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  • 1. Agostoni, C
    et al.
    Buonocore, G
    Carnielli, VP
    De Curtis, M
    Darmaun, D
    Decsi, T
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Embleton, ND
    Fusch, C
    Genzel-Boroviczeny, O
    Goulet, O
    Kalhan, SC
    Kolacek, S
    Koletzko, B
    Lapillonne, A
    Mihatsch, W
    Moreno, L
    Neu, J
    Poindexter, B
    Puntis, J
    Putet, G
    Rigo, J
    Riskin, A
    Salle, B
    Sauer, P
    Shamir, R
    Szajewska, H
    Thureen, P
    Turck, D
    van Goudoever, JB
    Ziegler, EE
    Enteral nutrient supply for preterm infants: commentary from the European society of paediatric gastroenterology, hepatology and nutrition committee on nutrition2010In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 50, no 1, p. 85-91Article in journal (Refereed)
    Abstract [en]

    The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infant's own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate.

  • 2. Agreus, Lars
    et al.
    Hellström, Per M.
    Talley, Nicholas J.
    Wallner, Bengt
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Forsberg, Anna
    Vieth, Michael
    Veits, Lothar
    Björkegren, Karin
    Engstrand, Lars
    Andreasson, Anna
    Towards a healthy stomach? Helicobacter pylori prevalence has dramatically decreased over 23 years in adults in a Swedish community2016In: United European Gastroenterology journal, ISSN 2050-6406, E-ISSN 2050-6414, Vol. 4, no 5, p. 686-696Article in journal (Refereed)
    Abstract [en]

    Background In Western countries the prevalence of Helicobacter pylori (H. pylori) infection may be declining but there is a lack of recent longitudinal population studies. We evaluated the changing epidemiology over a 23-year period in Sweden. Materials and methods In 1989, the validated Abdominal Symptom Questionnaire (ASQ) was mailed to a random sample of inhabitants (ages 22-80 years) in a Swedish community, and 1097 (87%) responded. H. pylori serology was analysed in a representative subsample (n=145). Twenty-three years later, the ASQ was mailed again using similar selection criteria, and 388 out of 1036 responders had an upper endoscopy with assessment of H. pylori and corpus atrophy status. Results The prevalence of positive H. pylori serology decreased from 37.9% (1989) to 15.8% (2012), corresponding to a decrease in odds of 75% per decade (odds ratio (OR): 0.25; 95% confidence interval (CI): 0.11-0.59, p=0.001) independent of age, gender, body mass index (BMI) and level of education, with a pattern consistent with a birth cohort effect. The prevalence increased with increasing age (p=0.001). The prevalence of H. pylori on histology in 2012 was 11.4% (95% CI 8.6-15.0). The prevalence of corpus atrophy on serology and/or histology in 2012 was 3.2% (95% CI 1.8-5.5); all cases were 57 years old. Conclusion The stomach is healthier in 2012 compared with 1989. H. pylori prevalence in adults has decreased over the last two decades to a level where clinical management might be affected.

  • 3.
    Alaish, Ram
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundgren, David
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Safety of azathioprine and 6-mercaptopurine in patients with inflammatory bowel disease naive to thiopurine treatment2017In: International journal of clinical pharmacology and therapeutics, ISSN 0946-1965, Vol. 55, no 7, p. 594-600Article in journal (Refereed)
    Abstract [en]

    Objectives: To determine if 6-mercaptopurine (MP) is better tolerated than azathioprine (AZA) as the initial thiopurine treatment in patients suffering from inflammatory bowel disease (IBD). Switching patients with IBD from AZA to MP is advocated in patients intolerant to AZA. However, no study has determined if MP is more suited than AZA as a first-line treatment for patients who are naive to thiopurine treatment. Study: The tolerance of AZA and MP treatments in clinical practice was retrospectively evaluated from start to 12 months after initiating treatment in 113 patients with IBD who were all naive to thiopurines (82 patients treated with AZA and 31 patients with MP). Results: 65% of the patients treated with AZA and 61% of the patients treated with MP tolerated their treatment during 12 months (i.e., no group difference, p = 0.742). No difference in reported side effects between the two treatments was observed. The mean equivalent initial dose (0.92 vs. 0.61 mg/kg; p < 0.001) and the mean equivalent dose at 12 months (1.98 vs. 1.65 mg/kg; p = 0.014) was significantly higher in the MP group vs. the AZA group. The proportion of patients with.MCV = 7 at 12 months was numerically higher in the MP group than in the AZA group (53% vs. 31%; p = 0.090). Conclusions: In this retrospective observational study, no differences in tolerance or adherence between AZA and MP were observed in patients naive to thiopurines. However, MP treatment was at a higher equivalent thiopurine dose than AZA treatment, which tended to be associated with better treatment response.

  • 4. Aleksandrova, Krasimira
    et al.
    Boeing, Heiner
    Nöthlings, Ute
    Jenab, Mazda
    Fedirko, Veronika
    Kaaks, Rudolf
    Lukanova-McGregor, Annekatrin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Boffetta, Paolo
    Trepo, Elisabeth
    Westhpal, Sabine
    Duarte-Salles, Talita
    Stepien, Magdalena
    Overvad, Kim
    Tjønneland, Anne
    Halkjær, Jytte
    Boutron-Ruault, Marie-Christine
    Dossus, Laure
    Racine, Antoine
    Lagiou, Pagona
    Bamia, Christina
    Benetou, Vassiliki
    Agnoli, Claudia
    Palli, Domenico
    Panico, Salvatore
    Tumino, Rosario
    Vineis, Paolo
    Bueno-de-Mesquita, Bas
    Peeters, Petra H
    Gram, Inger Torhild
    Lund, Eiliv
    Weiderpass, Elisabete
    Quirós, J Ramón
    Agudo, Antonio
    Sánchez, María-José
    Gavrila, Diana
    Barricarte, Aurelio
    Dorronsoro, Miren
    Ohlsson, Bodil
    Lindkvist, Björn
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Khaw, Kay-Tee
    Wareham, Nicholas
    Travis, Ruth C
    Riboli, Elio
    Pischon, Tobias
    Inflammatory and metabolic biomarkers and risk of liver and bilary tract cancer2014In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 60, no 3, p. 858-871Article in journal (Refereed)
    Abstract [en]

    Obesity and associated metabolic disorders have been implicated in liver carcinogenesis; however there is little data on the role of obesity-related biomarkers on liver cancer risk. We studied prospectively the association of inflammatory and metabolic biomarkers with risks of hepatocellular carcinoma (HCC), intra-hepatic bile duct (IBD) and gallbladder and bilary tract cancers outside of the liver (GBTC) in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Over an average of 7.7 years, 296 participants developed HCC (n=125), GBTC (n=137) or IBD (n=34). Using risk set sampling, controls were selected in a 2:1 ratio and matched for recruitment center, age, sex, fasting status, time of blood collection. Baseline serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), C-peptide, total, high-molecular-weight (HMW) adiponectin, leptin, fetuin-a, and glutamatdehydrogenase (GLDH) were measured and incidence rate ratios (IRRs) and 95% confidence intervals (CI-s) estimated using conditional logistic regression. After adjustment for lifestyle factors, diabetes, hepatitis infection and adiposity measures, higher concentrations of CRP, IL-6, C-peptide and non-HMW adiponectin were associated with higher risk of HCC (IRR per doubling of concentrations = 1.22; 95%CI = 1.02-1.46, P=0.03; 1.90; 95%CI = 1.30-2.77, P=0.001; 2.25; 95%CI = 1.43-3.54, P=0.0005 and 2.09; 95%CI = 1.19-3.67, P=0.01, respectively). CRP was associated also with risk of GBTC (IRR = 1.22; 95%CI = 1.05-1.42, P=0.01). GLDH was associated with risks of HCC (IRR = 1.62; 95%CI = 1.25-2.11, P=0.0003) and IBD (IRR = 10.5; 95%CI = 2.20-50.90, P=0.003). The continuous net reclassification index was 0.63 for CRP, IL-6, C-peptide and non-HMW adiponectin, and 0.46 for GLDH indicating good predictive ability of these biomarkers. Conclusion: Elevated levels of biomarkers of inflammation and hyperinsulinemia are associated with a higher risk of HCC, independent of obesity and established liver cancer risk factors.

  • 5.
    Anan, Intissar
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    El-Salhy, M
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ando, Y
    Forsgren, S
    Nyhlin, N
    Terazaki, H
    Sakashita, N
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Colonic enteric nervous system in patients with familial amyloidotic neuropathy.1999In: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 98, no 1, p. 48-54Article in journal (Refereed)
    Abstract [en]

    The colonic enteric nervous system was investigated in autopsy specimens from 12 patients with familial amyloidotic neuropathy (FAP) and 9 controls. The infiltration of amyloid deposits in the enteric nervous system was studied by double staining for amyloid and nerve elements. The myenteric plexus was immunostained for protein gene product (PGP) 9.5, vasoactive intestinal peptide (VIP), substance P and nitric oxide synthase (NOS). The immunostained nerve elements were quantified by computerised image analysis. Double staining revealed that there was no amyloid infiltration in the ganglia, or in the nerve fibres in the colonic enteric nervous system of FAP patients. The relative volume density of PGP 9.5-immunoreactive nerve fibres in both the circular and the longitudinal muscle layers in FAP patients did not differ significantly from that of controls. The relative volume density of VIP-immunoreactive nerve fibres in the circular muscle layer was significantly decreased in FAP patients compared with controls, but not in the longitudinal layer. The number of VIP-immunoreactive neurons/mm2 myenteric ganglia was significantly decreased in FAP patients. There were no statistical differences in the relative volume density for substance P- and NOS-immunoreactive nerve fibres between FAP patients and controls, nor was there any difference between FAP patients and controls regarding the number of NOS- and substance P-immunoreactive neurons/mm2 myenteric ganglia. It is concluded that the colonic enteric nervous system as a whole is intact and is not damaged by amyloid infiltration. The present observation of a reduction of VIP-immunoreactive nerve fibres and neurons in myenteric plexus of FAP patients might be one of the factors that contribute to the motility disorders seen in FAP patients.

  • 6.
    Anan, Intissar
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    El-Salhy, M
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ando, Y
    Nyhlin, N
    Terazaki, H
    Sakashita, N
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Colonic endocrine cells in patients with familial amyloidotic polyneuropathy.1999In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 245, no 5, p. 469-73Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To establish whether the endocrine cell number is affected in the colon in Japanese FAP patients.

    SETTING: Department of Medicine, Umeå University Hospital and Department of Internal Medicine and Pathology, University Hospital, Kumamoto, Japan.

    SUBJECTS: Autopsy colon tissue specimens from 11 FAP patients and nine controls as well as 12 control biopsy specimens were included in the study.

    MEASUREMENTS: Endocrine cells in the colon were detected by immunohistochemistry and quantified by computerized image analysis.

    RESULTS: The autopsy material showed a slight autolysis. Neither enteroglucagon nor pancreatic polypeptide positive cells could be detected in the autopsy material, but were present in biopsy material. There was no statistical difference between autopsy and biopsy specimens regarding the number of peptide YY (PYY), somatostatin and serotonin cells. No significant differences were noted in PYY, somatostatin and serotonin immunoreactive cells in FAP patients compared to autopsy controls, though PYY cells tended to be decreased and serotonin and somatostatin cells tended to be increased in FAP patients.

    CONCLUSION: The difference between the Swedish and Japanese patients in the endocrine cell content points to the possibility of involvement of other factors than the endocrine cell depletion of the colon might be involved in the pathogenesis of gastro-intestinal dysfunction in FAP. The tendency of PYY to decrease in Japanese FAP might contribute to the development of diarrhoea in these patients.

  • 7.
    Anan, Intissar
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    El-salhy, M
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ando, Y
    Terazaki, H
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Comparison of amyloid deposits and infiltration of enteric nervous system in the upper with those in the lower gastrointestinal tract in patients with familial amyloidotic polyneuropathy.2001In: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 102, no 3, p. 227-32Article in journal (Refereed)
    Abstract [en]

    Gastrointestinal (GI) complications in familial amyloidotic polyneuropathy (FAP) are invariably present during the course of the disease. The aim of this study was to investigate amyloid deposits in the myenteric plexus of the stomach and small intestine in FAP patients and compare the results with those of the colon. Six FAP patients were included in the study. The myenteric plexus and the number of macrophages (CD68) and blood vessels were immunostained and quantified by computerised image analysis. Double staining for amyloid and nerve elements was used to detect amyloid infiltration in the myenteric plexus. Amyloid was found predominantly in the walls of blood vessels, and was detected in the nerves of five FAP patients and in 18% of the examined ganglia of the myenteric plexus of the stomach. In the small intestine, 6% of examined ganglia showed amyloid deposits. In contrast, no deposits were found in the myenteric plexus of the colon. CD68-positive cells showed no difference in three parts of the GI tract. Most amyloid deposits were noted in the stomach, followed by the small intestine. There are significantly more blood vessels in the stomach and small intestine compared with the colon, and the amount of amyloid correlated with the number of blood vessels, and not with the amount of nerves and ganglia. The enteric nerve system is not a targeted organ for amyloid deposition in FAP.

  • 8.
    Anan, Intissar
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    El-Salhy, M
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nyhlin, N
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Liver transplantation restores endocrine cells in patients with familial amyloidotic polyneuropathy.2000In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 70, no 5, p. 794-9Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim of this study was to investigate familial amyloidotic polyneuropathy, Portuguese type patients' endocrine cell content in the stomach and duodenum before and after liver transplantation, and to relate the findings to the patients' gastrointestinal disturbances.

    METHODS: Ten liver-transplanted familial amyloidotic polyneuropathy, Portuguese type patients and 10 healthy controls were seen. Endocrine cells were identified by immunohistochemistry and quantified with computerized image analysis. The activity of the cells was appraised by measurements of the cell secretory index and nuclear area. Clinical symptoms were obtained from the patients' medical records.

    RESULTS: After transplantation, a significant increase of several endocrine cell types were noted, and the pretransplant depletion of several types of endocrine cells disappeared. For no type of endocrine cell was any difference compared with controls noted after transplantation. There was no significant decrease of the amount of amyloid in the biopsies after liver transplantation. The patients' symptoms remained generally unchanged after transplantation, although a substantial time lapse between pretransplant evaluation and transplantation was present.

    CONCLUSIONS: Liver transplantation restores the endocrine cells in the upper part of the gastrointestinal tract. The restoration was not correlated with an improvement of the patients' symptoms. No decrease of the amyloid deposits was noted.

  • 9. Andersen, Vibeke
    et al.
    Chan, Simon
    Luben, Robert
    Khaw, Kay-Tee
    Olsen, Anja
    Tjonneland, Anne
    Kaaks, R.
    Grip, Olof
    Bergmann, M. M.
    Boeing, H.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Overvad, Kim
    Oldenburg, Bas
    Opstelten, Jorrit
    Boutron-Ruault, Marie-Christine
    Carbonnel, Franck
    Racine, Antoine
    Key, Timothy
    Masala, Giovanna
    Palli, Domenico
    Tumino, R.
    Trichopoulou, A.
    Riboli, Elio
    Hart, Andrew
    Fibre intake and the development of inflammatory bowel disease: A European prospective multi-centre cohort study (EPIC-IBD)2018In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, no 2, p. 129-136Article in journal (Refereed)
    Abstract [en]

    Background and Aims: Population-based prospective cohort studies investigating fibre intake and development of inflammatory bowel disease are lacking. Our aim was to investigate the association between fibre intake and the development of Crohn's disease [CD] and ulcerative colitis [UC] in a large European population.

    Methods: In total, 401 326 participants, aged 20-80 years, were recruited in eight countries in Europe between 1991 and 1998. At baseline, fibre intake [total fibres, fibres from fruit, vegetables and cereals] was recorded using food frequency questionnaires. The cohort was monitored for the development of inflammatory bowel disease. Each case was matched with four controls and odds ratios [ORs] for the exposures were calculated using conditional logistic regression. Sensitivity analyses according to smoking status were computed.

    Results: In total, 104 and 221 participants developed incident CD and UC, respectively. For both CD and UC, there were no statistically significant associations with either quartiles, or trends across quartiles, for total fibre or any of the individual sources. The associations were not affected by adjusting for smoking and energy intake. Stratification according to smoking status showed null findings apart from an inverse association with cereal fibre and CD in non-smokers [Quartile 4 vs 1 OR = 0.12, 95% confidence interval = 0.02-0.75, p = 0.023, OR trend across quartiles = 0.50, 95% confidence interval = 0.29-0.86, p = 0.017].

    Conclusion: The results do not support the hypothesis that dietary fibre is involved in the aetiology of UC, although future work should investigate whether there may be a protective effect of specific types of fibre according to smoking status in CD.

  • 10. Ando, Y
    et al.
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Holmgren, G
    Costa, P M
    Detection of a variant protein in hair: new diagnostic method in Portuguese type familial amyloid polyneuropathy.1998In: BMJ (Clinical Research Edition), ISSN 0959-8138, Vol. 316, no 7143, p. 1500-1Article in journal (Refereed)
  • 11. Angelison, L.
    et al.
    Almer, S.
    Eriksson, A.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Fagerberg, U.
    Halfvarson, J.
    Thörn, M.
    Björk, J.
    Hindorf, U.
    Löfberg, R.
    Bajor, A.
    Hjortswang, H.
    Hammarlund, P.
    Grip, O.
    Torp, J.
    Marsal, J.
    Hertervig, E.
    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.

  • 12. Arslanoglu, Sertac
    et al.
    Corpeleijn, Willemijn
    Moro, Guido
    Braegger, Christian
    Campoy, Cristina
    Colomb, Virginie
    Decsi, Tamas
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Fewtrell, Mary
    Hojsak, Iva
    Mihatsch, Walter
    Molgaard, Christian
    Shamir, Raanan
    Turck, Dominique
    van Goudoever, Johannes
    Donor Human Milk for Preterm Infants: Current Evidence and Research Directions2013In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 57, no 4, p. 535-542Article in journal (Other academic)
    Abstract [en]

    The Committee on Nutrition of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition aims to document the existing evidence of the benefits and common concerns deriving from the use of donor human milk (DHM) in preterm infants. The comment also outlines gaps in knowledge and gives recommendations for practice and suggestions for future research directions. Protection against necrotizing enterocolitis is the major clinical benefit deriving from the use of DHM when compared with formula. Limited data also suggest unfortified DHM to be associated with improved feeding tolerance and with reduced cardiovascular risk factors during adolescence. Presence of a human milk bank (HMB) does not decrease breast-feeding rates at discharge, but decreases the use of formula during the first weeks of life. This commentary emphasizes that fresh own mother's milk (OMM) is the first choice in preterm infant feeding and strong efforts should be made to promote lactation. When OMM is not available, DHM is the recommended alternative. When neither OMM nor DHM is available, preterm formula should be used. DHM should be provided from an established HMB, which follows specific safety guidelines. Storage and processing of human milk reduces some biological components, which may diminish its health benefits. From a nutritional point of view, DHM, like HM, does not meet the requirements of preterm infants, necessitating a specific fortification regimen to optimize growth. Future research should focus on the improvement of milk processing in HMB, particularly of heat treatment; on the optimization of HM fortification; and on further evaluation of the potential clinical benefits of processed and fortified DHM.

  • 13.
    Basmarke-Wehelie, Rahma
    et al.
    Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Swede.
    Sjolinder, Hong
    Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Swede.
    Jurkowski, Wiktor
    Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
    Elofsson, Arne
    Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
    Arnqvist, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Engstrand, Lars
    Swedish Institute for Infectious Disease Control, Karolinska Institutet, Solna, Sweden .
    Hagner, Matthias
    Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Sweden.
    Wallin, Elin
    Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Sweden.
    Guan, Na
    Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Sweden.
    Kuranasekera, Hasanthi
    Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Sweden.
    Aro, Helena
    Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Sweden.
    Jonsson, Ann-Beth
    Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Sweden.
    The Complement Regulator CD46 Is Bactericidal to Helicobacter pylori and Blocks Urease Activity2011In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 141, no 3, p. 918-928Article in journal (Refereed)
    Abstract [en]

    Background & Aims: CD46 is a C3b/C4b binding complement regulator and a receptor  for several human pathogens. We examined the interaction between CD46 and Helicobacter pylori (a bacterium that colonizes the human gastric mucosa and causes gastritis), peptic ulcers, and cancer.

    Methods: Using gastric epithelial cells, we analyzed a set of H pylori strains and mutants for their ability to interact with CD46 and/or influence CD46 expression. Bacterial interaction with full-length CD46 and small CD46 peptides was evaluated by flow cytometry, fluorescence microscopy, enzyme-linked immunosorbent assay, and bacterial survival analyses.

    Results: H pylori infection caused shedding of CD46 into the extracellular environment. A soluble form of CD46 bound to H pylori and inhibited growth, in a dose- and time-dependent manner, by interacting with urease and alkyl hydroperoxide reductase, which are essential bacterial pathogenicity-associated factors. Binding of CD46 or CD46-derived synthetic peptides blocked theurease activity and ability of bacteria to survive in acidic environments. Oral administration of one CD46 peptide eradicated H pylori from infected mice.

    Conclusions: CD46 is an antimicrobial agent that can eradicate H pylori. CD46 peptides might be developed to treat H pylori infection.

  • 14.
    Berglund, Staffan K
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Westrup, Björn
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Iron Supplementation Until 6 Months Protects Marginally Low-Birth-Weight Infants From Iron Deficiency During Their First Year of Life2015In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 60, no 3, p. 390-395Article in journal (Refereed)
    Abstract [en]

    Objectives: Low-birth-weight (LBW) infants (<2500 g) have an increased risk of iron deficiency (ID) during their first 6 months of life. The optimal dose and duration of iron supplementation to LBW infants are, however, unknown. The objective of the present study was to investigate the long-term effect on iron status and growth in marginally LBW (2000-2500 g) infants, of iron supplements given until 6 months of life. Methods: In a randomized controlled trial, 285 healthy marginally LBW infants received 0, 1, or 2 mg . kg(-1).day(-1) of iron supplements from 6 weeks to 6 months of age: At 12 months and 3.5 years of life we measured length, weight, head circumference, and indicators of iron status (hemoglobin, ferritin, mean corpuscular volume, and transferrin saturation) and assessed the prevalence of iron depletion, functional ID, and ID anemia. Results: At 12 months of age, there was a significant difference in ferritin between the groups (P = 0.00 6). Furthermore, there was a significant difference in the prevalence of iron depletion (23.7%, 10.6%, and 6.8%, respectively, in the placebo, 1-mg, and 2-mg groups, P = 0.009) and similar nonsignificant trends for functional ID and ID anemia. At 3.5 years of life there were no significant differences in iron status and the mean prevalence of iron depletion was 3.2%. Anthropometric data were not affected by the intervention. Conclusions: Iron supplements with 2 mg . kg(-1) . day(-1) until 6 months of life effectively reduces the risk of ID during the first 12 months of life and is an effective intervention for preventing early ID in marginally LBW infants.

  • 15. Bergquist, Annika
    et al.
    Montgomery, Scott M
    Bahmanyar, Shahram
    Olsson, Rolf
    Danielsson, Åke
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindgren, Stefan
    Prytz, Hanne
    Hultcrantz, Rolf
    Lööf, Lars
    Sandberg-Gertzén, Hanna
    Almer, Sven
    Askling, Johan
    Ehlin, Anna
    Ekbom, Anders
    Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis2008In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 6, no 8, p. 939-943Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: The importance of genetic factors for the development of primary sclerosing cholangitis (PSC) is incompletely understood. This study assessed the risk of PSC and inflammatory bowel disease (IBD) among first-degree relatives of patients with PSC, compared with the first-degree relatives of a cohort without PSC.

    METHODS: Subjects from the national Swedish cohort of PSC patients (n = 678) were matched for date of birth, sex, and region to up to 10 subjects without a diagnosis of PSC (n = 6347). Linkage through general population registers identified first-degree relatives of subjects in both the PSC and comparison cohorts (n = 34,092). Diagnoses among first-degree relatives were identified by using the Inpatient Register.

    RESULTS: The risk of cholangitis was statistically significantly increased in offspring, siblings, and parents of the PSC patient cohort, compared with relatives of the comparison cohort, with the hazard ratios and 95% confidence intervals, 11.5 (1.6-84.4), 11.1 (3.3-37.8), and 2.3 (0.9-6.1), respectively. The hazard ratios for ulcerative colitis (UC) among first-degree relatives of all PSC patients was 3.3 (2.3-4.9) and for Crohn's disease 1.4 (0.8-2.5). The risk of UC for relatives of PSC patients without IBD was also increased, 7.4 (2.9-18.9).

    CONCLUSIONS: First-degree relatives of patients with PSC run an increased risk of PSC, indicating the importance of genetic factors in the etiology of PSC. First-degree relatives of PSC patients without IBD are also at an increased risk of UC, which might indicate shared genetic susceptibility factors for PSC and UC.

  • 16. Beyder, Arthur
    et al.
    Mazzone, Amelia
    Strege, Peter R.
    Tester, David J.
    Saito, Yuri A.
    Bernard, Cheryl E.
    Enders, Felicity T.
    Ek, Weronica E.
    Schmidt, Peter T.
    Dlugosz, Aldona
    Lindberg, Greger
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ohlsson, Bodil
    Gazouli, Maria
    Nardone, Gerardo
    Cuomo, Rosario
    Usai-Satta, Paolo
    Galeazzi, Francesca
    Neri, Matteo
    Portincasa, Piero
    Bellini, Massimo
    Barbara, Giovanni
    Camilleri, Michael
    Locke, G. Richard, III
    Talley, Nicholas J.
    D'Amato, Mauro
    Ackerman, Michael J.
    Farrugia, Gianrico
    Loss-of-Function of the Voltage-Gated Sodium Channel Na(V)1.5 (Channelopathies) in Patients With Irritable Bowel Syndrome2014In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 146, no 7, p. 1659-1668Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: SCN5A encodes the a-subunit of the voltage-gated sodium channel Na(V)1.5. Many patients with cardiac arrhythmias caused by mutations in SCN5A also have symptoms of irritable bowel syndrome (IBS). We investigated whether patients with IBS have SCN5A variants that affect the function of Na(V)1.5. METHODS: We performed genotype analysis of SCN5A in 584 persons with IBS and 1380 without IBS (controls). Mutant forms of SCN5A were expressed in human embryonic kidney-293 cells, and functions were assessed by voltage clamp analysis. A genome-wide association study was analyzed for an association signal for the SCN5A gene, and replicated in 1745 patients in 4 independent cohorts of IBS patients and controls. RESULTS: Missense mutations were found in SCN5A in 13 of 584 patients (2.2%, probands). Diarrhea-predominant IBS was the most prevalent form of IBS in the overall study population (25%). However, a greater percentage of individuals with SCN5A mutations had constipation-predominant IBS (31%) than diarrhea-predominant IBS (10%; P < .05). Electrophysiologic analysis showed that 10 of 13 detected mutations disrupted Na(V)1.5 function (9 loss-of-function and 1 gain-of-function function). The p. A997T-Na(V)1.5 had the greatest effect in reducing Na(V)1.5 function. Incubation of cells that expressed this variant with mexiletine restored their sodium current and administration of mexiletine to 1 carrier of this mutation (who had constipation-predominant IBS) normalized their bowel habits. In the genome-wide association study and 4 replicated studies, the SCN5A locus was strongly associated with IBS. CONCLUSIONS: About 2% of patients with IBS carry mutations in SCN5A. Most of these are loss-of-function mutations that disrupt Na(V)1.5 channel function. These findings provide a new pathogenic mechanism for IBS and possible treatment options.

  • 17. Bhoo-Pathy, Nirmala
    et al.
    Uiterwaal, Cuno S. P. M.
    Dik, Vincent K.
    Jeurnink, Suzanne M.
    Bech, Bodil H.
    Overvad, Kim
    Halkjær, Jytte
    Tjønneland, Anne
    Boutron-Ruault, Marie-Christine
    Fagherazzi, Guy
    Racine, Antoine
    Katzke, Verena A.
    Li, Kuanrong
    Boeing, Heiner
    Floegel, Anna
    Androulidaki, Anna
    Bamia, Christina
    Trichopoulou, Antonia
    Masala, Giovanna
    Panico, Salvatore
    Crosignani, Paolo
    Tumino, Rosario
    Vineis, Paolo
    Peeters, Petra H. M.
    Gavrilyuk, Oxana
    Skeie, Guri
    Weiderpass, Elisabete
    Duell, Eric J.
    Arguelles, Marcial
    Molina-Montes, Esther
    Navarro, Carmen
    Ardanaz, Eva
    Dorronsoro, Miren
    Lindkvist, Björn
    Wallström, Peter
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Ye, Weimin
    Umeå University, Faculty of Medicine, Department of Biobank Research. Karolinska institutet.
    Khaw, Kay-Tee
    Wareham, Nick
    Key, Timothy J.
    Travis, Ruth C.
    Duarte-Salles, Talita
    Freisling, Heinz
    Licaj, Idlir
    Gallo, Valentina
    Michaud, Dominique S.
    Riboli, Elio
    Bueno-de-Mesquita, H. Bas
    Intake of Coffee, Decaffeinated Coffee, or Tea Does Not Affect Risk for Pancreatic Cancer: Results From the European Prospective Investigation into Nutrition and Cancer Study2013In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 11, no 11, p. 1486-1492Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Few modifiable risk factors have been implicated in the etiology of pancreatic cancer. There is little evidence for the effects of caffeinated coffee, decaffeinated coffee, or tea intake on risk of pancreatic cancer. We investigated the association of total coffee, caffeinated coffee, decaffeinated coffee, and tea consumption with risk of pancreatic cancer.

    METHODS: This study was conducted within the European Prospective Investigation into Nutrition and Cancer cohort, comprising male and female participants from 10 European countries. Between 1992 and 2000, there were 477,312 participants without cancer who completed a dietary questionnaire, and were followed up to determine pancreatic cancer incidence. Coffee and tea intake was calibrated with a 24-hour dietary recall. Adjusted hazard ratios (HRs) were computed using multivariable Cox regression.

    RESULTS: During a mean follow-up period of 11.6 y, 865 first incidences of pancreatic cancers were reported. When divided into fourths, neither total intake of coffee (HR, 1.03; 95% confidence interval [CI], 0.83-1.27; high vs low intake), decaffeinated coffee (HR, 1.12; 95% CI, 0.76-1.63; high vs low intake), nor tea were associated with risk of pancreatic cancer (HR, 1.22, 95% CI, 0.95-1.56; high vs low intake). Moderately low intake of caffeinated coffee was associated with an increased risk of pancreatic cancer (HR, 1.33; 95% CI, 1.02-1.74), compared with low intake. However, no graded dose response was observed, and the association attenuated after restriction to histologically confirmed pancreatic cancers.

    CONCLUSIONS: Based on an analysis of data from the European Prospective Investigation into Nutrition and Cancer cohort, total coffee, decaffeinated coffee, and tea consumption are not related to the risk of pancreatic cancer.

  • 18.
    Birgisson, H
    et al.
    Department of Surgery, University Hospital, University of Uppsala, Uppsala, Sweden.
    Påhlman, Lars
    Department of Surgery, University Hospital, University of Uppsala, Uppsala, Sweden.
    Gunnarsson, Ulf
    Department of Surgery, University Hospital, University of Uppsala, Uppsala, Sweden.
    Glimelius, B
    Departments of Oncology, Radiology and Clinical Immunology, University Hospital, University of Uppsala, Uppsala, Sweden and Department of Oncology and Pathology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
    Late gastrointestinal disorders after rectal cancer surgery with and without preoperative radiation therapy.2008In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 95, no 2, p. 206-13Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim of the study was to analyse late gastrointestinal disorders necessitating hospital admission following rectal cancer surgery and to determine their relationship to preoperative radiation therapy.

    METHODS: Curatively treated patients participating in the Swedish Rectal Cancer Trial during 1987-1990, randomized to preoperative irradiation (454 patients) or surgery alone (454), were matched against the Swedish Hospital Discharge Registry. Hospital records for patients admitted with gastrointestinal diagnoses were reviewed.

    RESULTS: Irradiated patients had an increased relative risk (RR) of late small bowel obstruction (RR 2.49 (95 per cent confidence interval (c.i.) 1.48 to 4.19)) and abdominal pain (RR 2.09 (95 per cent c.i. 1.03 to 4.24)) compared with patients treated by surgery alone. The risk of late small bowel obstruction requiring surgery was greatly increased (RR 7.42 (95 per cent c.i. 2.23 to 24.66)). Irradiated patients with postoperative anastomotic leakage were at increased risk for late small bowel obstruction (RR 2.99 (95 per cent c.i. 1.07 to 8.31)). The risk of small bowel obstruction was also related to the radiation technique and energy used.

    CONCLUSION: Small bowel obstruction is more common in patients with rectal cancer treated with preoperative radiation therapy.

  • 19.
    Birgisson, H
    et al.
    Department of Surgery, Akademiska Sjukhuset, S-75185 Uppsala, Sweden.
    Talbäck, M
    Gunnarsson, Ulf
    Department of Surgery, Akademiska Sjukhuset, S-75185 Uppsala, Sweden.
    Påhlman, L
    Glimelius, B
    Improved survival in cancer of the colon and rectum in Sweden.2005In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 31, no 8, p. 845-53Article in journal (Refereed)
    Abstract [en]

    AIMS: To analyse time-trends in survival of patients with colon and rectal cancer in Sweden.

    PATIENTS AND METHODS: Data including all patients diagnosed with adenocarcinoma of the colon and rectum between 1960 and 1999, from the Swedish Cancer Registry, were analysed. The observed and relative survival rates were calculated according to the Hakulinen cohort method.

    RESULTS: Five-year relative survival rate for cancer of the colon improved significantly from 39.6% in 1960--1964 to 57.2% in 1995--1999 and for rectal cancer from 36.1 to 57.6%, respectively. Corresponding observed survival improved from 31.2 to 44.3% for colon cancer and from 28.4 to 45.4% for rectal cancer. The largest improvement of survival were seen during the later part of the period observed.

    CONCLUSION: The survival of patients with colon and rectal cancer in Sweden continues to improve, especially in rectal cancer, which now has a 5-year observed and relative survival rate comparable to that for colon cancer. The survival improvement in rectal cancer is probably a result of the implementation of total mesorectal excision and pre-operative radiotherapy.

  • 20. Bonfiglio, Ferdinando
    et al.
    Zheng, Tenghao
    Garcia-Etxebarria, Koldo
    Hadizadeh, Fatemeh
    Bujanda, Luis
    Bresso, Francesca
    Agreus, Lars
    Andreasson, Anna
    Dlugosz, Aldona
    Lindberg, Greger
    Schmidt, Peter T.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ohlsson, Bodil
    Simren, Magnus
    Walter, Susanna
    Nardone, Gerardo
    Cuomo, Rosario
    Usai-Satta, Paolo
    Galeazzi, Francesca
    Neri, Matteo
    Portincasa, Piero
    Bellini, Massimo
    Barbara, Giovanni
    Latiano, Anna
    Huebenthal, Matthias
    Thijs, Vincent
    Netea, Mihai G.
    Jonkers, Daisy
    Chang, Lin
    Mayer, Emeran A.
    Wouters, Mira M.
    Boeckxstaens, Guy
    Camilleri, Michael
    Franke, Andre
    Zhernakova, Alexandra
    D'Amato, Mauro
    Female-Specific Association Between Variants on Chromosome 9 and Self-Reported Diagnosis of Irritable Bowel Syndrome2018In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 155, no 1, p. 168-179Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Genetic factors are believed to affect risk for irritable bowel syndrome (IBS), but there have been no sufficiently powered and adequately sized studies. To identify DNA variants associated with IBS risk, we performed a genome-wide association study (GWAS) of the large UK Biobank population-based cohort, which includes genotype and health data from 500,000 participants. METHODS: We studied 7,287,191 high-quality single nucleotide polymorphisms in individuals who self-reported a doctor's diagnosis of IBS (cases; n = 9576) compared to the remainder of the cohort (controls; n = 336,499) (mean age of study subjects, 40-69 years). Genome-wide significant findings were further investigated in 2045 patients with IBS from tertiary centers and 7955 population controls from Europe and the United States, and a small general population sample from Sweden (n = 249). Functional annotation of GWAS results was carried out by integrating data from multiple biorepositories to obtain biological insights from the observed associations. RESULTS: We identified a genome-wide significant association on chromosome 9q31.2 (single nucleotide polymorphism rs10512344; P = 3.57 x 10(-8)) in a region previously linked to age at menarche, and 13 additional loci of suggestive significance (P < 5.0 x 10(-6)). Sex-stratified analyses revealed that the variants at 9q31.2 affect risk of IBS in women only (P = 4.29 x 10(-10) in UK Biobank) and also [GRAPHICS] associate with constipation-predominant IBS in women (P = .015 in the tertiary cohort) and harder stools in women (P = .0012 in the population-based sample). Functional annotation of the 9q31.2 locus identified 8 candidate genes, including the elongator complex protein 1 gene (ELP1 or IKB-KAP), which is mutated in patients with familial dysautonomia. CONCLUSIONS: In a sufficiently powered GWAS of IBS, we associated variants at the locus 9q31.2 with risk of IBS in women. This observation may provide additional rationale for investigating the role of sex hormones and autonomic dysfunction in IBS.

  • 21. Bruck, Wolfram M
    et al.
    Redgrave, Michele
    Tuohy, Kieran M
    Lönnerdal, Bo
    Graverholt, Gitte
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Gibson, Glenn R
    Effects of bovine alpha-lactalbumin and casein glycomacropeptide-enriched infant formulae on faecal microbiota in healthy term infants2006In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 43, no 5, p. 673-679Article in journal (Refereed)
    Abstract [en]

    Objective: Certain milk factors may promote the growth of a host-friendly gastrointestinal microbiota, for example, one that is predominated by bifidobacteria, a perceived healthpromoting genus. This may explain why breast-fed infants experience fewer intestinal infections than their formula-fed counterparts who are believed to have a more diverse microbiota, which is similar to that of adults. The effects of formulas supplemented with 2 such ingredients from bovine milk, a-lactalbumin (alpha-lac) and casein glycomacropeptide (GMP), on gut flora were investigated in this study.

    Patients and Methods: Six-week-old (4-8 wk), healthy term infants were randomised to a standard infant formula or 1 of 2 test formulae enriched in alpha-Jac with higher or lower GMP until 6 months. Faecal bacteriology was determined by the culture-independent procedure fluorescence in situ hybridisation.

    Results: There was a large fluctuation of bacterial counts within groups with no statistically significant differences between groups. Although all groups showed a. predominance of bifidobacteria, breast-fed infants had a small temporary increase in counts. Other bacterial levels varied in formula-fed groups, which overall showed an adult-like faecal microflora.

    Conclusions: It can be speculated that a prebiotic effect for alpha-lac and GMP is achieved only with low starting populations of beneficial microbiota (eg, infants not initially breast-fed).

  • 22.
    Brännström, Fredrik
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Department of Surgical Sciences, Uppsala University, Uppsala and Department of Surgical Sciences, Karolinska Institutet, Stockholm.
    Jestin, Pia
    Department of Surgical Sciences, Karolinska Institutet, Stockholm and Karlstad Hospital, Karlstad.
    Matthiessen, Peter
    Department of Surgery, Örebro University Hospital, Örebro.
    Gunnarsson, Ulf
    Department of Surgical Sciences, Karolinska Institutet, Stockholm, Sweden.
    Surgeon and hospital-related risk factors in colorectal cancer surgery2011In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 13, no 12, p. 1370-1376Article in journal (Refereed)
    Abstract [en]

    AIM: The aim of this study was to identify surgeon and hospital-related factors in a well-defined population-based cohort; the results of this study could possibly be used to improve outcome in colorectal cancer.

    METHOD: Data from the colonic (1997-2006) and rectal (1995-2006) cancer registers of the Uppsala/Örebro Regional Oncology Centre were used to assess 1697 patients with rectal and 2692 with colonic cancer. Putative risk factors and their impact on long-term survival were evaluated using the Cox proportional hazard model.

    RESULTS: The degree of specialization of the operating surgeon had no significant effect on long-term survival. When comparing the surgeons with the highest degree of specialization, noncolorectal surgeons demonstrated a slightly lower long-term survival for rectal cancer stage I and II (HR, 2.03; 95% CI, 1.05-3.92). Surgeons with a high case-load were not associated with better survival in any analysis model. Regional hospitals had a lower survival rate for rectal cancer stage III surgery (HR, 1.47; 95% CI, 1.08-2.00).

    CONCLUSION: Degree of specialization, surgeon case-load and hospital category could not be identified as important factors when determining outcome in colorectal cancer surgery in this study.

  • 23. Chan, Simon S. M.
    et al.
    Luben, Robert
    Olsen, Anja
    Tjonneland, Anne
    Kaaks, Rudolf
    Teucher, Birgit
    Lindgren, Stefan
    Grip, Olof
    Key, Timothy
    Crowe, Francesca L.
    Bergmann, Manuela M.
    Boeing, Heiner
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Overvad, Kim
    Palli, Domenico
    Masala, Giovanna
    Kennedy, Hugh
    vanSchaik, Fiona
    Bueno-de-Mesquita, Bas
    Oldenburg, Bas
    Khaw, Kay-Tee
    Riboli, Elio
    Hart, Andrew R.
    Body Mass Index and the Risk for Crohn's Disease and Ulcerative Colitis: Data From a European Prospective Cohort Study (The IBD in EPIC Study)2013In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 108, no 4, p. 575-582Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Obesity is associated with a proinflammatory state that may be involved in the etiology of inflammatory bowel disease (IBD), for which there are plausible biological mechanisms. Our aim was to perform the first prospective cohort study investigating if there is an association between obesity and the development of incident IBD. METHODS: A total of 300,724 participants were recruited into the European Prospective Investigation into Cancer and Nutrition study. At recruitment, anthropometric measurements of height and weight plus physical activity and total energy intake from validated questionnaires were recorded. The cohort was monitored identifying participants who developed either Crohn's disease (CD) or ulcerative colitis (UC). Each case was matched with four controls and conditional logistic regression used to calculate odds ratios (ORs) for body mass index (BMI) adjusted for smoking, energy intake, and physical activity. RESULTS: In the cohort, 177 participants developed incident UC and 75 participants developed incident CD. There were no associations with the four higher categories of BMI compared with a normal BMI for UC (P-trend = 0.36) or CD (P-trend = 0.83). The lack of associations was consistent when BMI was analyzed as a continuous or binary variable (BMI 18.5 <25.0 vs. >= 25 kg/m(2)). Physical activity and total energy intake, factors that influence BMI, did not show any association with UC (physical activity, P-trend = 0.79; total energy intake, P-trend = 0.18) or CD (physical activity, P-trend = 0.42; total energy, P-trend = 0.11). CONCLUSIONS: Obesity as measured by BMI is not associated with the development of incident UC or CD. Alternative measures of obesity are required to further investigate the role of obesity in the development of incident IBD.

  • 24. Coelho, T
    et al.
    Maia, L
    Martins da Silva, A
    Waddington Cruz, M
    Plante-Bordeneuve, V
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Conceicao, I
    Schmidt, H
    Trigo, P
    Packman, J
    Harnett, M
    Grogan, DR
    Long-term effects of tafamidis: a new therapeutic option for patients with transthyretin familial amyloid polyneuropathy (ttr-fap)2012In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 56, no Suppl 2, p. S543-S543Article in journal (Other academic)
  • 25.
    Danielsson Borssén, Åsa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Autoimmune hepatitis: life, death and in-between2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background Autoimmune hepatitis (AIH) is a chronic autoimmune liver disease that is overrepresented in women (75% of cases). Studies have described a 10-year survival after diagnosis near to that of the general population, but less is known about the long-term survival. The inflammation in AIH causes fibrotic tissue to form in the liver and about 1/3 of AIH patients have cirrhosis at diagnosis. Studies have shown that treatment of the underlying liver disease can reverse fibrosis, and sometimes even cirrhosis, but only a few studies have examined the response to treatment in AIH. AIH affects all ages and some women will have cirrhosis during pregnancy, which is a risk factor for an adverse outcome. Cirrhosis is also a risk factor for hepatocellular carcinoma (HCC), but the true risk for HCC in cirrhotic AIH patients is not known.

    Aim To study the epidemiology of AIH in Sweden, the causes of death and the risk of cancer for AIH patients, the efficacy of medical treatment on fibrosis and cirrhosis, and outcomes for the mother and child in pregnancy.

    Material and methods A cohort of 634 AIH patients was established at the Swedish University hospitals. Prevalence and incidence were calculated, and a relative survival analysis was performed in which survival after AIH diagnosis was compared to that of the general population. Causes of deaths were retrieved from the Cause of Death Registry.

    The Cancer Registry was used to calculate standard incidence ratios (SIR) and compare cancer risk to that of the general population.

    Two hundred fifty-eight liver biopsies from 101 patients were analyzed by a single pathologist and classified according to the Ishak grading and staging system. Liver histology was stratified according to the temporal changes of fibrosis stage, and groups were compared.

    A questionnaire was answered by 138 women with AIH about medication, pregnancies, disease behavior during and after pregnancy, and pregnancy outcomes.

    Results The incidence and prevalence of AIH were 1.2/100 000 and 17.3/100 000 respectively. The relative survival started to decline after 4 years compared to the reference population, and was even more pronounced after 10 years. Men were diagnosed (33.5 years versus 48.0 years, p<0.001) and died (59.7 versus 75.4 years, p=0.002) at a younger age than women. Patients with cirrhosis at diagnosis had an inferior survival (p<0.001). Liver-related death was the most common cause of death (32.7%). Among AIH patients a higher incidence of cancer was found compared with that of the general Swedish population, SIR of 2.08 (95% Confidence Interval (CI) 1.68-2.55). SIR for non-melanoma skin cancer was 9.87 (95% CI 6.26-14.81) and hepatobiliary cancer was 54.55 (95% CI 19.92-99.99). HCC was found in 4% of the cirrhotic patients and the incidence rate was 0.3% per year. A reduction of fibrosis stage from first to last biopsy was common (62.4% of patients) and patients on a continuous glucocorticoid medication more often had a decreased fibrosis stage than those with withdrawal attempts (p=0.002). One hundred children were born by 58 women with AIH, of which 23 women had 43 children after diagnosis of cirrhosis. Malformations were reported in 3%, and pre-term births (<week 38) in 22% of the pregnancies. Cirrhotic women gave birth without more complications than others, but with a higher frequency of caesarean sections than non-cirrhotic women (p=0.047).

    Conclusion Contrary to previous reports, AIH patients’ life expectancy was significantly inferior to that of the control population already 4 years after onset of disease, and liver disease was the most common cause of death. AIH patients had an overall enhanced risk for cancer, mainly from an increased risk of non-melanoma skin cancer and HCC. However, the annual risk of HCC was only 0.3% in cirrhotic patients. Histological improvement of liver fibrosis was common in AIH. The proportion of pre-term births was high, but overall pregnancy and childbirth appear to be safe in AIH, even in compensated cirrhosis. 

  • 26.
    Danielsson Borssén, Åsa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Departments of Medicine, Sections for Hepatology and Gastroenterology, Umeå University Hospital, Umeå, Sweden.
    Almer, Sven
    Prytz, Hanne
    Wallerstedt, Sven
    Friis-Liby, Inga-Lill
    Bergquist, Annika
    Nyhlin, Nils
    Hultcrantz, Rolf
    Sangfelt, Per
    Weiland, Ola
    Lindgren, Stefan
    Verbaan, Hans
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Departments of Medicine, Sections for Hepatology and Gastroenterology, Umeå University Hospital, Umeå, Sweden.
    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.

  • 27.
    Danielsson Borssén, Åsa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Marschall, Hanns-Ulrich
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg.
    Bergquist, Annika
    Department of Medicine, Section of Hepatology and Gastroenterology, Karolinska Institutet, Karolinska University Hospital Huddinge.
    Rorsman, Fredrik
    Department of Medical Sciences, Section of Gastroenterology and Hepatology, Uppsala University.
    Weiland, Ola
    Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge.
    Kechagias, Stergios
    Department of Gastroenterology and Hepatology, Department of Medical and Health Sciences, Linköping University.
    Nyhlin, Nils
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University.
    Verbaan, Hans
    Gastroenterology Division, Department of Clinical Sciences, Lund University, University Hospital Skane.
    Nilsson, Emma
    Gastroenterology Division, Department of Clinical Sciences, Lund University, University Hospital Skane.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Epidemiology and causes of death in a Swedish cohort of patients with autoimmune hepatitisManuscript (preprint) (Other academic)
    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 Västerbotten 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<0.001) and died younger than women (p=0.002). No gender differences were found concerning transplant-free, overall survival and liver-related death. Cirrhosis at diagnosis was linked to an inferior survival (p<0.001). 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. 

  • 28.
    Danielsson Borssén, Åsa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Kechagias, Stergios
    Department of Gastroenterology and Hepatology, Department of Medical and Health Sciences, Linköping University.
    Marschall, Hanns-Ulrich
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg.
    Bergquist, Annika
    Department of Medicine, Section of Hepatology and Gastroenterology, Karolinska Institutet.
    Rorsman, Fredrik
    Department of Medical Sciences, Section of Gastroenterology and Hepatology, Uppsala University.
    Weiland, Ola
    Division of Infectious Diseases, Department of Medicine, Karolinska Institutet.
    Verbaan, Hans
    Gastroenterology Division, Department of Clinical Sciences, Lund University.
    Nyhlin, Nils
    Department of Medicine, Section of Hepatology and Gastroenterology, Örebro University Hospital and Faculty of Medicine and Health, Örebro University.
    Nilsson, Emma
    Gastroenterology Division, Department of Clinical Sciences, Lund University.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Histological improvement of liver fibrosis in well-treated patients with autoimmune hepatitis: a cohort study2017In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 96, no 34, article id e7708Article in journal (Refereed)
    Abstract [en]

    Objectives 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.

    Methods Two hundred fifty-eight liver biopsies from 101 patients (72 women, 29 men) were analysed by a single pathologist and classified accordingly 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.

    Results 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 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 five patients at the last biopsy.

    Conclusions 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.

  • 29.
    Danielsson, Åke
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    [When should liver biopsy be considered? Slightly increased ALAT can indicate steatosis--but a histological test is necessary for prognosis]2004In: Läkartidningen, ISSN 0023-7205, Vol. 101, no 38, p. 2862-Article in journal (Other academic)
  • 30. Del Chiaro, Marco
    et al.
    Besselink, Marc G.
    Scholten, Lianne
    Bruno, Marco J.
    Cahen, Djuna L.
    Gress, Thomas M.
    van Hooft, Jeanin E.
    Lerch, Markus M.
    Mayerle, Julia
    Hackert, Thilo
    Satoi, Sohei
    Zerbi, Alessandro
    Cunningham, David
    De Angelis, Claudio
    Giovanni, Marc
    de-Madaria, Enrique
    Hegyi, Peter
    Rosendahl, Jonas
    Friess, Helmut
    Manfredi, Riccardo
    Levy, Philippe
    Real, Francisco X.
    Sauvanet, Alain
    Abu Hilal, Mohammed
    Marchegiani, Giovanni
    Esposito, Irene
    Ghaneh, Paula
    Engelbrecht, Marc R. W.
    Fockens, Paul
    van Huijgevoort, Nadine C. M.
    Wolfgang, Christopher
    Bassi, Claudio
    Gubergrits, Natalya B.
    Verbeke, Caroline
    Kloppel, Gunter
    Scarpa, Aldo
    Zamboni, Giuseppe
    Lennon, Anne Marie
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Kartalis, Nikolaos
    Grenacher, Lars
    Falconi, Massimo
    Arnelo, Urban
    Kopchak, Kostantin V.
    Oppong, Kofi
    McKay, Colin
    Hauge, Truls
    Conlon, Kevin
    Adham, Mustapha
    Ceyhan, Guralp O.
    Salvia, Roberto
    Dervenis, Christos
    Allen, Peter
    Paye, Francois
    Bartsch, Detlef K.
    Lohr, Matthias
    Mutignani, Massimiliano
    Laukkarinen, Johanna
    Schulick, Richard
    Valente, Roberto
    Seufferlein, Thomas
    Capurso, Gabriele
    Siriwardena, Ajith
    Neoptolemos, John P.
    Pukitis, Aldis
    Segersvard, Ralf
    Aghdassi, A.
    Andrianello, S.
    Bossuyt, P.
    Bulow, R.
    Cardenas-Jaen, K.
    Cortegoso, P.
    Fontana, M.
    Haeberle, L.
    Heckler, M.
    Litvin, A.
    Mann, K.
    Michalski, C.
    Michl, P.
    Nappo, G.
    Perri, G.
    Persson, S.
    Scheufele, F.
    Sclafani, F.
    Schmidt, M.
    Venezia, L.
    Volker, F.
    Vullierm, M-P
    Wusten, L.
    European evidence-based guidelines on pancreatic cystic neoplasms2018In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 67, no 5, p. 789-804Article in journal (Refereed)
    Abstract [en]

    Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring < 40 mm without an enhancing nodule. Relative indications for surgery in IPMN include a main pancreatic duct (MPD) diameter between 5 and 9.9 mm or a cyst diameter >= 40 mm. Absolute indications for surgery in IPMN, due to the high-risk of malignant transformation, include jaundice, an enhancing mural nodule > 5 mm, and MPD diameter > 10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN.

  • 31.
    Domellöf, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Braegger, Christian
    Campoy, Cristina
    Colomb, Virginie
    Decsi, Tamas
    Fewtrell, Mary
    Hojsak, Iva
    Mihatsch, Walter
    Molgaard, Christian
    Shamir, Raanan
    Turck, Dominique
    van Goudoever, Johannes
    Iron Requirements of Infants and Toddlers2014In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 58, no 1, p. 119-129Article in journal (Refereed)
    Abstract [en]

    Iron deficiency (ID) is the most common micronutrient deficiency worldwide and young children are a special risk group because their rapid growth leads to high iron requirements. Risk factors associated with a higher prevalence of ID anemia (IDA) include low birth weight, high cow's-milk intake, low intake of iron-rich complementary foods, low socioeconomic status, and immigrant status. The aim of this position paper was to review the field and provide recommendations regarding iron requirements in infants and toddlers, including those of moderately or marginally low birth weight. There is no evidence that iron supplementation of pregnant women improves iron status in their offspring in a European setting. Delayed cord clamping reduces the risk of ID. There is insufficient evidence to support general iron supplementation of healthy European infants and toddlers of normal birth weight. Formula-fed infants up to 6 months of age should receive iron-fortified infant formula, with an iron content of 4 to 8 mg/L (0.6-1.2 mg <bold></bold> kg(-1) <bold></bold> day(-1)). Marginally low-birth-weight infants (2000-2500 g) should receive iron supplements of 1-2 mg <bold></bold> kg(-1) <bold></bold> day(-1). Follow-on formulas should be iron-fortified; however, there is not enough evidence to determine the optimal iron concentration in follow-on formula. From the age of 6 months, all infants and toddlers should receive iron-rich (complementary) foods, including meat products and/or iron-fortified foods. Unmodified cow's milk should not be fed as the main milk drink to infants before the age of 12 months and intake should be limited to <500 mL/day in toddlers. It is important to ensure that this dietary advice reaches high-risk groups such as socioeconomically disadvantaged families and immigrant families.

  • 32. Efe, Cumali
    et al.
    Al Taii, Haider
    Ytting, Henriette
    Aehling, Niklas
    Bhanji, Rahima A.
    Hagstrom, Hannes
    Purnak, Tugrul
    Muratori, Luigi
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Muratori, Paolo
    Klintman, Daniel
    Schiano, Thomas D.
    Montano-Loza, Aldo J.
    Berg, Thomas
    Larsen, Fin Stolze
    Alkhouri, Naim
    Ozaslan, Ersan
    Heneghan, Michael A.
    Yoshida, Eric M.
    Wahlin, Staffan
    Tacrolimus and Mycophenolate Mofetil as Second-Line Therapies for Pediatric Patients with Autoimmune Hepatitis2018In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 63, no 5, p. 1348-1354Article in journal (Refereed)
    Abstract [en]

    We studied the efficacy and safety of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy in pediatric patients with autoimmune hepatitis (AIH) who were intolerant or non-responders to standard therapy (corticosteroid and azathioprine). We performed a retrospective study of data from 13 centers in Europe, USA, and Canada. Thirty-eight patients (< 18 years old) who received second-line therapy (18 MMF and 20 tacrolimus), for a median of 72 months (range 8-182) were evaluated. Patients were categorized into two groups: Group 1 (n = 17) were intolerant to corticosteroid or azathioprine, and group 2 (n = 21) were non-responders to standard therapy. Overall complete response rates were similar in patients treated with MMF and tacrolimus (55.6 vs. 65%, p = 0.552). In group 1, MMF and tacrolimus maintained a biochemical remission in 88.9 and 87.5% of patients, respectively (p = 0.929). More patients in group 2 given tacrolimus compared to MMF had a complete response, but the difference was not statistically significant (50.0 vs. 22.2%, p = 0.195). Biochemical remission was achieved in 71.1% (27/38) of patients by tacrolimus and/or MMF. Decompensated cirrhosis was more commonly seen in MMF and/or tacrolimus non-responders than in responders (45.5 vs. 7.4%, p = 0.006). Five patients who received second-line therapy (2 MMF and 3 tacrolimus) developed side effects that led to therapy withdrawal. Long-term therapy with MMF or tacrolimus was generally well tolerated by pediatric patients with AIH. Both MMF and tacrolimus had excellent efficacy in patients intolerant to corticosteroid or azathioprine. Tacrolimus might be more effective than MMF in patients failing previous therapy.

  • 33. Efe, Cumali
    et al.
    Hagström, Hannes
    Ytting, Henriette
    Bhanji, Rahima A.
    Müller, Niklas F.
    Wang, Qixia
    Purnak, Tugrul
    Muratori, Luigi
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Marschall, Hanns-Ulrich
    Muratori, Paolo
    Gunşar, Fulya
    Klintman, Daniel
    Parés, Albert
    Heurgué-Berlot, Alexandra
    Schiano, Thomas D.
    Cengiz, Mustafa
    Tana, Michele May-Sien
    Ma, Xiong
    Montano-Loza, Aldo J.
    Berg, Thomas
    Verma, Sumita
    Larsen, Fin Stolze
    Ozaslan, Ersan
    Heneghan, Michael A.
    Yoshida, Eric M.
    Wahlin, Staffan
    Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis2017In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 15, no 12, p. 1950-1956Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Predniso(lo) ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. METHODS: We performed a retrospective study of data (from 19 centers in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6-190 mo). Patients were categorized according to their response to SOC. Patients in group 1 (n = 108) had a complete response to the SOC, but were switched to second-line therapy as a result of side effects of predniso(lo) ne or azathioprine, whereas patients in group 2 (n = 93) had not responded to SOC. RESULTS: There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P = .639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P = .682). Significantly more group 2 patients given tacrolimus compared with MMF had a complete response (56.5% vs 34%, respectively; P = .029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P = .472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal. CONCLUSIONS: Long-term therapy with MMF or tacrolimus generally was well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous nonresponder patients compared with MMF.

  • 34.
    Ekblom, Kim
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    UGT1A1*33 (TA)5 is more common in Romania and Northern Sweden than previously believed2017In: Journal of Gastrointestinal and Liver Diseases, ISSN 1841-8724, E-ISSN 1842-1121, Vol. 26, no 4, p. 427-428Article in journal (Refereed)
  • 35.
    Enell, Jacob
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Bayadsi, Haytham
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Lundgren, Ewa
    Hennings, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Primary Hyperparathyroidism is Underdiagnosed and Suboptimally Treated in the Clinical Setting2018In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 42, no 9, p. 2825-2834Article in journal (Refereed)
    Abstract [en]

    To evaluate whether patients presenting with laboratory results consistent with primary hyperparathyroidism (pHPT) are managed in accordance with guidelines. The laboratory database at a hospital in Sweden, serving 127,000 inhabitants, was searched for patients with biochemically determined pHPT. During 2014, a total of 365 patients with biochemical laboratory tests consistent with pHPT were identified. Patients with possible differential diagnoses or other reasons for not being investigated according to international guidelines were excluded after scrutinizing records, after new blood tests, and clinical assessments by endocrine surgeons. Altogether, 92 patients had been referred to specialists and 82 had not. The latter group had lower serum calcium (median 2.54 mmol/L) and PTH (5.7 pmol/L). Out of these 82 cases, 9 patients were diagnosed with pHPT or had some sort of long-term follow-up planned as outpatients. Primary hyperparathyroidism is overlooked and underdiagnosed in a number of patients in the clinical setting. It is important to provide local guidelines for the management of patients presenting with mild pHPT to ensure that these patients receive proper evaluation and follow-up according to current research.

  • 36.
    Englund, Hanna
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lidén K., Katarina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lind, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Sundström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Radiation exposure in patients with inflammatory bowel disease and irritable bowel syndrome in the years 2001-20112017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 3, p. 300-305Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To compare cumulative ionizing radiation in patients with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) for the years 2001-2011. To study how radiation exposure change over time in patients with newly diagnosed IBD and factors associated with radiation exposure.

    MATERIAL AND METHODS: All radiological investigations performed between 1 January 2001 and 31 December 2011 were retrospectively recorded in patients with Crohn's disease (CD) (n = 103), ulcerative colitis (UC) (n = 304) and IBS (n = 149). Analyses were done with Mann-Whitney and Chi-Square test.

    RESULTS: The median total cumulative radiation exposure in mSv for CD (20.0, inter quartile range (IQR) 34.8), UC (7.01, IQR 23.8), IBS (2.71, IQR 9.15) and the proportion of patients who had been exposed for more than 50 mSv during the study period (CD 19%, UC 11%, IBS 3%) were significantly higher in the patients with CD compared to patients with UC (p < .001) and IBS (p < .001), respectively. In turn, patients with UC had significantly higher doses than patients with IBS (p = .005). Risk factors for radiation exposure were female gender (CD), early onset (UC), ileocolonic location (CD), previous surgery (CD and UC), depression (IBS) and widespread pain (IBS). In newly diagnosed CD, there was a significant decline in median cumulative radiation dose in mSv (17.2 vs. 12.0; p = .048) during the study period.

    CONCLUSIONS: Patients with CD are at greatest risk for high cumulative radiation exposure, but there is a decline in exposure during the late 2000s. Non-colectomized patients with UC and patients with IBS have a relatively low risk of cumulative radiation exposure.

  • 37. Ericzon, Bo-Göran
    et al.
    Wilczek, Henryk E.
    Larsson, Marie
    Wijayatunga, Priyantha
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Stangou, Arie
    Pena, João Rodrigues
    Furtado, Emanuel
    Barroso, Eduardo
    Daniel, Jorge
    Samuel, Didier
    Adam, Rene
    Karam, Vincent
    Poterucha, John
    Lewis, David
    Ferraz-Neto, Ben-Hur
    Cruz, Márcia Waddington
    Munar-Ques, Miguel
    Fabregat, Juan
    Ikeda, Shu-Ichi
    Ando, Yukio
    Heaton, Nigel
    Otto, Gerd
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Liver transplantation for hereditary transthyretin amyloidosis: after 20 years still the best therapeutic alternative?2015In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 99, no 9, p. 1847-1854Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Until recently, liver transplantation (Ltx) was the only available treatment for hereditary transthyretin (TTR) amyloidosis; today, however, several pharmacotherapies are tested. Herein, we present survival data from the largest available database on transplanted hereditary TTR patients to serve as a base for comparison.

    METHODS: Liver transplantation was evaluated in a 20-year retrospective analysis of the Familial Amyloidosis Polyneuropathy World Transplant Registry.

    RESULTS: From April 1990 until December 2010, data were accumulated from 77 liver transplant centers. The Registry contains 1940 patients, and 1379 are alive. Eighty-eight Ltx were performed in combination with a heart and/or kidney transplantation. Overall, 20-year survival after Ltx was 55.3%. Multivariate analysis revealed modified body mass index, early onset of disease (<50 years of age), disease duration before Ltx, and TTR Val30Met versus non-TTR Val30Met mutations as independent significant survival factors. Early-onset patients had an expected mortality rate of 38% that of the late-onset group (P < 0.001). Furthermore, Val30Met patients had an expected mortality rate of 61% that of non-TTR Val30Met patients (P < 0.001). With each year of duration of disease before Ltx, expected mortality increased by 11% (P < 0.001). With each 100-unit increase in modified body mass index at Ltx, the expected mortality decreased to 89% of the expected mortality (P < 0.001). Cardiovascular death was markedly more common than that observed in patients undergoing Ltx for end-stage liver disease.

    CONCLUSIONS: Long-term survival after Ltx, especially for early-onset TTR Val30Met patients, is excellent. The risk of delaying Ltx by testing alternative treatments, especially in early-onset TTR Val30Met patients, requires consideration.

  • 38. Eriksson, Carl
    et al.
    Marsal, Jan
    Bergemalm, Daniel
    Vigren, Lina
    Bjork, Jan
    Eberhardson, Michael
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Soderman, Charlotte
    Myrelid, Par
    Cao, Yang
    Sjoberg, Daniel
    Thorn, Mari
    Karlen, Per
    Hertervig, Erik
    Strid, Hans
    Ludvigsson, Jonas F
    Almer, Sven
    Halfvarson, Jonas
    Long-term effectiveness of vedolizumab in inflammatory bowel disease: a national study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG)2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 6-7, p. 722-729Article in journal (Refereed)
    Abstract [en]

    Objectives: Clinical trials have demonstrated the efficacy of vedolizumab in inflammatory bowel disease (IBD). However, these findings may not reflect the clinical practice. Therefore, we aimed to describe a vedolizumab-treated patient population and assess long-term effectiveness.

    Materials and methods: Patients initiating vedolizumab between 1 June 2014 and 30 May 2015 were identified through the Swedish National Quality Registry for IBD. Prospectively collected data on treatment and disease activity were extracted. Clinical remission was defined as Patient Harvey Bradshaw index <5 in Crohn’s disease (CD) and Patient Simple Clinical Colitis Activity index <3 in ulcerative colitis (UC).

    Results: Two-hundred forty-six patients (147 CD, 92 UC and 7 IBD-Unclassified) were included. On study entry, 86% had failed TNF-antagonist and 48% of the CD patients had undergone ≥1 surgical resection. After a median follow-up of 17 (IQR: 14–20) months, 142 (58%) patients remained on vedolizumab. In total, 54% of the CD- and 64% of the UC patients were in clinical remission at the end of follow-up, with the clinical activity decreasing (p < .0001 in both groups). Faecal-calprotectin decreased in CD (p < .0001) and in UC (p = .001), whereas CRP decreased in CD (p = .002) but not in UC (p = .11). Previous anti-TNF exposure (adjusted HR: 4.03; 95% CI: 0.96–16.75) and elevated CRP at baseline (adjusted HR: 2.22; 95% CI: 1.10–4.35) seemed to be associated with discontinuation because of lack of response. Female sex was associated with termination because of intolerance (adjusted HR: 2.75; 95% CI: 1.16–6.48).

    Conclusion: Vedolizumab-treated patients represent a treatment-refractory group. A long-term effect can be achieved, even beyond 1 year of treatment.

  • 39. Fidler Mis, Nataša
    et al.
    Braegger, Christian
    Bronsky, Zjiri
    Campoy, Cristina
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Embleton, Nicholas D.
    Hojsak, Iva
    Hulst, Jessie
    Indrio, Flavia
    Lapillonne, Alexandre
    Mihatsch, Walter
    Molgaard, Christian
    Vora, Rakesh
    Fewtrell, Mary
    Response to Letter: How Much Free Sugars Intake Should Be Recommended for Children Younger Than 2 Years Old?2018In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 66, no 3, p. E87-E88Article in journal (Refereed)
  • 40.
    Folkesson, J
    et al.
    Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Nilsson, J
    Påhlman, L
    Glimelius, B
    Gunnarsson, Ulf
    Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    The circular stapling device as a risk factor for anastomotic leakage.2004In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 6, no 4, p. 275-9Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate the relation between the type of circular stapler and anastomotic leak in rectal cancer surgery.

    BACKGROUND: During the past decades results from rectal cancer surgery have improved considerably regarding risk of local recurrence and survival. Two main paradigm changes are considered to be the cause for this: the introduction of total mesorectal excision (TME) and the increasing use of radiotherapy. However, rectal cancer surgery is associated with an unacceptably high frequency of complications of which anastomotic leak is one of the most severe ones. The hypothesis was raised that the choice of stapler influenced the leakage rates.

    METHODS: A questionnaire was sent to all departments of surgery (n = 66) performing rectal cancer surgery in Sweden to determine the choice of circular stapler when performing anterior resection for rectal cancer. These data were linked to the Swedish Rectal Cancer Registry for the period 1995-99.

    RESULTS: A total of 3316 patients had an anterior resection. The choice of circular stapling device was determined in 70% of the cases. When stapler A was used, the leakage rate was 11% whereas it was 7% when stapler B was used (P = 0.0039). In the cases where it was impossible to determine which stapler had been used the leakage rate was 8%.

    CONCLUSION: Quality control is an important part of medicine and the present study suggests that it also must include surgical instruments. A prospective randomised study is needed to confirm the results.

  • 41.
    Forsberg, Göte
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Fahlgren, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hörstedt, Per
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Hammarström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Presence of bacteria and innate immunity of intestinal epithelium in childhood celiac disease2004In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 99, no 5, p. 894-904Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Exposure to gliadin and related prolamins and appropriate HLA-DQ haplotype are necessary but not sufficient for contracting celiac disease (CD). Aberrant innate immune reactions could be contributing risk factors. Therefore, jejunal biopsies were screened for bacteria and the innate immune status of the epithelium investigated.

    METHODS: Children with untreated, treated, challenged CD, and controls were analyzed. Bacteria were identified by scanning electron microscopy. Glycocalyx composition and mucin and antimicrobial peptide production were studied by quantitative RT-PCR, antibody and lectin immunohistochemistry.

    RESULTS: Rod-shaped bacteria were frequently associated with the mucosa of CD patients, with both active and inactive disease, but not with controls. The lectin Ulex europaeus agglutinin I (UEAI) stained goblet cells in the mucosa of all CD patients but not of controls. The lectin peanut agglutinin (PNA) stained glycocalyx of controls but not of CD patients. mRNA levels of mucin-2 (MUC2), alpha-defensins HD-5 and HD-6, and lysozyme were significantly increased in active CD and returned to normal in treated CD. Their expression levels correlated to the interferon-gamma mRNA levels in intraepithelial lymphocytes. MUC2, HD-5, and lysozyme proteins were seen in absorptive epithelial cells. beta-defensins hBD-1 and hBD-2, carcinoembryonic antigen (CEA), CEA cell adhesion molecule-1a (CEACAM1a), and MUC3 were not affected.

    CONCLUSIONS: Unique carbohydrate structures of the glycocalyx/mucous layer are likely discriminating features of CD patients. These glycosylation differences could facilitate bacterial adhesion. Ectopic production of MUC2, HD-5, and lysozyme in active CD is compatible with goblet and Paneth cell metaplasia induced by high interferon-gamma production by intraepithelial lymphocytes.

  • 42.
    Forsberg, Göte
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Hernell, O
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Melgar, S
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Israelsson, A
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Hammarström, Sten
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Hammarström, Marie-Louise
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Paradoxical coexpression of proinflammatory and down-regulatory cytokines in intestinal T cells in childhood celiac disease2002In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 123, no 3, p. 667-678Article in journal (Refereed)
  • 43. Fox, Adam T.
    et al.
    Wopereis, Harm
    Van Ampting, Marleen T. J.
    Nijhuis, Manon M. Oude
    Butt, Assad M.
    Peroni, Diego G.
    Vandenplas, Yvan
    Candy, David C. A.
    Shah, Neil
    West, Christina E.
    Umeå University.
    Garssen, Johan
    Harthoorn, Lucien F.
    Knol, Jan
    Michaelis, Louise J.
    Smets, Francoise
    Mullier, Sandra
    Noimark, Lee
    Muraro, Antonella
    A specific synbiotic-containing amino acid-based formula in dietary management of cow's milk allergy: a randomized controlled trial2019In: Clinical and Translational Allergy, ISSN 2045-7022, E-ISSN 2045-7022, Vol. 9, article id 5Article in journal (Refereed)
    Abstract [en]

    Background: Here we report follow-up data from a double-blind, randomized, controlled multicenter trial, which investigated fecal microbiota changes with a new amino acid-based formula (AAF) including synbiotics in infants with non-immunoglobulin E (IgE)-mediated cow’s milk allergy (CMA).

    Methods: Subjects were randomized to receive test product (AAF including fructo-oligosaccharides and Bifidobacterium breve M-16V) or control product (AAF) for 8 weeks, after which infants could continue study product until 26 weeks. Fecal percentages of bifidobacteria and Eubacterium rectale/Clostridium coccoidesgroup (ER/CC) were assessed at 0, 8, 12, and 26 weeks. Additional endpoints included stool markers of gut immune status, clinical symptoms, and safety assessments including adverse events and medication use.

    Results: The trial included 35 test subjects, 36 controls, and 51 in the healthy reference group. Study product was continued by 86% and 92% of test and control subjects between week 8–12, and by 71% and 80%, respectively until week 26. At week 26 median percentages of bifidobacteria were significantly higher in test than control [47.0% vs. 11.8% (p < 0.001)], whereas percentages of ER/CC were significantly lower [(13.7% vs. 23.6% (p = 0.003)]. Safety parameters were similar between groups. Interestingly use of dermatological medication and reported ear infections were lower in test versus control, p = 0.019 and 0.011, respectively. Baseline clinical symptoms and stool markers were mild (but persistent) and low, respectively. Symptoms reduced towards lowest score in both groups.

    Conclusion: Beneficial effects of this AAF including specific synbiotics on microbiota composition were observed over 26 weeks, and shown suitable for dietary management of infants with non-IgE-mediated CMA.

  • 44. Garcia-Etxebarria, Koldo
    et al.
    Zheng, Tenghao
    Bonfiglio, Ferdinando
    Bujanda, Luis
    Dlugosz, Aldona
    Lindberg, Greger
    Schmidt, Peter T.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ohlsson, Bodil
    Simren, Magnus
    Walter, Susanna
    Nardone, Gerardo
    Cuomo, Rosario
    Usai-Satta, Paolo
    Galeazzi, Francesca
    Neri, Matteo
    Portincasa, Piero
    Bellini, Massimo
    Barbara, Giovanni
    Jonkers, Daisy
    Eswaran, Shanti
    Chey, William D.
    Kashyap, Purna
    Chang, Lin
    Mayer, Emeran A.
    Wouters, Mira M.
    Boeckxstaens, Guy
    Camilleri, Michael
    Franke, Andre
    D'Amato, Mauro
    Increased Prevalence of Rare Sucrase-isomaltase Pathogenic Variants in Irritable Bowel Syndrome Patients2018In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 16, no 10, p. 1673-1676Article, review/survey (Refereed)
  • 45.
    Gerold, Gisa
    et al.
    Center for Experimental and Clinical Infection Research Institute of Experimental Virology, TWINCORE Hannover Germany.
    Pietschmann, Thomas
    A circuit of paracrine signals between liver sinusoid endothelial cells and hepatocytes regulates hepatitis C virus replication2014In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 59, no 2, p. 363-5Article in journal (Refereed)
  • 46.
    Gerold, Gisa
    et al.
    Institute of Experimental Virology Twincore – Center for Experimental and Clinical Infectious Disease Research Hannover, Germany.
    Pietschmann, Thomas
    Hepatitis C virus NS5B polymerase primes innate immune signaling2013In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 57, no 3, p. 1275-1277Article in journal (Refereed)
    Abstract [en]

    Innate immunity controls pathogen replication and spread. Yet, certain pathogens, such as Hepatitis C Virus (HCV), escape immune elimination and establish persistent infections that promote chronic inflammation and related diseases. Whereas HCV regulatory proteins that attenuate antiviral responses are known, those that promote inflammation and liver injury remain to be identified. Here, we show that transient expression of HCV RNA-dependent RNA polymerase (RdRp), NS5B, in mouse liver and human hepatocytes results in production of small RNA species that activate innate immune signaling via TBK1-IRF3 and NF-kappa B and induce cytokine production, including type I interferons (IFN) and IL-6. NS5B-expression also results in liver damage.

  • 47.
    Gerold, Gisa
    et al.
    TWINCORE – Institute of Experimental Virology, Centre for Experimental and Clinical Infection Research, Hannover , Germany.
    Pietschmann, Thomas
    The HCV life cycle: in vitro tissue culture systems and therapeutic targets2014In: Digestive Diseases, ISSN 0257-2753, E-ISSN 1421-9875, Vol. 32, no 5, p. 525-537Article in journal (Refereed)
    Abstract [en]

    Hepatitis C virus (HCV) is a highly variable plus-strand RNA virus of the family Flaviviridae. Viral strains are grouped into six epidemiologically relevant genotypes that differ from each other by more than 30% at the nucleotide level. The variability of HCV allows immune evasion and facilitates persistence. It is also a substantial challenge for the development of specific antiviral therapies effective across all HCV genotypes and for prevention of drug resistance. Novel HCV cell culture models were instrumental for identification and profiling of therapeutic strategies. Concurrently, these models revealed numerous host factors critical for HCV propagation, some of which have emerged as targets for antiviral therapy. It is generally assumed that the use of host factors is conserved among HCV isolates and genotypes. Additionally, the barrier to viral resistance is thought to be high when interfering with host factors. Therefore, current drug development includes both targeting of viral factors but also of host factors essential for virus replication. In fact, some of these host-targeting agents, for instance inhibitors of cyclophilin A, have advanced to late stage clinical trials. Here, we highlight currently available cell culture systems for HCV, review the most prominent host-targeting strategies against hepatitis C and critically discuss opportunities and risks associated with host-targeting antiviral strategies.

  • 48. Gremel, Gabriela
    et al.
    Wanders, Alkwin
    Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University.
    Cedernaes, Jonathan
    Fagerberg, Linn
    Hallström, Björn
    Edlund, Karolina
    Sjöstedt, Evelina
    Uhlén, Mathias
    Pontén, Fredrik
    The human gastrointestinal tract-specific transcriptome and proteome as defined by RNA sequencing and antibody-based profiling2015In: Journal of gastroenterology, ISSN 0944-1174, E-ISSN 1435-5922, Vol. 50, no 1, p. 46-57Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The gastrointestinal tract (GIT) is subdivided into different anatomical organs with many shared functions and characteristics, but also distinct differences. We have combined a genome-wide transcriptomics analysis with immunohistochemistry-based protein profiling to describe the gene and protein expression patterns that define the human GIT. METHODS: RNA sequencing data derived from stomach, duodenum, jejunum/ileum and colon specimens were compared to gene expression levels in 23 other normal human tissues analysed with the same method. Protein profiling based on immunohistochemistry and tissue microarrays was used to sub-localize the corresponding proteins with GIT-specific expression into sub-cellular compartments and cell types. RESULTS: Approximately 75% of all human protein-coding genes were expressed in at least one of the GIT tissues. Only 51 genes showed enriched expression in either one of the GIT tissues and an additional 83 genes were enriched in two or more GIT tissues. The list of GIT-enriched genes with validated protein expression patterns included various well-known but also previously uncharacterised or poorly studied genes. For instance, the colon-enriched expression of NXPE family member 1 (NXPE1) was established, while NLR family, pyrin domain-containing 6 (NLRP6) expression was primarily found in the human small intestine. CONCLUSIONS: We have applied a genome-wide analysis based on transcriptomics and antibody-based protein profiling to identify genes that are expressed in a specific manner within the human GIT. These genes and proteins constitute important starting points for an improved understanding of the normal function and the different states of disease associated with the GIT.

  • 49.
    Gunnarsson, Ulf
    et al.
    Department of Surgical Sciences, University Hospital, Uppsala, Sweden.
    Karlbom, U
    Docker, M
    Raab, Y
    Påhlman, L
    Proctocolectomy and pelvic pouch--is a diverting stoma dangerous for the patient?2004In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 6, no 1, p. 23-7Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: A diverting loop ileostomy was previously considered mandatory for minimizing the effects of septic complications in pelvic pouch surgery. During the past decade there has been a trend towards omission of the loop ileostomy without obvious signs of increased numbers of pouch complications or impaired long-term function. The aim of the present study was to evaluate the risk of complications associated with the construction and closure of the loop ileostomy itself.

    PATIENTS AND METHODS: Complications following diverting loop ileostomies in 143 patients subjected to restorative pelvic pouch surgery during the period 1983-97 were studied retrospectively by evaluation of case records.

    RESULTS: In the period between discharge after pelvic pouch surgery and closure of the loop ileostomy, 20 (14%) patients were hospitalized because of excessive stoma flow and 19 (13%) patients were treated for other surgical complications, of whom 10 (7%) required surgical intervention. In the early postoperative period (within 30 days) after closure of the loop ileostomy, 18 (13%) patients suffered complications necessitating surgery. Another 12 (8%) patients were hospitalized because of intestinal obstruction that could be treated conservatively.

    CONCLUSION: The proportion of complications associated with diverting loop ileostomies in pelvic pouch surgery was considerable. A randomised controlled multicentre study is ethically defensible and is recommended.

  • 50.
    Gustafsson, Carl Pontus
    et al.
    Department of Surgery, Visby Hospital, Gotland, Sweden..
    Gunnarsson, Ulf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Dahlstrand, Ursula
    Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institutet, and Centre for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden..
    Lindforss, Ulrik
    Department of Molecular Medicine and Surgery, Karolinska Institutet, and Centre for Digestive Diseases, Karolinska University Hospital, Solna, Sweden..
    Loop-ileostomy reversal: patient-related characteristics influencing time to closure2018In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 33, no 5, p. 593-600Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To identify factors associated with timing of stoma reversal after rectal cancer surgery in a large Swedish register-based cohort.

    METHODS: Three thousand five hundred sixty-four patients with rectal cancer who received a protective stoma during surgery in 2007-2013 were identified in the Swedish colorectal cancer register. Time to stoma reversal was evaluated over a follow-up period of one and a half years. Factors associated with timing of stoma reversal were analysed using Cox regression analysis. Reversal within 9 months (12 months if adjuvant chemotherapy) was considered latest expected time to closure.

    RESULTS: Stoma reversal was performed in 2954 (82.9%) patients during follow-up. Patients with post-secondary education had an increased chance for early stoma reversal (HR 1.13; 95% CI 1.02-1.25). Postoperative complications (0.67; 0.62-0.73), adjuvant chemotherapy (0.63; 0.57-0.69), more advanced cancer stage (stage III 0.74; 0.66-0.83 and stage IV 0.38; 0.32-0.46) and higher ASA score (0.80; 0.71-0.90 for ASA 3-4) were associated with longer time to reversal. Two thousand four hundred thirty-seven (68.4%) patients had stoma reversal within latest expected time to closure. Factors associated to decreased chance of timely reversal were more advanced cancer stage (stage III 0.64; 0.50-0.81 and stage IV 0.19; 0.13-0.27), postoperative complications (0.50; 0.42-0.59) and higher ASA score (0.77; 0.61-0.96 for ASA 3-4).

    CONCLUSIONS: Patients with a high level of education had a higher chance of timely reversal but medical factors had a stronger association to time to reversal. Patients with advanced rectal cancer are at high risk for non-reversal and should be considered for permanent stoma.

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