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  • 1.
    Almer, Sven
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences.
    Hjortswang, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences.
    Hindorf , U
    Lund University.
    6-Thioguanine therapy in Crohns disease-Observational data in Swedish patients2009In: Digestive and Liver Disease, ISSN 1590-8658, E-ISSN 1878-3562, Vol. 41, no 3, p. 194-200Article in journal (Refereed)
    Abstract [en]

    Background and aims: Adverse events (AE) leading to discontinuation or dose-reduction of thiopurine therapy (TP) occur in 9-28% of patients with inflammatory bowel disease. 6-Thioguanine (6-TG) has been proposed as an alternative treatment in patients intolerant for azathioprine (AZA), but some concerns have been raised about drug safety.

    Methods: We evaluated in a prospective manner the tolerance and efficacy of 6-TG in 23 Crohns disease (CD) patients (13 men, median age 41 (19-65) years) with prior intolerance (n = 18) or resistance (It = 5) to AZA and/or 6-mercaptopurine (6-MP). In addition, eight patients had tried mycophenolate mofetil. Seventeen patients (74%) had undergone intestinal resection, often several times.

    Results: Patients were treated with a median daily dose of 40 mg 6-TG (range 20-60) for 259 (15-2272) days. Seven of 13 patients (54%) with active disease went into remission after 8 (4-26) weeks. Sixteen patients (70%) experienced AE that lead to discontinuation (n=10) after 85 (15-451) days or dose reduction (n=6) after 78 (10-853) days. Ten of 18 patients (56%) with prior TP-intolerance discontinued 6-TG treatment due to AE compared to none of five patients with TP-resistance (p=0.046). Of 13 patients that tolerated 6-TG, eight discontinued the drug due to therapeutic failure (n=5) or safety concerns (n=3). Eight patients (35%) continued treatment beyond 12 months. There was no significant difference in maximum thioguanine nucleotide levels between patients with AE leading to discontinuation/dose reduction and patients without AE, 652 (99-2488) vs. 551 (392-1574) pmol/8 x 10(8) RBC; p=0.80.

    Conclusions: In this cohort of CD patients with severe disease failing traditional thiopurine treatment, a small fraction (22%) had long-term benefit of 6-TG-treatment. 6-TG therapy seems to offer a limited therapeutic gain for patients intolerant to both AZA and 6-MP and other treatment options should be considered.

  • 2.
    Halfvarson, Jonas
    et al.
    Division of Gastroenterology, Department of Internal Medicine, Örebro University Hospital, Örebro, Sweden.
    Bresso, F.
    IRIS Center, Karolinska Institute-MTC, Stockholm, Sweden.
    D'Amato, M.
    IRIS Center, Karolinska Institute-MTC, Stockholm, Sweden.
    Järnerot, Gunnar
    Division of Gastroenterology, Department of Internal Medicine, Örebro University Hospital, Örebro, Sweden.
    Pettersson, S.
    IRIS Center, Karolinska Institute-MTC, Stockholm, Sweden.
    Tysk, Curt
    Division of Gastroenterology, Department of Internal Medicine, Örebro University Hospital, Örebro, Sweden.
    CARD15/NOD2 polymorphisms do not explain concordance of Crohn's disease in Swedish monozygotic twins2005In: Digestive and Liver Disease, ISSN 1590-8658, E-ISSN 1878-3562, Vol. 37, no 10, p. 768-772Article in journal (Refereed)
    Abstract [en]

    Background.

    CARD15/NOD2 polymorphisms are associated with Crohn's disease. There is a high concordance for disease and disease phenotype in monozygotic twin pairs with Crohn's disease.

    Aim.

    We studied CARD15/NOD2 polymorphisms in a Swedish, population-based cohort of monozygotic twins with Crohn's disease to assess whether these variants explain disease concordance.

    Subjects and methods.

    Twenty-nine monozygotic twin pairs (concordant n = 9, discordant n = 20) with Crohn's disease and 192 healthy controls were investigated for the CARD15/NOD2 variants Arg702Trp, Gly908Arg and Leu1007fsinsC.

    Results.

    CARD15/NOD2 mutations were found in 5/38 (13%) twins with Crohn's disease, corresponding to a total allele frequency of 6.6%. Only 2/9 concordant twin pairs carried any of the variants and the remaining seven were wild type genotype. The total allele frequency was 4.4 times higher (95% confidence interval 1.0–21.5, p = 0.06) in concordant twins than in discordant ones, 11.1% versus 2.5%. In healthy controls the total allele frequency was 2.6%.

    Conclusions.

    CARD15/NOD2 polymorphisms contribute but do not alone explain concordance of Crohn's disease in monozygotic twins and, at least in a Swedish population, other polymorphisms are required. The low occurrence of CARD15/NOD2 mutations in the study and other Northern European populations suggests that these variants are of less importance in Northern Europe.

  • 3.
    Laszkowska, Monika
    et al.
    Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.
    Roy, Abhik
    Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.
    Lebwohl, Benjamin
    Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Green, Peter H. R.
    Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.
    Sundelin, Helene E. K.
    Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Ludvigsson, Jonas F.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK.
    Nationwide population-based cohort study of celiac disease and risk of Ehlers-Danlos syndrome and joint hypermobility syndrome2016In: Digestive and Liver Disease, ISSN 1590-8658, E-ISSN 1878-3562, Vol. 48, no 9, p. 1030-1034Article in journal (Refereed)
    Abstract [en]

    Background: Patients with celiac disease (CD) often have articular complaints, and small prior studies suggest an association with Ehlers-Danlos syndrome (EDS)/joint hypermobility syndrome (JHS). Aims: This study examines the risks of EDS/JHS in patients with CD. Methods: This cohort study compared all individuals in Sweden diagnosed with CD based on small intestinal biopsy between 1969-2008 (n = 28,631) to 139,832 matched reference individuals, and to a second reference group undergoing biopsy without having CD (n = 16,104). Rates of EDS/JHS were determined based on diagnostic codes in the Swedish Patient Register. Hazard ratios (HRs) for EDS/JHS were estimated through Cox regression. Results: There are 45 and 148 cases of EDS/JHS in patients with CD and reference individuals, respectively. This corresponds to a 49% increased risk of EDS/JHS in CD (95% CI = 1.07-2.07). The HR for EDS was 2.43 (95% CI = 1.20-4.91) and for JHS 1.34 (95% CI = 0.93-1.95). Compared to reference individuals undergoing intestinal biopsy, CD was not a risk factor for EDS/JHS. A stronger association was seen in patients initially diagnosed with EDS/JHS and subsequently diagnosed with CD (odds ratio = 2.29; 95% CI = 1.21-4.34). Conclusions: Individuals with CD have higher risk of EDS/JHS than the general population, which may be due to surveillance bias or factors intrinsic to celiac development. (C) 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  • 4.
    Mathiesen, UL
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology.
    Franzén, LE
    Åselius, H
    Resjö, M
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Radiology. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology UHL.
    Jacobsson, L
    Foberg, U
    Frydén, Aril
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Bodemar, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, EMK-magtarm.
    Increased liver echogenicity at ultrasound examination reflects degree of steatosis but not of fibrosis in asymptomatic patients with mild/moderate abnormalities of liver transaminases2002In: Digestive and Liver Disease, ISSN 1590-8658, E-ISSN 1878-3562, Vol. 34, no 7, p. 516-522Article in journal (Refereed)
    Abstract [en]

    Aims. To investigate whether hyperechogenicity of liver can reliably be interpreted as liver steatosis and if any concomitant or isolated fibrosis can be disclosed. Patients and methods. A series of 165 patients with no signs or symptoms of liver disease referred because of slightly to moderately raised aminotransferases (alanine aminotransferase and/or aspartate aminotransferase 0.7-5.0 ╡kat/l) for more than 6 months were prospectively investigated with a comprehensive laboratory profile, ultrasound examination of liver and percutaneous liver biopsy. Fibrosis was assessed quantitatively and according to Metavir. Steatosis was graded as none, mild, moderate or severe. Results. Of 98 (59.4%) patients with raised echogenicity, 85 (86.7%) had liver steatosis of at least moderate degree, 9 patients with same degree of steatosis had normal echogenicity and 13 patients with no or only mild steatosis had normal echogenicity liver (sensitivity 0.90, specificity 0.82, positive predictive value 0.87, negative predictive value 0.87). About the same relations were found regardless of body mass index and degree of fibrosis. With increased echogenicity together with high attenuation (n=59) and reduced portal vessel wall distinction (n=79), positive predictive value increased to 0.93 and 0.94, respectively. Quantitatively assessed fibrosis (mean ▒ SD) was 3.2▒4.6% of biopsy area with normal and 2.3▒1.8% with raised echogenicity [ns]. Echogenicity was normal in 5 out of 9 patients with septal fibrosis and in 4 out of 6 patients with cirrhosis. Any structural, non-homogenous findings at ultrasound were not associated with architectural fibrotic changes and none had nodular contours of liver surface. Conclusions. Assessment of liver echogenicity is of value for detection or exclusion of moderate to pronounced fatty infiltration (correct classification 86.6%) but cannot be relied upon in diagnosing fibrosis, not even cirrhosis in asymptomatic patients with mild to moderately elevated liver transaminases.

  • 5.
    Roos, Susanne
    et al.
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences.
    Kärner, Anita
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences.
    Hallert, Claes
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Psychological well-being of adult coeliac patients treated for 10 years2006In: Digestive and Liver Disease, ISSN 1590-8658, E-ISSN 1878-3562, Vol. 38, no 3, p. 177-180Article in journal (Refereed)
    Abstract [en]

    Background

    Adults with longstanding coeliac disease generally report reduced quality of life. Uncertainty remains whether this is a sign of depression, thought to be a feature of the disorder.

    Aim

    To assess the psychological well-being in adults with long-treated coeliac disease.

    Patients and methods

    Fifty-one coeliac disease adults (59% women) aged 45–64 years diagnosed in 1984–1988 and showing evidence of remission 8–12 years later were examined by the Psychological General Well-being index. One hundred and eighty-two (57% women) adults of same age served as population controls.

    Results

    The coeliac disease patients showed no more signs of anxiety, depressed mood or distress than the controls as assessed by the Psychological General Well-being index, 103 (95% confidence interval (95% CI) = 99–107) versus 103 (95% CI = 100–106). However, unlike controls, the coeliac disease women showed a significantly lower Psychological General Well-being index than the coeliac disease men, 97 (95% CI = 91–103) versus 111 (95% CI = 106–117) (P < 0.003).

    Conclusion

    Long-treated adult coeliac disease patients showed no difference in psychological well-being to population controls, suggesting that signs of depressed mood is no feature of well-treated coeliac disease. The observation that coeliac disease women living in Sweden experience poorer outcome of treatment than coeliac disease men is a cause of concern and calls for further studies.

  • 6.
    Tapsas, Dimitrios
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Hollén, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Stenhammar, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Fälth-Magnusson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    The clinical presentation of celiac disease in 1030 Swedish children: changing features over the past 41 years: a long-term follow-up study2016In: Digestive and Liver Disease, ISSN 1590-8658, E-ISSN 1878-3562, Vol. 48, no 1, p. 16-22Article in journal (Refereed)
    Abstract [en]

    Background- Aims

    The features of pediatric celiac disease have changed in recent decades. We hypothesized that the age at diagnosis continued to increase, whereas the severity of symptoms should decrease.

    Methods

    In the present study, filed data about 1030 pediatric patients diagnosed with celiac disease between 1973 and 2013 were analysed. Available information covered 99.8% of the small bowel biopsies, and included information on sex, age, and clinical symptoms.

    Results

    The age at diagnosis increased significantly, from a mean of 2.2 years during the first 10 years to 8.2 years the current years. The proportion of children with severe symptoms declined from 92.8% to 78%, as did the proportion of biopsies characterized by severe pathology. In recent years, the monosymptomatic form of celiac disease has been more common, and the number of patients detected at screening has increased. The frequency of patients with gastrointestinal symptoms, extra-intestinal symptoms, and failure to thrive and/or short stature at presentation decreased.

    Conclusions

    The mean age of newly diagnosed patients increased the last 15 years. Currently celiac disease shows a less severe picture in terms of symptoms and intestinal pathology. Younger children suffer primarily from gastrointestinal symptoms and growth failure, and adolescents from extra-intestinal manifestations.

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