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1.
  • van Bragt, JJMH, et al. (author)
  • Characteristics and treatment regimens across ERS SHARP severe asthma registries
  • 2020
  • In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
  • Journal article (peer-reviewed)abstract
    • Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
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  • Andersson-Assarsson, Johanna C., 1974, et al. (author)
  • Evolution of age-related mutation-driven clonal haematopoiesis over 20 years is associated with metabolic dysfunction in obesity
  • 2023
  • In: Ebiomedicine. - 2352-3964. ; 92
  • Journal article (peer-reviewed)abstract
    • Background Haematopoietic clones caused by somatic mutations with >= 2% variant allele frequency (VAF) increase with age and are linked to risk of haematological malignancies and cardiovascular disease. Recent observations suggest that smaller clones (VAF<2%) are also associated with adverse outcomes. Our aims were to determine the prevalence of clonal haematopoiesis driven by clones of variable sizes in individuals with obesity treated by usual care or bariatric surgery (a treatment that improves metabolic status), and to examine the expansion of clones in relation to age and metabolic dysregulation over up to 20 years.Methods Clonal haematopoiesis-driver mutations (CHDMs) were identified in blood samples from participants of the Swedish Obese Subjects intervention study. Using an ultrasensitive assay, we analysed single-timepoint samples from 1050 individuals treated by usual care and 841 individuals who had undergone bariatric surgery, and multiple-timepoint samples taken over 20 years from a subset (n = 40) of the individuals treated by usual care.Findings In this explorative study, prevalence of CHDMs was similar in the single-timepoint usual care and bariatric surgery groups (20.6% and 22.5%, respectively, P = 0.330), with VAF ranging from 0.01% to 31.15%. Clone sizes increased with age in individuals with obesity, but not in those who underwent bariatric surgery. In the multiple-timepoint analysis, VAF increased by on average 7% (range -4% to 24%) per year and rate of clone growth was negatively associated with HDL-cholesterol (R = -0.68, 1.74 E-04).Interpretation Low HDL-C was associated with growth of haematopoietic clones in individuals with obesity treated by usual care.
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  • Pistidda, C., et al. (author)
  • Hydrogen storage systems from waste Mg alloys
  • 2014
  • In: Journal of Power Sources. - : Elsevier BV. - 1873-2755 .- 0378-7753. ; 270, s. 554-563
  • Journal article (peer-reviewed)abstract
    • The production cost of materials for hydrogen storage is one of the major issues to be addressed in order to consider them suitable for large scale applications. In the last decades several authors reported on the hydrogen sorption properties of Mg and Mg-based systems. In this work magnesium industrial wastes of AZ91 alloy and Mg-10 wt.% Gd alloy are used for the production of hydrogen storage materials. The hydrogen sorption properties of the alloys were investigated by means of volumetric technique, in situ synchrotron radiation powder X-ray diffraction (SR-PXD) and calorimetric methods. The measured reversible hydrogen storage capacity for the alloys AZ91 and Mg-10 wt.% Gd are 4.2 and 5.8 wt.%, respectively. For the Mg-10 wt.% Gd alloy, the hydrogenated product was also successfully used as starting reactant for the synthesis of Mg(NH2)(2) and as MgH2 substitute in the Reactive Hydride Composite (RHC) 2LiBH(4) + MgH2. The results of this work demonstrate the concrete possibility to use Mg alloy wastes for hydrogen storage purposes. (C) 2014 Elsevier B.V. All rights reserved.
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  • Hollo, G, et al. (author)
  • Referral for first glaucoma surgery in Europe, the ReF-GS study
  • 2019
  • In: European journal of ophthalmology. - : SAGE Publications. - 1724-6016 .- 1120-6721. ; 29:4, s. 406-416
  • Journal article (peer-reviewed)abstract
    • To analyze the appropriateness of referrals for incisional glaucoma-surgery in Europe. Methods: Referrals for the first open-angle glaucoma surgery between January and October 2017 were analyzed in 18 countries: 8 “old” European Union, 7 “new” European Union and 3 non-European Union European countries. Results: Most eyes had primary open-angle or exfoliative glaucoma. The average mean deviation was −13.8 dB with split fixation in 44.3%. No structural progression analysis was made before the referrals. The most common medications were the combination of a prostaglandin analog, timolol and a carbonic anhydrase inhibitor (30.0%), and all other combinations comprising ⩾ 3 molecules (33.8%). Laser trabeculoplasty was reported in only 18.4%. Of the 294 referrals, 41.5% were appropriate and timely, 35.0% appropriate but later than optimal, and 17.6% appropriate but too late (minimal vision maintained). The treatment period was significantly longer (median: 7 years) in the “old” European Union countries than in the other groups (3 and 2 years, respectively). No between-group differences were seen in intraocular pressure and mean deviation, but the non-European Union group referred the patients at significantly lower cup/disk ratio and eye drop usage than the other groups. Split fixation was significantly more common in the “old” (60.6%) than the “new” European Union countries (38.7%), and in both EU country-groups than in the non-European Union countries (13.6%). Conclusions: Of 294 European open-angle glaucoma referrals for first glaucoma-surgery, 41.5% were completely satisfactory. The damage was typically advanced, and the care varied considerably among the countries. This suggests that further efforts are necessary to improve glaucoma care in Europe.
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  • Messner, Christoph B., et al. (author)
  • Ultra-High-Throughput Clinical Proteomics Reveals Classifiers of COVID-19 Infection
  • 2020
  • In: Cell Systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 11:1, s. 11-24.E4
  • Journal article (peer-reviewed)abstract
    • The COVID-19 pandemic is an unprecedented global challenge, and point-of-care diagnostic classifiers are urgently required. Here, we present a platform for ultra-high-throughput serum and plasma proteomics that builds on ISO13485 standardization to facilitate simple implementation in regulated clinical laboratories. Our low-cost workflow handles up to 180 samples per day, enables high precision quantification, and reduces batch effects for large-scale and longitudinal studies. We use our platform on samples collected from a cohort of early hospitalized cases of the SARS-CoV-2 pandemic and identify 27 potential biomarkers that are differentially expressed depending on the WHO severity grade of COVID-19. They include complement factors, the coagulation system, inflammation modulators, and pro-inflammatory factors upstream and downstream of interleukin 6. All protocols and software for implementing our approach are freely available. In total, this work supports the development of routine proteomic assays to aid clinical decision making and generate hypotheses about potential COVID-19 therapeutic targets.
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14.
  • Santoru, A, et al. (author)
  • A new potassium-based intermediate and its role in the desorption properties of the K-Mg-N-H system.
  • 2016
  • In: Physical chemistry chemical physics : PCCP. - : Royal Society of Chemistry (RSC). - 1463-9084 .- 1463-9076. ; 18:5, s. 3910-3920
  • Journal article (peer-reviewed)abstract
    • New insights into the reaction pathways of different potassium/magnesium amide-hydride based systems are discussed. In situ SR-PXD experiments were for the first time performed in order to reveal the evolution of the phases connected with the hydrogen releasing processes. Evidence of a new K-N-H intermediate is shown and discussed with particular focus on structural modification. Based on these results, a new reaction mechanism of amide-hydride anionic exchange is proposed.
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  • Shulman, Alexander, 1978, et al. (author)
  • Incidence of end-stage renal disease following bariatric surgery in the Swedish Obese Subjects Study.
  • 2018
  • In: International journal of obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 42, s. 964-973
  • Journal article (peer-reviewed)abstract
    • Obesity is a major public health problem leading to co-morbidities such as diabetes, hypertension and kidney failure. Bariatric surgery results in pronounced and maintained weight loss and prevention of obesity-related diseases and their complications. Most studies of bariatric surgery on kidney disease show improvements after surgery. However, long-term studies analyzing hard end-points are lacking. Here we report on the long-term effects of bariatric surgery compared to usual obesity care on incidence of end-stage renal disease (ESRD) alone and in combination with chronic kidney disease stage 4 (CKD4/ESRD).4047 patients were included in the Swedish Obese Subjects (SOS) study. Inclusion criteria were age 37-60 years and BMI≥34 in men and BMI≥38 in women. Patients in the bariatric surgery group (N=2010) underwent banding (18%), vertical banded gastroplasty (69%), or gastric bypass (13%); controls (N=2037) received usual obesity care. In this analysis, patients were followed up for a median time of 18 years. The incidence of ESRD and CKD4 was obtained by crosschecking the SOS database with the Swedish National Patient Register.During follow-up, ESRD occurred in 13 patients in the surgery group and in 26 patients in the control group (adjusted hazard ratio (HR)=0.27; 95% CI 0.12-0.60; p=0.001). The number of CKD4/ESRD events was 23 in the surgery group and 39 in the control group (adjusted HR=0.33; 95% CI 0.18-0.62; p<0.001). In both analyses, bariatric surgery had a more favorable effect in patients with baseline serum insulin levels above median compared to those with lower insulin levels (interaction p=0.010). Treatment benefit of bariatric surgery was also greater in patients with macroalbuminuria at baseline compared to those without macroalbuminuria (interaction p<0.001).Our study showed for the first time that bariatric surgery is associated with a long-term protection against ESRD and CKD4/ESRD.
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  • Zhang, Yuan, et al. (author)
  • Adiponectin Associates with Rheumatoid Arthritis Risk in Overweight and Obesity Independently of Other Adipokines
  • 2021
  • In: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 10:13
  • Journal article (peer-reviewed)abstract
    • We recently reported that increased serum adiponectin was associated with rheumatoid arthritis (RA) risk in subjects with obesity. We hereby aim to determine if other adipokines associate with RA risk and if the association between adiponectin and RA is independent of other adipokines. Two nested-case control studies were performed in two different cohorts: 82 participants of the Swedish Obese Subjects (SOS) study who developed RA during follow-up matched with 410 controls, and 88 matched pairs from the Medical Biobank of Northern Sweden. Baseline levels of circulating adipokines were measured using ELISA. In a multivariable analysis in the SOS cohort, higher adiponectin was associated with an increased risk of RA independently of other adipokines (OR for RA risk: 1.06, 95% CI: 1.01-1.12, p = 0.02). No association between leptin, resistin, and visfatin levels and the risk of RA was detected. In the cohort from the Medical Biobank of Northern Sweden, higher adiponectin was associated with an increased risk of RA only in participants with overweight/obesity (OR: 1.17, 95% CI: 1.01-1.36, p = 0.03), independently of other adipokines. Our results show that in individuals with overweight/obesity, higher circulating levels of adiponectin, but not leptin, resistin, or visfatin, were associated with an increased RA risk.
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  • Ahlin, Sofie, 1985, et al. (author)
  • Fracture risk after three bariatric surgery procedures in Swedish obese subjects : up to 26 years follow-up of a controlled intervention study
  • 2020
  • In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 287:5, s. 546-557
  • Journal article (peer-reviewed)abstract
    • Background: Previous studies have reported an increased fracture risk after bariatric surgery. Objective: To investigate the association between different bariatric surgery procedures and fracture risk. Methods: Incidence rates and hazard ratios for fracture events were analysed in the Swedish Obese Subjects study; an ongoing, nonrandomized, prospective, controlled intervention study. Hazard ratios were adjusted for risk factors for osteoporosis and year of inclusion. Information on fracture events were captured from the Swedish National Patient Register. The current analysis includes 2007 patients treated with bariatric surgery (13.3% gastric bypass, 18.7% gastric banding, and 68.0% vertical banded gastroplasty) and 2040 control patients with obesity matched on group level based on 18 variables. Median follow-up was between 15.1 and 17.9 years for the different treatment groups. Results: During follow-up, the highest incidence rate for first-time fracture was observed in the gastric bypass group (22.9 per 1000 person-years). The corresponding incidence rates were 10.4, 10.7 and 9.3 per 1000 person-years for the vertical banded gastroplasty, gastric banding and control groups, respectively. The risk of fracture was increased in the gastric bypass group compared with the control group (adjusted hazard ratio [adjHR] 2.58; 95% confidence interval [CI] 2.02–3.31; P < 0.001), the gastric banding group (adjHR 1.99; 95%CI 1.41–2.82; P < 0.001), and the vertical banded gastroplasty group (adjHR 2.15; 95% CI 1.66–2.79; P < 0.001). Conclusions: The risk of fracture is increased after gastric bypass surgery. Our findings highlight the need for long-term follow-up of bone health for patients undergoing this treatment.
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  • Alcantara, K. Suarez, et al. (author)
  • 3CaH(2)+4MgB(2) + CaF2 Reactive Hydride Composite as a Potential Hydrogen Storage Material: Hydrogenation and Dehydrogenation Pathway
  • 2012
  • In: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 116:12, s. 7207-7212
  • Journal article (peer-reviewed)abstract
    • A reactive hydride composite (RHC) with initial composition 3CaH(2) + 4MgB(2) + CaF2 was studied by in situ synchrotron radiation powder X-ray diffraction (SR-PXD) and X-ray absorption near edge structure (XANES) at the B K-edge and at the Ca K-edge. The hydrogenation reaction proceeds by an unknown intermediate. No evidence of intermediates was observed during the dehydrogenation reaction. B and Ca K-edge XANES results hint to a closed interaction of CaF2 and Ca(BH4)(2). The main function of CaF2 in the 3CaH(2) + 4MgB(2) + CaF2 RHC is as a dopant for the hydrogenation and dehydrogenation reactions.
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  • Anveden, Åsa, et al. (author)
  • Long-term incidence of female-specific cancer after bariatric surgery or usual care in the Swedish Obese Subjects Study
  • 2017
  • In: Gynecologic Oncology. - : Elsevier BV. - 0090-8258. ; 145:2, s. 224-229
  • Journal article (peer-reviewed)abstract
    • Objective. To examine the long-term effects of bariatric surgery on female-specific cancer in women with obesity. Methods. The prospective, matched Swedish Obese Subjects (SOS) study was designed to examine outcomes after bariatric surgery. This study includes 1420 women from the SOS cohort that underwent bariatric surgery and 1447 contemporaneously matched controls who received conventional obesity treatment. Age was 3760 years and BMI was >= 38 kg/m(2). Information on cancer events was obtained from the Swedish National Cancer Registry. Median follow-up time was 18.1 years (interquartile range 14.8-20.9 years, maximum 26 years). This study is registered with ClinicalTrials.gov, NCT01479452. Results. Bariatric surgery was associated with reduced risk of overall cancer (hazard ratio = 0.71; 95% CI 0.59-0.85; p < 0.001). About half of the observed cancers were female-specific, and the incidence of these were lower in the surgery group compared with the control group (hazard ratio = 0.68; 95% CI 0.52-0.88; p = 0.004). The surgical treatment benefit with respect to female-specific cancer was significantly associated with baseline serum insulin (interaction p value = 0.022), with greater relative treatment benefit in patients with medium or high insulin levels. Separate analyses of different types of female-specific cancers showed that bariatric surgery was associated with reduced risk of endometrial cancer (hazard ratio = 0.56: 95% CI 035-0.89; p = 0.014). Conclusions. In this long-term study, bariatric surgery was associated with reduced risk of female-specific cancer, especially in women with hyperinsulinemia at baseline.
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  • Carlsson, Lena M S, 1957, et al. (author)
  • Life expectancy after bariatric surgery or usual care in patients with or without baseline type 2 diabetes in Swedish Obese Subjects.
  • 2023
  • In: International journal of obesity (2005). - 1476-5497. ; 47, s. 931-8
  • Journal article (peer-reviewed)abstract
    • To determine life expectancy and causes of death after bariatric surgery in relation to baseline type 2 diabetes (T2D) in the prospective, Swedish Obese Subjects study.The study included 2010 patients with obesity who underwent bariatric surgery and 2037 matched controls, eligible for surgery. The surgery group underwent gastric bypass (n=265), banding (n=376), or vertical banded gastroplasty (n=1369). The control group (n=2037) received usual obesity care. Causes of death were obtained from the Swedish Cause of Death Register, case sheets and autopsy reports, in patients with baseline T2D (n=392 surgery patients/n=305 controls) or non-T2D (n=1609 surgery patients/n=1726 controls) during a median follow-up 26 years.In T2D and non-T2D subgroups, bariatric surgery was associated with increased life expectancy (2.1, 95% confidence interval (95% CI) 0.2-4.0; and 1.6, 0.5-2.7 years, respectively) and reduced overall mortality (adjusted hazard ratio (adjHR)=0.77, 95% CI: 0.61-0.97; and 0.82, 0.72-0.94, respectively), and the treatment benefit was similar (interaction p=0.615). Bariatric surgery was associated with reduced cardiovascular mortality in both subgroups (adjHR=0.65, 95% CI: 0.46-0.91; and 0.70, 0.55-0.88, respectively (interaction p=0.516)).Bariatric surgery is associated with similar reduction of overall and cardiovascular mortality and increased life expectancy regardless of baseline diabetes status.
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  • Carlsson, Lena M S, 1957, et al. (author)
  • Long-term incidence of microvascular disease after bariatric surgery or usual care in patients with obesity, stratified by baseline glycaemic status: a post-hoc analysis of participants from the Swedish Obese Subjects study.
  • 2017
  • In: The lancet. Diabetes & endocrinology. - 2213-8595. ; 5:4, s. 271-279
  • Journal article (peer-reviewed)abstract
    • Bariatric surgery is associated with remission of diabetes and prevention of diabetic complications in patients with obesity and type 2 diabetes. Long-term effects of bariatric surgery on microvascular complications in patients with prediabetes are unknown. The aim of this study was to examine the effects of bariatric surgery on incidence of microvascular complications in patients with obesity stratified by baseline glycaemic status.Patients were recruited to the Swedish Obese Subjects (SOS) study between Sept 1, 1987, and Jan 31, 2001. Inclusion criteria were age 37-60 years and BMI of 34 kg/m(2) or greater in men and 38 kg/m(2) or greater in women. Exclusion criteria were identical in surgery and control groups and designed to exclude patients not suitable for surgery. The surgery group (n=2010) underwent gastric bypass (265 [13%]), gastric banding (376 [19%]), or vertical-banded gastroplasty (1369 [68%]). Participants in the control group (n=2037) received usual care. Bodyweight was measured and questionnaires were completed at baseline and at 0·5 years, 1 year, 2 years, 3 years, 4 years, 6 years, 8 years, 10 years, 15 years, and 20 years. Biochemical variables were measured at baseline and at 2 years, 10 years, and 15 years. We categorised participants into subgroups on the basis of baseline glycaemic status (normal [fasting blood glucose concentration <5·0 mmol/L], prediabetes [5·0-6·0 mmol/L], screen-detected diabetes [≥6·1 mmol/L at baseline visit without previous diagnosis], and established diabetes [diagnosis of diabetes before study inclusion]). We obtained data about first incidence of microvascular disease from nationwide registers and about diabetes incidence at study visits at 2 years, 10 years, and 15 years. We did the main analysis by intention to treat, and subgroup analyses after stratification by baseline glycaemic status and by diabetes status at the 15 year follow-up. The SOS study is registered with ClinicalTrials.gov, NCT01479452.4032 of the 4047 participants in the SOS study were included in this analysis. We excluded four patients with suspected type 1 diabetes, and 11 patients with unknown glycaemic status at baseline. At baseline, 2838 patients had normal blood glucose, 591 had prediabetes, 246 had screen-detected diabetes, and 357 had established diabetes. Median follow-up was 19 years (IQR 16-21). We identified 374 incident cases of microvascular disease in the control group and 224 in the surgery group (hazard ratio [HR] 0·56, 95% CI 0·48-0·66; p<0·0001). Interaction between baseline glycaemic status and effect of treatment on incidence of microvascular disease was significant (p=0·0003). Unadjusted HRs were lowest in the subgroup with prediabetes (0·18, 95% CI 0·11-0·30), followed by subgroups with screen-detected diabetes (0·39, 0·24-0·65), established diabetes (0·54, 0·40-0·72), and normoglycaemia (0·63, 0·48-0·81). Surgery was associated with reduced incidence of microvascular events in people with prediabetes regardless of whether they developed diabetes during follow-up.Bariatric surgery was associated with reduced risk of microvascular complications in all subgroups, but the greatest relative risk reduction was observed in patients with prediabetes at baseline. Our results suggest that prediabetes should be treated aggressively to prevent future microvascular events, and effective non-surgical treatments need to be developed for this purpose.US National Institutes of Health, Swedish Research Council, Sahlgrenska University Hospital Regional Agreement on Medical Education and Research, and Swedish Diabetes Foundation.
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  • Carlsson, Lena M S, 1957, et al. (author)
  • Long-term incidence of serious fall-related injuries after bariatric surgery in Swedish obese subjects.
  • 2019
  • In: International journal of obesity (2005). - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 43:4, s. 933-937
  • Journal article (peer-reviewed)abstract
    • Obesity increases risk of falling, but the effect of bariatric surgery on fall-related injuries is unknown. The aim of this study was therefore to study the association between bariatric surgery and long-term incidence of fall-related injuries in the prospective, controlled Swedish Obese Subjects study. At inclusion, body mass index was≥34kg/m2 in men and ≥38kg/m2 in women. The surgery per-protocol group (n=2007) underwent gastric bypass (n=266), banding (n=376), or vertical banded gastroplasty (n=1365), and controls (n=2040) received usual care. At the time of analysis (31 December 2013), median follow-up was 19 years (maximal 26 years). Fall-related injuries requiring hospital treatment were captured using data from the Swedish National Patient Register. During follow-up, there were 617 first-time fall-related injuries in the surgery group and 513 in the control group (adjusted hazard ratio 1.21, 95% CI, 1.07-1.36; P=0.002). The incidence differed between treatment groups (P<0.001, log-rank test) and was higher after gastric bypass than after usual care, banding and vertical banded gastroplasty (adjusted hazard ratio 0.50-0.52, P<0.001 for all three comparisons). In conclusion, gastric bypass surgery was associated with increased risk of serious fall-related injury requiring hospital treatment.
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  • Frei, K. M., et al. (author)
  • A matter of months: High precision migration chronology of a Bronze Age female
  • 2017
  • In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:6
  • Journal article (peer-reviewed)abstract
    • Establishing the age at which prehistoric individuals move away from their childhood residential location holds crucial information about the socio dynamics and mobility patterns in ancient societies. We present a novel combination of strontium isotope analyses performed on the over 3000 year old "Skrydstrup Woman" from Denmark, for whom we compiled a highly detailed month-scale model of her migration timeline. When combined with physical anthropological analyses this timeline can be related to the chronological age at which the residential location changed. We conducted a series of high-resolution strontium isotope analyses of hard and soft human tissues and combined these with anthropological investigations including CT-scanning and 3D visualizations. The Skrydstrup Woman lived during a pan-European period characterized by technical innovation and great social transformations stimulated by long-distance connections; consequently she represents an important part of both Danish and European prehistory. Our multidisciplinary study involves complementary biochemical, biomolecular and microscopy analyses of her scalp hair. Our results reveal that the Skrydstrup Woman was between 17-18 years old when she died, and that she moved from her place of origin -outside present day Denmark- to the Skrydstrup area in Denmark 47 to 42 months before she died. Hence, she was between 13 to 14 years old when she migrated to and resided in the area around Skrydstrup for the rest of her life. From an archaeological standpoint, this one-time and one-way movement of an elite female during the possible "age of marriageability" might suggest that she migrated with the aim of establishing an alliance between chiefdoms. Consequently, this detailed multidisciplinary investigation provides a novel tool to reconstruct high resolution chronology of individual mobility with the perspective of studying complex patterns of social and economic interaction in prehistory.
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  • Heaney, Liam G., et al. (author)
  • Eosinophilic and Noneosinophilic Asthma : An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort
  • 2021
  • In: Chest. - : Elsevier BV. - 0012-3692. ; 160:3, s. 814-830
  • Journal article (peer-reviewed)abstract
    • Background: Phenotypic characteristics of patients with eosinophilic and noneosinophilic asthma are not well characterized in global, real-life severe asthma cohorts. Research Question: What is the prevalence of eosinophilic and noneosinophilic phenotypes in the population with severe asthma, and can these phenotypes be differentiated by clinical and biomarker variables? Study Design and Methods: This was an historical registry study. Adult patients with severe asthma and available blood eosinophil count (BEC) from 11 countries enrolled in the International Severe Asthma Registry (January 1, 2015-September 30, 2019) were categorized according to likelihood of eosinophilic phenotype using a predefined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic and clinical characteristics were defined at baseline (ie, 1 year before or closest to date of BEC). Results: One thousand seven hundred sixteen patients with prospective data were included; 83.8% were identified as most likely (grade 3), 8.3% were identified as likely (grade 2), and 6.3% identified as least likely (grade 1) to have an eosinophilic phenotype, and 1.6% of patients showed a noneosinophilic phenotype (grade 0). Eosinophilic phenotype patients (ie, grades 2 or 3) showed later asthma onset (29.1 years vs 6.7 years; P < .001) and worse lung function (postbronchodilator % predicted FEV1, 76.1% vs 89.3%; P = .027) than those with a noneosinophilic phenotype. Patients with noneosinophilic phenotypes were more likely to be women (81.5% vs 62.9%; P = .047), to have eczema (20.8% vs 8.5%; P = .003), and to use anti-IgE (32.1% vs 13.4%; P = .004) and leukotriene receptor antagonists (50.0% vs 28.0%; P = .011) add-on therapy. Interpretation: According to this multicomponent, consensus-driven, and evidence-based eosinophil gradient algorithm (using variables readily accessible in real life), the severe asthma eosinophilic phenotype was more prevalent than previously identified and was phenotypically distinct. This pragmatic gradient algorithm uses variables readily accessible in primary and specialist care, addressing inherent issues of phenotype heterogeneity and phenotype instability. Identification of treatable traits across phenotypes should improve therapeutic precision.
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  • Jacobson, Peter, 1962, et al. (author)
  • 9p21.3 Coronary Artery Disease Locus Identifies Patients With Treatment Benefit From Bariatric Surgery in the Nonrandomized Prospective Controlled Swedish Obese Subjects Study.
  • 2020
  • In: Circulation. Genomic and precision medicine. - 2574-8300. ; 13:5, s. 460-465
  • Journal article (peer-reviewed)abstract
    • Sequence variation at chromosome 9p21.3 accounts for 20% of myocardial infarctions (MIs) in several populations. Whereas the risk conferred by the 9p21.3 locus appears to act independently of traditional risk factors, studies suggest that the association between 9p21.3 and MI is modified by glucose homeostasis and lifestyle. We examined if the 9p21.3 variant rs1333049, along with the previously identified predictor fasting insulin, modifies the preventive effect of bariatric surgery on MI incidence.rs1333049 was genotyped in 1852 patients treated by bariatric surgery and 1803 controls given usual care in the SOS study (Swedish Obese Subjects). MI incidence was determined using national registers. Median follow-up was 21 years (interquartile range 18-24 years).Overall, 366 MIs occurred during follow-up. Among rs1333049 risk-allele carriers (CC+GC), the incidence of MI was reduced in the surgery group compared with the control group (hazard ratio=0.72 [95% CI, 0.57-0.92], P=0.008). By contrast, noncarriers (GG) showed no significant differences in MI incidence between the treatment groups (hazard ratio=1.28 [0.86-1.90], P=0.227; interaction between treatment and the risk-allele P=0.016). In addition, carriers with higher fasting insulin (above the median [17 mmol/L]) experienced significantly higher MI incidence than carriers with lower fasting insulin (hazard ratio=0.58 [0.42-0.78], P<0.001, interaction P=0.031).In the SOS cohort, patients with the chromosome 9p21.3 rs1333049 risk allele together with high fasting insulin levels benefitted from bariatric surgery in terms of reduced incidence of MI. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01479452.
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27.
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28.
  • Kristensson, Felipe M., et al. (author)
  • Breast Cancer Risk After Bariatric Surgery and Influence of Insulin Levels: A Nonrandomized Controlled Trial
  • 2024
  • In: JAMA Surgery. - 2168-6254 .- 2168-6262.
  • Journal article (peer-reviewed)abstract
    • Importance: Obesity and insulin are risk factors for breast cancer, and retrospective studies suggest bariatric surgery reduces breast cancer risk in women. However, long-term prospective data on breast cancer risk after bariatric surgery and the role of baseline insulin levels are lacking. Objective: To examine if bariatric surgery is associated with breast cancer incidence in women and if treatment benefit is modified by baseline insulin levels. Design, Setting, and Participants: The Swedish Obese Subjects (SOS) study was a nonrandomized intervention trial designed to investigate the long-term effects of bariatric surgery on obesity-related mortality and morbidity. Study recruitment took place between 1987 and 2001, and median (IQR) follow-up time was 23.9 years (20.1-27.1) years. The study was conducted at 25 public surgical departments and 480 primary health care centers in Sweden and included 2867 women aged 37 to 60 years and with body mass index 38 or greater (calculated as weight in kilograms divided by height in meters squared). Intervention: In the surgery group (n = 1420), 260 women underwent gastric banding, 970 vertical banded gastroplasty, and 190 gastric bypass. The remaining contemporaneously matched control individuals (n = 1447) received usual obesity care. Main Outcome and Measures: Breast cancer, the main outcome of this secondary report, was not a predefined outcome in the SOS study. Breast cancer events were identified in the Swedish National Cancer Registry. Results: The study population comprised 2867 women with a mean (SD) age of 48.0 (6.2) years. During follow-up, there were 154 breast cancer events, 66 in the surgery group and 88 in the usual care group, and a decreased risk of breast cancer was observed in the bariatric surgery group (hazard ratio [HR], 0.68; 95% CI, 0.49-0.94; P =.019; adjusted HR, 0.72; 95% CI, 0.52-1.01; P =.06). The surgical treatment benefit on breast cancer risk was greater in women with baseline insulin levels above the median 15.8 μIU/L (HR, 0.48; 95% CI, 0.31-0.74; P =.001; adjusted HR, 0.55; 95% CI, 0.35-0.86; P =.008) compared to those below (HR, 0.95; 95% CI, 0.59-1.53; P =.84; adjusted HR, 1.01; 95% CI, 0.61-1.66; P =.97; interaction P =.02). Conclusions and Relevance: This prospective clinical trial indicated a reduced risk of breast cancer after bariatric surgery in women with obesity. The surgical treatment benefit was predominantly seen in women with hyperinsulinemia.
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29.
  • Lena, Carlsson, et al. (author)
  • Life Expectancy after Bariatric Surgery in the Swedish Obese Subjects Study.
  • 2020
  • In: The New England journal of medicine. - 1533-4406. ; 383:16, s. 1535-1543
  • Journal article (peer-reviewed)abstract
    • Obesity shortens life expectancy. Bariatric surgery is known to reduce the long-term relative risk of death, but its effect on life expectancy is unclear.We used the Gompertz proportional hazards regression model to compare mortality and life expectancy among patients treated with either bariatric surgery (surgery group) or usual obesity care (control group) in the prospective, controlled Swedish Obese Subjects (SOS) study and participants in the SOS reference study (reference cohort), a random sample from the general population.In total, 2007 and 2040 patients were included in the surgery group and the control group, respectively, and 1135 participants were included in the reference cohort. At the time of the analysis (December 31, 2018), the median duration of follow-up for mortality was 24 years (interquartile range, 22 to 27) in the surgery group and 22 years (interquartile range, 21 to 27) in the control group; data on mortality were available for 99.9% of patients in the study. In the SOS reference cohort, the median duration of follow-up was 20 years (interquartile range, 19 to 21), and data on mortality were available for 100% of participants. In total, 457 patients (22.8%) in the surgery group and 539 patients (26.4%) in the control group died (hazard ratio, 0.77; 95% confidence interval [CI], 0.68 to 0.87; P<0.001). The corresponding hazard ratio was 0.70 (95% CI, 0.57 to 0.85) for death from cardiovascular disease and 0.77 (95% CI, 0.61 to 0.96) for death from cancer. The adjusted median life expectancy in the surgery group was 3.0 years (95% CI, 1.8 to 4.2) longer than in the control group but 5.5 years shorter than in the general population. The 90-day postoperative mortality was 0.2%, and 2.9% of the patients in the surgery group underwent repeat surgery.Among patients with obesity, bariatric surgery was associated with longer life expectancy than usual obesity care. Mortality remained higher in both groups than in the general population. (Funded by the Swedish Research Council and others; SOS ClinicalTrials.gov number, NCT01479452.).
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30.
  • Lohmander, L. S., et al. (author)
  • Bariatric surgery, osteoarthritis and arthroplasty of the hip and knee in Swedish Obese Subjects - up to 31 years follow-up of a controlled intervention study.
  • 2023
  • In: Osteoarthritis and cartilage. - : Elsevier BV. - 1522-9653 .- 1063-4584. ; 31:5, s. 636-646
  • Journal article (peer-reviewed)abstract
    • To study the long-term effect of obesity and bariatric surgery on incidences of osteoarthritis and arthroplasty of hip and knee.Hazard ratios (HR) and incidence rates (IR) of osteoarthritis and arthroplasty of hip and knee were studied in the prospective, controlled, non-randomized Swedish Obese Subjects (SOS) study (bariatric surgery group, n=2007; matched controls given usual obesity care, n=2040) and the SOS reference cohort (n=1135, general population). Osteoarthritis diagnosis and arthroplasty for osteoarthritis were captured from the National Swedish Patient Register. Median follow-up time was 21.2 (IQR 16.4-24.8), 22.9 (IQR 19.1-25.7), and 20.1 years (IQR 18.7-20.9) for the control group, surgery group and reference cohort, respectively.The surgery group displayed lower incidence of hip osteoarthritis (IR 5.3, 95% CI 4.7-6.1) compared to controls (IR 6.6, 95% CI 5.9-7.5, adjHR 0.83, 95% CI 0.69-1.00) but similar incidence of hip arthroplasty. Similar incidence of knee osteoarthritis was observed in the surgery group and controls, but knee arthroplasty was more common in the surgery group (IR 7.4, 95% CI 6.6-8.2 and 5.6, 95% CI 4.9-6.4, adjHR 1.45, 95% CI 1.22-1.74). The reference cohort displayed lower incidences of osteoarthritis and arthroplasty of hip and knee compared with the surgery group and controls.Bariatric surgery did not normalize the increased risk of knee and hip osteoarthritis in patients with obesity but was associated with an increased incidence of knee arthroplasty compared to the control group. With the limitations inherent to the present data, additional studies are needed to confirm these results.clinicaltrials.gov Identifier: NCT01479452.
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31.
  • Nookaew, Intawat, 1977, et al. (author)
  • Adipose Tissue Resting Energy Expenditure and Expression of Genes Involved in Mitochondrial Function Are Higher in Women than in Men.
  • 2013
  • In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 98:2
  • Journal article (peer-reviewed)abstract
    • Context:Men and women differ in body fat distribution and adipose tissue metabolism as well as in obesity comorbidities and their response to obesity treatment.Objective:The objective of the study was a search for sex differences in adipose tissue function.Design and Setting:This was an exploratory study performed at a university hospital.Participants and Main Outcome Measures:Resting metabolic rate (RMR), body composition, and sc adipose tissue genome-wide expression were measured in the SOS Sib Pair study (n = 732).Results:The relative contribution of fat mass to RMR and the metabolic rate per kilogram adipose tissue was higher in women than in men (P value for sex by fat mass interaction = .0019). Women had increased expression of genes involved in mitochondrial function, here referred to as a mitochondrial gene signature. Analysis of liver, muscle, and blood showed that the pronounced mitochondrial gene signature in women was specific for adipose tissue. Brown adipocytes are dense in mitochondria, and the expression of the brown adipocyte marker uncoupling protein 1 was 5-fold higher in women compared with men in the SOS Sib Pair Study (P = 7.43 × 10(-7)), and this was confirmed in a cross-sectional, population-based study (n = 83, 6-fold higher in women, P = .00256).Conclusions:The increased expression of the brown adipocyte marker uncoupling protein 1 in women indicates that the higher relative contribution of the fat mass to RMR in women is in part explained by an increased number of brown adipocytes.
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32.
  • Oertli, Mathias, et al. (author)
  • DC-derived IL-18 drives Treg differentiation, murine Helicobacter pylori-specific immune tolerance, and asthma protection.
  • 2012
  • In: The Journal of clinical investigation. - 1558-8238. ; 122:3, s. 1082-96
  • Journal article (peer-reviewed)abstract
    • Persistent colonization with the gastric bacterial pathogen Helicobacter pylori causes gastritis and predisposes infected individuals to gastric cancer. Conversely, it is also linked to protection from allergic, chronic inflammatory, and autoimmune diseases. We demonstrate here that H. pylori inhibits LPS-induced maturation of DCs and reprograms DCs toward a tolerance-promoting phenotype. Our results showed that DCs exposed to H. pylori in vitro or in vivo failed to induce T cell effector functions. Instead, they efficiently induced expression of the forkhead transcription factor FoxP3, the master regulator of Tregs, in naive T cells. Depletion of DCs in mice infected with H. pylori during the neonatal period was sufficient to break H. pylori-specific tolerance. DC depletion resulted in improved control of the infection but also aggravated T cell-driven immunopathology. Consistent with the mouse data, DCs infiltrating the gastric mucosa of human H. pylori carriers exhibited a semimature DC-SIGN(+)HLA-DR(hi)CD80(lo)CD86(lo) phenotype. Mechanistically, the tolerogenic activity of H. pylori-experienced DCs was shown to require IL-18 in vitro and in vivo; DC-derived IL-18 acted directly on T cells to drive their conversion to Tregs. CD4(+)CD25(+) Tregs from infected wild-type mice but not Il18(-/-) or Il18r1(-/-) mice prevented airway inflammation and hyperresponsiveness in an experimental model of asthma. Taken together, our results indicate that tolerogenic reprogramming of DCs ensures the persistence of H. pylori and protects against allergic asthma in a process that requires IL-18.
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33.
  • Pereira, Maria J., 1981-, et al. (author)
  • Human adipose tissue gene expression of solute carrier family 19 member 3 (SLC19A3); relation to obesity and weight-loss
  • 2022
  • In: Obesity Science & Practice. - : Wiley. - 2055-2238. ; 8:1, s. 21-31
  • Journal article (peer-reviewed)abstract
    • Objective: Adipose tissue is a specialized endocrine organ that is involved in modulating whole-body energy homeostasis and expresses a specific subset of genes, which may play a role in adipose tissue metabolism. The aim of this study was to search for novel adipose tissue-specific genes using a tissue panel of RNAseq expression profiles. Methods: RNAseq expression profiles from 53 human tissues were downloaded from the GTex database. SLC19A3 expression was analyzed by microarray or real-time PCR in two sets of paired subcutaneous and omental adipose tissue samples, in two studies with adipose tissue from persons with high or low body mass index (BMI), in adipose tissue from patients who underwent weight loss with a very-low caloric diet and during preadipocyte-adipocyte differentiation. Results: The RNAseq-based tissue distribution expression screen identified SLC19A3 (encoding the thiamine transporter 2) as adipose tissue-specific. SLC19A3 expression was higher in subcutaneous compared with omental adipose tissue in both sample sets (p = 0.043 and p < 0.001). Preadipocyte differentiation towards adipocytes resulted in increased SLC19A3 gene expression (p = 0.018 or less at all-time points). Subcutaneous adipose tissue expression of SLC19A3 was lower in persons with high BMI in both cohorts (p = 0.008, and p < 0.001) and increased during a weight-loss intervention (p = 0.006). Conclusion: The specific adipose tissue expression pattern of SLC19A3, together with its regulation in obesity and during weight loss, indicate that it plays a key role in adipocyte metabolism.
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34.
  • Porsbjerg, Celeste M., et al. (author)
  • Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma
  • 2024
  • In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 15
  • Journal article (peer-reviewed)abstract
    • Background: To date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials.Aim: To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life.Methods: This was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers.Results: Overall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for antiI-IL4R alpha. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/mu L), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and - anti- IL4R alpha, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4R alpha, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R-2: 0.751), compared to BEC (adjusted R-2: 0.747) or FeNO alone (adjusted R-2: 0.743) (p=0.005 and <0.001, respectively); however, this prediction was not improved by the addition of IgE.Conclusions: The ability of higher baseline BEC, FeNO and their combination to predict biologic-associated lung function improvement may encourage earlier intervention in patients with impaired lung function or at risk of accelerated lung function decline.
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35.
  • Rahman, M, et al. (author)
  • GABA-site antagonism and pentobarbital actions do not depend on the alpha-subunit type in the recombinant rat GABA receptor.
  • 2006
  • In: Acta physiologica (Oxford, England). - : Wiley. - 1748-1708 .- 1748-1716. ; 187:4, s. 479-88
  • Journal article (peer-reviewed)abstract
    • The roles of alpha-subunits on the gamma-aminobutyric acid (GABA)-site antagonism and pentobarbital actions were examined in rat recombinant GABA(A) receptors in Xenopus oocytes.Experiments were performed with binary and ternary GABA(A) receptors containing alpha1-, alpha4- or alpha5-subunit by the two-electrode voltage-clamp technique.The potency of GABA was significantly higher in the alpha1beta2, alpha4beta2 and alpha5beta2 receptors compared with the alpha1beta2gamma2L, alpha4beta2gamma2L and alpha5beta2gamma2L receptors. However, the alpha5beta2 receptor possessed significantly lower GABA efficacy compared with the alpha5beta2gamma2L receptor. While the gamma2-subunit was essential to the potency of GABA, its influence on the apparent GABA-site antagonism was less profound. The antagonist affinity constants (K(B)) of bicuculline inhibition and slopes of Schild plots were similar between all types of ternary and binary receptors except alpha5beta2 receptor which was not tested. The pK(B)s and IC(50)s of the GABA-site antagonism were not significantly different between the alpha1beta2gamma2L, alpha4beta2gamma2L and alpha5beta2gamma2L receptors. Bicuculline blocked pentobarbital-activated currents in a reversible and non-competitive manner with the alpha1beta2gamma2L, alpha4beta2gamma2L, and alpha5beta2gamma2L receptors, indicating an allosteric inhibition of the GABA-site. No significant difference of bicuculline potencies in inhibiting GABA- and pentobarbital-activated currents was found between the alpha1beta2gamma2L, alpha4beta2gamma2L and alpha5beta2gamma2L receptors.The GABA-site antagonism does not depend on the subtype of alpha-subunits. Similarly, pentobarbital activates ternary receptors composed of different alpha-subunits in a bicuculline-sensitive manner. The potencies of bicuculline to inhibit pentobarbital-activated currents are identical with receptors containing alpha1, alpha4 or alpha5-subunit. The alpha1beta2 and alpha4beta2 receptors possess higher GABA potencies compared with the alpha1beta2gamma2L and alpha4beta2gamma2L receptors.
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36.
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37.
  • Sachs, Lisbeth, et al. (author)
  • Risk in numbers - Difficulties in the transformation of genetic knowledge from research to people - The case of hereditary cancer
  • 2001
  • In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 40:4, s. 445-453
  • Journal article (peer-reviewed)abstract
    • Difficulties in communicating diagnostic information are exacerbated when the 'diagnosis' is a 'genetic risk' for cancer. The risk estimation demanded in this situation differs from other types of probability estimations. Observations of participants in 45 consultation sessions between physicians and potential patients were conducted at a clinic for hereditary cancer to explore the communication of genetic information. Thirty-three sessions were audiotaped, transcribed verbatim and analyzed, along with notes from the other sessions. A dominant theme was found to be numerical discussion of risk. Further analysis resulted in the description of problems for practitioners in the process of translating scientific knowledge into clinical management. Problems in providing information include unclear aims of the consultation sessions, mixing various types of background information and probabilities, recognizing how low the predictive values are, and difficulties in communicating the relationship between probability and conclusions. Problems in communicating information about the genetic risk for cancer are of at least two types: dilemmas arising from uncertainties implicit in the nature of the information itself and difficulties in communicating information in a manner that those concerned can interpret. These issues need clarification, so that information with far-reaching consequences can be made as clear and comprehensible as possible for those involved.
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38.
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39.
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40.
  • Sjöholm, Kajsa, 1971, et al. (author)
  • Association of Bariatric Surgery With Cancer Incidence in Patients With Obesity and Diabetes: Long-Term Results From the Swedish Obese Subjects Study.
  • 2022
  • In: Diabetes care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 45:2, s. 444-450
  • Journal article (peer-reviewed)abstract
    • Obesity and type 2 diabetes are associated with serious adverse health effects, including cancer. Although bariatric surgery has been shown to reduce cancer risk in patients with obesity, the effect of bariatric surgery on cancer risk in patients with obesity and diabetes is less studied. We therefore examined the long-term incidence of cancer after bariatric surgery and usual care in patients with obesity and diabetes in the matched prospective Swedish Obese Subjects (SOS) study.The SOS study examines long-term outcomes following bariatric surgery or usual care. The current analysis includes 701 patients with obesity and type 2 diabetes at baseline, 393 of whom underwent bariatric surgery and 308 who received conventional obesity treatment. Information on cancer events was obtained from the Swedish National Cancer Register. Median follow-up time was 21.3 years (interquartile range 17.6-24.8 years, maximum 30.7 years).During follow-up, the incidence rate for first-time cancer was 9.1 per 1,000 person-years (95% CI 7.2-11.5) in patients with obesity and diabetes treated with bariatric surgery and 14.1 per 1,000 person-years (95% CI 11.2-17.7) in patients treated with usual obesity care (adjusted hazard ratio 0.63 [95% CI 0.44-0.89], P = 0.008). Moreover, surgery was associated with reduced cancer incidence in women (0.58 [0.38-0.90], P = 0.016), although the sex-treatment interaction was nonsignificant (P = 0.630). In addition, diabetes remission at the 10-year follow-up was associated with reduced cancer incidence (0.40 [0.22-0.74], P = 0.003).These results suggest that bariatric surgery prevents cancer in patients with obesity and diabetes and that durable diabetes remission is associated with reduced cancer risk.
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41.
  • Sjöholm, Kajsa, 1971, et al. (author)
  • Evaluation of Prediction Models for Type 2 Diabetes Relapse After Post-bariatric Surgery Remission: a Post hoc Analysis of 15-Year Follow-up Data from the Swedish Obese Subjects (SOS) Study.
  • 2020
  • In: Obesity surgery. - : Springer Science and Business Media LLC. - 1708-0428 .- 0960-8923. ; 30, s. 3955-60
  • Journal article (peer-reviewed)abstract
    • Many patients achieve type 2 diabetes (T2D) remission after bariatric surgery, but relapse after post-surgery remission is common. Scoring models accurately predict remission up to 5years after surgery but have not been tested for prediction of long-term T2D relapse. The aim of this work was to test the ability of prediction models and single predictors to identify patients at risk of long-term relapse (10-15years) after post-surgery T2D remission.We identified 222 individuals with T2D from the surgically treated group in the prospective Swedish Obese Subjects study, who were in remission at the 2-year follow-up and had data available for prediction of long-term T2D relapse. T2D remission/relapse was assessed after 10 and 15years. Model performance (discrimination) was evaluated by the area under the receiver operating characteristic (AUROC) curves.Preoperative prediction of relapse using scores DiaRem, Ad-DiaRem, and DiaBetter and T2D duration alone was poor, as indicated by AUROC curves between 0.61-0.64 at 10years and 0.62-0.66 at 15years. Likewise, the 5y-Ad-DiaRem score, which includes early postoperative measures, resulted in AUROC curves of 0.65 and 0.70 for relapse at 10 and 15years, respectively. Two-year weight change alone had higher discriminatory capacity than the 5y-Ad-DiaRem model at 10years (AUROC=0.70; p=0.036) and similar capacity at 15years (AUROC=0.78; p=0.188).Predictive performance of all tested models is low for T2D relapse. By contrast, a single measure of 2-year weight change after surgery was associated with relapse, supporting a key role for initial weight reduction in long-term T2D control.
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42.
  • Sjöholm, Kajsa, 1971, et al. (author)
  • Long-term incidence of hypoglycaemia-related events after bariatric surgery or usual care in the Swedish Obese Subjects study: A register-based analysis
  • 2021
  • In: Diabetes Obesity & Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 23:8, s. 1917-1925
  • Journal article (peer-reviewed)abstract
    • Aims To examine the incidence of hypoglycaemia-related events over a period of up to 31 years in patients treated with bariatric surgery in the prospective, controlled Swedish Obese Subjects (SOS) study. Materials and Methods The SOS study (n = 4047) is a prospective controlled intervention study. The present analysis included 1989 patients treated with bariatric surgery and 2027 control patients with obesity who received usual care. Diagnosed hypoglycaemia and events commonly attributed to hypoglycaemia (confusion, syncope, epilepsy and seizures), requiring hospital or specialist outpatient treatment, were identified by searching the National Patient Register. Analyses were stratified by baseline glycaemic status. Hazard ratios were adjusted for inclusion year, age, sex, smoking, glycated haemoglobin (HbA1c) level and body mass index at baseline. At the time of analysis (December 31, 2018), the median follow-up was 22 years. Results Compared with usual care, bariatric surgery was associated with increased incidence of hypoglycaemia-related events in patients without baseline diabetes (168 and 219 events, respectively; log-rank P = .011), with a more pronounced risk during the first years of follow-up (test of time-treatment interaction P = .010). Multivariate analyses in patients without baseline diabetes indicated that male sex (P < .001), older age (P = .001) and higher HbA1c levels (P = .006) were associated with hypoglycaemia-related events. No association was found between risk of hypoglycaemia-related events and bariatric surgery in patients with baseline diabetes. Conclusions Bariatric surgery is associated with an increased incidence of hypoglycaemia-related events in patients without baseline diabetes, especially during the first years after treatment.
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43.
  •  
44.
  • Svensson, Per-Arne, 1969, et al. (author)
  • Non-alcohol substance use disorder after bariatric surgery in the prospective, controlled Swedish Obese Subjects study.
  • 2023
  • In: Obesity (Silver Spring, Md.). - 1930-739X. ; 31:8, s. 2171-2177
  • Journal article (peer-reviewed)abstract
    • The goal of this study was to investigate whether bariatric surgery is associated with substance use disorder (SUD) with substances other than alcohol.The prospective, controlled Swedish Obese Subjects study enrolled 2010 patients with obesity who underwent bariatric surgery (gastric bypass n=265; vertical banded gastroplasty n=1369; gastric banding n=376) and 2037 matched control individuals receiving usual obesity care. Participants with SUD other than alcohol use disorder were identified using International Statistical Classification of Diseases (ICD) codes from the Swedish National Patient Register (covering treatment in hospital but not primary care). Those with a history of non-alcohol SUD were excluded. Median follow-up was 23.8years.During follow-up, non-alcohol SUD incidence rates per 1000 person-years with 95% CI were 1.6 (0.8-3.1), 0.8 (0.5-1.2), 1.1 (0.5-2.2), and 0.6 (0.4-0.8) for gastric bypass, vertical banded gastroplasty, gastric banding, and control individuals, respectively. Only gastric bypass was associated with increased incidence of non-alcohol SUD (adjusted hazard ratio 2.54 [95% CI: 1.14-5.65], p=0.022) compared with control participants.Gastric bypass surgery was associated with increased risk of non-alcohol SUD, and this should be considered in long-term postoperative care.
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45.
  • Svensson, Per-Arne, 1969, et al. (author)
  • The TGR5 gene is expressed in human subcutaneous adipose tissue and is associated with obesity,Weight loss and resting metabolic rate
  • 2013
  • In: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 433:4, s. 563-566
  • Journal article (peer-reviewed)abstract
    • Bile acids have emerged as a new class of signaling molecules that play a role in metabolism. Studies in mice have shown that the bile acid receptor TGR5 mediates several of these effects but the metabolic function of TGR5 in humans is less well established. Here we show that human adipose tissue TGR5 expression is positively correlated to obesity and reduced during diet-induced weight loss. Adipose tissue TGR5 expression was also positively correlated to resting metabolic rate. Our study indicates that human adipose tissue contributes to the TGR5 mediated metabolic effects of bile acids and plays a role in energy expenditure. (C) 2013 Elsevier Inc. All rights reserved.
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46.
  • Taube, Magdalena, et al. (author)
  • Association of Bariatric Surgery With Skin Cancer Incidence in Adults With Obesity: A Nonrandomized Controlled Trial.
  • 2020
  • In: JAMA dermatology. - : American Medical Association (AMA). - 2168-6084 .- 2168-6068. ; 156:1, s. 38-43
  • Journal article (peer-reviewed)abstract
    • Obesity is a cancer risk factor, and bariatric surgery in patients with obesity is associated with reduced cancer risk. However, evidence of an association among obesity, bariatric surgery, and skin cancer, including melanoma, is limited.To investigate the association of bariatric surgery with skin cancer (squamous cell carcinoma and melanoma) and melanoma incidence.This nonrandomized controlled trial, the Swedish Obese Subjects (SOS) study, is ongoing at 25 surgical departments and 480 primary health care centers in Sweden and was designed to examine outcomes after bariatric surgery. The study included 2007 patients with obesity who underwent bariatric surgery and 2040 contemporaneously matched controls who received conventional obesity treatment. Patients were enrolled between September 1, 1987, and January 31, 2001. Data analysis was performed from June 29, 2018, to November 22, 2018.Patients in the surgery group underwent gastric bypass (n=266), banding (n=376), or vertical banded gastroplasty (n=1365). The control group (n=2040) received the customary treatment for obesity at their primary health care centers.The SOS study was cross-linked to the Swedish National Cancer Registry, the Cause of Death Registry, and the Registry of the Total Population for data on cancer incidence, death, and emigration.The study included 4047 participants (mean [SD] age, 47.9 [6.1] years; 2867 [70.8%] female). Information on cancer events was available for 4042 patients. The study found that bariatric surgery was associated with a markedly reduced risk of melanoma (adjusted subhazard ratio, 0.43; 95% CI, 0.21-0.87; P=.02; median follow-up, 18.1 years) and risk of skin cancer in general (adjusted subhazard ratio, 0.59; 95% CI, 0.35-0.99; P=.047). The skin cancer risk reduction was not associated with baseline body mass index or weight; insulin, glucose, lipid, and creatinine levels; diabetes; blood pressure; alcohol intake; or smoking.The results of this study suggest that bariatric surgery in individuals with obesity is associated with a reduced risk of skin cancer, including melanoma.ClinicalTrials.gov identifier: NCT01479452.
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47.
  • Taube, Magdalena, et al. (author)
  • Evaluation of reference genes for gene expression studies in human brown adipose tissue.
  • 2015
  • In: Adipocyte. - : Informa UK Limited. - 2162-3945 .- 2162-397X. ; 4:4, s. 280-5
  • Journal article (peer-reviewed)abstract
    • Human brown adipose tissue (BAT) has during the last 5 year been subjected to an increasing research interest, due to its putative function as a target for future obesity treatments. The most commonly used method for molecular studies of human BAT is the quantitative polymerase chain reaction (qPCR). This method requires normalization to a reference gene (genes with uniform expression under different experimental conditions, e.g. similar expression levels between human BAT and WAT), but so far no evaluation of reference genes for human BAT has been performed. Two different microarray datasets with samples containing human BAT were used to search for genes with low variability in expression levels. Seven genes (FAM96B, GNB1, GNB2, HUWE1, PSMB2, RING1 and TPT1) identified by microarray analysis, and 8 commonly used reference genes (18S, B2M, GAPDH, LRP10, PPIA, RPLP0, UBC, and YWHAZ) were selected and further analyzed by quantitative PCR in both BAT containing perirenal adipose tissue and subcutaneous adipose tissue. Results were analyzed using 2 different algorithms (Normfinder and geNorm). Most of the commonly used reference genes displayed acceptably low variability (geNorm M-values <0.5) in the samples analyzed, but the novel reference genes identified by microarray displayed an even lower variability (M-values <0.25). Our data suggests that PSMB2, GNB2 and GNB1 are suitable novel reference genes for qPCR analysis of human BAT and we recommend that they are included in future gene expression studies of human BAT.
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48.
  • Taube, Magdalena, et al. (author)
  • Long-term incidence of colorectal cancer after bariatric surgery or usual care in the Swedish Obese Subjects study.
  • 2021
  • In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 16:3
  • Journal article (peer-reviewed)abstract
    • Bariatric surgery in patients with obesity is generally considered to reduce cancer risk in patients with obesity. However, for colorectal cancer some studies report an increased risk with bariatric surgery, whereas others report a decreased risk. These conflicting results demonstrate the need of more long-term studies analyzing the effect of bariatric surgery on colorectal cancer risk. Therefore, data from the Swedish Obese Subjects (SOS) study, ClinicalTrials.gov identifier: NCT01479452, was used to examine the impact of bariatric surgery on long-term incidence of colorectal cancer. The SOS study includes 2007 patients who underwent bariatric surgery and 2040 contemporaneously matched controls who received conventional obesity treatment. Patients in the surgery group underwent gastric bypass (n = 266), banding (n = 376) or vertical banded gastroplasty (n = 1365). Information on colorectal cancer events was obtained from the Swedish National Cancer Registry. Median follow-up was 22.2 years (inter-quartile range 18.3-25.2). During follow up there were 58 colorectal cancer events in the surgery group and 67 colorectal cancer events in the matched control group with a hazard ratio (HR) of 0.79 (95% CI:0.55-1.12; p = 0.183). After adjusting for age, body mass index, alcohol intake, smoking status, and diabetes, the adjusted HR was 0.89 (95% CI:0.62-1.29; p = 0.551). When analyzing rectal cancer events separately- 19 events in the surgery group and 31 events in the control group-a decreased risk of rectal cancer with surgery was observed (HR = 0.56; 95% CI:0.32-0.99; p = 0.045, adjusted HR = 0.61 (95% CI:0.34-1.10; p = 0.099), while the risk of colon cancer was unchanged. To conclude- in this long-term, prospective study, bariatric surgery was not associated with altered colorectal cancer risk.
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