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- Weismuller, T. J., et al.
(författare)
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Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis
- 2017
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 152:8, s. 1975-1984.e8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large international cohort of patients with PSC. METHODS: We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia. For each patient, we collected data on sex, clinician-reported age at and date of PSC and IBD diagnoses, phenotypes of IBD and PSC, and date and indication of IBD-related surgeries. The primary and secondary endpoints were liver transplantation or death (LTD) and hepatopancreatobiliary malignancy, respectively. Cox proportional hazards models were applied to determine the effects of individual covariates on rates of clinical events, with time-to-event analysis ascertained through Kaplan-Meier estimates. RESULTS: Of the 7121 patients in the cohort, 2616 met the primary endpoint (median time to event of 14.5 years) and 721 developed hepatopancreatobiliary malignancy. The most common malignancy was cholangiocarcinoma (n = 594); patients of advanced age at diagnosis had an increased incidence compared with younger patients (incidence rate: 1.2 per 100 patient-years for patients younger than 20 years old, 6.0 per 100 patient-years for patients 21-30 years old, 9.0 per 100 patient-years for patients 31-40 years old, 14.0 per 100 patient-years for patients 4150 years old, 15.2 per 100 patient-years for patients 51-60 years old, and 21.0 per 100 patient-years for patients older than 60 years). Of all patients with PSC studied, 65.5% were men, 89.8% had classical or large-duct disease, and 70.0% developed IBD at some point. Assessing the development of IBD as a time-dependent covariate, Crohn's disease and no IBD (both vs ulcerative colitis) were associated with a lower risk of LTD (unadjusted hazard ratio [HR], 0.62; P <.001 and HR, 0.90; P =.03, respectively) and malignancy (HR, 0.68; P =.008 and HR, 0.77; P =.004, respectively). Small-duct PSC was associated with a lower risk of LTD or malignancy compared with classic PSC (HR, 0.30 and HR, 0.15, respectively; both P <.001). Female sex was also associated with a lower risk of LTD or malignancy (HR, 0.88; P =.002 and HR, 0.68; P <.001, respectively). In multivariable analyses assessing the primary endpoint, small-duct PSC characterized a low-risk phenotype in both sexes (adjusted HR for men, 0.23; P <.001 and adjusted HR for women, 0.48; P =.003). Conversely, patients with ulcerative colitis had an increased risk of liver disease progression compared with patients with Crohn's disease (HR, 1.56; P <.001) or no IBD (HR, 1.15; P =.002). CONCLUSIONS: In an analysis of data from individual patients with PSC worldwide, we found significant variation in clinical course associated with age at diagnosis, sex, and ductal and IBD subtypes. The survival estimates provided might be used to estimate risk levels for patients with PSC and select patients for clinical trials.
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| 3. |
- Schulze, E D, et al.
(författare)
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The European carbon balance. Part 4: integration of carbon and other trace-gas fluxes
- 2010
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Ingår i: GLOBAL CHANGE BIOLOGY. - : Blackwell Publishing Ltd. - 1354-1013 .- 1365-2486. ; 16:5, s. 1451-1469
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Forskningsöversikt (refereegranskat)abstract
- Overviewing the European carbon (C), greenhouse gas (GHG), and non-GHG fluxes, gross primary productivity (GPP) is about 9.3 Pg yr-1, and fossil fuel imports are 1.6 Pg yr-1. GPP is about 1.25% of solar radiation, containing about 360 x 1018 J energy - five times the energy content of annual fossil fuel use. Net primary production (NPP) is 50%, terrestrial net biome productivity, NBP, 3%, and the net GHG balance, NGB, 0.3% of GPP. Human harvest uses 20% of NPP or 10% of GPP, or alternatively 1 parts per thousand of solar radiation after accounting for the inherent cost of agriculture and forestry, for production of pesticides and fertilizer, the return of organic fertilizer, and for the C equivalent cost of GHG emissions. C equivalents are defined on a global warming potential with a 100-year time horizon. The equivalent of about 2.4% of the mineral fertilizer input is emitted as N2O. Agricultural emissions to the atmosphere are about 40% of total methane, 60% of total NO-N, 70% of total N2O-N, and 95% of total NH3-N emissions of Europe. European soils are a net C sink (114 Tg yr-1), but considering the emissions of GHGs, soils are a source of about 26 Tg CO2 C-equivalent yr-1. Forest, grassland and sediment C sinks are offset by GHG emissions from croplands, peatlands and inland waters. Non-GHGs (NH3, NOx) interact significantly with the GHG and the C cycle through ammonium nitrate aerosols and dry deposition. Wet deposition of nitrogen (N) supports about 50% of forest timber growth. Land use change is regionally important. The absolute flux values total about 50 Tg C yr-1. Nevertheless, for the European trace-gas balance, land-use intensity is more important than land-use change. This study shows that emissions of GHGs and non-GHGs significantly distort the C cycle and eliminate apparent C sinks.
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