive clinical studies.
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| 17. |
- Armandi, Angelo, et al.
(författare)
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Serum ferritin levels can predict long-term outcomes in patients with metabolic dysfunction-associated steatotic liver disease
- 2024
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Ingår i: Gut. - : BMJ PUBLISHING GROUP. - 0017-5749 .- 1468-3288.
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Tidskriftsartikel (refereegranskat)abstract
- Objective Hyperferritinaemia is associated with liver fibrosis severity in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), but the longitudinal implications have not been thoroughly investigated. We assessed the role of serum ferritin in predicting long-term outcomes or death. Design We evaluated the relationship between baseline serum ferritin and longitudinal events in a multicentre cohort of 1342 patients. Four survival models considering ferritin with confounders or non-invasive scoring systems were applied with repeated five-fold cross-validation schema. Prediction performance was evaluated in terms of Harrell's C-index and its improvement by including ferritin as a covariate. Results Median follow-up time was 96 months. Liver-related events occurred in 7.7%, hepatocellular carcinoma in 1.9%, cardiovascular events in 10.9%, extrahepatic cancers in 8.3% and all-cause mortality in 5.8%. Hyperferritinaemia was associated with a 50% increased risk of liver-related events and 27% of all-cause mortality. A stepwise increase in baseline ferritin thresholds was associated with a statistical increase in C-index, ranging between 0.02 (lasso-penalised Cox regression) and 0.03 (ridge-penalised Cox regression); the risk of developing liver-related events mainly increased from threshold 215.5 mu g/L (median HR=1.71 and C-index=0.71) and the risk of overall mortality from threshold 272 mu g/L (median HR=1.49 and C-index=0.70). The inclusion of serum ferritin thresholds (215.5 mu g/L and 272 mu g/L) in predictive models increased the performance of Fibrosis-4 and Non-Alcoholic Fatty Liver Disease Fibrosis Score in the longitudinal risk assessment of liver-related events (C-indices>0.71) and overall mortality (C-indices>0.65). Conclusions This study supports the potential use of serum ferritin values for predicting the long-term prognosis of patients with MASLD.
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| 18. |
- Arnold, Melina, et al.
(författare)
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The burden of stomach cancer in indigenous populations : a systematic review and global assessment
- 2014
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 63:1, s. 64-71
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Tidskriftsartikel (refereegranskat)abstract
- Objective Stomach cancer is a leading cause of cancer death, especially in developing countries. Incidence has been associated with poverty and is also reported to disproportionately affect indigenous peoples, many of whom live in poor socioeconomic circumstances and experience lower standards of health. In this comprehensive assessment, we explore the burden of stomach cancer among indigenous peoples globally.Design The literature was searched systematically for studies on stomach cancer incidence, mortality and survival in indigenous populations, including Indigenous Australians, Maori in New Zealand, indigenous peoples from the circumpolar region, native Americans and Alaska natives in the USA, and the Mapuche peoples in Chile. Data from the New Zealand Health Information Service and the Surveillance Epidemiology and End Results (SEER) Program were used to estimate trends in incidence.Results Elevated rates of stomach cancer incidence and mortality were found in almost all indigenous peoples relative to corresponding non-indigenous populations in the same regions or countries. This was particularly evident among Inuit residing in the circumpolar region (standardised incidence ratios (SIR) males: 3.9, females: 3.6) and in Maori (SIR males: 2.2, females: 3.2). Increasing trends in incidence were found for some groups.Conclusions We found a higher burden of stomach cancer in indigenous populations globally, and rising incidence in some indigenous groups, in stark contrast to the decreasing global trends. This is of major public health concern requiring close surveillance and further research of potential risk factors. Given evidence that improving nutrition and housing sanitation, and Helicobacter pylori eradication programmes could reduce stomach cancer rates, policies which address these initiatives could reduce inequalities in stomach cancer burden for indigenous peoples.
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| 19. |
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| 20. |
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| 21. |
- Asnicar, Francesco, et al.
(författare)
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Blue poo : Impact of gut transit time on the gut microbiome using a novel marker
- 2021
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 70:9, s. 1665-1674
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Gut transit time is a key modulator of host-microbiome interactions, yet this is often overlooked, partly because reliable methods are typically expensive or burdensome. The aim of this single-arm, single-blinded intervention study is to assess (1) the relationship between gut transit time and the human gut microbiome, and (2) the utility of the a € blue dye' method as an inexpensive and scalable technique to measure transit time. Methods: We assessed interactions between the taxonomic and functional potential profiles of the gut microbiome (profiled via shotgun metagenomic sequencing), gut transit time (measured via the blue dye method), cardiometabolic health and diet in 863 healthy individuals from the PREDICT 1 study. Results: We found that gut microbiome taxonomic composition can accurately discriminate between gut transit time classes (0.82 area under the receiver operating characteristic curve) and longer gut transit time is linked with specific microbial species such as Akkermansia muciniphila, Bacteroides spp and Alistipes spp (false discovery rate-adjusted p values <0.01). The blue dye measure of gut transit time had the strongest association with the gut microbiome over typical transit time proxies such as stool consistency and frequency. Conclusions: Gut transit time, measured via the blue dye method, is a more informative marker of gut microbiome function than traditional measures of stool consistency and frequency. The blue dye method can be applied in large-scale epidemiological studies to advance diet-microbiome-health research. Clinical trial registry website https://clinicaltrials.gov/ct2/show/NCT03479866 and trial number NCT03479866.
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| 22. |
- Axelrad, Jordan E., et al.
(författare)
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Inflammatory bowel disease and risk of small bowel cancer : a binational population-based cohort study from Denmark and Sweden
- 2021
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:2, s. 297-308
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Crohn's disease (CD) is associated with increased risk of small bowel cancer (SBC), but previous studies have been small. We aimed to examine the risk of incident SBC and death from SBC in patients with inflammatory bowel disease (IBD).DESIGN: In a binational, population-based cohort study from Sweden and Denmark of patients with IBD during 1969-2017 and matched reference individuals from the general population, we evaluated the risk of incident SBC and death from SBC. Cox regression was used to estimate adjusted hazard ratios (aHRs).RESULTS: We identified 161 896 individuals with IBD (CD: 47 370; UC: 97 515; unclassified IBD: 17 011). During follow-up, 237 cases of SBC were diagnosed in patients with IBD (CD: 24.4/100 000 person-years; UC: 5.88/100 000 person-years), compared with 640 cases in reference individuals (2.81/100 000 person-years and 3.32/100 000 person-years, respectively). This corresponded to one extra case of SBC in 385 patients with CD and one extra case in 500 patients with UC, followed up for 10 years. The aHR for incident SBC was 9.09 (95% CI 7.34 to 11.3) in CD and 1.85 (95% CI 1.43 to 2.39) in UC. Excluding the first year after an IBD diagnosis, the aHRs for incident SBC decreased to 4.96 in CD and 1.69 in UC. Among patients with CD, HRs were independently highest for recently diagnosed, childhood-onset, ileal and stricturing CD. The relative hazard of SBC-related death was increased in both patients with CD (aHR 6.59, 95% CI 4.74 to 9.15) and patients with UC (aHR 1.57; 95% CI 1.07 to 2.32).CONCLUSION: SBC and death from SBC were more common in patients with IBD, particularly among patients with CD, although absolute risks were low.
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| 24. |
- Axelson, Jan, et al.
(författare)
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Importance of the stomach in maintaining calcium homeostatis in the rat
- 1991
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 32:11, s. 1298-1302
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Tidskriftsartikel (refereegranskat)abstract
- The stomach helps to maintain calcium homoeostasis by making dietary calcium accessible for uptake in the intestines, although the effect of the stomach on calcium homoeostasis is poorly understood. We examined the effect on blood calcium of gastric surgery in the rat. Within three weeks gastrectomy and fundectomy (excision of the acid producing part of the stomach) induced a slight lowering of the blood calcium concentration. When parathyroidectomy was combined with either gastrectomy or fundectomy the blood calcium concentrations promptly dropped to values lower than after parathyroidectomy alone. The mortality was close to 100% during the first three weeks after combined parathyroidectomy and gastric surgery. It was nil in rats subjected to parathyroidectomy alone. Gastrectomised rats absorbed Ca2+ better than unoperated control rats, possibly reflecting the fact that the serum 1,25-dihydroxyvitamin D concentration was raised. Gastrectomised rats had a food intake that was about 70% of that in intact rats, and the amount of dietary calcium absorbed (net absorption per kg body weight) by the gastrectomised rats was approximately 65% of that in intact control rats. We conclude that the acid producing part of the stomach is important for calcium homoeostasis, since its removal induced lethal hypocalcaemia in parathyroidectomised rats. One possible explanation for the hypocalcaemia induced by gastrectomy is a progressive calcium deficit. In addition, the loss of calciotrophic hormones originating in the stomach may contribute.
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| 25. |
- Bahram, Mohammad
(författare)
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Antibiotics-induced monodominance of a novel gut bacterial order
- 2019
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 68, s. 1781-1790
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Tidskriftsartikel (refereegranskat)abstract
- Objective The composition of the healthy human adult gut microbiome is relatively stable over prolonged periods, and representatives of the most highly abundant and prevalent species have been cultured and described. However, microbial abundances can change on perturbations, such as antibiotics intake, enabling the identification and characterisation of otherwise low abundant species.Design Analysing gut microbial time-series data, we used shotgun metagenomics to create strain level taxonomic and functional profiles. Community dynamics were modelled postintervention with a focus on conditionally rare taxa and previously unknown bacteria.Results In response to a commonly prescribed cephalosporin (ceftriaxone), we observe a strong compositional shift in one subject, in which a previously unknown species, (U)Borkfalki ceftriaxensis, was identified, blooming to 92% relative abundance. The genome assembly reveals that this species (1) belongs to a so far undescribed order of Firmicutes, (2) is ubiquitously present at low abundances in at least one third of adults, (3) is opportunistically growing, being ecologically similar to typical probiotic species and (4) is stably associated to healthy hosts as determined by single nucleotide variation analysis. It was the first coloniser after the antibiotic intervention that led to a long-lasting microbial community shift and likely permanent loss of nine commensals.Conclusion The bloom of B-U. ceftriaxensis and a subsequent one of Parabacteroides distasonis demonstrate the existence of monodominance community states in the gut. Our study points to an undiscovered wealth of low abundant but common taxa in the human gut and calls for more highly resolved longitudinal studies, in particular on ecosystem perturbations.
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