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  • 1.
    Ahmad, Awais
    et al.
    Linköping Univ, Dept Biomed & Clin Sci, Div Inflammat & Infect, Clin Immunol & Transfus Med, SE-58183 Linköping, Sweden..
    Dahle, Charlotte
    Linköping Univ, Dept Biomed & Clin Sci, Div Inflammat & Infect, Clin Immunol & Transfus Med, SE-58183 Linköping, Sweden..
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Sjowall, Christopher
    Linköping Univ, Dept Biomed & Clin Sci, Div Inflammat & Infect Rheumatol, SE-58183 Linköping, Sweden..
    Kechagias, Stergios
    Linköping Univ, Dept Hlth Med & Caring Sci, Div Diagnost & Specialist Med Gastroenterol & Hep, SE-58183 Linköping, Sweden..
    Autoantibodies Associated with Autoimmune Liver Diseases in a Healthy Population: Evaluation of a Commercial Immunoblot Test2022In: Diagnostics, ISSN 2075-4418, Vol. 12, no 7, article id 1572Article in journal (Refereed)
    Abstract [en]

    Autoantibodies constitute important tools for diagnosing the autoimmune liver diseases (AILD) autoimmune hepatitis and primary biliary cholangitis. The EUROLINE immunoblot assay, detecting multiple specificities, is widely used, but the clinical importance of weakly positive findings is unclear. The manufacturer's recommended cut-off was evaluated by investigating AILD-associated autoantibodies in 825 blood donors and 60 confirmed AILD cases. Positive findings were followed up with immunofluorescence microscopy on rat tissue, anti-M2-ELISA, alternative immunoblot assay, and liver function tests. Thirty-six (4.4%) blood donors were positive with EUROLINE. The most common specificities were LC-1 (1.6%), gp210 (1.3%), and AMA-M2 (1.1%). In general, the positive results were higher in patients than in blood donors, whereas anti-LC-1 was higher in blood donors. The liver function tests were slightly elevated in 2 of the 36 immunoblot positive blood donors. The majority of the positive EUROLINE findings could not be confirmed with the follow-up tests. The EUROLINE-Autoimmune Liver Diseases-(IgG) immunoblot detected autoantibodies in 4.4% of blood donors without signs of AILD. Our findings indicate that the recommended cut-off can be raised for most specificities without loss of diagnostic sensitivity. The prevalence of anti-LC-1 among blood donors indicates a problem with the antigen source.

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  • 2.
    Ahmad, Shafqat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Carrasquilla, Germán
    Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Langner, Taro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Menzel, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Malmberg, Filip
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hammar, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Censin, Jenny C.
    Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK; 7Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
    Sayols-Baixeras, Sergi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nguyen, Diem
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Mora, Andrés Martínez
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Jan W.
    Clinical Diabetes and Metabolism, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Genetics of liver fat and volume associate with altered metabolism and whole body magnetic resonance imaging2022In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 77, p. S40-S40Article in journal (Other academic)
  • 3.
    Akbari, Camilla
    et al.
    Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden..
    Dodd, Maja
    Karolinska Univ Hosp, Dept Upper GI, Div Hepatol, Stockholm, Sweden..
    Stål, Per
    Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Upper GI, Div Hepatol, Stockholm, Sweden..
    Nasr, Patrik
    Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden.;Linköping Univ, Dept Gastroenterol & Hepatol, Div Internal Med, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Ekstedt, Mattias
    Kechagias, Stergios
    Linköping Univ, Dept Gastroenterol & Hepatol, Div Internal Med, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Vessby, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Zhang, Xiao
    Merck & Co Inc, Rahway, NJ USA..
    Wang, Tongtong
    Merck & Co Inc, Rahway, NJ USA..
    Jemielita, Thomas
    Merck & Co Inc, Rahway, NJ USA..
    Fernandes, Gail
    Merck & Co Inc, Rahway, NJ USA..
    Engel, Samuel S.
    Merck & Co Inc, Rahway, NJ USA..
    Hagström, Hannes
    Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Upper GI, Div Hepatol, Stockholm, Sweden.;Karolinska Univ Hosp, Div Hepatol, C1 77, S-14186 Stockholm, Sweden..
    Shang, Ying
    Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden..
    Long-term major adverse liver outcomes in 1,260 patients with non-cirrhotic NAFLD2024In: JHEP Reports, E-ISSN 2589-5559, Vol. 6, no 2, article id 100915Article in journal (Refereed)
    Abstract [en]

    Background & Aims

    Long-term studies of the prognosis of NAFLD are scarce. Here, we investigated the risk of major adverse liver outcomes (MALO) in a large cohort of patients with NAFLD.

    Methods

    We conducted a cohort study with data from Swedish university hospitals. Patients (n = 1,260) with NAFLD without cirrhosis were diagnosed through biopsy or radiology, and had fibrosis estimated through vibration-controlled transient elastography, biopsy, or FIB-4 score between 1974 and 2020 and followed up through 2020. Each patient was matched on age, sex, and municipality with up to 10 reference individuals from the general population (n = 12,529). MALO were ascertained from Swedish national registers. The rate of events was estimated by Cox regression.

    Results

    MALO occurred in 111 (8.8%, incidence rate = 5.9/1,000 person-years) patients with NAFLD and 197 (1.6%, incidence rate = 1.0/1,000 person-years) reference individuals during a median follow up of 13 years. The rate of MALO was higher in patients with NAFLD (hazard ratio = 6.6; 95% CI = 5.2–8.5). The risk of MALO was highly associated with the stage of fibrosis at diagnosis. In the biopsy subcohort (72% of total sample), there was no difference in risk between patients with and without non-alcoholic steatohepatitis. The 20-year cumulative incidences of MALO were 2% for the reference population, 3% for patients with F0, and 35% for F3. Prognostic information from biopsy was comparable to FIB-4 (C-indices around 0.73 vs. 0.72 at 10 years).

    Conclusions

    This study provides updated information on the natural history of NAFLD, showing a high rate of progression to cirrhosis in F3 and a similar prognostic capacity of non-invasive tests to liver biopsy.

    Impact and implications

    Several implications for clinical care and future research may be noted based on these results. First, the risk estimates for cirrhosis development are important when communicating risk to patients and deciding on clinical monitoring and treatment. Estimates can also be used in updated health-economic evaluations, and for regulatory agencies. Second, our results again highlight the low predictive information obtained from ascertaining NASHstatus by histology and call for more objective means by which to define NASH. Such methods may include artificial intelligence-supported digital pathology. We highlight that NASH is most likely the causal factor for fibrosis progression in NAFLD, but the subjective definition makes the prognostic value of a histological NASH diagnosis of limited value. Third, the finding that prognostic information from biopsy and the very simple Fibrosis-4 score were comparable is important as it may lead to fewer biopsies and further move the field towards non-invasive means by which to define fibrosis and, importantly, use non-invasive tests as outcomes in clinical trials. However, all modalities had modest discriminatory capacity and new risk stratification systems are needed in NAFLD. Repeated measures of non-invasive scores may be a potential solution.

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  • 4.
    Alexander, Tobias
    et al.
    Charite Univ Med Berlin, Dept Rheumatol & Clin Immunol, Berlin, Germany.;Free Univ Berlin, Berlin, Germany.;Humboldt Univ, Berlin, Germany.;Berlin Inst Hlth BIH, Berlin, Germany.;Deutsch Rheuma Forschungszentrum DRFZ Berlin, Berlin, Germany..
    Snowden, John A.
    Sheffield Teaching Hospitals Fdn NHS Trust, Dept Haematol, Sheffield, S Yorkshire, England.;Univ Sheffield, Dept Oncol & Metab, Sheffield, S Yorkshire, England..
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Chang, Hyun-Dong
    Deutsch Rheuma Forschungszentrum DRFZ Berlin, Berlin, Germany.;Tech Univ Berlin, Inst Biotechnol, Berlin, Germany..
    Del Papa, Nicoletta
    ASST G PiniCTO, Dip Reumatol, Scleroderma Clin, Milan, Italy..
    Farge, Dominique
    CRMR MATHEC, Malad AutoImmunes & Therapie Cellulaire, Unite Med Interne UF 04, Paris, France.;Univ Paris, IRSL, Rech Clin Appl Hematol, Paris, France.;McGill Univ, Dept Med, Montreal, PQ, Canada..
    Lindsay, James O.
    Queen Mary Univ London, Blizard Inst, Ctr Immunobiol, Barts & London Sch Med, London, England..
    Malard, Florent
    Sorbonne Univ, Serv Hematol Clin & Therapie Cellulaire, Hop St Antoine, AP HP,INSERM,UMRs 938, Paris, France..
    Muraro, Paolo A.
    Imperial Coll London, Dept Brain Sci, London, England..
    Nitti, Rosamaria
    Univ Vita Salute San Raffaele, IRCCS San Raffaele Sci Inst, Unit Hematol & Bone Marrow Transplantat, Milan, Italy..
    Salas, Azucena
    IDIBAPS, CIBER, EHD, Barcelona, Spain..
    Sharrack, Basil
    Sheffield Teaching Hosp NHS, Dept Neurosci, Fdn Trust, Sheffield, S Yorkshire, England.;Univ Sheffield, NIHR Neurosci BioMed Res Ctr, Sheffield, S Yorkshire, England..
    Mohty, Mohamad
    Sorbonne Univ, Serv Hematol Clin & Therapie Cellulaire, Hop St Antoine, AP HP,INSERM,UMRs 938, Paris, France..
    Greco, Raffaella
    Univ Vita Salute San Raffaele, IRCCS San Raffaele Sci Inst, Unit Hematol & Bone Marrow Transplantat, Milan, Italy..
    Intestinal Microbiome in Hematopoietic Stem Cell Transplantation For Autoimmune Diseases: Considerations and Perspectives on Behalf of Autoimmune Diseases Working Party (ADWP) of the EBMT2021In: Frontiers in Oncology, E-ISSN 2234-943X, Vol. 11, article id 722436Article in journal (Refereed)
    Abstract [en]

    Over the past decades, hematopoietic stem cell transplantation (HSCT) has been evolving as specific treatment for patients with severe and refractory autoimmune diseases (ADs), where mechanistic studies have provided evidence for a profound immune renewal facilitating the observed beneficial responses. The intestinal microbiome plays an important role in host physiology including shaping the immune repertoire. The relationships between intestinal microbiota composition and outcomes after HSCT for hematologic diseases have been identified, particularly for predicting the mortality from infectious and non-infectious causes. Furthermore, therapeutic manipulations of the gut microbiota, such as fecal microbiota transplant (FMT), have emerged as promising therapeutic approaches for restoring the functional and anatomical integrity of the intestinal microbiota post-transplantation. Although changes in the intestinal microbiome have been linked to various ADs, studies investigating the effect of intestinal dysbiosis on HSCT outcomes for ADs are scarce and require further attention. Herein, we describe some of the landmark microbiome studies in HSCT recipients and patients with chronic ADs, and discuss the challenges and opportunities of microbiome research for diagnostic and therapeutic purposes in the context of HSCT for ADs.

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  • 5.
    Alexandersson, Bjarki T.
    et al.
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden..
    Hugerth, Luisa W.
    Karolinska Inst, Tumour & Cell Biol MTC, Dept Microbiol, Sci Life Lab,CTMR, Solna, Sweden..
    Hedin, Charlotte
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Gastroenterol Dermatovenereol & Rheumatol, Gastroenterol Unit, Stockholm, Sweden..
    Forsberg, Anna
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden..
    Talley, Nicholas J.
    Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW, Australia..
    Agreus, Lars
    Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden..
    Jarbrink-Sehgal, Ellionore
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden.;Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Sect Gastroenterol & Hepatol, Houston, TX USA..
    Engstrand, Lars
    Karolinska Inst, Tumour & Cell Biol MTC, Dept Microbiol, Sci Life Lab,CTMR, Solna, Sweden..
    Andreasson, Anna
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden.;Stockholm Univ, Stress Res Inst, Stockholm, Sweden.;Macquarie Univ, Dept Psychol, N Ryde, NSW, Australia..
    Schmidt, Peter T.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology. Karolinska Inst, Dept Med Solna, Stockholm, Sweden..
    Diverticulosis is not associated with altered gut microbiota nor is it predictive of future diverticulitis: a population-based colonoscopy study2023In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 58, no 10, p. 1131-1138, article id 2194010Article in journal (Refereed)
    Abstract [en]

    Background: The etiopathogenesis of diverticular disease is unknown. Objective: To compare the fecal and mucosa-associated microbiota between participants with and without diverticulosis and participants who later developed diverticulitis versus those that did not from a population-based study. Methods: The PopCol study, conducted in Stockholm, Sweden, invited a random sample of 3556 adults to participate, of which 745 underwent colonoscopy. Overall, 130 participants (17.5%) had diverticulosis. 16S rRNA gene sequencing was conducted on available sigmoid biopsy samples from 529 and fecal samples from 251 individuals. We identified individuals who subsequently developed acute diverticulitis up to 13 years after sample collection. In a case-control design matching for gender, age (+/-5 years), smoking and antibiotic exposure, we compared taxonomic composition, richness and diversity of the microbiota between participants with or without diverticulosis, and between participants who later developed acute diverticulitis versus those who did not. Results: No differences in microbiota richness or diversity were observed between participants with or without diverticulosis, nor for those who developed diverticulitis compared with those who did not. No bacterial taxa were significantly different between participants with diverticulosis compared with those without diverticulosis. Individuals who later developed acute diverticulitis (2.8%) had a higher abundance of genus Comamonas than those who did not (p =.027). Conclusions: In a population-based cohort study the only significant difference was that those who later develop diverticulitis had more abundance of genus Comamonas. The significance of Comamonas is unclear, suggesting a limited role for the gut microbiota in the etiopathogenesis of diverticular disease.

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  • 6.
    Alfonsson, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Weineland-Strandskov, Sandra
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Self-Reported Hedonism Predicts 12-Month Weight Loss After Roux-en-Y Gastric Bypass2017In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 27, no 8, p. 2073-2078Article in journal (Refereed)
    Abstract [en]

    Introduction Research regarding psychological risk factors for reduced weight loss after bariatric surgery has yielded mixed results, especially for variables measured prior to surgery. More profound personality factors have shown better promise and one such factor that may be relevant in this context is time perspective, i.e., the tendency to focus on present or future consequences. The aim of this study was to investigate the predictive value of time perspective for 12-month weight loss after Roux-en-Y gastric bypass surgery.

    Methods A total of 158 patients were included and completed self-report instruments prior to surgery. Weight loss was measured after 12 months by medical staff. Background variables as well as self-reported disordered eating, psychological distress, and time perspective were analyzed with regression analysis to identify significant predictors for 12-month weight loss.

    Results The mean BMI loss at 12 months was 14 units, from 45 to 30 kg/m(2). Age, sex, and time perspective could significantly predict weight loss but only male sex and self-reported hedonism were independent risk factors for reduced weight loss in the final regression model.

    Conclusion In this study, self-reported hedonistic time perspective proved to be a better predictor for 12-month weight loss than symptoms of disordered eating and psychological distress. It is possible that a hedonistic tendency of focusing on immediate consequences and rewards is analogous to the impaired delay discounting seen in previous studies of bariatric surgery candidates. Further studies are needed to identify whether these patients may benefit from extended care and support after surgery.

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  • 7.
    Al-Saffar, Ahmad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Takemi, Shota
    Saitama Univ, Grad Sch Sci & Engn, Div Life Sci, Area Regulatory Biol,Sakura Ku, 255 Shimo Ohkubo, Saitama 3388570, Japan.
    Saaed, Hiwa K.
    Univ Sulaimani, Coll Pharm, Dept Pharmacol & Toxicol, Sulaymaniyah, Iraq.
    Sakata, Ichiro
    Saitama Univ, Grad Sch Sci & Engn, Div Life Sci, Area Regulatory Biol,Sakura Ku, 255 Shimo Ohkubo, Saitama 3388570, Japan.
    Sakai, Takafumi
    Saitama Univ, Grad Sch Sci & Engn, Div Life Sci, Area Regulatory Biol,Sakura Ku, 255 Shimo Ohkubo, Saitama 3388570, Japan;Saitama Univ, Grad Sch Sci & Engn, Div Strategy Res, Area Life NanoBio,Sakura Ku, 255 Shimo Ohkubo, Saitama 3388570, Japan.
    Utility of animal gastrointestinal motility and transit models in functional gastrointestinal disorders2019In: Baillière's Best Practice & Research: Clinical Gastroenterology, ISSN 1521-6918, E-ISSN 1532-1916, Vol. 40-41, article id 101633Article, review/survey (Refereed)
    Abstract [en]

    Alteration in the gastrointestinal (GI) motility and transit comprises an important component of the functional gastrointestinal disorders (FGID). Available animal GI motility and transit models are to study symptoms (delayed gastric emptying, constipation, diarrhea) rather than biological markers to develop an effective treatment that targets the underlying mechanism of altered GI motility in patients. Animal data generated from commonly used methods in human like scintigraphy, breath test and wireless motility capsule may directly translate to the clinic. However, species differences in the control mechanism or pharmacological responses of GI motility may compromise the predictive and translational value of the preclinical data to human. In this review we aim to provide a summary on animal models used to mimic GI motility alteration in FGID, and the impact of the species differences in the physiological and pharmacological responses on the translation of animal GI motility and transit data to human. 

  • 8.
    Al-Saffar, Anas K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology. Baghdad Univ, Coll Vet Medicine, Dept Surg & Obstet, Baghdad, Iraq..
    Halim, Md Abdul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Hall, G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Hellström, Per M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Webb, Dominic-Luc
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Small intestinal lactulose and sucralose hyper-permeability in inflammatory bowel disease2018In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, p. S124-S124Article in journal (Other academic)
  • 9.
    Al-Saffar, Anas Kh.
    et al.
    Baghdad University/ College of Veterinary Medicine.
    Halim, Abdul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Hellström, Per M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Webb, Dominic-Luc
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Concurrent small and large intestinal permeability in inflammatory bowel disease: Hyper-permeability in IBDManuscript (preprint) (Other (popular science, discussion, etc.))
    Abstract [en]

    Hyper-permeability in inflammatory bowel disease (IBD) has mostly been explored in the colon, where symptomatic inflammation is prevalent. Relationships between small and large intestine barrier function were examined. Fasted (4h) IBD (19 ulcerative colitis, 11 Crohn's disease) and 25 healthy control subjects’ were investigated. Lactulose (10g), mannitol (5g), riboflavin (0.05g) and sucralose (5g) were ingested with 500 mL water. Urine lactulose and mannitol were measured by enzyme assays, riboflavin by intrinsic fluorescence and sucralose by HPLC. CRP was measured by nephelometry. In IBD, small intestine lactulose and sucralose % recoveries were 1.77 and 2.73 fold higher than controls; combined data revealed the two probes were correlated (R2=0.6). In IBD, large intestine sucralose % recovery was 2.6 fold higher than controls and correlated with small intestine sucralose % recovery (R2=0.6). Conclusions: Sucralose yields similar result as lactulose for small intestine permeability, while having higher S:N, implying sucralose is more sensitive. No evidence was found for riboflavin malabsorption in IBD. There is concurrent small and large intestine hyper-permeability in IBD. Small intestine hyper-permeability is presumably related to inflammation in the large intestine, but without obvious deficiency in transporter mediated micronutrient absorption (i.e., riboflavin) in the small intestine.

  • 10.
    Al-Saffar, Anas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Meijer, Carl Hampus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Gannavarapu, Venkata Ram
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Hall, Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Li, Yichen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Diaz Tartera, Hetzel O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Lördal, Mikael
    Department of Medicine, Division of Gastroenterology and Hepatology, Danderyds Sjukhus, Danderyd, Sweden.
    Ljung, Tryggve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology. Abbvie, Solna, Sweden.
    Hellström, Per M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Webb, Dominic-Luc
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Parallel Changes in Harvey-Bradshaw Index, TNFα, and Intestinal Fatty Acid Binding Protein  in Response to Infliximab in Crohn’s Disease2017In: Gastroenterology Research and Practice, ISSN 1687-6121, E-ISSN 1687-630X, p. 1-8, article id 1745918Article in journal (Refereed)
    Abstract [en]

    Intestinal fatty acid binding protein (I-FABP) indicates barrier integrity. Aims: determine if I-FABP is elevated in active Crohn's disease (CD) and if I-FABP parallels anti-TNF alpha antibody (infliximab) induced lowering of TNF alpha and Harvey-Bradshaw Index (HBI) as potential indicator of mucosal healing. I-FABP distribution along human gut was determined. Serum from 10 CD patients collected during first three consecutive infliximab treatments with matched pretreatment and follow-up samples one week after each treatment and corresponding HBI data were analyzed. I-FABP reference interval was established from 31 healthy subjects with normal gut permeability. I-FABP and TNF alpha were measured by ELISA; CRP was measured by nephelometry. Healthy tissue was used for I-FABP immunohistochemistry. Pretreatment CD patient TNF alpha was 1.6-fold higher than in-house reference interval, while I-FABP was 2.5-fold higher, which lowered at follow-ups. Combining all 30 infusion/follow-up pairs also revealed changes in I-FABP. HBI followed this pattern; CRP declined gradually. I-FABP was expressed in epithelium of stomach, jejunum, ileum, and colon, with the highest expression in jejunum and ileum. I-FABP is elevated in active CD with a magnitude comparable to TNF alpha. Parallel infliximab effects on TNF alpha, HBI, and I-FABP were found. I-FABP may be useful as an intestine selective prognostic marker in CD.

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  • 11.
    Alsaqal, Salem
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hockings, Paul
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical, Mölndal, Sweden.
    Gummesson, Anders
    Hedström, Anders
    Hulthe, Johannes
    Johansson, Lars
    Niessen, Heiko G
    Schoelch, Corinna
    Schultheis, Christian
    Vessby, Johan
    Wanders, Alkwin
    Rorsman, Fredrik
    Ebeling Barbier, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    The Combination of MR Elastography and Proton Density Fat Fraction Improves Diagnosis of Nonalcoholic Steatohepatitis.2022In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 56, no 2, p. -379Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is rapidly increasing worldwide. It is subdivided into nonalcoholic fatty liver (NAFL) and the more aggressive form, nonalcoholic steatohepatitis (NASH), which carries a higher risk of developing fibrosis and cirrhosis. There is currently no reliable non-invasive method for differentiating NASH from NAFL.

    PURPOSE: To investigate the ability of magnetic resonance imaging (MRI)-based imaging biomarkers to diagnose NASH and moderate fibrosis as well as assess their repeatability.

    STUDY TYPE: Prospective.

    SUBJECTS: Sixty-eight participants (41% women) with biopsy-proven NAFLD (53 NASH and 15 NAFL). Thirty participants underwent a second MRI in order to assess repeatability.

    FIELD STRENGTH/SEQUENCE: 3.0 T; MR elastography (MRE) (a spin-echo echo-planar imaging [SE-EPI] sequence with motion-encoding gradients), MR proton density fat fraction (PDFF) and R2* mapping (a multi-echo three-dimensional gradient-echo sequence), T1 mapping (a single-point saturation-recovery technique), and diffusion-weighted imaging (SE-EPI sequence).

    ASSESSMENT: Quantitative MRI measurements were obtained and assessed alone and in combination with biochemical markers (cytokeratin-18 [CK18] M30, alanine transaminase [ALT], and aspartate transaminase [AST]) using logistic regression models. Models that could differentiate between NASH and NAFL and between moderate to advanced fibrosis (F2-4) and no or mild fibrosis (F0-1), based on the histopathological results, were identified.

    STATISTICAL TESTS: Independent samples t-test, Pearson's chi-squared test, area under the receiver operating characteristic curve (AUROC), Spearman's correlation, intra-individual coefficient of variation, and intraclass correlation coefficient (ICC). Statistical significance was set at P < 0.05.

    RESULTS: There was a significant difference between the NASH and NAFL groups with liver stiffness assessed with MRE, CK18 M30, and ALT, with an AUROC of 0.74, 0.76, and 0.70, respectively. Both MRE and PDFF contributed significantly to a bivariate model for diagnosing NASH (AUROC = 0.84). MRE could significantly differentiate between F2-4 and F0-1 (AUROC = 0.74). A model combining MRE with AST improved the diagnosis of F2-4 (AUROC = 0.83). The ICC for repeatability was 0.94 and 0.99 for MRE and PDFF, respectively.

    DATA CONCLUSION: MRE can potentially diagnose NASH and differentiate between fibrosis stages. Combining MRE with PDFF improves the diagnosis of NASH.

    LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

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  • 12.
    Amcoff, K.
    et al.
    Orebro Univ, Dept Gastroenterol, Fac Med & Hlth, Orebro, Sweden..
    Cao, Y.
    Univ Orebro, Sch Med Sci, Clin Epidemiol & Biostat, Orebro, Sweden..
    Zhulina, Y.
    Orebro Univ, Dept Gastroenterol, Fac Med & Hlth, Orebro, Sweden..
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Halfvarson, J.
    Orebro Univ, Dept Gastroenterol, Fac Med & Hlth, Orebro, Sweden..
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Prognostic significance of eosinophil granule proteins in inflammatory bowel disease2018In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, p. S181-S182Article in journal (Other academic)
  • 13.
    Amcoff, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology. Orebro Univ, Fac Med & Hlth, Dept Gastroenterol, Orebro, Sweden.
    Cao, Yang
    Orebro Univ, Sch Med Sci, Clin Epidemiol & Biostat, Orebro, Sweden;Karolinska Inst, Inst Environm Med, Unit Biostat, Stockholm, Sweden.
    Zhulina, Yaroslava
    Orebro Univ, Fac Med & Hlth, Dept Gastroenterol, Orebro, Sweden.
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Halfvarson, Jonas
    Orebro Univ, Fac Med & Hlth, Dept Gastroenterol, Orebro, Sweden.
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Prognostic significance of faecal eosinophil granule proteins in inflammatory bowel disease2019In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 54, no 10, p. 1237-1244Article in journal (Refereed)
    Abstract [en]

    Background: Non-invasive markers for predicting relapse would be a useful tool for the management of patients with inflammatory bowel disease. Eosinophil granulocytes and their granule proteins eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) have previously been shown to reflect disease activity in Crohn's disease and ulcerative colitis.

    Aim: To examine the capacity of faecal ECP and EDN to predict relapse in ulcerative colitis and Crohn's disease, and to compare these proteins with faecal calprotectin.

    Methods: Patients with Crohn's disease (n?=?49) and ulcerative colitis (n?=?55) were followed prospectively until relapse or end of the two-year study period. Faecal samples were obtained every third month. The predictive value of ECP and EDN was assessed in Cox regression models.

    Results: In ulcerative colitis, a doubled EDN or ECP concentration was associated with a 31% and 27% increased risk of relapse, respectively. EDN levels were increased both at relapse and three months prior. By contrast, in Crohn's disease, the concentration of EDN was higher among patients in remission than in those who relapsed. Correlations between faecal calprotectin, ECP and EDN were observed in both diseases.

    Conclusions: We demonstrate that the risk of relapse in ulcerative colitis can be predicted by consecutively measuring faecal EDN every third month, and suggest EDN as a complementary faecal marker to calprotectin to predict future relapse in ulcerative colitis. Our finding of higher EDN in Crohn's disease-patients staying in remission than in those who relapsed indicates different functions of the protein in ulcerative colitis and Crohn's disease.

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  • 14.
    Amcoff, Karin
    et al.
    Univ Orebro, Fac Med & Hlth, Dept Gastroenterol, SE-70182 Orebro, Sweden..
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Magnuson, Anders
    Univ Orebro, Sch Med Sci, Clin Epidemiol & Biostat, Orebro, Sweden..
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Halfvarson, Jonas
    Univ Orebro, Fac Med & Hlth, Dept Gastroenterol, SE-70182 Orebro, Sweden..
    Clinical implications of assay specific differences in f-calprotectin when monitoring inflammatory bowel disease activity over time2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 3, p. 344-350Article in journal (Refereed)
    Abstract [en]

    Objective: With several faecal calprotectin (FC) assays on the market, it has been difficult to define a uniform threshold for discriminating between remission and active disease in patients with inflammatory bowel disease (IBD). We aimed to compare the results of different FC-assays in IBD patients, followed over time.Material and methods: IBD patients provided faecal samples and reported clinical activity every third month prospectively over a two year period. FC was measured with two ELISA - (Buhlmann and Immunodiagnostik) and one automated fluoroimmunoassay (Phadia).Results: In total, 13 patients provided 91 faecal samples. The median (IQR) concentration of FC was higher at active disease than at remission for all assays: Buhlmann 845 (1061-226) g/g versus 62 (224-39) g/g, Phadia 369 (975-122) g/g versus 11 (52-11) g/g, and Immundiagnostik 135 (302-69) g/g versus 8 (56-4) g/g. The Buhlmann assay produced the largest absolute difference but the corresponding relative difference seemed to be more pronounced when analysed by the Phadia - (ratio of means 8.5; 95% CI 3.3-21.9) or the Immundiagnostik assay (ratio of means 7.4; 95% CI 3.1-17.6) than by the Buhlmann assay (ratio of means 5.3; 95% CI 2.7-10.6). Consequently, the specificity for discriminating active disease from remission varied between assays (34-75%) when the cut-off 50g/g was used, whereas the differences in sensitivity were less pronounced.Conclusions: Cross-comparisons revealed overall poor agreement between the assays as well as differences in the dynamics of FC. These findings suggest that standardisation of the method is needed to implement FC as a disease monitoring tool at large-scale.

  • 15.
    Amid Hägg, Shadi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Emilsson, Össur Ingi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
    Franklin, Karl
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Nocturnal gastroesophageal reflux increases the risk of daytime sleepiness in women2019In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 53, p. 94-100Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Daytime sleepiness is common in women and has negative health effects. Nocturnal gastroesophageal reflux (nGER) and snoring are risk factors for daytime sleepiness, but the effect of their interaction remains unknown. The aim of this study was to examine how nGER and snoring combined affected daytime sleepiness and involuntary falling asleep in women.

    METHODS: A questionnaire was sent to randomly selected women in 2000 and 2010. Participants who answered questions regarding both nGER and snoring in both questionnaires were included (N = 4882). Daytime sleepiness was defined as severe or very severe problems with daytime sleepiness. Involuntary falling asleep was defined as sometimes, often or very often falling asleep involuntarily during the day. Respondents snoring loudly and disturbingly sometimes, often or very often were defined as snorers. Having nocturnal heartburn or acid reflux sometimes, often or very often was defined as having nGER.

    RESULTS: Daytime sleepiness was reported by 14% of the participants, involuntary falling asleep by 11%. After adjustment for age, smoking, physical activity, caffeine intake and alcohol dependency, increased odd ratios (ORs) for both daytime sleepiness (adjusted OR 4.2, 95% confidence interval (CI): 1.9-9.2) and involuntary falling asleep (adjusted OR 3.1, 95% CI: 1.5-6.4) were seen in women with the combination of nGER and snoring at both baseline and follow-up. The association with daytime sleepiness was also strong for those with only persistent nGER but not for those with only persistent snoring.

    CONCLUSION: Women with nGER were at increased risk of developing daytime sleepiness and snoring augmented this association. In addition, women with both nGER and snoring were also at increased risk of developing involuntary falling asleep.

  • 16.
    Analatos, Apostolos
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research Sörmland. Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Surg, Stockholm, Sweden.;Nyköping Hosp, Dept Surg, Olrogsvag 1, S-61139 Nyköping, Sweden.
    Hakanson, Bengt S.
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden.;Ersta Hosp, Dept Surg & Anaesthesiol, Stockholm, Sweden.
    Ansorge, Christoph
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Surg, Stockholm, Sweden.;Nyköping Hosp, Dept Surg, Olrogsvag 1, S-61139 Nyköping, Sweden.
    Lindblad, Mats
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Upper Abdominal Surg, Stockholm, Sweden.
    Lundell, Lars
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Surg, Stockholm, Sweden.;Odense Univ Hosp, Dept Surg, Odense, Denmark.
    Thorell, Anders
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden.
    Clinical Outcomes of a Laparoscopic Total vs a 270 degrees Posterior Partial Fundoplication in Chronic Gastroesophageal Reflux Disease: A Randomized Clinical Trial2022In: JAMA Surgery, ISSN 2168-6254, E-ISSN 2168-6262, Vol. 157, no 6, p. 473-480Article in journal (Refereed)
    Abstract [en]

    Importance The efficacy of fundoplication operations in the management of gastroesophageal reflux disease (GERD) has been documented. However, few prospective, controlled series report long-term (>10 years) efficacy and postfundoplication concerns, particularly when comparing various types of fundoplication.

    Objective To compare long-term (>15 years) results regarding mechanical complications, reflux control, and quality of life between patients undergoing posterior partial fundoplication (PF) or total fundoplication (TF) (270 degrees vs 360 degrees) in surgical treatment for GERD.

    Design, setting and participants A double-blind randomized clinical trial was performed at a single center (Ersta Hospital, Stockholm, Sweden) from November 19, 2001, to January 24, 2006. A total of 456 patients were recruited and randomized. Data for this analysis were collected from August 1, 2019, to January 31, 2021.

    Interventions Laparoscopic 270 degrees posterior PF vs 360 degrees TF.

    Main Outcomes and Measures The main outcome was dysphagia scores for solid and liquid food items after more than 15 years. Generic (36-Item Short-Form Health Survey) and disease-specific (Gastrointestinal Symptom Rating Scale) quality of life and proton pump inhibitor consumption were also assessed.

    Results Among 407 available patients, relevant data were obtained from 310 (response rate, 76%; mean [SD] age, 66 [11.2] years; 184 [59%] men). A total of 159 were allocated to a PF and 151 to a TF. The mean (SD) follow-up time was 16 (1.3) years. At 15 years after surgery, mean (SD) dysphagia scores were low for both liquids (PF, 1.2 [0.5]; TF, 1.2 [0.5]; P = .58) and solids (PF, 1.3 [0.6]; TF, 1.3 [0.5]; P = .97), without statistically significant differences between the groups. Reflux symptoms were equally well controlled by the 2 types of fundoplications as were the improvements of quality-of-life scores.

    Conclusions and Relevance The long-term findings of this randomized clinical trial indicate that PF and TF are equally effective for controlling GERD and quality of life in the long term. Although PF was superior in the first years after surgery in terms of less dysphagia recorded, this difference did not prevail when assessed a decade later.

  • 17.
    Andreasson, Anna
    et al.
    Karolinska Inst, Dept Med, Unit Clin Med, Stockholm, Sweden;Stockholm Univ, Stress Res Inst, Stockholm, Sweden;Macquarie Univ, Dept Psychol, N Ryde, NSW, Australia.
    Hagström, Hannes
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden;Karolinska Univ Hosp, Dept Upper GI, Unit Hepatol, Stockholm, Sweden.
    Sköldberg, Filip
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Onnerhag, Kristina
    Skane Univ Hosp, Dept Gastroenterol & Hepatol, Malmo, Sweden.
    Carlsson, Axel C.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Huddinge, Sweden.
    Schmidt, Peter T.
    Karolinska Inst, Dept Med, Unit Clin Med, Stockholm, Sweden.
    Forsberg, Anna M.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.
    The prediction of colorectal cancer using anthropometric measures: A Swedish population-based cohort study with 22 years of follow-up2019In: United European Gastroenterology journal, ISSN 2050-6406, E-ISSN 2050-6414, Vol. 7, no 9, p. 1250-1260Article in journal (Refereed)
    Abstract [en]

    Background Obesity is a risk factor for colorectal cancer (CRC). Objective The objective of this article is to investigate whether anthropometric measures reflecting visceral obesity are better predictors of CRC than body mass index (BMI). Methods Data were analysed from the Malmo Diet and Cancer study in Sweden, comprising 16,669 women and 10,805 men (median age 56.6 and 59.1 years) followed for a median 21.5 years. Diagnoses of CRC were identified using Swedish national registers. Cox regression was used to test the associations of BMI, waist circumference (WC), waist-hip ratio, waist-to-height ratio, waist-to-hip-to-height ratio, A Body Shape Index (ABSI) and percentage body fat with the development of CRC adjusted for age, alcohol consumption, smoking, education and physical activity in men and women. Results None of the measures were significantly associated with an increased risk for CRC in women. WC was the strongest predictor of colon cancer (CC) in men and the only measure that was independent of BMI. ABSI was the only measure significantly associated with the risk of rectal cancer in men. Conclusions Visceral obesity, best expressed as WC, is a risk factor for CC in men but a poor predictive marker for CRC in women.

  • 18.
    Andreasson, Anna
    et al.
    Stockholm Univ, Stress Res Inst, Dept Psychol, Stockholm, Sweden.;Macquarie Univ, Dept Psychol, N Ryde, NSW, Australia.;Karolinska Inst, Dept Med Solna, Solna, Sweden..
    Talley, Nicholas J.
    Univ Newcastle, Fac Hlth & Med, Newcastle, NSW, Australia.;NHMRC Ctr Res Excellence Digest Hlth, Newcastle, NSW, Australia..
    Walker, Marjorie M.
    Univ Newcastle, Fac Hlth & Med, Newcastle, NSW, Australia.;NHMRC Ctr Res Excellence Digest Hlth, Newcastle, NSW, Australia..
    Jones, Michael P.
    Macquarie Univ, Dept Psychol, N Ryde, NSW, Australia..
    Platts, Loretta G.
    Stockholm Univ, Stress Res Inst, Dept Psychol, Stockholm, Sweden..
    Wallner, Bengt
    Umeå Univ, Umeå, Sweden..
    Kjellstrom, Lars
    Gastromottagningen City, Stockholm, Sweden..
    Hellström, Per M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Forsberg, Anna
    Karolinska Inst, Dept Med Solna, Solna, Sweden..
    Agreus, Lars
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden..
    An Increasing Incidence of Upper Gastrointestinal Disorders Over 23 Years: A Prospective Population-Based Study in Sweden2021In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 116, no 1, p. 210-213Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: We hypothesized that the prevalence of functional dyspepsia and gastroesophageal reflux disease in the community may be increasing.

    METHODS: Randomly selected adults were surveyed on 4 occasions: 1988 (n = 1,151, 21-79 years, response rate [rr] = 90%), 1989 (n = 1,097, 22-80 years, rr = 87%), 1995 (n = 1,139, 20-85 years, rr = 76%), and 2011 (n = 1,175, 20-93 years, rr = 63%).

    RESULTS: In functional dyspepsia, the odds of postprandial distress syndrome tripled over 23 years' follow-up (odds ratio [OR]: 3.55; 95% confidence interval [CI]: 2.60-4.84, mixed-effect regression analysis), whereas a small decrease in epigastric pain syndrome was observed (OR: 0.65, 95% CI: 0.42-1.00). The odds of reporting gastroesophageal reflux disease doubled (OR: 2.02; 95% CI: 1.50-2.73).

    DISCUSSION: The underlying mechanisms behind the increase in postprandial distress syndrome and gastroesophageal reflux disease remain to be determined.

  • 19.
    Angelison, L.
    et al.
    Helsingborg Hosp, Dept Med, Charlotte Yhlens Gata 10, S-25187 Helsingborg, Sweden..
    Almer, S.
    Karolinska Inst, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Eriksson, A.
    Sahlgrenska Univ Hospital Ostra, Dept Gastroenterol, Gothenburg, Sweden..
    Karling, P.
    Umea Univ, Dept Publ Hlth & Clin Med, Div Med, Umea, Sweden..
    Fagerberg, U.
    Vastmanlands Hosp, Clin Res Ctr, Vasteras, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Halfvarson, J.
    Univ Orebro, Dept Gastroenterol, Fac Med & Hlth, Orebro, Sweden..
    Thörn, Mari
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Björk, J.
    Karolinska Inst, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Hindorf, U.
    Lund Univ, Div Gastroenterol, Dept Clin Sci, Lund, Sweden..
    Löfberg, R.
    Karolinska Inst, Dept Med, IBD Unit, Stockholm Gastro Ctr, Stockholm, Sweden. Sodra Alvsborgs Sjukhus, Dept Med, Boras, Sweden..
    Bajor, A.
    Hjortswang, H.
    Linkoping Univ, Dept Gastroenterol, Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Hammarlund, P.
    Angelholm Hosp, Dept Med, Angelholm, Sweden..
    Grip, O.
    Skane Univ Hosp, Dept Gastroenterol, Malmo, Sweden..
    Torp, J.
    Kristianstad Cent Hosp, Dept Med, Kristianstad, Sweden..
    Marsal, J.
    Hertervig, E.
    Skane Univ Hosp, Dept Gastroenterol, Lund, Sweden..
    Long-term outcome of infliximab treatment in chronic active ulcerative colitis: a Swedish multicentre study of 250 patients2017In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 45, no 4, p. 519-532Article in journal (Refereed)
    Abstract [en]

    Background Real-life long-term data on infliximab treatment in ulcerative colitis are limited. Aim To study the long-term efficacy and safety of infliximab in chronic active ulcerative colitis and possible predictors of colectomy and response were also examined. Methods A retrospective multi-centre study of infliximab treatment in 250 patients with chronic active ulcerative colitis with inclusion criteria: age 18 years, ambulatory treated, steroid-dependent or intolerant and/or immunomodulator refractory or intolerant. Results Steroid-free clinical remission was achieved by 123/250 patients (49.2%) at 12 months and in 126/250 patients at a median follow-up of 2.9 years (50.4%). Primary response at 3 months was achieved by 190/250 (76.0%) patients and associated with a high probability of response 168/190 (88.4%) at 12 months and 143/190 (75.3%) at follow-up. Long-term rate of colectomy in primary responders was 6/190 (3.2%) at 12 months and 27/190 (14.2%) at last follow-up. Failure to achieve response at 3 months was associated with a high risk of subsequent colectomy, 29/60 (48.3%) at 12 months and 41/60 (68.3%) at follow-up. Response at 12 months was associated with a low risk of subsequent colectomy, 14/181 (7.7%) compared with non-response 19/34 (55.9%) (P < 0.0001). Non-response at 3 months was an independent predictor of subsequent colectomy (HR = 9.40, 95% CI = 5.10-17.35, P < 0.001). Concomitant azathioprine therapy did not influence outcome in terms of colectomy. Conclusions Long-term efficacy of infliximab treatment in chronic active ulcerative colitis is excellent especially in patients who respond to induction treatment. Conversely, non-response at 3 months predicts a poor outcome, with a high risk of subsequent colectomy.

  • 20.
    Anthony, Lowell
    et al.
    Univ Kentucky, Lexington, KY USA..
    Hoersch, Dieter
    Zentralklin Bad Berka, Bad Berka, Germany..
    Ervin, Claire
    RTI Hlth Solut, Res Triangle Pk, NC USA..
    Kulke, Matthew H.
    Dana Farber Canc Inst, Boston, MA 02115 USA..
    Pavel, Marianne
    Charite, D-13353 Berlin, Germany..
    Bergsland, Emily
    UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA..
    Caplin, Martyn
    Royal Free Hosp, Pond St, London NW3 2QG, England..
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Warner, Richard
    Icahn Sch Med Mt Sinai, New York, NY 10029 USA..
    Kunz, Pamela
    Stanford Univ, Palo Alto, CA 94304 USA..
    Metz, David C.
    Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA..
    Pasieka, Janice
    Tom Baker Canc Ctr Calgary, Calgary, AB, Canada..
    Pavlakis, Nick
    Royal N Shore Hosp, St Leonards, NSW 2065, Australia..
    DiBenedetti, Dana
    RTI Hlth Solut, Res Triangle Pk, NC USA..
    Haydysch, Emily
    RTI Hlth Solut, Res Triangle Pk, NC USA..
    Yang, Qi Melissa
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Jackson, Shanna
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Arnold, Karie
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Law, Linda
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Lapuerta, Pablo
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Assessing Treatment Benefit of Telotristat Etiprate in Patients with Carcinoid Syndrome: Patient Exit Interviews2016In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 45, no 3, p. 470-470Article in journal (Other academic)
  • 21.
    Antonodimitrakis, Pantelis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Tsolakis, Apostolos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kozlovacki, Gordana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gastric carcinoid in a patient infected with Helicobacter pylori: A new entity?2011In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 17, no 25, p. 3066-3068Article in journal (Refereed)
    Abstract [en]

    There are four types of gastric carcinoid tumors, classified according to their histology and malignant potential. Only a few cases of carcinoid tumors in patients infected with Helicobacter pylori (H. pylon) have been reported so far. We report a patient infected with H. pylori presenting with a small solitary gastric carcinoid tumor with very low proliferative rate and normal gastrin levels. The tumor was endoscopically removed and the patient received an eradication therapy against H. pylori. No signs of metastatic disease have been found so far during more than 3 year of follow-up. Infection with H. pylon may cause chronic gastritis with normal or elevated gastrin levels, leading to the development of gastric carcinoids by mechanisms unrelated to gastrin. Enterochromaffin-like cell tumors related to a chronic H. pylori infection may be considered as a distinct type of gastric carcinoid tumors.

  • 22.
    Anvari, Ebrahim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Fred, Rikard G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Welsh, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    The H-1-Receptor Antagonist Cetirizine Protects Partially Against Cytokine- and Hydrogen Peroxide-Induced beta-TC6 Cell Death In Vitro2014In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 43, no 4, p. 624-629Article in journal (Refereed)
    Abstract [en]

    Objective It has been proposed that the histamine 1 (H-1) receptor not only promotes allergic reactions but also modulates autoimmune diseases, such as type 1 diabetes. In line with this, it has recently been reported that the H-1-receptor antagonist cetirizine can counteract the activation of signals/factors pertinent to the pathogenesis of type 1 diabetes and cytokine-induced beta-cell destruction. Therefore, the overall aim of this study was to determine whether H-1-receptor antagonists affect cytokine-induced beta-cell death and signaling in vitro. Methods The insulin-producing cell line beta-TC6 was exposed to the proinflammatory cytokines interleukin 1 beta(+) interferon gamma, or hydrogen peroxide. The H-1-receptor antagonists desloratadine and cetirizine were added to the cell cultures and cell viability; macrophage inhibitory factor levels, c-Jun N-terminal kinase phosphorylation, c-Jun expression, and beta-catenin levels were analyzed by flow cytometry, real-time polymerase chain reaction, and immunoblotting. Results Cetirizine protected partially against both cytokine- and hydrogen peroxide-induced cell death. This effect was paralleled by an inhibition of cytokine-induced c-Jun N-terminal kinase phosphorylation, c-Jun induction, and a restoration of macrophage inhibitory factor contents. Cetirizine also increased the beta-TC6 cell contents of beta-catenin at basal conditions. Conclusions Our results indicate a protective effect of a specific H-1-receptor antagonist.

  • 23.
    Archambault, Alexi N.
    et al.
    NYU, Div Epidemiol, Dept Populat Hlth, Sch Med, New York, NY USA..
    Su, Yu-Ru
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Jeon, Jihyoun
    Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Thomas, Minta
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Lin, Yi
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Conti, David V.
    Univ Southern Calif, USC Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90007 USA..
    Win, Aung Ko
    Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia..
    Sakoda, Lori C.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.;Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA..
    Lansdorp-Vogelaar, Iris
    Erasmus MC, Univ Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands..
    Peterse, Elisabeth F. P.
    Erasmus MC, Univ Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands..
    Zauber, Ann G.
    Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA..
    Duggan, David
    Translat Genom Res Inst, Phoenix, AZ USA..
    Holowatyj, Andreana N.
    Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.;Univ Utah, Dept Populat Hlth Sci, Salt Lake City, UT USA..
    Huyghe, Jeroen R.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Brenner, Hermann
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.;German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.;Natl Ctr Tumor Dis NCT, Heidelberg, Germany.;German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany..
    Cotterchio, Michelle
    Canc Care Ontario, Populat Hlth & Prevent, Toronto, ON, Canada..
    Bezieau, Stephane
    CHU Nantes, Serv Genet Med, Nantes, France..
    Schmit, Stephanie L.
    Univ Southern Calif, USC Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90007 USA.;H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA..
    Edlund, Christopher K.
    Univ Southern Calif, USC Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90007 USA..
    Southey, Melissa C.
    Univ Melbourne, Genet Epidemiol Lab, Dept Pathol, Melbourne, Vic, Australia..
    MacInnis, Robert J.
    Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia.;Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic, Australia..
    Campbell, Peter T.
    Amer Canc Soc, Behav & Epidemiol Res Grp, Atlanta, GA USA..
    Chang-Claude, Jenny
    German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.;UCCH, Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany..
    Slattery, Martha L.
    Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA..
    Chan, Andrew T.
    Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.;Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA USA.;Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.;Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA..
    Joshi, Amit D.
    Harvard Med Sch, Boston, MA 02115 USA.;Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA USA.;Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA..
    Song, Mingyang
    Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA..
    Cao, Yin
    Harvard Med Sch, Boston, MA 02115 USA.;Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA USA.;Washington Univ, Div Publ Hlth Sci, Dept Surg, St Louis, MO 63110 USA..
    Woods, Michael O.
    Mem Univ Newfoundland, Discipline Genet, St John, NF, Canada..
    White, Emily
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.;Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA..
    Weinstein, Stephanie J.
    NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA..
    Ulrich, Cornelia M.
    Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.;Univ Utah, Dept Populat Hlth Sci, Salt Lake City, UT USA..
    Hoffmeister, Michael
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany..
    Bien, Stephanie A.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Harrison, Tabitha A.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Hampe, Jochen
    Tech Univ Dresden, Univ Hosp Dresden, Dept Med 1, Dresden, Germany..
    Li, Christopher I.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Schafmayer, Clemens
    Univ Hosp Schleswig Holstein, Dept Gen & Thorac Surg, Campus Kiel, Kiel, Germany..
    Offit, Kenneth
    Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, 1275 York Ave, New York, NY 10021 USA.;Weill Cornell Med Coll, Dept Med, New York, NY USA..
    Pharoah, Paul D.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Moreno, Victor
    Catalan Inst Oncol IDIBELL, Canc Prevent & Control Program, Barcelona, Spain.;CIBERESP, Madrid, Spain.;Univ Barcelona, Fac Med, Dept Clin Sci, Barcelona, Spain..
    Lindblom, Annika
    Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Wolk, Alicja
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Wu, Anna H.
    Univ Southern Calif, USC Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90007 USA..
    Li, Li
    Univ Virginia, Dept Family Med, Charlottesville, VA USA..
    Gunter, Marc J.
    WHO, Int Agcy Res Canc, Nutr & Metab Sect, Lyon, France..
    Gsur, Andrea
    Med Univ Vienna, Dept Med 1, Inst Canc Res, Vienna, Austria..
    Keku, Temitope O.
    Univ N Carolina, Ctr Gastrointestinal Biol & Dis, Chapel Hill, NC 27515 USA..
    Pearlman, Rachel
    Ohio State Univ, Dept Internal Med, Div Human Genet, Ctr Comprehens Canc, Columbus, OH 43210 USA..
    Bishop, D. Timothy
    Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England..
    Castellvi-Bel, Sergi
    Univ Barcelona, CIBEREHD, IDIBAPS, Dept Gastroenterol,Hosp Clin, Barcelona, Spain..
    Moreira, Leticia
    Univ Barcelona, CIBEREHD, IDIBAPS, Dept Gastroenterol,Hosp Clin, Barcelona, Spain..
    Vodicka, Pavel
    Czech Acad Sci, Inst Expt Med, Dept Mol Biol Canc, Prague, Czech Republic.;Charles Univ Prague, Fac Med 1, Inst Biol & Med Genet, Prague, Czech Republic.;Charles Univ Prague, Fac Med, Plzen, Czech Republic.;Charles Univ Prague, Biomed Ctr Pilsen, Plzen, Czech Republic..
    Kampman, Ellen
    Wageningen Univ & Res, Div Human Nutr & Hlth, Wageningen, Netherlands..
    Giles, Graham G.
    Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia.;H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA..
    Albanes, Demetrius
    Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA..
    Baron, John A.
    Univ N Carolina, Dept Med, Sch Med, Chapel Hill, NC 27515 USA..
    Berndt, Sonja I.
    Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA..
    Brezina, Stefanie
    Med Univ Vienna, Dept Med 1, Inst Canc Res, Vienna, Austria..
    Buch, Stephan
    Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.;Univ Utah, Dept Populat Hlth Sci, Salt Lake City, UT USA..
    Buchanan, Daniel D.
    Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia.;Univ Melbourne, Dept Clin Pathol, Colorectal Oncogenom Grp, Parkville, Vic, Australia.;Royal Melbourne Hosp, Genom Med & Family Canc Clin, Parkville, Vic, Australia.;Univ Melbourne, Ctr Canc Res, Victorian Comprehens Canc Ctr, Parkville, Vic, Australia..
    Trichopoulou, Antonia
    Hellen Hlth Fdn, Athens, Greece..
    Severi, Gianluca
    Chirlaque, Maria-Dolores
    CIBERESP, Madrid, Spain..
    Sanchez, Maria-Jose
    Palli, Domenico
    Kuhn, Tilman
    German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany..
    Murphy, Neil
    Cross, Amanda J.
    Burnett-Hartman, Andrea N.
    Chanock, Stephen J.
    Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA..
    de la Chapelle, Albert
    Easton, Douglas F.
    Weill Cornell Med Coll, Dept Med, New York, NY USA..
    Elliott, Faye
    Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England..
    English, Dallas R.
    Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia.;Univ Virginia, Dept Family Med, Charlottesville, VA USA..
    Feskens, Edith J. M.
    Wageningen Univ & Res, Div Human Nutr & Hlth, Wageningen, Netherlands..
    FitzGerald, Liesel M.
    Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic, Australia..
    Goodman, Phyllis J.
    Hopper, John L.
    Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia..
    Hudson, Thomas J.
    Hunter, David J.
    Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA..
    Jacobs, Eric J.
    Amer Canc Soc, Behav & Epidemiol Res Grp, Atlanta, GA USA..
    Joshu, Corinne E.
    Kury, Sebastien
    Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic, Australia..
    Markowitz, Sanford D.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Milne, Roger L.
    Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia.;Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic, Australia..
    Platz, Elizabeth A.
    Rennert, Gad
    Rennert, Hedy S.
    Schumacher, Fredrick R.
    Sandler, Robert S.
    Univ N Carolina, Ctr Gastrointestinal Biol & Dis, Chapel Hill, NC 27515 USA..
    Seminara, Daniela
    Tangen, Catherine M.
    Thibodeau, Stephen N.
    Toland, Amanda E.
    van Duijnhoven, Franzel J. B.
    Wageningen Univ & Res, Div Human Nutr & Hlth, Wageningen, Netherlands..
    Visvanathan, Kala
    Vodickova, Ludmila
    Czech Acad Sci, Inst Expt Med, Dept Mol Biol Canc, Prague, Czech Republic.;Charles Univ Prague, Fac Med 1, Inst Biol & Med Genet, Prague, Czech Republic.;Charles Univ Prague, Fac Med, Plzen, Czech Republic.;Charles Univ Prague, Biomed Ctr Pilsen, Plzen, Czech Republic..
    Potter, John D.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Mannisto, Satu
    Weigl, Korbinian
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany..
    Figueiredo, Jane
    Univ Southern Calif, USC Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90007 USA..
    Martin, Vicente
    CIBERESP, Madrid, Spain..
    Larsson, Susanna C
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Parfrey, Patrick S.
    Huang, Wen-Yi
    NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA..
    Lenz, Heinz-Josef
    Castelao, Jose E.
    Gago-Dominguez, Manuela
    Munoz-Garzon, Victor
    Mancao, Christoph
    Haiman, Christopher A.
    Univ Southern Calif, USC Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90007 USA..
    Wilkens, Lynne R.
    Siegel, Erin
    H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA..
    Barry, Elizabeth
    Younghusband, Ban
    Mem Univ Newfoundland, Discipline Genet, St John, NF, Canada..
    Van Guelpen, Bethany
    Harlid, Sophia
    Zeleniuch-Jacquotte, Anne
    NYU, Div Epidemiol, Dept Populat Hlth, Sch Med, New York, NY USA..
    Liang, Peter S.
    Du, Mengmeng
    Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA..
    Casey, Graham
    Lindor, Noralane M.
    Le Marchand, Loic
    Gallinger, Steven J.
    Jenkins, Mark A.
    Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia..
    Newcomb, Polly A.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Gruber, Stephen B.
    Schoen, Robert E.
    Hampel, Heather
    Ohio State Univ, Dept Internal Med, Div Human Genet, Ctr Comprehens Canc, Columbus, OH 43210 USA..
    Corley, Douglas A.
    Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA..
    Hsu, Li
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Peters, Ulrike
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.;Mem Univ Newfoundland, Discipline Genet, St John, NF, Canada..
    Hayes, Richard B.
    NYU, Div Epidemiol, Dept Populat Hlth, Sch Med, New York, NY USA..
    Cumulative Burden of Colorectal Cancer Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer2020In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 158, no 5, p. 1274-1286.e12Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC.

    METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants.

    RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 x 10(-5)). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings.

    CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.

  • 24.
    Ardesjö Lundgren, Brita
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Portela-Gomes, Guida M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Grimelius, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Ekdahl, Kristina Nilsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Ekwall, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Identification of complement C3 as an autoantigen in inflammatory bowel disease2010In: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 22, no 4, p. 429-436Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Autoantibodies against goblet cells in the gastrointestinal mucosa have been described in patients with inflammatory bowel disease (IBD) but a corresponding autoantigen has not yet been identified. The aim of this study was to identify such an antigen. METHODS: First, 10 candidate autoantigens were discarded based on double stainings of appendiceal sections and a mucin-producing cell line (HT29-mtx). Second, an appendiceal cDNA library was immunoscreened with IBD sera. RESULTS: Three out of 48 positive clones were identified as complement C3. Using immunoprecipitation of in vitro transcribed and translated C3, seven of 17 primary sclerosing cholangitis patient sera, 15 of 65 IBD sera, and none out of 54 sera from healthy blood donors showed C3 immunoreactivity. The results were confirmed using western blot and an enzyme-linked immunosorbent assay with alternative sources of C3 protein. CONCLUSION: In conclusion, we have identified complement C3 as a potential autoantigen in IBD and primary sclerosing cholangitis.

  • 25.
    Aziz, Sarkar
    et al.
    Erbil Polytech Univ, Erbil Tech Hlth Coll, Dept Med Lab Technol, Erbil, Iraq.;Erbil Polytech Univ Erbil, Erbil Tech Hlth Coll, Dept Med Lab Technol, Erbil 44001, Iraq..
    Hamad, Bahra
    Erbil Polytech Univ, Erbil Tech Hlth Coll, Dept Med Lab Technol, Erbil, Iraq..
    Hamad, Hero
    Erbil Polytech Univ, Erbil Tech Hlth Coll, Dept Med Lab Technol, Erbil, Iraq..
    Qader, Muzhda
    Erbil Polytech Univ, Erbil Tech Hlth Coll, Dept Med Lab Technol, Erbil, Iraq..
    Ali, Eman
    Erbil Polytech Univ, Erbil Tech Hlth Coll, Dept Med Lab Technol, Erbil, Iraq..
    Muhammed, Rayan
    Erbil Polytech Univ, Erbil Tech Hlth Coll, Dept Med Lab Technol, Erbil, Iraq..
    Shekha, Mudhir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Salahaddin Univ, Coll Sci, Res Ctr, Dept Biol, Erbil, Iraq..
    Estimation of the prevalence of Hemoglobinopathies in Erbil governorate, Kurdistan region of Iraq2022In: IRAQI JOURNAL OF HEMATOLOGY, ISSN 2072-8069, Vol. 11, no 1, p. 19-24Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Thalassemia syndromes and structural hemoglobin variants generate blood crisis of variable clinical symptoms, ranging from mild-to-moderate hematological disorder to severe, lifelong, transfusion-dependent anemia. The aim of current study was to uncover the prevalence of thalassemia and other hemoglobinopathies in the Erbil governorate, Kurdistan region of Iraq. MATERIALS AND METHODS: The available data of thalassemia major, thalassemia intermedia, sickle cell disease, sickle cell trait, and HbH and HbE until the end of 2020 were collected retrospectively from Erbil Thalassemia Center in Erbil governorate, Kurdistan region of Iraq and analyzed by using Microsoft Excel (Version 2016). RESULTS: An increase in the prevalence of thalassemia syndromes from 30.8/100,000 in 2015 to 37.3/100,000 individuals in the population in 2020 was revealed. The prevalence of all hemoglobinopathies combined increased from 31.9/100,000 to 42.7/100,000 individuals of the population. Thalassemia major was the predominant condition among the hemoglobinopathies with 758 (78.71%) cases out of 963 cases at the end of 2020. CONCLUSION: This rise might be attributed to a large number of consanguineous marriages, the lack of effective prevention programs, and poor legislation. There is an emergent requirement for a preventive program, entailing identification of carriers, genetic counseling, guidelines to differentiate between other microcytic anemias with thalassemia traits, antenatal diagnosis, public education, and sustained legislation.

  • 26.
    Barratt, Jonathan
    et al.
    Univ Leicester, Coll Med Biol Sci & Psychol, Leicester, England..
    Lafayette, Richard A.
    Stanford Univ, Dept Med, Div Nephrol, Stanford, CA USA..
    Rovin, Brad H.
    Ohio State Univ, Wexner Med Ctr, Div Nephrol, Columbus, OH USA..
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Budesonide delayed-release capsules to reduce proteinuria in adults with primary immunoglobulin A nephropathy2023In: Expert Review of Clinical Immunology, ISSN 1744-666X, E-ISSN 1744-8409, Vol. 19, no 7, p. 699-710Article in journal (Refereed)
    Abstract [en]

    IntroductionImmunoglobulin A nephropathy (IgAN) is characterized by mesangial deposition of immune complexes containing galactose-deficient IgA1 (Gd-IgA1). This Gd-IgA1 is believed to originate from mucosally sited B cells, which are abundant in the Peyer's patches-rich distal ileum. Nefecon is a targeted-release form of budesonide developed to act in the distal ileum, thereby exerting a direct action on the mucosal tissue implicated in the pathogenesis of the disease.Areas coveredThis review discusses IgAN pathophysiology and provides an overview of the current therapeutic landscape, focusing on Nefecon, the first drug to receive accelerated US approval and conditional EU approval for the treatment of patients with IgAN at risk of rapid disease progression.Expert opinionNefecon trial data thus far have demonstrated a promising efficacy profile, with a predictable pattern of adverse events. Treatment with Nefecon for 9 months reduces proteinuria substantially (Part A of the Phase 3 trial and the Phase 2b trial). A nearly complete prevention of deterioration of renal function has been observed at 12 months in patients at greatest risk of rapid disease progression. Long-term data from Part B of the Phase 3 study will provide 24-month data, furthering understanding of the durability of the 9-month treatment course.

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  • 27.
    Bartlett, S. R.
    et al.
    Univ New South Wales, Kirby Inst, Sydney, NSW, Australia..
    Grebely, J.
    Univ New South Wales, Kirby Inst, Sydney, NSW, Australia..
    Eltahla, A. A.
    Univ New South Wales, Kirby Inst, Sydney, NSW, Australia..
    Reeves, J. D.
    Lab Corp Amer Holdings, Monogram Biosci, San Francisco, CA USA..
    Howe, A.
    St Pauls Hosp, BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada..
    Miller, V.
    Univ Calif Berkeley, Forum Collaborat HIV Res, Washington, DC USA..
    Bull, R. A.
    Univ New South Wales, Kirby Inst, Sydney, NSW, Australia..
    Ceccherini-Silberstein, F.
    Univ Roma Tor Vergata, Dept Expt Med & Surg, Rome, Italy..
    Douglas, M. W.
    Westmead Inst Med Res, Storr Liver Ctr, Sydney, NSW, Australia..
    Dore, G. J.
    Univ New South Wales, Kirby Inst, Sydney, NSW, Australia..
    Harrington, P.
    US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA..
    Lloyd, A. R.
    Univ New South Wales, Kirby Inst, Sydney, NSW, Australia..
    Jacka, B.
    Univ New South Wales, Kirby Inst, Sydney, NSW, Australia..
    Matthews, G. V.
    Univ New South Wales, Kirby Inst, Sydney, NSW, Australia..
    Wang, G. P.
    Univ Florida, Coll Med, Dept Med, Gainesville, FL USA..
    Pawlotsky, J. -M
    Feld, J. J.
    Univ Toronto, Univ Hlth Network, Toronto Western Hosp, Ctr Liver, Toronto, ON, Canada..
    Schinkel, J.
    Acad Med Ctr, Dept Med Microbiol, Amsterdam, Netherlands..
    Garcia, F.
    Complejo Hosp Univ Granada, Clin Microbiol Serv, Granada, Spain..
    Lennerstrand, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Applegate, T. L.
    Univ New South Wales, Kirby Inst, Sydney, NSW, Australia..
    Systematic review & expert guidance on methods for sequencing of hepatitis C virus for detection of direct-acting antiviral resistance2017In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 66, no 1, p. S323-S323Article in journal (Other academic)
  • 28.
    Bartlett, Sofia R.
    et al.
    Univ New South Wales, Kirby Inst, Sydney, NSW 2052, Australia.
    Grebely, Jason
    Univ New South Wales, Kirby Inst, Sydney, NSW 2052, Australia.
    Eltahla, Auda A.
    Univ New South Wales, Kirby Inst, Sydney, NSW 2052, Australia;Univ New South Wales, Fac Med, Sch Med Sci, Sydney, NSW, Australia.
    Reeves, Jacqueline D.
    Monogram Biosci, Lab Corp Amer Holdings, San Francisco, CA USA.
    Howe, Anita Y. M.
    St Pauls Hosp, British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada.
    Miller, Veronica
    Univ Calif Berkeley, Forum Collaborat HIV Res, Washington, DC USA.
    Ceccherini-Silberstein, Francesca
    Univ Roma Tor Vergata, Dept Expt Med & Surg, Rome, Italy.
    Bull, Rowena A.
    Univ New South Wales, Kirby Inst, Sydney, NSW 2052, Australia;Univ New South Wales, Fac Med, Sch Med Sci, Sydney, NSW, Australia.
    Douglas, Mark W.
    Univ Sydney, Westmead Inst Med Res, Storr Liver Ctr, Sydney, NSW, Australia.
    Dore, Gregory J.
    Univ New South Wales, Kirby Inst, Sydney, NSW 2052, Australia.
    Harrington, Patrick
    US FDA, Ctr Drug Evaluat & Res, Div Antiviral Prod, Silver Spring, MD USA.
    Lloyd, Andrew R.
    Univ New South Wales, Kirby Inst, Sydney, NSW 2052, Australia;Univ New South Wales, Fac Med, Sch Med Sci, Sydney, NSW, Australia.
    Jacka, Brendan
    Univ New South Wales, Kirby Inst, Sydney, NSW 2052, Australia.
    Matthews, Gail V.
    Univ New South Wales, Kirby Inst, Sydney, NSW 2052, Australia.
    Wang, Gary P.
    Univ Florida, Coll Med, Dept Med, Gainesville, FL USA.
    Pawlotsky, Jean-Michel
    Univ Paris Est, Hop Henri Mondor, Dept Virol, Natl Reference Ctr Viral Hepatitis B C & D, Creteil, France;Univ Paris Est, Hop Henri Mondor, INSERM, U955, Creteil, France.
    Feld, Jordan J.
    Univ Toronto, Univ Hlth Network, Toronto Western Hosp, Liver Ctr, Toronto, ON, Canada.
    Schinkel, Janke
    Acad Med Ctr, Dept Med Microbiol, Amsterdam, Netherlands.
    Garcia, Federico
    Complejo Hosp Univ Granada, Clin Microbiol Serv, Granada, Spain.
    Lennerstrand, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Applegate, Tanya L.
    Univ New South Wales, Kirby Inst, Sydney, NSW 2052, Australia.
    Sequencing of Hepatitis C Virus for Detection of Resistance to Direct-Acting Antiviral Therapy: A Systematic Review2017In: HEPATOLOGY COMMUNICATIONS, ISSN 2471-254X, Vol. 1, no 5, p. 379-390Article, review/survey (Refereed)
    Abstract [en]

    The significance of the clinical impact of direct-acting antiviral (DAA) resistance-associated substitutions (RASs) in hepatitis C virus (HCV) on treatment failure is unclear. No standardized methods or guidelines for detection of DAA RASs in HCV exist. To facilitate further evaluations of the impact of DAA RASs in HCV, we conducted a systematic review of RAS sequencing protocols, compiled a comprehensive public library of sequencing primers, and provided expert guidance on the most appropriate methods to screen and identify RASs. The development of standardized RAS sequencing protocols is complicated due to a high genetic variability and the need for genotype- and subtype-specific protocols for multiple regions. We have identified several limitations of the available methods and have highlighted areas requiring further research and development. The development, validation, and sharing of standardized methods for all genotypes and subtypes should be a priority.

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  • 29.
    Bengtsson, Daniel
    et al.
    Dept Internal Med, Halsogrand 2, S-39185 Kalmar, Region Of Kalma, Sweden.;Linköping Univ, Dept Biomed & Clin Sci, Linköping, Sweden..
    Ragnarsson, Oskar
    Univ Gothenburg, Inst Med, Dept Internal Med & Clin Nutr, Sahlgrenska Acad, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Endocrinol, Gothenburg, Sweden..
    Berinder, Katarina
    Karolinska Univ Hosp, Dept Endocrinol, Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Dahlqvist, Per
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Edén Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism. Uppsala Univ Hosp, Dept Endocrinol & Diabet, Uppsala, Sweden..
    Ekman, Bertil
    Linköping Univ, Dept Endocrinol, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Hoybye, Charlotte
    Karolinska Univ Hosp, Dept Endocrinol, Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Jaras, Jacob
    Reg Canc Ctr, Stockholm, Sweden..
    Valdemarsson, Stig
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Lund, Sweden..
    Burman, Pia
    Lund Univ, Skane Univ Hosp, Dept Endocrinol, Malmö, Sweden..
    Wahlberg, Jeanette
    Linköping Univ, Dept Endocrinol, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Örebro Univ, Fac Med Sci, Örebro, Sweden..
    Increased Mortality Persists after Treatment of Cushing's Disease: A Matched Nationwide Cohort Study2022In: Journal of the Endocrine Society, E-ISSN 2472-1972, Vol. 6, no 6Article in journal (Refereed)
    Abstract [en]

    Context: Whether biochemical remission normalizes life expectancy in Cushing's disease (CD) patients remains unclear. Previous studies evaluating mortality in CD are limited by using the expected number of deaths in the background population instead of the actual number in matched controls. Objective and setting: To study mortality by time-to-event analysis in an unselected nationwide CD patient cohort. Design and participants: Longitudinal data from the Swedish Pituitary Register of 371 patients diagnosed with CD from 1991 to 2018 and information from the Swedish Cause of Death Register were evaluated. Four controls per patient (n = 1484) matched at the diagnosis date by age, sex, and residential area were included. Main outcome measures: Mortality and causes of death. Results: The median diagnosis age was 44 years (interquartile range 32-56), and the median follow-up was 10.6 years (5.7-18.0). At the 1-, 5-, 10-, 15-, and 20-year follow-ups, the remission rates were 80%, 92%, 96%, 91%, and 97%, respectively. Overall mortality was increased in CD patients compared with matched controls [hazard ratio (HR) 2.1 (95% CI 1.5-2.8)1. The HRs were 1.5 (1.02-2.2) for patients in remission at the last follow-up In = 303), 1.7 (1.03-2.8) for those in remission after a single pituitary surgery In = 177), and 5.6 (2.7-11.6) for those not in remission (n = 31). Cardiovascular diseases (32/66) and infections (12/66) were overrepresented causes of death. Conclusions: Mortality was increased in CD patients despite biochemical remission compared to matched controls. The study highlights the importance of careful comorbidity monitoring, regardless of remission status.

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  • 30.
    Benno, P.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.
    Norin, E.
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.
    Midtvedt, T.
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.
    Hellström, Per M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Therapeutic potential of an anaerobic cultured human intestinal microbiota, ACHIM, for treatment of IBS2019In: Baillière's Best Practice & Research: Clinical Gastroenterology, ISSN 1521-6918, E-ISSN 1532-1916, Vol. 40-41, article id 101607Article, review/survey (Refereed)
    Abstract [en]

    By administering an anaerobic cultivated human intestinal microbiota (ACHIM) via upper gastrointestinal route using endoscopy we aimed to rectify intestinal dysbiosis and simultaneously achieve a treatment response in IBS patients. The study population fulfilled the Rome III IBS criteria and comprised 50 patients. During 10 days, patients recorded the irritable bowel syndrome symptom severity scale (IBS-SSS) along with the Bristol stool scale and number of stools/day. The enrolled patients were categorized as follows: 37 with diarrhea, 5 with constipation and 8 with mixed symptoms. The treatment response showed reduction in a majority of patients, 32 of which with 50-point reduction of IBS-SSS and 21 with a 100-point IBS-SSS reduction. The percentage improvement was 36 (23-49) and 28 (18-38) for women and men respectively. Short-chain fatty acids were not changed. We consider fecal microbiota transplantation in the form of ACHIM as an option for the future therapeutic armamentarium in IBS. (C) 2019 Published by Elsevier Ltd.

  • 31. Benno, Peter
    et al.
    Bark, Johan
    Collinder, Eje
    Hellström, Per M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Midtvedt, Tore
    Norin, Elisabeth
    Major alterations in metabolic activity of intestinal microflora in Crohn's disease2012In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 47, no 2, p. 251-252Article in journal (Refereed)
  • 32.
    Benno, Peter
    et al.
    Lakarhuset Hotorgsc, Stockholm, Sweden;Karolinska Inst, Stockholm, Sweden.
    Dahlgren, Atti-La
    Karolinska Inst, Stockholm, Sweden.
    Befrits, Ragnar
    Lakarhuset Hotorgsc, Stockholm, Sweden.
    Norin, Elisabeth
    Karolinska Inst, Stockholm, Sweden.
    Hellström, Per M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology. Uppsala Univ, Uppsala, Sweden.
    Midtvedt, Tore
    Karolinska Inst, Stockholm, Sweden.
    From IBS to DBS: The Dysbiotic Bowel Syndrome2016In: JOURNAL OF INVESTIGATIVE MEDICINE HIGH IMPACT CASE REPORTS, ISSN 2324-7096, Vol. 4, no 2, article id UNSP 2324709616648458Article in journal (Refereed)
    Abstract [en]

    Irritable bowel syndrome is a chronic gastrointestinal disorder characterized by abdominal pain and altered bowel habits in the absence of organic disease. We present 2 cases where diarrhea-predominant irritable bowel syndrome occurred in association with earlier intestinal infection or antibiotic treatment. Both were successfully treated with instillation of an anaerobic cultivated human intestinal microbiota. Thereafter, they were symptom free for at least 12 months. We now introduce the term dysbiotic bowel syndrome covering cases where a disturbed intestinal microbiota is assumed to be present. We recommend that restoration of the dysbiotic gut microbiota should be first-line treatment in these conditions.

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  • 33.
    Berglund, Sofia
    et al.
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden;Karolinska Inst, Dept Clin Neurosci, Therapeut Immune Design, Stockholm, Sweden;Karolinska Univ Hosp, Cell Therapy & Allogene Stem Cell Transplantat CA, Stockholm, Sweden.
    Watz, Emma
    Karolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Stockholm, Sweden;Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.
    Remberger, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. KFUE, Uppsala, Sweden.
    Garming Legert, Karin
    Karolinska Inst, Dept Dent Med, Stockholm, Sweden.
    Axdorph-Nygell, Ulla
    Karolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Stockholm, Sweden;Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.
    Sundin, Mikael
    Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Pediat Hematol Immunol & Hematopoiet Cell Transpl, Stockholm, Sweden.
    Uhlin, Michael
    Karolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Stockholm, Sweden;Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden;Royal Inst Technol, Dept Appl Phys, Stockholm, Sweden.
    Mattsson, Jonas
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden;Princess Margaret Canc Ctr, Div Med Oncol & Hematol, Toronto, ON, Canada;Univ Toronto, Dept Med, Toronto, ON, Canada.
    Granulocyte transfusions could benefit patients with severe oral mucositis after allogeneic hematopoietic stem cell transplantation2019In: Vox Sanguinis, ISSN 0042-9007, E-ISSN 1423-0410, Vol. 114, no 7, p. 769-777Article in journal (Refereed)
    Abstract [en]

    Background and objectives

    Mucositis is a common complication after allogeneic hematopoietic stem cell transplantation (HSCT), and is caused by a combination of conditioning‐induced mucosal damage and severe neutropenia. The symptoms include oral and abdominal pain, inability to swallow food and fluids, and severe diarrhoea. Severe mucositis is associated with increased risk of Graft‐versus‐Host disease and infection. Granulocyte transfusions (GCX) could be a treatment option, and our objective was to study its feasibility and potential benefits.

    Material and methods

    This retrospective, single‐centre study included 30 patients receiving GCX because of severe oral mucositis after HSCT during 2005–2017. Clinical outcome, response to GCX, change in opiate administration and adverse events were studied.

    Results

    Twenty‐seven patients received GCX from donors pre‐treated with steroids and G‐CSF, and three from donors pre‐treated with steroids only. Overall response was 83% (24/29 evaluable patients). Fifteen patients reached a complete response. In 14 of 24 responders, a reduction of the administration of opiate pain relief was seen. In eight patients this reduction was ≥50% of the dose. Adverse events (AEs) were reported in 14 cases, and were mild to moderate, and well manageable with symptomatic treatment. No life‐threatening or fatal AEs were recorded.

    Conclusions

    These results indicate that GCX could be a safe and effective treatment for oral mucositis after HSCT with the potential to reduce the necessity of opiate analgesic treatment in this disorder. No severe AEs were seen in this study, but the risk for severe pulmonary AEs after GCX needs to be considered.

  • 34.
    Bergquist, Annika
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Huddinge, Unit Gastroenterol & Rheumatol, Stockholm, Sweden.;European Reference Network Hepatol Dis, Stockholm, Sweden..
    Weismueller, Tobias J.
    Univ Bonn, Univ Hosp Bonn, Dept Internal Med 1, Bonn, Germany..
    Levy, Cynthia
    Univ Miami, Div Digest Hlth & Liver Dis, Miami, FL USA.;Univ Miami, Schiff Ctr Liver Dis, Miami, FL USA..
    Rupp, Christian
    Heidelberg Univ Hosp, Dept Gastroenterol Infect Dis Intoxicat, Heidelberg, Germany..
    Joshi, Deepak
    Kings Coll Hosp London, Inst Liver Studies, London, England..
    Shanika Nayagam, Jeremy
    Kings Coll Hosp London, Inst Liver Studies, London, England..
    Montano-Loza, Aldo J.
    Univ Alberta, Dept Med, Div Gastroenterol, Liver Unit, Edmonton, AB, Canada..
    Lytvyak, Ellina
    Univ Alberta, Dept Med, Div Gastroenterol, Liver Unit, Edmonton, AB, Canada..
    Wunsch, Ewa
    Pomeranian Med Univ, Translat Med Grp, Szczecin, Poland..
    Milkiewicz, Piotr
    Pomeranian Med Univ, Translat Med Grp, Szczecin, Poland.;Med Univ Warsaw, Liver & Internal Med Unit, Warsaw, Poland..
    Zenouzi, Roman
    Univ Med Ctr Hamburg Eppendorf, Martin Zeitz Ctr Rare Dis, Dept Med, Hamburg, Germany..
    Schramm, Christoph
    Univ Med Ctr Hamburg Eppendorf, Martin Zeitz Ctr Rare Dis, Dept Med, Hamburg, Germany..
    Cazzagon, Nora
    Univ Padua, Dept Surg Oncol & Gastroenterol, Padua, Italy.;Univ Padua, Azienda Ospedaliera, European Reference Network Hepatol Dis, Padua, Italy..
    Floreani, Annarosa
    Univ Padua, Sci Consultant IRCCS Negrar, Verona, Italy..
    Friis Liby, Ingalill
    Sahlgrens Univ Hosp, Dept Gastroenterol & Hepatol, Gothenburg, Sweden..
    Wiestler, Miriam
    Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany.;European Reference Network Hepatol Dis, Hannover, Germany..
    Wedemeyer, Heiner
    Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany.;European Reference Network Hepatol Dis, Hannover, Germany..
    Zhou, Taotao
    Univ Bonn, Univ Hosp Bonn, Dept Internal Med 1, Bonn, Germany..
    Strassburg, Christian P.
    Univ Bonn, Univ Hosp Bonn, Dept Internal Med 1, Bonn, Germany..
    Rigopoulou, Eirini
    Gen Univ Hosp Larissa, Natl Expertise Ctr Greece Autoimmune Liver Dis, Dept Med & Res Lab Internal Med, Larisa, Greece..
    Dalekos, George
    Gen Univ Hosp Larissa, Natl Expertise Ctr Greece Autoimmune Liver Dis, Dept Med & Res Lab Internal Med, Larisa, Greece..
    Narasimman, Manasa
    Univ Miami, Schiff Ctr Liver Dis, Miami, FL USA..
    Verhelst, Xavier
    Ghent Univ Hosp, Dept Gastroenterol & Hepatol, Ghent, Belgium.;Univ Ghent, Ghent Liver Res Ctr, Ghent, Belgium.;European Reference Network Hepatol Dis, Ghent, Belgium..
    Degroote, Helena
    Ghent Univ Hosp, Dept Gastroenterol & Hepatol, Ghent, Belgium.;Univ Ghent, Ghent Liver Res Ctr, Ghent, Belgium.;European Reference Network Hepatol Dis, Ghent, Belgium..
    Vesterhus, Mette
    Oslo Univ Hosp, Norwegian PSC Res Ctr, Div Surg Inflammatory Dis & Transplantat, Rikshosp,Dept Transplantat Med, Oslo, Norway.;Univ Bergen, Dept Clin Sci, Bergen, Norway.;Haraldsplass Deaconess Hosp, Dept Med, Bergen, Norway..
    Kremer, Andreas E.
    Friedrich Alexander Univ Erlangen Nurnberg, Dept Med 1, Erlangen, Germany.;Univ Hosp Erlangen, Erlangen, Germany.;Univ Hosp Zurich, Dept Gastroenterol & Hepatol, Zurich, Switzerland..
    Bündgens, Bennet
    Univ Duisburg, Univ Hosp Essen, Dept Gastroenterol & Hepatol, Essen, Germany..
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Nilsson, Emma
    Lund Univ, Dept Clin Sci, Lund, Sweden.;Skane Univ Hosp, Gastroenterol Clin, Malmö, Sweden..
    Kaasen Jørgensen, Kristin
    Akershus Univ Hosp, Dept Gastroenterol, Lorenskog, Norway..
    von Seth, Erik
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Huddinge, Unit Gastroenterol & Rheumatol, Stockholm, Sweden.;European Reference Network Hepatol Dis, Stockholm, Sweden..
    Cornillet Jeannin, Martin
    Karolinska Univ Hosp, Karolinska Inst, Ctr Infect Med, Dept Med Huddinge, Stockholm, Sweden..
    Nyhlin, Nils
    Örebro Univ, Fac Med & Hlth, Dept Gastroenterol, Örebro, Sweden..
    Martin, Harry
    Univ Coll Hosp NHS Fdn Trust, Dept Gastroenterol, London, England..
    Kechagias, Stergios
    Linköping Univ, Dept Hlth Med & Caring Sci, Unit Internal Med, Linköping, Sweden..
    Wiencke, Kristine
    Oslo Univ Hosp, Norwegian PSC Res Ctr, Div Surg Inflammatory Dis & Transplantat, Rikshosp,Dept Transplantat Med, Oslo, Norway..
    Werner, Mårten
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Terziroli Beretta-Piccoli, Benedetta
    Univ Svizzera Italiana, Epatocentro Ticino, Lugano, Switzerland..
    Marzioni, Marco
    Univ Politecn Marche, Univ Hosp, Clin Gastroenterol & Hepatol, Ospedali Riuniti, Ancona, Italy..
    Isoniemi, Helena
    Helsinki Univ Hosp, Abdominal Ctr, Transplantat & Liver Surg, Helsinki, Finland..
    Arola, Johanna
    Univ Helsinki, Helsinki Univ Hosp, Dept Pathol & Huslab, Helsinki, Finland..
    Wefer, Agnes
    Karolinska Univ Hosp, Div Surg, Stockholm, Sweden..
    Söderling, Jonas
    Karolinska Inst, Dept Med, Clin Epidmiol Div, Stockholm, Sweden..
    Färkkilä, Martti
    Univ Helsinki, Abdominal Ctr, Clin Gastroenterol, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland..
    Lenzen, Henrike
    Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany.;European Reference Network Hepatol Dis, Hannover, Germany.;Univ Duisburg, Univ Hosp Essen, Dept Gastroenterol & Hepatol, Essen, Germany..
    Impact on follow-up strategies in patients with primary sclerosing cholangitis2023In: Liver international, ISSN 1478-3223, E-ISSN 1478-3231, Vol. 43, no 1, p. 127-138Article in journal (Refereed)
    Abstract [en]

    Background & Aims

    Evidence for the benefit of scheduled imaging for early detection of hepatobiliary malignancies in primary sclerosing cholangitis (PSC) is limited. We aimed to compare different follow-up strategies in PSC with the hypothesis that regular imaging improves survival.

    Methods

    We collected retrospective data from 2975 PSC patients from 27 centres. Patients were followed from the start of scheduled imaging or in case of clinical follow-up from 1 January 2000, until death or last clinical follow-up alive. The primary endpoint was all-cause mortality.

    Results

    A broad variety of different follow-up strategies were reported. All except one centre used regular imaging, ultrasound (US) and/or magnetic resonance imaging (MRI). Two centres used scheduled endoscopic retrograde cholangiopancreatography (ERCP) in addition to imaging for surveillance purposes. The overall HR (CI95%) for death, adjusted for sex, age and start year of follow-up, was 0.61 (0.47–0.80) for scheduled imaging with and without ERCP; 0.64 (0.48–0.86) for US/MRI and 0.53 (0.37–0.75) for follow-up strategies including scheduled ERCP. The lower risk of death remained for scheduled imaging with and without ERCP after adjustment for cholangiocarcinoma (CCA) or high-grade dysplasia as a time-dependent covariate, HR 0.57 (0.44–0.75). Hepatobiliary malignancy was diagnosed in 175 (5.9%) of the patients at 7.9 years of follow-up. Asymptomatic patients (25%) with CCA had better survival if scheduled imaging had been performed.

    Conclusions

    Follow-up strategies vary considerably across centres. Scheduled imaging was associated with improved survival. Multiple factors may contribute to this result including early tumour detection and increased endoscopic treatment of asymptomatic benign biliary strictures.

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  • 35. Beyder, A.
    et al.
    Strege, P.
    Rainey, J.
    Bernard, C.
    Giandomenico, Valeria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kashyap, P.
    Farrugia, G.
    Shear sensitivity of the voltage-gated sodium selective ion channels (NaV) in the neuroendocrine cell line QGP-12014In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 26, no S1, p. 26-26Article in journal (Other academic)
  • 36.
    Bhoday, J.
    et al.
    Croydon Univ Hosp, Royal Marsden NHS Fdn Trust, Croydon, England.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Tait, D.
    Royal Marsden NHS Fdn Trust, London, England.
    Glynne-Jones, R.
    Mt Vernon Ctr Canc Treatment, Mt Vernon, Middx, England.
    Adams, R.
    Cardiff Univ, Cardiff, S Glam, Wales;Velindre Canc Ctr, Cardiff, S Glam, Wales.
    Brown, G.
    Imperial Coll London, London, England.
    Session 4: What should we do for poor responders after chemoradiotherapy: bad biology or should the fight go on?2018In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 20, no Suppl. 1, p. 97-99Article in journal (Refereed)
    Abstract [en]

    Just over 50% of patients with advanced rectal cancer have a poor response to chemoradiotherapy with resultant poor outcomes. Professor Glimelius reviews the evidence base for defining such patients and the potential role, if any, of further treatment.

  • 37.
    Bonfiglio, F.
    et al.
    Biodonostia Hlth Res Inst, Dept Gastrointestinal & Liver Dis, Donostia San Sebastian, Gipuzkoa, Spain; Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.
    Henstrom, M.
    Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.
    Nag, A.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.
    Hadizadeh, F.
    Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.
    Zheng, T.
    Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.
    Cenit, M. C.
    Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
    Tigchelaar, E.
    Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
    Williams, F.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.
    Reznichenko, A.
    Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.
    Ek, Weronica E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.
    Rivera, N. V.
    Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.
    Homuth, G.
    Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Dept Funct Gen, Greifswald, Germany.
    Aghdassi, A. A.
    Univ Med Greifswald, Dept Med A, Greifswald, Germany.
    Kacprowski, T.
    Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Dept Funct Gen, Greifswald, Germany.
    Mannikko, M.
    Univ Oulu, Ctr Life Course Hlth Res, Oulu, Finland.
    Karhunen, V.
    Univ Oulu, Ctr Life Course Hlth Res, Oulu, Finland; Oulu Univ Hosp, Oulu, Finland;Imperial Coll London, Dept Epidemiol & Biostat, London, England.
    Bujanda, L.
    Biodonostia Hlth Res Inst, Dept Gastrointestinal & Liver Dis, Donostia San Sebastian, Gipuzkoa, Spain; Univ Basque Country, UPV EHU, Ctr Invest Biomed Red Enfermedades Hepat & Digest, San Sebastian, Spain.
    Rafter, J.
    Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.
    Wijmenga, C.
    Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
    Ronkainen, J.
    Univ Oulu, Ctr Life Course Hlth Res, Oulu, Finland; Primary Hlth Care Ctr, Tornio, Finland.
    Hysi, P.
    Kings Coll London, Dept Ophthalmol, St Thomas Hosp Campus, London, England.
    Zhernakova, A.
    Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
    D'Amato, M.
    Biodonostia Hlth Res Inst, Dept Gastrointestinal & Liver Dis, Donostia San Sebastian, Gipuzkoa, Spain; Karolinska Inst, Dept Med Solna, Unit Clin Epidemiol, Stockholm, Sweden; BioCruces Hlth Res Inst, Bilbao, Spain; Basque Sci Fdn, IKERBASQUE, Bilbao, Spain.
    A GWAS meta-analysis from 5 population-based cohorts implicates ion channel genes in the pathogenesis of irritable bowel syndrome2018In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 30, no 9, article id e13358Article in journal (Refereed)
    Abstract [en]

    BackgroundIrritable bowel syndrome (IBS) shows genetic predisposition, however, large-scale, powered gene mapping studies are lacking. We sought to exploit existing genetic (genotype) and epidemiological (questionnaire) data from a series of population-based cohorts for IBS genome-wide association studies (GWAS) and their meta-analysis. MethodsBased on questionnaire data compatible with Rome III Criteria, we identified a total of 1335 IBS cases and 9768 asymptomatic individuals from 5 independent European genotyped cohorts. Individual GWAS were carried out with sex-adjusted logistic regression under an additive model, followed by meta-analysis using the inverse variance method. Functional annotation of significant results was obtained via a computational pipeline exploiting ontology and interaction networks, and tissue-specific and gene set enrichment analyses. Key ResultsSuggestive GWAS signals (P5.0x10(-6)) were detected for 7 genomic regions, harboring 64 gene candidates to affect IBS risk via functional or expression changes. Functional annotation of this gene set convincingly (best FDR-corrected P=3.1x10(-10)) highlighted regulation of ion channel activity as the most plausible pathway affecting IBS risk. Conclusion & InferencesOur results confirm the feasibility of population-based studies for gene-discovery efforts in IBS, identify risk genes and loci to be prioritized in independent follow-ups, and pinpoint ion channels as important players and potential therapeutic targets warranting further investigation.

  • 38. Bonfiglio, F
    et al.
    Hysi, P G
    Ek, Weronica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Karhunen, V
    Rivera, N V
    Männikkö, M
    Nordenstedt, H
    Zucchelli, M
    Bresso, F
    Williams, F
    Tornblom, H
    Magnusson, P K
    Pedersen, N L
    Ronkainen, J
    Schmidt, P T
    D'Amato, M
    A meta-analysis of reflux genome-wide association studies in 6750 Northern Europeans from the general population2017In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 29, no 2, article id e12923Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Gastroesophageal reflux disease (GERD), the regurgitation of gastric acids often accompanied by heartburn, affects up to 20% of the general population. Genetic predisposition is suspected from twin and family studies but gene-hunting efforts have so far been scarce and no conclusive genome-wide study has been reported. We exploited data available from general population samples, and studied self-reported reflux symptoms in relation to genome-wide single nucleotide polymorphism (SNP) genotypes.

    METHODS: We performed a GWAS meta-analysis of three independent population-based cohorts from Sweden, Finland, and UK. GERD cases (n=2247) and asymptomatic controls (n=4503) were identified using questionnaire-derived symptom data. Upon stringent quality controls, genotype data for more than 2.5M markers were used for association testing. Bioinformatic characterization of genomic regions associated with GERD included gene-set enrichment analysis (GSEA), in silico prediction of genetic risk effects on gene expression, and computational analysis of drug-induced gene expression signatures using Connectivity Map (cMap).

    KEY RESULTS: We identified 30 GERD suggestive risk loci (P≤5×10(-5) ), with concordant risk effects in all cohorts, and predicted functional effects on gene expression in relevant tissues. GSEA revealed involvement of GERD risk genes in biological processes associated with the regulation of ion channel and cell adhesion. From cMap analysis, omeprazole had significant effects on GERD risk gene expression, while antituberculosis and anti-inflammatory drugs scored highest among the repurposed compounds.

    CONCLUSIONS: We report a large-scale genetic study of GERD, and highlight genes and pathways that contribute to further our understanding of its pathogenesis and therapeutic opportunities.

  • 39. Borssen, Asa Danielsson
    et al.
    Almer, Sven
    Prytz, Hanne
    Wallerstedt, Sven
    Friis-Liby, Inga-Lill
    Bergquist, Annika
    Nyhlin, Nils
    Hultcrantz, Rolf
    Sangfelt, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Weiland, Ola
    Lindgren, Stefan
    Verbaan, Hans
    Werner, Marten
    Hepatocellular and extrahepatic cancer in patients with autoimmune hepatitis - a long-term follow-up study in 634 Swedish patients2015In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 50, no 2, p. 217-223Article in journal (Refereed)
    Abstract [en]

    Objectives. Cirrhosis is a well-known risk factor for hepatocellular cancer, but the true risk in autoimmune hepatitis (AIH) is scarcely studied. Other cancers may arise after prolonged use of immune-modulating drugs. The aim of this study was to investigate the cancer risk in a large cohort of AIH patients. Material and methods. Six hundred and thirty-four Swedish patients in a well-defined cohort were matched to the Cause of Death Registry and the Cancer Registry. Standard incidence ratios were calculated by relating the incidences in the cohort to an age-matched material from the Swedish background population. Results. A higher overall incidence of malignancies than the background population was found, counting from the date of diagnosis (standard incidence ratio (SIR) 2.08, 95% CI 1.68-2.55). The highest risk was found for hepatocellular carcinoma (HCC). We found 10 cases (4.0%) in 248 patients with cirrhosis, which gives an incidence rate of 0.3%. Standard incidence ratio for developing hepatobiliary cancer was 54.55 (95% CI 19.92-99.99). HCC only occurred in cirrhotic patients. There was also an increased risk for non-melanoma skin cancer (SIR 9.87, 95% CI 6.26-14.81). Conclusion. A slightly enhanced risk for malignancies in general compared to the background population was found. The risk of hepatobiliary cancer was increased, but the annual risk over the observational period was well under the postulated 1.5% when surveillance in cirrhotic patients is considered to be cost-effective.

  • 40.
    Borssen, Åsa D.
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Palmqvist, Richard
    Umea Univ, Dept Med Biosci, Pathol, Umea, Sweden..
    Kechagias, Stergios
    Linkoping Univ, Dept Med & Hlth Sci, Dept Gastroenterol & Hepatol, Linkoping, Sweden..
    Marschall, Hanns-Ulrich
    Univ Gothenburg, Dept Mol & Clin Med, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden..
    Bergquist, Annika
    Karolinska Univ, Huddinge Hosp, Dept Med, Sect Hepatol & Gastroenterol,Karolinska Inst, Stockholm, Sweden..
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Weiland, Ola
    Karolinska Univ, Huddinge Hosp, Div Infect Dis, Dept Med,Karolinska Inst, Stockholm, Sweden..
    Verbaan, Hans
    Lund Univ, Gastroenterol Div, Dept Clin Sci, Univ Hosp Skane, Lund, Sweden..
    Nyhlin, Nils
    Orebro Univ, Dept Gastroenterol, Fac Med & Hlth, Orebro, Sweden..
    Nilsson, Emma
    Lund Univ, Gastroenterol Div, Dept Clin Sci, Univ Hosp Skane, Lund, Sweden..
    Werner, Mårten
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Histological improvement of liver fibrosis in well-treated patients with autoimmune hepatitis A cohort study2017In: Medicine, ISSN 0025-7974, E-ISSN 1536-5964, Vol. 96, no 34, article id e7708Article in journal (Refereed)
    Abstract [en]

    Autoimmune hepatitis (AIH) is a chronic autoimmune liver disease that if left untreated may lead to the development of cirrhosis. Previous studies on AIH patients have suggested that fibrosis and even cirrhosis can be reversed by medical treatment. The aim of this study was to evaluate the efficacy of medical treatment for protection of developing fibrosis and cirrhosis. A total of 258 liver biopsies from 101 patients (72 women, 29 men) were analyzed by a single pathologist and classified according to the Ishak grading (inflammation) and staging (fibrosis) system. Liver histology was stratified according to the temporal changes of fibrosis stage (increased, decreased, or stable), and groups were compared. Complete or partial response to medical treatment was 94.9%. Reduction of fibrosis stage from the first to the last biopsy was seen in 63 patients (62.4%). We found an association between a reduction in the fibrosis stage and continuous glucocorticoid medication, as well as lowered scores of inflammation at last biopsy. Twenty-one patients had cirrhosis (Ishak stage 6) at least in one of the previous biopsies, but only 5 patients at the last biopsy. Histological improvement is common in AIH patients that respond to medical treatment, and a reduction or stabilization of fibrosis stage occurs in about 2/3 of such patients.

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  • 41.
    Borssen, Åsa Danielsson
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden..
    Marschall, Hanns-Ulrich
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden..
    Bergquist, Annika
    Karolinska Univ Hosp Huddinge, Karolinska Inst, Sect Hepatol & Gastroenterol, Dept Med, Stockholm, Sweden..
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Weiland, Ola
    Karolinska Univ Hosp Huddinge, Karolinska Inst, Div Infect Dis, Dept Med, Stockholm, Sweden..
    Kechagias, Stergios
    Univ Hosp, Dept Gastroenterol & Hepatol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Nyhlin, Nils
    Orebro Univ, Fac Med & Hlth, Dept Gastroenterol, Orebro, Sweden..
    Verbaan, Hans
    Lund Univ, Univ Hosp Skane, Div Gastroenterol, Dept Clin Sci, Malmo, Sweden..
    Nilsson, Emma
    Lund Univ, Univ Hosp Skane, Div Gastroenterol, Dept Clin Sci, Lund, Sweden..
    Werner, Mårten
    Umea Univ, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden..
    Epidemiology and causes of death in a Swedish cohort of patients with autoimmune hepatitis2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 9, p. 1022-1028Article in journal (Refereed)
    Abstract [en]

    Background: Epidemiological studies of autoimmune hepatitis (AIH) show varying figures on prevalence and incidence, and data on the long-term prognosis are scarce.Objective To investigate the epidemiology, long-term prognosis and causes of death in a Swedish AIH cohort.Material and methods: Data collected from 634 AIH patients were matched to the Cause of Death Registry, and survival analyses were made. Prevalence and incidence were calculated for university hospitals with full coverage of cases and compared to the County of Vasterbotten in Northern Sweden.Results: AIH point prevalence was 17.3/100,000 inhabitants in 2009, and the yearly incidence 1990-2009 was 1.2/100,000 inhabitants and year. The time between diagnosis and end of follow-up, liver transplantation or death was in median 11.3 years (range 0-51.5 years). Men were diagnosed earlier (p<.001) and died younger than women (p=.002). No gender differences were found concerning transplant-free, overall survival and liver-related death. Cirrhosis at diagnosis was linked to an inferior survival (p<.001). Liver-related death was the most common cause of death (32.7%). The relative survival started to diverge from the general population 4 years after diagnosis but a distinct decline was not observed until after more than 10 years.Conclusions: Long-term survival was reduced in patients with AIH. No gender difference regarding prognosis was seen but men died younger, probably as a result of earlier onset of disease. Cirrhosis at diagnosis was a risk factor for poor prognosis and the overall risk of liver-related death was increased.

  • 42. Brusselaers, Nele
    et al.
    Sadr-Azodi, Omid
    Karolinska institutet; St Göran Hospital.
    Engstrand, Lars
    Proton pump inhibitors and the risk of pancreatic cancer2021In: Journal of gastroenterology, ISSN 0944-1174, E-ISSN 1435-5922, Vol. 56, no 3, p. 295-296Article in journal (Other academic)
  • 43. Bucinskaite, V
    et al.
    Tolessa, T
    Pedersen, J
    Rydqvist, B
    Zerihun, L
    Holst, J J
    Hellström, Per M.
    Receptor-mediated activation of gastric vagal afferents by glucagon-like peptide-1 in the rat2009In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 21, no 9, p. 978-e78Article in journal (Refereed)
    Abstract [en]

    The vagus nerve plays a role in mediating effects of the two glucagon-like peptides GLP-1 and GLP-2 on gastrointestinal growth, functions and eating behaviour. To obtain electrophysiological and molecular evidence for the contribution of afferent pathways in chemoreception from the gastrointestinal tract, afferent mass activity in the ventral gastric branch of the vagus nerve and gene expression of GLP-1 receptors and GLP-2 receptors in the nodose ganglion were examined in Sprague–Dawley rats. Intravenous administration of GLP-1 (30–1000 pmol kg−1), reaching high physiological plasma concentrations, increased vagal afferent mass activity peaking (13–52% above basal level, < 0.05) 3–5 min after injection. Repeated administration of GLP-1 (1000 pmol kg−1; five times, 15 min intervals) elicited similar responses. Pretreatment with GLP-1 receptor antagonist exendin(9-39)amide (500 pmol kg−1) abolished the GLP-1 response to doses 30–300 pmol kg−1 but had no effect on the vagal response to gastric distension. For comparison, GLP-2 (1000 pmol kg−1) had no effect on vagal afferent activity. Vagal chemoreception of GLP-1 is supported by expression of the GLP-1 receptor gene in the nodose ganglion. However, the GLP-2 receptor was also expressed. To conclude, our results show that peripherally administered GLP-1, differently from GLP-2, activates vagal afferents, with no evidence of desensitisation. The GLP-1 effect was blocked by exendin(9-39)amide, suggesting that GLP-1 receptors on vagal afferent nerves mediate sensory input from the gastrointestinal tract or pancreas; either directly or indirectly via the release of another mediator. GLP-2 receptors appear not be functionally expressed on vagal afferents.

  • 44.
    Cai, Demin
    et al.
    College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China..
    Li, Yanwei
    College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China..
    Zhang, Kexin
    College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China..
    Zhou, Bo
    Institute of Digestive Disease, Zhengzhou University, Zhengzhou, China..
    Guo, Feilong
    Department of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China..
    Holm, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Liu, Haoyu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China.
    Co-option of PPARα in the regulation of lipogenesis and fatty acid oxidation in CLA-induced hepatic steatosis2021In: Journal of Cellular Physiology, ISSN 0021-9541, E-ISSN 1097-4652, Vol. 236, no 6, p. 4387-4402Article in journal (Refereed)
    Abstract [en]

    Nonalcoholic-fatty-liver-disease (NAFLD) is the result of imbalances in hepatic lipid partitioning and is linked to dietary factors. We demonstrate that conjugated linoleic acid (CLA) when given to mice as a dietary supplement, induced an enlarged liver, hepatic steatosis, and increased plasma levels of fatty acid (FA), alanine transaminase, and triglycerides. The progression of NAFLD and insulin resistance was reversed by GW6471 a small-molecule antagonist of peroxisome proliferator-activated receptor α (PPARα). Transcriptional profiling of livers revealed that the genes involved in FA oxidation and lipogenesis as two core gene programs controlled by PPARα in response to CLA and GW6471 including Acaca and Acads. Bioinformatic analysis of PPARα ChIP-seq data set and ChIP-qPCR showed that GW6471 blocks PPARα binding to Acaca and Acads and abolishes the PPARα-mediated local histone modifications of H3K27ac and H3K4me1 in CLA-treated hepatocytes. Thus, our findings reveal a dual role of PPARα in the regulation of lipid homeostasis and highlight its druggable nature in NAFLD.

  • 45.
    Cameron, Raquel
    et al.
    Univ Newcastle, Coll Hlth Med & Wellbeing, Newcastle, NSW, Australia.;NHMRC Ctr Res Excellence Digest Hlth, Newcastle, NSW, Australia.;Hunter Med Res Inst, Newcastle, NSW, Australia..
    Walker, Marjorie M.
    Univ Newcastle, Coll Hlth Med & Wellbeing, Newcastle, NSW, Australia.;NHMRC Ctr Res Excellence Digest Hlth, Newcastle, NSW, Australia..
    Thuresson, Marcus
    Statisticon AB, Uppsala, Sweden..
    Roelstraete, Bjorn
    Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden..
    Sköldberg, Filip
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Olen, Ola
    Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden..
    Talley, Nicholas J.
    Univ Newcastle, Coll Hlth Med & Wellbeing, Newcastle, NSW, Australia.;NHMRC Ctr Res Excellence Digest Hlth, Newcastle, NSW, Australia.;Hunter Med Res Inst, Newcastle, NSW, Australia..
    Ludvigsson, Jonas F.
    Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.;Örebro Univ Hosp, Dept Pediat, Örebro, Sweden.;Univ Nottingham, Sch Med, Div Epidemiol & Publ Hlth, Nottingham, England.;Columbia Univ, Celiac Dis Ctr, Dept Med, Coll Phys & Surg, New York, NY USA..
    Mortality risk increased in colonic diverticular disease: a nationwide cohort study2022In: Annals of Epidemiology, ISSN 1047-2797, E-ISSN 1873-2585, Vol. 76, p. 39-49Article in journal (Refereed)
    Abstract [en]

    Introduction: There are limited population cohort data on overall and cause-specific mortality in colonic diverticular disease.Objective: To measure overall and cause-specific mortality in colonic diverticular disease, compared to matched reference individuals and siblings.Methods: Population-based cohort study ("the ESPRESSO study") in Sweden. There were 97,850 cases with a medical diagnosis of diverticular disease (defined by international classification of disease codes) and colorectal histology identified in 1987-2017 from histopathology reports. The mortality risk between individuals with colonic diverticular disease and matched reference individuals ( n = 453/634) from the general population was determined. Cox regression models adjusted for comorbidity estimated hazard ratios (HRs) for all-cause mortality.

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  • 46.
    Carlsson, Jennifer
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Elevated IgG4 is associated with higher risk for cholangitis, cirrhosis, ERCP and liver-transplantation among patients with primary sclerosing cholangitis2022Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Primary sclerosing cholangitis (PSC) is a rare inflammatory chronic liver disease that causes damage to the intra- and or extrahepatic bile ducts leading to cholestasis. As the disease proceeds the development of cirrhosis and eventually liver failure occurs. This study aims to determine the role of IgG subclasses in the prognosis of PSC and its outcome. A retrospective analysis was performed of 183 patients followed at the Department of Upper Abdominal Diseases at the Karolinska University Hospital. Factors that were analysed were sex, age at PSC diagnosis, total IgG values, IgG subclasses values and events of autoimmune hepatitis (AIH), inflammatory bowel disease (IBD), colectomy, cirrhosis, cholangitis, endoscopic retrograde cholangiopancreatography (ERCP), liver transplantation and cholangiocarcinoma. This study showed that high IgG4 levels were associated with a higher incidence of cirrhosis, liver transplantation, cholangitis and ERCP, while low IgG4 levels were associated with a prior IBD diagnosis. In conclusion, elevated IgG4 levels were associated with a higher occurrence of cirrhosis, cholangitis, ERCP and liver transplantation. It seems that IgG4 could be of importance for outcome prediction in PSC.

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  • 47.
    Casado-Bedmar, Maite
    et al.
    Linköping Univ, Dept Biomed & Clin Sci, Linköping, Sweden..
    de-Faria, Felipe Meira
    Linköping Univ, Dept Biomed & Clin Sci, Linköping, Sweden..
    Biskou, Olga
    Linköping Univ, Dept Biomed & Clin Sci, Linköping, Sweden..
    Lindqvist, Carl Marten
    Örebro Univ, Dept Med Sci, Örebro, Sweden..
    Ranasinghe, Purnika Damindi
    Queens Univ Belfast, Sch Biol Sci, Inst Global Food Secur, Belfast, Antrim, North Ireland..
    Bednarska, Olga
    Linköping Univ, Dept Biomed & Clin Sci, Linköping, Sweden.;Dept Gastroenterol, Linköping, Sweden..
    Peterson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Diagnost Dev, Uppsala, Sweden..
    Walter, Susanna A.
    Linköping Univ, Dept Biomed & Clin Sci, Linköping, Sweden.;Dept Gastroenterol, Linköping, Sweden..
    Carlsson, Maria E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness.
    Keita, Asa, V
    Linköping Univ, Dept Biomed & Clin Sci, Linköping, Sweden..
    Elevated F-EDN correlates with mucosal eosinophil degranulation in patients with IBS-A possible association with microbiota?2022In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 111, no 3, p. 655-665Article in journal (Refereed)
    Abstract [en]

    Eosinophils have been linked to functional dyspepsia; however, less is known about their role in irritable bowel syndrome (IBS). This study tested the hypothesis of alterations in levels of fecal eosinophil-derived neurotoxin (F-EDN) and eosinophil density and degranulation within the colonic mucosa of IBS patients compared with healthy controls (HC). Colonic biopsies were collected from 37 IBS patients and 20 HC and analyzed for eosinophil numbers and local degranulation of eosinophil cationic protein (ECP) by histologic procedures. Fecal samples were collected for F-EDN and microbiota analysis. Differentiated 15HL-60 cells were used in vitro to investigate the direct effect of live bacteria on eosinophil activation measured by a colorimetric assay with o-phenylenediamine (OPD) substrate. We observed a higher number of eosinophils and increased extracellular ECP in the mucosa of IBS patients compared with HC. Moreover, F-EDN levels in IBS samples were elevated compared with HC and positively correlated to extracellular ECP. Metagenomic analysis showed significant correlations between bacterial composition and eosinophil measurements in both HC and IBS patients. In vitro experiments revealed an increased degranulation of 15HL-60 after stimulation with Salmonella typhimurium, Salmonella enterica, and Yersinia enterocolitica. To conclude, we could demonstrate alterations related to eosinophils in IBS, and, for the first time, a positive correlation between F-EDN levels and degranulated eosinophils in the colonic mucosa of IBS patients. Together our results suggest that eosinophils play a role in the pathophysiology of IBS and the mechanisms might be linked to an altered microbiota.

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  • 48.
    Cashin, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery. Akad Sjukhuset, S-75185 Uppsala, Sweden..
    A new technique to improve surgery for peritoneal colorectal metastases?2016In: The Lancet Gastroenterology & Hepatology, ISSN 2468-1253, Vol. 1, no 4, p. 263-264Article in journal (Other academic)
  • 49. Cesarini, M.
    et al.
    Collins, G.
    Rönnblom, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Santos, A.
    Sjöberg, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Parkes, M.
    Keshav, S.
    Travis, S.
    Predicting the risk of acute severe colitis (ASC) at diagnosis of Ulcerative Colitis (UC): external validation2015In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 9, no S1, p. S117-S118Article in journal (Other academic)
  • 50.
    Cesarini, Monica
    et al.
    Oxford Univ Hosp, Translat Gastroenterol Unit, Oxford, England.;Sapienza Univ Rome, Dipartimento Med Interna & Specialita Med, Rome, Italy..
    Collins, Gary S.
    Univ Oxford, Ctr Stat Med, Oxford, England..
    Rönnblom, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Santos, Antonieta
    Cambridge Univ Hosp, Gastroenterol Unit, Cambridge, England.;Hosp Amato Lusitano, Gastroenterol Unit, Castelo Branco, Portugal..
    Wang, Lai Mun
    Oxford Univ Hosp, Dept Cellular Pathol, Oxford, England..
    Sjöberg, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Parkes, Miles
    Oxford Univ Hosp, Translat Gastroenterol Unit, Oxford, England..
    Keshav, Satish
    Oxford Univ Hosp, Translat Gastroenterol Unit, Oxford, England..
    Travis, Simon P. L.
    Oxford Univ Hosp, Translat Gastroenterol Unit, Oxford, England..
    Predicting the Individual Risk of Acute Severe Colitis at Diagnosis2017In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 11, no 3, p. 335-341Article in journal (Refereed)
    Abstract [en]

    Background and Aims: Acute severe colitis [ASC] is associated with major morbidity. We aimed to develop and externally validate an index that predicted ASC within 3 years of diagnosis. Methods: The development cohort included patients aged 16-89 years, diagnosed with ulcerative colitis [UC] in Oxford and followed for 3 years. Primary outcome was hospitalization for ASC, excluding patients admitted within 1 month of diagnosis. Multivariable logistic regression examined the adjusted association of seven risk factors with ASC. Backwards elimination produced a parsimonious model that was simplified to create an easy-to-use index. External validation occurred in separate cohorts from Cambridge, UK, and Uppsala, Sweden. Results: The development cohort [Oxford] included 34/111 patients who developed ASC within a median 14 months [range 1-29]. The final model applied the sum of 1 point each for extensive disease, C-reactive protein [CRP] >10 mg/l, or haemoglobin < 12 g/dl F or < 14 g/dl M at diagnosis, to give a score from 0/3 to 3/3. This predicted a 70% risk of developing ASC within 3 years [score 3/3]. Validation cohorts included different proportions with ASC [Cambridge = 25/96; Uppsala = 18/298]. Of those scoring 3/3 at diagnosis, 18/18 [Cambridge] and 12/13 [Uppsala] subsequently developed ASC. Discriminant ability [c-index, where 1.0 = perfect discrimination] was 0.81 [Oxford], 0.95 [Cambridge], 0.97 [Uppsala]. Internal validation using bootstrapping showed good calibration, with similar predicted risk across all cohorts. A nomogram predicted individual risk. Conclusions: An index applied at diagnosis reliably predicts the risk of ASC within 3 years in different populations. Patients with a score 3/3 at diagnosis may merit early immunomodulator therapy.

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