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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.

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  • 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, Section of 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.

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  • 10.
    Andersson, P.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Infectious events in patients with inflammatory bowel disease: The impact of immunomodulators and tumour necrosis factor antagonist therapy2020In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 14, p. S338-S339Article in journal (Refereed)
  • 11.
    Andersson, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Impact of treatment with immunomodulators and tumour necrosis factor antagonists on the incidence of infectious events in patients with inflammatory bowel disease2022In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 127, article id e8167Article in journal (Refereed)
    Abstract [en]

    Background: Corticosteroids, immunomodulators (IM) and tumour necrosis factor antagonists (anti-TNF) are commonly used in the treatment of inflammatory bowel disease (IBD) but they also supress the defence against infectious disease. The aim of this study was to analyse the incidence of infectious events in patients with IBD and the association to concomitant medical therapy.

    Methods: We performed a retrospective medical chart review of patients with IBD aged 18–65 years included in the Swedish Registry of Inflammatory Bowel Disease in the catchment area of Umeå University Hospital, Sweden. Data were collected from the period 01 January 2006, to 31 January 2019. An infectious event was defined as an outpatient prescription of antimicrobials or a positive diagnostic test for infection.

    Results: During a period of 5,120 observation-years, we observed 1,394 events in 593 patients. The mean number of infectious events per 100 person-years was 27.2 (standard deviation [SD]: 0.46). There were no differences in mean incidence rates between patients treated with no immunosuppression (23.0 events per 100 person-years, SD: 50.4), patients treated with IM monotherapy (27.6 events per 100 person-years, SD: 49.9), patients treated with anti-TNF monotherapy (34.3 events per 100 person-years, SD: 50.1) and patients on combination therapy (22.5 events per 100-person-years, SD: 44.2). In a multivariate logistic regression, female gender (adjusted odds ratio [AOR]: 2.24; 95% confidence interval [CI]: 1.49–3.37) and combination therapy (AOR: 3.46; 95% CI: 1.52–7.85) were associated with higher risks of infection (>32 events per 100 person years). Also, patients treated with any immunosuppression treatment for 25–75% (AOR: 2.29; 95% CI: 1.21–4.34) and for >75% (AOR: 1.93; 95% CI: 1.19–3.12) of the observation period were at higher risks compared to patients treated with immunosuppression <25% of the observation period.

    Conclusion: We observed no significant difference in risk for infections between patients on monotherapy with IM or anti-TNF and patients with low use of immunosuppression, but there was a significant risk for combination therapy.

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  • 12. 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)
  • 13. Andreasson, Anna
    et al.
    Talley, Nicholas J.
    Walker, Marjorie M.
    Jones, Michael P.
    Platts, Loretta G.
    Wallner, Bengt
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Kjellstrom, Lars
    Hellstrom, Per M.
    Forsberg, Anna
    Agreus, Lars
    An Increasing Incidence of Upper Gastrointestinal Disorders Over 23 Years: A Prospective Population-Based Study in Sweden2021In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 116, no 1, p. 210-213Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: We hypothesized that the prevalence of functional dyspepsia and gastroesophageal reflux disease in the community may be increasing. METHODS: Randomly selected adults were surveyed on 4 occasions: 1988 (n = 1,151, 21-79 years, response rate [rr] = 90%), 1989 (n = 1,097, 22-80 years, rr = 87%), 1995 (n = 1,139, 20-85 years, rr = 76%), and 2011 (n = 1,175, 20-93 years, rr = 63%). RESULTS: In functional dyspepsia, the odds of postprandial distress syndrome tripled over 23 years' follow-up (odds ratio [OR]: 3.55; 95% confidence interval [CI]: 2.60-4.84, mixed-effect regression analysis), whereas a small decrease in epigastric pain syndrome was observed (OR: 0.65, 95% CI: 0.42-1.00). The odds of reporting gastroesophageal reflux disease doubled (OR: 2.02; 95% CI: 1.50-2.73). DISCUSSION: The underlying mechanisms behind the increase in postprandial distress syndrome and gastroesophageal reflux disease remain to be determined.

  • 14. 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.

  • 15. 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.

  • 16.
    Axman, Erik
    et al.
    Sahlgrenska University Hospital/Östra Hospital, Department of Surgery, Gothenburg, Sweden; Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Nordin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Modin, Marina
    Department of Research, Development, Education and Innovation, Skaraborg Hospital, Skövde, Sweden.
    de la Croix, Hanna
    Sahlgrenska University Hospital/Östra Hospital, Department of Surgery, Gothenburg, Sweden; Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Assessing the Validity and Cover Rate of the National Swedish Hernia Register2021In: Clinical Epidemiology, E-ISSN 1179-1349, Vol. 13, p. 1129-1134Article in journal (Refereed)
    Abstract [en]

    Aim: To assess the validity and cover rate of the Swedish hernia register.

    Material and Methods: Since the start of the Swedish Hernia register an annual review of randomly selected hospitals has been carried out, and since 2013 in a more standardized form to allow a systematic data collection and evaluation. 10% of all clinics were randomly selected each year in a specific region of Sweden, ensuring a systematic validation of all regions from north to south. Data from 2013 to 2018 were analyzed regarding data quality and from 2014 to 2018 regarding cover rate. All operations registered at the validated clinics were compared with the Swedish Hernia Register to assess cover rate. Fifty operations were randomly selected at each clinic and data in the Swedish Hernia register were compared with the medical records to evaluate data quality.

    Results: Fifty-five clinics was evaluated and a total of 73,764 variables were compared with the medical records. Cover rate between 2014 and 2018 was 97%. The proportion of correct variables was 98% between 2013 and 2018. Most frequent errors were ASA score, date at which the patient was put on the waiting list and postoperative complications.

    Conclusion: This unique validation of a national hernia register shows a high cover rate and good quality of data. Efforts to maintain and improve national registers are of great importance. Research with data from the Swedish hernia register should be evaluated on the basis of the results presented in this study.

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  • 17.
    Backman, Olof
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery. Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Bruze, Gustaf
    Naslund, Ingmar
    Ottosson, Johan
    Marsk, Richard
    Neovius, Martin
    Naslund, Erik
    Gastric Bypass Surgery Reduces De Novo Cases of Type 2 Diabetes to Population Levels A Nationwide Cohort Study From Sweden2019In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 269, no 5, p. 895-902Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to determine long-term changes in pharmacological treatment of type 2 diabetes after primary Roux-en-Y gastric bypass (RYGB) surgery, in patients with and without pharmacological treatment of diabetes preoperatively.

    Summary of Background Data: Several studies have shown that gastric bypass has good effect on diabetes, at least in the short-term. This study is a nationwide cohort study using Swedish registers, with basically no patients lost to follow-up during up to 7 years after surgery.

    Methods: The effect of RYGB on type 2 diabetes drug treatment was evaluated in this nationwide matched cohort study. Participants were 22,047 adults with BMI ≥30 identified in the nationwide Scandinavian Surgical Obesity Registry, who underwent primary RYGB between 2007 and 2012. For each individual, up to 10 general population comparators were matched on birth year, sex, and place of residence. Prescription data were retrieved from the nationwide Swedish Prescribed Drug Register through September 2015. Incident use of pharmacological treatment was analyzed using Cox regression.

    Results: Sixty-seven percent of patients with pharmacological treatment of type 2 diabetes before surgery were not using diabetes drugs 2 years after surgery and 61% of patients were not pharmacologically treated up to 7 years after surgery. In patients not using diabetes drugs at baseline, there were 189 new cases of pharmacological treatment of type 2 diabetes in the surgery group and 2319 in the matched general population comparators during a median follow-up of 4.6 years (incidence: 21.4 vs 27.9 per 10,000 person-years; adjusted hazard ratio 0.77, 95% confidence interval 0.67–0.89; P < 0.001).

    Conclusions: Gastric bypass surgery not only induces remission of pharmacological treatment of type 2 diabetesbut also protects from new onset of pharmacological diabetes treatment. The effect seems to persist in most, but not all, patients over 7 years of follow-up.

  • 18.
    Baldaque-Silva, Francisco
    et al.
    Division of Medicine, Department of Upper Gastrointestinal Diseases, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden.
    Moro, Carlos Fernández
    Department of Clinical Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden; Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
    Arnelo, Urban
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    A Nerve-Wracking Cyst2021In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 161, no 5, p. e12-e13Article in journal (Refereed)
  • 19.
    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.

  • 20.
    Bengtsson, Daniel
    et al.
    Department Of Biomedical And Clinical Sciences, Linköping University, Linköping, Sweden.
    Ragnarsson, Oskar
    Department Of Internal Medicine And Clinical Nutrition, Institute Of Medicine, Sahlgrenska Academy, University Of Gothenburg, Gothenburg, Sweden; Department Of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Berinder, Katarina
    Department Of Endocrinology, Karolinska University Hospital, Stockholm, Sweden; Department Of Molecular Medicine And Surgery, Karolinska Institutet, Stockholm, Sweden.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Edén Engström, Britt
    Department Of Medical Sciences Endocrinology And Mineral Metabolism, Uppsala University, Uppsala, Sweden; Department Of Endocrinology And Diabetes, Uppsala University Hospital, Uppsala, Sweden.
    Ekman, Bertil
    Department Of Endocrinology, Linköping University, Linköping, Sweden; Department Of Health Medicine And Caring Sciences, Linköping University, Linköping, Sweden.
    Höybye, Charlotte
    Department Of Endocrinology, Karolinska University Hospital, Stockholm, Sweden; Department Of Molecular Medicine And Surgery, Karolinska Institutet, Stockholm, Sweden.
    Järås, Jacob
    Regional Cancer Centre, Stockholm/Gotland, Stockholm, Sweden.
    Valdemarsson, Stig
    Department Of Clinical Sciences, Skåne University Hospital, University Of Lund, Lund, Sweden.
    Burman, Pia
    Department Of Endocrinology, Skåne University Hospital, University Of Lund, Malmö, Sweden.
    Wahlberg, Jeanette
    Department Of Endocrinology, Linköping University, Linköping, Sweden; Department Of Health Medicine And Caring Sciences, Linköping University, Linköping, Sweden; Faculty Of Medical Sciences, Örebro University, Örebro, Sweden.
    Increased Mortality Persists after Treatment of Cushing's Disease: A Matched Nationwide Cohort Study2022In: Journal of the Endocrine Society, E-ISSN 2472-1972, Vol. 6, no 6, article id bvac045Article in journal (Refereed)
    Abstract [en]

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

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  • 21.
    Bergemalm, Daniel
    et al.
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Andersson, Erik
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Eriksson, Carl
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Rush, Stephen T.
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Kalla, Rahul
    Medical Research Council Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
    Adams, Alex T.
    Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
    Keita, Åsa V.
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    D'Amato, Mauro
    CIC bioGUNE Basque Research and Technology Alliance and Basque Science Foundation, Bilbao, Spain; Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Gomollon, Fernando
    Hospital Clinico Universitario Lozano Blesa, IIS Aragón, Zaragoza, Spain.
    Jahnsen, Jørgen
    Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Arnott, Ian D.
    Bayes, Monica
    Bonfiglio, Ferdinando
    Boyapati, Ray K.
    Carstens, Adam
    Casén, Christina
    Ciemniejewska, Ewa
    Dahl, Fredrik A.
    Detlie, Trond Espen
    Drummond, Hazel E.
    Ekeland, Gunn S.
    Ekman, Daniel
    Frengen, Anna B.
    Gullberg, Mats
    Gut, Ivo G.
    Gut, Marta
    Heath, Simon C.
    Hjelm, Fredrik
    Hjortswang, Henrik
    Ho, Gwo-Tzer
    Jonkers, Daisy
    Söderholm, Johan
    Kennedy, Nicholas A.
    Lees, Charles W.
    Lindahl, Torbjørn
    Lindqvist, Mårten
    Merkel, Angelika
    Modig, Eddie
    Moen, Aina E.F.
    Nilsen, Hilde
    Nimmo, Elaine R.
    Noble, Colin L.
    Nordberg, Niklas
    O'Leary, Kate R.
    Ocklind, Anette
    Olbjørn, Christine
    Pettersson, Erik
    Pierik, Marieke
    Dominique,
    Ricanek, Petr
    Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway.
    Satsangi, Jack
    Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Repsilber, Dirk
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Halfvarson, Jonas
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Systemic Inflammation in Preclinical Ulcerative Colitis2021In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 161, no 5, p. 1526-1539.e9Article in journal (Refereed)
    Abstract [en]

    Background & Aims: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins.

    Methods: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored.

    Results: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1β, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-κB, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis.

    Conclusions: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors.

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  • 22.
    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.

  • 23.
    Bergmann, Katarzyna
    et al.
    Department of Laboratory Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Torun, Poland.
    Stefanska, Anna
    Department of Laboratory Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Torun, Poland.
    Krintus, Magdalena
    Department of Laboratory Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Torun, Poland.
    Szternel, Lukasz
    Department of Laboratory Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Torun, Poland.
    Bilinski, Wojciech J.
    Department of Orthopaedics, KoMed Poddebice Health Center, Poddebice, Poland.
    Paradowski, Przemyslaw T.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics. Clinical Epidemiology Unit, Orthopedics, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
    Sypniewska, Grazyna
    Department of Laboratory Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Torun, Poland.
    Diagnostic performance of biomarker-based scores as predictors of metabolic dysfunction-associated fatty liver disease risk in healthy children2023In: Nutrients, E-ISSN 2072-6643, Vol. 15, no 16, article id 3667Article in journal (Refereed)
    Abstract [en]

    Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD)—a new definition for non-alcoholic fatty liver disease—reflects the impact of metabolic abnormalities on liver function. We assessed the diagnostic accuracy of biomarker-based scores for prediction of MAFLD in apparently healthy children.

    Methods: This study included 144 children aged 9–11. MAFLD was recognized in 14 girls and 29 boys. Anthropometric indices, glycemia, insulin resistance, lipid profile, enzymes (ALT, AST, GGT, ALP), CRP, N-terminal propeptide of type I procollagen (P1NP) and collagen type I C-telopeptide (CTX-1) levels were measured. Fatty liver and hepatic steatosis index (FLI, HSI) and potential indicators of liver fibrogenesis: P1NP/ALP, P1NP/ALPxALT, P1NP/ALPxCRP were calculated.

    Results: P1NP/ALPxALT and P1NP/ALPxCRP were significantly higher in subjects with MAFLD. FLI was a good, significant predictor of MAFLD occurrence, regardless of sex. In boys, P1NP/ALPxCRP was a comparable predictor as CRP (OR 1.14 vs. 1.17; p < 0.001). P1NP/ALPxCRP had better discrimination capability in boys (AUC = 0.79; p < 0.001). However, the use of this algorithm did not improve discriminatory power in comparison to CRP (AUC = 0.81; p < 0.001), but gave a better sensitivity for MAFLD prediction (86% vs. 59%).

    Conclusions: We suggest that P1NP/ALPXCRP is a reliable tool for MAFLD prediction in routine pediatric practice.

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  • 24. 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.

  • 25.
    Bergquist, Annika
    et al.
    Department of Medicine Huddinge, Unit of Gastroenterology and Rheumatology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; European Reference Network for Hepatological Diseases, Stockholm, Sweden.
    Weismüller, Tobias J.
    Department of Internal Medicine I, University Hospital Bonn, University of Bonn, Bonn, Germany.
    Levy, Cynthia
    Division of Digestive Health and Liver Diseases, University of Miami, FL, United States; Schiff Center for Liver Diseases, University of Miami, FL, United States.
    Rupp, Christian
    Department of Gastroenterology, Infectious Diseases, Intoxication, Heidelberg University Hospital, Heidelberg, Germany.
    Joshi, Deepak
    Institute of Liver Studies, King's College Hospital, London, United Kingdom.
    Nayagam, Jeremy Shanika
    Institute of Liver Studies, King's College Hospital, London, United Kingdom.
    Montano-Loza, Aldo J.
    Division of Gastroenterology and Liver Unit, Department of Medicine, University of Alberta, AB, Edmonton, Canada.
    Lytvyak, Ellina
    Division of Gastroenterology and Liver Unit, Department of Medicine, University of Alberta, AB, Edmonton, Canada.
    Wunsch, Ewa
    Translational Medicine Group, Pomeranian Medical University, Szczecin, Poland.
    Milkiewicz, Piotr
    Translational Medicine Group, Pomeranian Medical University, Szczecin, Poland; Liver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland.
    Zenouzi, Roman
    Department of Medicine and Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
    Schramm, Christoph
    Department of Medicine and Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
    Cazzagon, Nora
    Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy; European Reference Network on Hepatological Disease, European Reference Network for Hepatological Diseases, Azienda Ospedaliera-Università di Padova, Padova, Italy.
    Floreani, Annarosa
    Studiosa Senior University of Padova, Italy and Scientific Consultant IRCCS Negrar, Verona, Italy.
    Liby, Ingalill Friis
    Department of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Wiestler, Miriam
    Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; European Reference Network for Hepatological Diseases, Hannover, Germany.
    Wedemeyer, Heiner
    Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; European Reference Network for Hepatological Diseases, Hannover, Germany.
    Zhou, Taotao
    Department of Internal Medicine I, University Hospital Bonn, University of Bonn, Bonn, Germany.
    Strassburg, Christian P.
    Department of Internal Medicine I, University Hospital Bonn, University of Bonn, Bonn, Germany.
    Rigopoulou, Eirini
    Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece.
    Dalekos, George
    Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece.
    Narasimman, Manasa
    Schiff Center for Liver Diseases, University of Miami, FL, United States.
    Verhelst, Xavier
    Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium; Ghent Liver Research Center, Ghent University, Ghent, Belgium; European Reference Network for Hepatological Diseases, Ghent, Belgium.
    Degroote, Helena
    Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium; Ghent Liver Research Center, Ghent University, Ghent, Belgium; European Reference Network for Hepatological Diseases, Ghent, Belgium.
    Vesterhus, Mette
    Norwegian PSC Research Centre, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway.
    Kremer, Andreas E.
    Department of Medicine 1, Friedrich-Alexander-University Erlangen-Nürnberg and University Hospital Erlangen, Erlangen, Germany; Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland.
    Bündgens, Bennet
    Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
    Rorsman, Fredrik
    Department of Gastroenterology and Hepatology, University Hospital, Uppsala, Sweden.
    Nilsson, Emma
    Department of Clinical Sciences, Lund University, Lund, Sweden; Gastroenterology Clinic, Skåne University Hospital, Sweden.
    Jørgensen, Kristin Kaasen
    Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway.
    von Seth, Erik
    Department of Medicine Huddinge, Unit of Gastroenterology and Rheumatology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; European Reference Network for Hepatological Diseases, Stockholm, Sweden.
    Cornillet Jeannin, Martin
    Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Nyhlin, Nils
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Martin, Harry
    Department of Gastroenterology, University College Hospitals NHS Foundation Trust, London, United Kingdom.
    Kechagias, Stergios
    Unit of Internal Medicine, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
    Wiencke, Kristine
    Norwegian PSC Research Centre, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Beretta-Piccoli, Benedetta Terziroli
    Epatocentro Ticino, Università della Svizzera Italiana, Lugano, Switzerland.
    Marzioni, Marco
    Clinic of Gastroenterology and Hepatology, Università Politecnica delle Marche, Ospedali Riuniti - University Hospital, Ancona, Italy.
    Isoniemi, Helena
    Transplantation and Liver Surgery, Abdominal Center, Helsinki University Hospital, Helsinki, Finland.
    Arola, Johanna
    Department of Pathology and Huslab, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Wefer, Agnes
    Division of Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Söderling, Jonas
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Färkkilä, Martti
    Clinic of Gastroenterology, Abdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Lenzen, Henrike
    Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; European Reference Network for Hepatological Diseases, Hannover, Germany; Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
    the International PSC Study Group,
    Impact on follow-up strategies in patients with primary sclerosing cholangitis2023In: Liver international, ISSN 1478-3223, E-ISSN 1478-3231, Vol. 43, no 1, p. 127-138Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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  • 26.
    Bertl, Kristina
    et al.
    Department of Periodontology, Dental Clinic, Faculty of Medicine, Sigmund Freud University, Vienna, Austria; Department of Periodontology, Faculty of Odontology, University of Malmö, Malmö, Sweden.
    Tsakos, Georgios
    Department of Epidemiology and Public Health, University College London, London, United Kingdom.
    Pandis, Nikolaos
    Department of Orthodontics and Dentofacial Orthopedics, School of Dental Medicine, University of Bern, Bern, Switzerland.
    Bogren, Anna
    Umeå University, Faculty of Medicine, Department of Odontology.
    Burisch, Johan
    Gastrounit, Medical Division, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark; Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark.
    Stavropoulos, Andreas
    Department of Periodontology, Faculty of Odontology, University of Malmö, Malmö, Sweden; Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria.
    Health-related quality of life aspects of the ‘Periodontitis prevalence in ulcerative colitis and Crohn's disease’ (PPCC) cohort2023In: Journal of Clinical Periodontology, ISSN 0303-6979, E-ISSN 1600-051X, Vol. 50, no 12, p. 1601-1620Article in journal (Refereed)
    Abstract [en]

    Aim: To assess whether oral health problems affect disease-specific quality of life (QoL) of inflammatory bowel disease (IBD) patients, and vice versa, whether IBD affects oral-health-related QoL.

    Materials and Methods: Individuals reporting IBD and matched controls were surveyed on general anamnestic information, oral-health-related questions and the Oral Health Impact Profile (OHIP)-5. IBD patients were additionally surveyed on years since diagnosis, disease activity and severity as well as health-related QoL (Short Inflammatory Bowel Disease Questionnaire, sIBDQ). OHIP-5 and sIBDQ were defined as primary outcome parameters, and several predictors and confounders were used in adjusted univariable and multivariable regression analyses.

    Results: Answers from 1108 IBD patients and 3429 controls were analysed. Compared with controls, IBD patients reported significantly more frequently an oral impact on daily life and worse oral-health-related QoL, with Crohn's disease (CD) patients being more severely affected than ulcerative colitis (UC) patients. The diagnosis of UC and CD, having <20 teeth, severe periodontitis and stressful daily-life experience were associated with a higher prevalence of poor oral-health-related QoL. Among IBD patients, an impaired IBD-specific, health-related QoL was significantly associated with the diagnosis of CD and depression, IBD activity and severity, having <20 teeth, presence of oral lesions and stressful daily-life experience, while a longer time since diagnosis was significantly associated with an improved IBD-specific, health-related QoL.

    Conclusions: The results of the present study indicate, for the first time, that oral health problems are associated with an impairment of IBD-specific health-related QoL, and vice versa, IBD is associated with an impaired oral health-related QoL. This emphasizes the potential advantages of including dental professionals in the multi-disciplinary treatment teams of IBD patients.

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  • 27. 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.

  • 28. 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.

  • 29.
    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.

  • 30.
    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.

  • 31.
    Bjurström, Oliver
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    The association between drugs and repeated treatment with budesonide in patients with microscopic colitis: a retrospective observational study2024In: Therapeutic Advances in Gastroenterology, ISSN 1756-283X, E-ISSN 1756-2848, Vol. 17, no January-DecemberArticle in journal (Refereed)
    Abstract [en]

    Background: Smoking and the use of non-steroidal anti-inflammatory drugs (NSAIDs) acetylsalicylic acid (ASA), proton pump inhibitors (PPIs), serotonin reuptake inhibitors (SSRIs), and statins have been associated with microscopic colitis (MC).

    Objectives: We investigated whether these factors were associated with repeated budesonide treatments in patients diagnosed with MC.

    Design: Retrospective observational study.

    Methods: All patients with a histologically verified diagnosis of MC at our clinic between the years 2006 and 2022 were identified. Baseline factors and drugs prescribed before and after diagnosis were registered. The influence of risk factors on the odds of having a prescription of oral budesonide and the odds of having a second course of budesonide was studied.

    Results: Patients with MC (n = 183) with a mean age of 62.3 years [standard deviation (SD): 13.3 years] were followed for a median of 5 years (25th–75th percentile 4–10 years) after diagnosis. In all, 138 patients (75%) had at least one prescription of budesonide after diagnosis, and 90 patients (49%) had at least one clinical relapse treated with budesonide. Patients who had been prescribed NSAIDs within 1 year before clinical relapse had higher odds for clinical relapse [odds ratio (OR): 3.70, 95% confidence interval (CI): 1.06–12.9] but there was no increased risk for clinical relapse for the use of ASA (OR: 0.99, 95% CI: 0.39–2.90), PPIs (OR: 1.09, 95% CI: 0.45–2.63), SSRI (OR: 1.41, 95% CI: 0.82–2.44), or statins (OR: 0.83, 95% CI: 0.35–1.99). No association was seen between being a smoker and/or being prescribed NSAID, ASA, PPI, SSRI, and statins at baseline and the odds of having a prescription of oral budesonide within 1 year after diagnosis.

    Conclusion: The risk of being prescribed a second course of budesonide is associated with receiving a prescription of NSAIDs but not with the use of ASA, PPIs, SSRIs, and statins.

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  • 32.
    Björmsjö, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Hernell, Olle
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Lönnerdal, Bo
    Department of Nutrition, University of California, Davis, CA.
    Berglund, Staffan
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Immunological Effects of Adding Bovine Lactoferrin and Reducing Iron in Infant Formula: A Randomized Controlled Trial2022In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 74, no 3, p. e65-e72Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Compared to formula-fed infants, breastfed infants have a lower risk of infections. Two possible reasons for this are the presence of the anti-infective and anti-inflammatory protein lactoferrin and the lower level of iron in breast milk. We explored how adding bovine lactoferrin and reducing the iron concentration in infant formula affect immunology and risk of infections in healthy infants.

    METHODS: In a double-blind controlled trial, term formula-fed (FF) Swedish infants (n = 180) were randomized to receive, from 6 weeks to 6 months of age, a low-iron formula (2 mg/L) with added bovine lactoferrin (1.0 g/L) (Lf+; n = 72); low-iron formula with no added lactoferrin (Lf-; n = 72); and standard formula at 8 mg/L iron and no added lactoferrin (control formula [CF]; n = 36). Cytokines, infections, and infection related treatments were assessed until 12 months of age.

    RESULTS: No adverse effects were observed. There were no apparent effects on transforming growth factor beta (TGF-β)1, TGF-β2, tumor necrosis factor alfa (TNF-α) or interleukin2 (IL-2) at 4, 6, or 12 months, except of higher TGF-β2 at 6 months in the CF group in comparison to the low iron groups combined (P = 0.033). No significant differences in otitis, respiratory infections, gastroenteritis, or other monitored infections and treatments were detected for any of the study feeding groups during the first 6 months and only a few and diverging effects were observed between 6 and 12 months.

    CONCLUSIONS: Adding bovine lactoferrin and reducing iron from 8 to 2 mg/L in infant formula was safe. No clinically relevant effects on cytokines or infection related morbidity were observed in this well-nourished and healthy population.

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  • 33.
    Bodecker-Zingmark, L.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Widbom, Lovisa
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Eriksson, Catharina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Anti-Saccharomyces Cerevisiae antibodies are only modestly more common in subjects later developing Crohn's disease2023In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 68, p. 608-615Article in journal (Refereed)
    Abstract [en]

    Background: The pathogenic processes in the preclinical phase of inflammatory bowel disease (IBD) are mainly unknown.

    Aims: To study typical antibodies for IBD in the preclinical phase in a cohort of Northern Sweden.

    Methods: Antibodies typical for IBD (ASCA, pANCA, lactoferrin-ANCA, antibodies to goblet cells, and pancreas antigen) were analyzed in 123 subjects with preclinical ulcerative colitis (UC), 54 subjects with preclinical Crohn's disease (CD) and in 390 sex- and age-matched controls. In addition, in a subset of subjects, inflammatory markers (CRP, albumin, calprotectin and ferritin) were measured in plasma.

    Results: The mean years between blood samples and IBD diagnosis were for UC 5.1 (SD 3.5) years and CD 5.6 (SD 3.5) years. There was no difference in the proportion of overall positive antibodies between subjects who later developed IBD compared to controls (16.9% vs. 12.3%; p = 0.137). The subjects who later developed CD had a significantly higher proportion of positive ASCA compared to controls (9.3% vs 2.8%; p = 0.034), but for all other antibodies, there were no differences compared to control subjects. Subjects with preclinical IBD and elevated antibodies showed significantly higher plasma calprotectin levels compared to subjects without antibodies (980 μg/L vs 756 μg/L; p = 0.042), but there was no difference in the levels of CRP, albumin and ferritin.

    Conclusions: We found no significant increase in antibodies typical for IBD years before diagnosis except for ASCA, which was slightly more common in subjects who later developed CD. Very few subjects had detectable antibodies to goblet cells and pancreas antigen.

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  • 34.
    Boks, Marije
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Lilja, Mikael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Widerström, Micael
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Lindam, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Eriksson, Axel
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Sjöström, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Increased incidence of late-onset inflammatory bowel disease and microscopic colitis after a Cryptosporidium hominis outbreak2022In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 57, no 12, p. 1443-1449Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: In 2010, 27,000 inhabitants (45% of the population) of Östersund, Sweden, contracted clinical cryptosporidiosis after drinking water contaminated with Cryptosporidium hominis. After the outbreak, local physicians perceived that the incidence of inflammatory bowel disease (IBD), including ulcerative colitis (UC), Crohn's disease (CD), and IBD-unclassified, and microscopic colitis (MC) increased. This study assessed whether this perception was correct.

    MATERIALS AND METHODS: This observational study included adult patients (≥18 years old) from the local health care region who were diagnosed with pathology-confirmed IBD or MC during 2006-2019. We collected and validated the diagnosis, date of diagnosis, age at diagnosis, and sex from the Swedish quality register SWIBREG and electronic patient records. Population data were collected from Statistics Sweden. The incidences for 2006-2010 (pre-outbreak) and 2011-2019 (post-outbreak) were evaluated by negative binomial regression analysis and presented as incidence rate ratios (IRRs). Data were analyzed for IBD, for UC and CD separately, and MC.

    RESULTS: During the study period, we identified 410 patients with new onset IBD and 155 new cases of MC. Overall, we found a trend toward an increased incidence of IBD post-outbreak (IRR 1.39, confidence interval (CI) 0.99-1.94). In individuals ≥40 years old, the post-outbreak incidence significantly increased for IBD (IRR 1.69, CI 1.13-2.51) and CD (IRR 2.23, CI 1.08-4.62). Post-outbreak incidence of MC increased 6-fold in all age groups (IRR 6.43, CI 2.78-14.87).

    CONCLUSIONS: The incidence of late-onset IBD and MC increased after the Cryptosporidium outbreak. Cryptosporidiosis may be an environmental risk factor for IBD and MC.

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  • 35.
    Boman, Erika
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Nylander, Malin
    Oja, Josefine
    Olofsson, Birgitta
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Transanal Irrigation for People With Neurogenic Bowel Dysfunction: An Integrative Literature Review2022In: Gastroenterology Nursing, ISSN 1042-895X, E-ISSN 1538-9766, Vol. 45, no 4, p. 211-230Article, review/survey (Refereed)
    Abstract [en]

    Transanal irrigation has been introduced as a complement to standard bowel care for people with neurogenic bowel dysfunction. There is no contemporary integrative review of the effectiveness and feasibility of transanal irrigation from a holistic nursing perspective, only fragments of evidence to date. The aim was to investigate the effectiveness and feasibility of transanal irrigation for people with neurogenic bowel dysfunction. An integrative literature review was conducted. Nineteen studies were included. According to the results, transanal irrigation can reduce difficulties associated with defecation, episodes of incontinence, and the time needed for evacuation and bowel care. Transanal irrigation can increase general satisfaction with bowel habits and quality of life and decrease level of dependency. However, there are practical problems to overcome and adverse effects to manage. Discontinuation is relatively common. The results support the effectiveness of transanal irrigation, but feasibility is inconclusive. Users, including caregivers, report practical problems, and compliance was not always easy to achieve. It is important that users, including caregivers, are well informed and supported during transanal irrigation treatment, especially during introduction. The quality of the studies found was generally weak; therefore, high-quality quantitative and qualitative studies are needed on the topic.

  • 36. 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.

  • 37.
    Borgmästars, Emmy
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lundberg, Erik
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Öhlund, Daniel
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nyström, Hanna
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Franklin, Oskar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lundin, Christina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Jonsson, Pär
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Circulating tissue polypeptide-specific antigen in pre-diagnostic pancreatic cancer samples2021In: Cancers, ISSN 2072-6694, Vol. 13, no 21, article id 5321Article in journal (Refereed)
    Abstract [en]

    Early detection of pancreatic ductal adenocarcinoma (PDAC) is challenging, and late diagnosis partly explains the low 5-year survival. Novel and sensitive biomarkers are needed to enable early PDAC detection and improve patient outcomes. Tissue polypeptide specific antigen (TPS) has been studied as a biomarker in PDAC diagnostics, and it has previously been shown to reflect clinical status better than the ‘golden standard’ biomarker carbohydrate antigen 19-9 (CA 19-9) that is most widely used in the clinical setting. In this cross-sectional case-control study using pre-diagnostic plasma samples, we aim to evaluate the potential of TPS as a biomarker for early PDAC detection. Furthermore, in a subset of individuals with multiple samples available at different time points before diagnosis, a longitudinal analysis was used. We assessed plasma TPS levels using enzyme-linked immunosorbent assay (ELISA) in 267 pre-diagnostic PDAC plasma samples taken up to 18.8 years before clinical PDAC diagnosis and in 320 matched healthy controls. TPS levels were also assessed in 25 samples at PDAC diagnosis. Circulating TPS levels were low both in pre-diagnostic samples of future PDAC patients and in healthy controls, whereas TPS levels at PDAC diagnosis were significantly increased (odds ratio 1.03; 95% confidence interval: 1.01–1.05) in a logistic regression model adjusted for age. In conclusion, TPS levels increase late in PDAC progression and hold no potential as a biomarker for early detection.

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  • 38.
    Botteri, Edoardo
    et al.
    Section for Colorectal Cancer Screening, Cancer Registry of Norway, Oslo, Norway; Department of Research, Cancer Registry of Norway, Oslo, Norway.
    Peveri, Giulia
    Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Berstad, Paula
    Section for Colorectal Cancer Screening, Cancer Registry of Norway, Oslo, Norway.
    Bagnardi, Vincenzo
    Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy.
    Chen, Sairah L.F.
    Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
    Sandanger, Torkjel M.
    Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
    Hoff, Geir
    Section for Colorectal Cancer Screening, Cancer Registry of Norway, Oslo, Norway; Department of Research, Telemark Hospital, Skien, Norway.
    Dahm, Christina C.
    Department of Public Health, Aarhus University, Denmark.
    Antoniussen, Christian S.
    Department of Public Health, Aarhus University, Denmark.
    Tjønneland, Anne
    Danish Cancer Society Research Center, Copenhagen, Denmark.
    Eriksen, Anne Kirstine
    Danish Cancer Society Research Center, Copenhagen, Denmark.
    Skeie, Guri
    Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
    Perez-Cornago, Aurora
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Huerta, José María
    Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
    Jakszyn, Paula
    Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
    Harlid, Sophia
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sundström, Björn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Barricarte, Aurelio
    CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Navarra Public Health Institute, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
    Monninkhof, Evelyn M.
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
    Derksen, Jeroen W.G.
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
    Schulze, Matthias B.
    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
    Bueno-De-Mesquita, Bas
    Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.
    Sánchez, Maria-Jose
    CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain.
    Cross, Amanda J.
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Tsilidis, Konstantinos K.
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Department of Hygiene and Epidemiology, University of Ioannina, School of Medicine, Ioannina, Greece.
    De Magistris, Maria Santucci
    Azienda Ospedaliera Universitaria Federico II di Napoli, Napoli, Italy.
    Kaaks, Rudolf
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Katzke, Verena
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Rothwell, Joseph A.
    Université Paris-Saclay, UVSQ, Inserm, CESP U1018, 'Exposome, Heredity, Cancer and Health' Team, Gustave Roussy, Villejuif, France.
    Laouali, Nasser
    Université Paris-Saclay, UVSQ, Inserm, CESP U1018, 'Exposome, Heredity, Cancer and Health' Team, Gustave Roussy, Villejuif, France.
    Severi, Gianluca
    Université Paris-Saclay, UVSQ, Inserm, CESP U1018, 'Exposome, Heredity, Cancer and Health' Team, Gustave Roussy, Villejuif, France; Department of Statistics, Computer Science, Applications 'G. Parenti' (DISIA), University of Florence, Florence, Italy.
    Amiano, Pilar
    Ministry of Health of the Basque Government, Sub Directorate for Public Health and Addictions of Gipuzkoa, San Sebastian, Spain; Biodonostia Health Research Institute, Epidemiology of Chronic and Communicable Diseases Group, San Sebastián, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain.
    Contiero, Paolo
    Environmental Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
    Sacerdote, Carlotta
    Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital, Turin, Italy.
    Goldberg, Marcel
    Population-based Epidemiologic Cohorts Unit, Inserrm UMS 11, Villejuif, France.
    Touvier, Mathilde
    Nutritional Epidemiology Research Team (EREN), Sorbonne Paris Nord University, Inserm U1153, Inrae U1125, Cnam, Epidemiology and Statistics Research Center - University of Paris (CRESS), Bobigny, France; Public Health Department, Avicenne Hospital, AP-HP, Bobigny, France.
    Freisling, Heinz
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Viallon, Vivian
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Weiderpass, Elisabete
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Riboli, Elio
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Gunter, Marc J.
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Jenab, Mazda
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Ferrari, Pietro
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Changes in lifestyle and risk of colorectal cancer in the european prospective investigation into cancer and nutrition2023In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 118, no 4, p. 702-711Article in journal (Refereed)
    Abstract [en]

    Introduction: We investigated the impact of changes in lifestyle habits on colorectal cancer (CRC) risk in a multicountry European cohort.

    Methods: We used baseline and follow-up questionnaire data from the European Prospective Investigation into Cancer cohort to assess changes in lifestyle habits and their associations with CRC development. We calculated a healthy lifestyle index (HLI) score based on smoking status, alcohol consumption, body mass index, and physical activity collected at the 2 time points. HLI ranged from 0 (most unfavorable) to 16 (most favorable). We estimated the association between HLI changes and CRC risk using Cox regression models and reported hazard ratios (HR) with 95% confidence intervals (CI).

    Results: Among 295,865 participants, 2,799 CRC cases were observed over a median of 7.8 years. The median time between questionnaires was 5.7 years. Each unit increase in HLI from the baseline to the follow-up assessment was associated with a statistically significant 3% lower CRC risk. Among participants in the top tertile at baseline (HLI > 11), those in the bottom tertile at follow-up (HLI ≤ 9) had a higher CRC risk (HR 1.34; 95% CI 1.02-1.75) than those remaining in the top tertile. Among individuals in the bottom tertile at baseline, those in the top tertile at follow-up had a lower risk (HR 0.77; 95% CI 0.59-1.00) than those remaining in the bottom tertile.

    Discussion: Improving adherence to a healthy lifestyle was inversely associated with CRC risk, while worsening adherence was positively associated with CRC risk. These results justify and support recommendations for healthy lifestyle changes and healthy lifestyle maintenance for CRC prevention.

  • 39.
    Boyanov, Nikola
    et al.
    Medical Simulation Training Center at Research Institute of Medical University of Plovdiv, Plovdiv, Bulgaria.
    Georgiou, Konstantinos
    1st Department of Propaedeutic Surgery, Hippokration General Hospital of Athens, Athens Medical School, National and Kapodistrian University of Athens, Athens, Greece.
    Thanasas, Dimitrios
    Medical Physics Laboratory Simulation Center, Athens Medical School, National and Kapodistrian University of Athens, Athens, Greece.
    Deneva, Tanya
    Central Clinical Laboratory, University Hospital St. George, Plovdiv, Bulgaria; Department of Clinical Laboratory, Medical University of Plovdiv, Plovdiv, Bulgaria.
    Oussi, Ninos
    Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden; Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden.
    Marinov, Blagoi
    Medical Simulation Training Center at Research Institute of Medical University of Plovdiv, Plovdiv, Bulgaria.
    Enochsson, Lars
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Use of saliva stress biomarkers to estimate novice male endoscopist’s stress during training in a high-end simulator2021In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 56, no 11, p. 1380-1385Article in journal (Refereed)
    Abstract [en]

    Objective: Simulated endoscopic training can be challenging and stressful for the novice trainee. The absence of a reliable stress detection method during simulated endoscopic training makes estimating trainees’ mental stress difficult to quantify. This study concomitantly measures the responses of four saliva stress biomarkers and compares them to the video score (VS) achieved by novice endoscopists in a reproducibly stressful simulation environment.

    Methods: Thirty-six male endoscopy naïve surgery residents were enrolled. After an orientation phase, a saliva specimen was collected for cortisol (sC), alpha-amylase (sAA), Chromogranin A (sCgA), and immunoglobulin A (sIgA) measurements (baseline phase, BL). Thereafter, the simulation exercise phase (E) started, practicing in the Fundamentals of Endoscopic Surgery Skills module (GI-Bronch Mentor). Immediately after, a second saliva sample for measuring the above-cited biomarkers was collected. The whole experiment was videotaped, and the VS was calculated. The percentage (E-BL)diff of each of the four saliva biomarkers was calculated and examined for correlation to VS.

    Results: sCgAdiff showed the best correlation with VS, followed by sAAdiff.

    Conclusions: sCgA and sAA, are saliva stress biomarkers that are easy to collect non-invasively and showed the best correlation with novice endoscopist’s performance in our simulation setting, and therefore, they could be used for monitoring stress.

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  • 40. Bronsky, Jiri
    et al.
    Campoy, Cristina
    Embleton, Nicholas
    Fewtrell, Mary
    Mis, Nataša Fidler
    Gerasimidis, Konstantinos
    Hojsak, Iva
    Hulst, Jessie
    Indrio, Flavia
    Lapillonne, Alexandre
    Molgaard, Christian
    Moltu, Sissel Jennifer
    Verduci, Elvira
    Vora, Rakesh
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Palm Oil and Beta-palmitate in Infant Formula: A Position Paper by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) Committee on Nutrition2019In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 68, no 5, p. 742-760Article in journal (Refereed)
    Abstract [en]

    Background: Palm oil (PO) is used in infant formulas in order to achieve palmitic acid (PA) levels similar to those in human milk. PA in PO is esterified predominantly at the SN-1,3 position of triacylglycerol (TAG), and infant formulas are now available in which a greater proportion of PA is in the SN-2 position (typical configuration in human milk). As there are some concerns about the use of PO, we aimed to review literature on health effects of PO and SN-2-palmitate in infant formulas. Methods: PubMed and Cochrane Database of Systematic Reviews were systematically searched for relevant studies on possible beneficial effects or harms of either PO or SN-2-palmitate in infant formula on various health outcomes. Results: We identified 12 relevant studies using PO and 21 studies using SN-2-palmitate. Published studies have variable methodology, subject characteristics, and some are underpowered for the key outcomes. PO is associated with harder stools and SN-2-palmitate use may lead to softer stool consistency. Bone effects seem to be short-lasting. For some outcomes (infant colic, faecal microbiota, lipid metabolism), the number of studies is very limited and summary evidence inconclusive. Growth of infants is not influenced. There are no studies published on the effect on markers of later diseases. Conclusions: There is insufficient evidence to suggest that PO should be avoided as a source of fat in infant formulas for health reasons. Inclusion of high SN-2-palmitate fat blend in infant formulas may have short-term effects on stool consistency but cannot be considered essential.

  • 41. Bronsky, Jiri
    et al.
    Campoy, Cristina
    Embleton, Nicholas
    Fewtrell, Mary
    Mis, Nataša Fidler
    Gerasimidis, Konstantinos
    Hojsak, Iva
    Hulst, Jessie
    Indrio, Flavia
    Lapillonne, Alexandre
    Molgaard, Christian
    Moltu, Sissel Jennifer
    Verduci, Elvira
    Vora, Rakesh
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Response to Letter to the Editor: Palm Oil and Beta-Palmitate in Infant Formula2020In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 70, no 3, p. E64-E64Article in journal (Refereed)
  • 42. 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).

  • 43.
    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.

  • 44.
    Brännström, Lisa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Wallner, Bengt
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Karling, Pontus
    What is the significance of the Hill classification?2023In: Diseases of the esophagus, ISSN 1120-8694, E-ISSN 1442-2050, Vol. 36, no 9, article id doad004Article in journal (Refereed)
    Abstract [en]

    This study aimed to investigate the significance of Hill classification to predict esophagitis, Barrett's esophagus, gastroesophageal reflux disease (GERD) symptomatology, and future prescriptions of proton pump inhibitors in clinical practice. A total of 922 patients (546 women and 376 men; mean age 54.3 [SD 18.4] years) who underwent gastroscopy between 2012 and 2015 were analyzed. Patient questionnaire regarding symptoms were compared with endoscopy findings. A medical chart review was done that focused on the prescription of PPIs, additional gastroscopies, and GERD surgery in a 3-year period before the index gastroscopy and in a 6-year period afterward. In patients naïve to PPI prescriptions (n = 466), Hill grade III was significantly associated with esophagitis (AOR 2.20; 95% CI 1.00-4.84) and > 2 PPI prescriptions 6 year after the index gastroscopy (AOR 1.95; 95% CI 1.01-3.75), whereas Hill grade IV was significantly associated with esophagitis (AOR 4.41; 95% CI 1.92-10.1), with Barrett's esophagus (AOR 12.7; 95% CI 1.45-112), with reported heartburn (AOR 2.28; 95% CI 1.10-4.74), and with >2 PPI prescriptions (AOR 2.16; 95% CI 1.02-4.55). In patients 'non-naïve' to PPI prescription (n = 556), only Hill grade IV was significantly associated with esophagitis, reported heartburn, and with >2 PPI prescriptions. The gastroscopic classification in Hill grades III and IV is important in clinical practice because they are associated with esophagitis, Barrett's esophagus, symptoms of GERD, and prescriptions of PPIs, whereas a differentiation between Hill grades I and II is not.

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  • 45.
    Butt, Julia
    et al.
    Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Jenab, Mazda
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Werner, Jill
    Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Fedirko, Veronika
    Department of Public Health, Aarhus University, Aarhus, Denmark.
    Weiderpass, Elisabete
    Department of Epidemiology, Rollins School of Public Health, Emory University, GA, Atlanta, United States.
    Dahm, Christina C.
    Department of Public Health, Aarhus University, Aarhus, Denmark.
    Tjønneland, Anne
    Exposome and Heredity Team, CESP (Centre de Recherche en Epidemiologie et Santé des Populations), Danish Cancer Society Research Center, Diet, Genes and Environment, Nutrition and Biomarkers (NAB), Copenhagen, Denmark; Department of Public Health, University of Copenhagen, Denmark.
    Olsen, Anja
    Exposome and Heredity Team, CESP (Centre de Recherche en Epidemiologie et Santé des Populations), Danish Cancer Society Research Center, Diet, Genes and Environment, Nutrition and Biomarkers (NAB), Copenhagen, Denmark; Department of Public Health, University of Aarhus, Denmark.
    Boutron-Ruault, Marie-Christine
    Cesp (Umr1018), Médecine Université Paris-Saclay, Inserm, Gustave Roussy, Villejuif, France.
    Rothwell, Joseph A.
    Cesp (Umr1018), Médecine Université Paris-Saclay, Inserm, Gustave Roussy, Villejuif, France.
    Severi, Gianluca
    Cesp (Umr1018), Médecine Université Paris-Saclay, Inserm, Gustave Roussy, Villejuif, France; Department of Statistics, Computer Science and Applications (DISIA), University of Florence, Italy.
    Kaaks, Rudolf
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Turzanski-Fortner, Renée
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Aleksandrova, Krasimira
    Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany.
    Schulze, Matthias
    Department of Molecular Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
    Palli, Domenico
    Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy.
    Pala, Valeria
    Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy.
    Panico, Salvatore
    Dipartimento Di Medicina Clinica E Chirurgia, Federico II University, Naples, Italy.
    Tumino, Rosario
    Cancer Registry and Histopathology Department, Provincial Health Authority (ASP 7), Ragusa, Italy.
    Sacerdote, Carlotta
    Unit of Cancer Epidemiology, Città Della Salute E Della, Scienza University-Hospital, Turin, Italy.
    Bueno-de-Mesquita, Bas
    Former Senior Scientist, Dept. For Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands; Former Associate Professor, Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, Netherlands; Dept. Of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom; Dept. Of Social Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
    Van Gils, Carla H.
    Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, Netherlands.
    Gram, Inger Torhild
    Department of Community Medicine, University of Tromsø, Arctic University of Norway, Tromsø, Norway.
    Lukic, Marko
    Department of Community Medicine, UiT, The Arctic University of Norway, Tromsø, Norway.
    Sala, Núria
    Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program and Translational Research Laboratory, Catalan Institute of Oncology (ICO), Biomedical Research Institute (IDIBELL), Barcelona, Spain.
    Sánchez Pérez, María José
    Escuela Andaluza De Salud Pública (EASP), Granada, Spain; Instituto De Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Centro De Investigación Biomédica En Red De Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain; Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain.
    Ardanaz, Eva
    Navarra Public Health Institute, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain; CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain.
    Chirlaque, María-Dolores
    Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain; CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Löwenmark, Thyra
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Travis, Ruth C.
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Heath, Alicia
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Cross, Amanda J.
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Cancer Biology and Therapeutics Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland.
    Freisling, Heinz
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Zouiouich, Semi
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Aglago, Elom
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Waterboer, Tim
    Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Hughes, David J.
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Association of Pre-diagnostic Antibody Responses to Escherichia coli and Bacteroides fragilis Toxin Proteins with Colorectal Cancer in a European Cohort2021In: Gut microbes, ISSN 1949-0976, E-ISSN 1949-0984, Vol. 13, no 1, p. e1903825-1-e1903825-14, article id e1903825Article in journal (Refereed)
    Abstract [en]

    Experimental evidence has implicated genotoxic Escherichia coli (E. coli) and enterotoxigenic Bacteroides fragilis (ETBF) in the development of colorectal cancer (CRC). However, evidence from epidemiological studies is sparse. We therefore assessed the association of serological markers of E. coli and ETBF exposure with odds of developing CRC in the European Prospective Investigation into Nutrition and Cancer (EPIC) study. Serum samples of incident CRC cases and matched controls (n = 442 pairs) were analyzed for immunoglobulin (Ig) A and G antibody responses to seven E. coli proteins and two isoforms of the ETBF toxin via multiplex serology. Multivariable-adjusted conditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of sero-positivity to E. coli and ETBF with CRC. The IgA-positivity of any of the tested E. coli antigens was associated with higher odds of developing CRC (OR: 1.42; 95% CI: 1.05–1.91). Dual-positivity for both IgA and IgG to E. coli and ETBF was associated with >1.7-fold higher odds of developing CRC, with a significant association only for IgG (OR: 1.75; 95% CI: 1.04, 2.94). This association was more pronounced when restricted to the proximal colon cancers (OR: 2.62; 95% CI: 1.09, 6.29) compared to those of the distal colon (OR: 1.24; 95% CI: 0.51, 3.00) (pheterogeneity = 0.095). Sero-positivity to E. coli and ETBF was associated with CRC development, suggesting that co-infection of these bacterial species may contribute to colorectal carcinogenesis. These findings warrant further exploration in larger prospective studies and within different population groups.

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  • 46.
    Byenfeldt, Marie
    Umeå University, Faculty of Medicine, Department of Nursing.
    Influence of postural changes on shear wave elastography of the liverManuscript (preprint) (Other academic)
  • 47.
    Byenfeldt, Marie
    Umeå University, Faculty of Medicine, Department of Nursing.
    Sex-based differences in shear wave elastography of the liverManuscript (preprint) (Other academic)
  • 48.
    Byenfeldt, Marie
    Umeå University, Faculty of Medicine, Department of Nursing.
    Ultrasound based shear wave elastography of the liver: a non-invasive method for evaluation of liver disease2020Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Detecting liver disease at an early stage is important, given that early intervention decreases the risk of developing cirrhosis and subsequently hepatocellular cancer (HCC). The non-invasive ultrasound-based shear wave elastography (SWE) has been used clinically for a decade to assess liver stiffness. This method is reliable, rapid and can be performed in an outpatient setting without known risks for the patient. However, increased variance in SWE results has been detected, without clear explanation. Factors that affect SWE results needs to be identified. Data are insufficient regarding the reliability of SWE with different body positions and probe pressures. Men have higher SWE results than women, also for unclear reasons. Increasing the reliability of SWE is crucial for understanding how factors such as overweight and obesity, cardiovascular and antiviral medication, age, sex, smoking habits, hepatic steatosis and cirrhosis affect SWE results.

    Aims: The overall aim of the studies included in this thesis was to increase the reliability of SWE liver. The specific aims were to investigate patient-related factors associated with increased uncertainty in SWE results. Another aim was to investigate the influence of increased intercostal probe pressure on liver stiffness assessment with SWE liver.  The final aims were to investigate the influence of postural changes, sagittal abdominal diameter (SAD) and skin-to-liver capsule distance (SCD) on SWE results, along with sex-based differences for SWE results and cardiovascular medication.

    Methods: All enrolled participants in these studies were consecutive patients with various liver diseases presenting at the radiology department Östersunds Hospital. The patients were examined using SWE liver method at the ultrasound unit between April 2014 and May 2018. Inclusion criteria were that participants be adults (age ≥18 years) who had provided written consent for participating in the study. The exclusion criterion was an inability to communicate. Current guidelines for SWE of the liver were used in the thesis with the following exceptions: In study II, increased intercostal probe pressure was used, and in study III, postural change was used. Study I included 188 patients; study II included 112 patients, and studies III and IV involved 200 patients. The four studies were conducted as cross-sectional and clinical trial, using quantitative methods.

    Results: Factors associated with low variance for SWE results were age, sex, and presence of cirrhosis, the use of antiviral and/or cardiovascular medication, smoking habits, and body mass index.  Factors associated with increased uncertainty in SWE results were increased SCD and the presence of steatosis. With increased probe pressure SCD decreased and the quality of shear wave increased. The results showed that the number of required measurements can be reduced. A postural change to left decubitus decreased SCD. For patients with increased SAD and increased SWE result in the supine position, SWE result decreased with a postural change to left decubitus.  The SWE results, SCD and SAD significantly differed between women and men. SWE results was higher in the presence of increased SAD (≥23 cm) among men, but not among women.

    Conclusions:  SWE of the liver is a reliable, non-invasive method for diagnosing liver disease. Results in this thesis suggest that for patients with SCD ≥2.5 cm, shear wave measures could be of poor quality and the SWE exam less reliable. In these cases, increased probe pressure may facilitate a reliable SWE exam. With such adjustments in probe pressure, the ultrasound-based SWE method can be superior for examination in patients with overweight or obesity. An effect of SAD ≥23 cm was seen for men with liver fibrosis only, which may explain the higher SWE result for men compared to women. Depending on the severity of liver disease and SAD, a postural change to left decubitus can produce a different outcome. As SAD increased, liver stiffness did, as well. Increased SAD thus is linked to increased liver stiffness, indicating that SAD should be taken into account when performing SWE of the liver.

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  • 49. Bzioueche, Hanene
    et al.
    Sjödin, Kotryna Simonyte
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Khemis, Abdallah
    Rocchi, Stéphane
    Passeron, Thierry
    Tulic, Meri K.
    Analysis of Matched Skin and Gut Microbiome of Patients with Vitiligo Reveals Deep Skin Dysbiosis: Link with Mitochondrial and Immune Changes2021In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 141, no 9, p. 2280-2290Article in journal (Refereed)
    Abstract [en]

    Vitiligo is an autoimmune disease characterized by patchy, white skin owing to melanocyte loss. Commensal cutaneous or gut dysbiosis has been linked to various dermatological disorders. In this study, we studied the skin and gut microbiota of patients with vitiligo compared with those of healthy controls. We obtained swabs and biopsies from both lesional and nonlesional skin as well as stool and blood samples from each individual. We detected reduced richness and diversity of microbiota in the stools of subjects with vitiligo compared with the stools of the controls (P < 0.01). Skin swabs had greater α-diversity than biopsies (P < 0.001); swabs from lesional sites were primarily depleted of Staphylococcus compared with those from nonlesional sites (P < 0.02). Sampling deeper layers from the same patients showed differences in both α- and β-diversity between samples with decreased richness and distribution of species (P < 0.01) in the lesional site. Biopsy microbiota from the lesional skin had distinct microbiota composition, which was depleted of protective Bifidobacterium and Bacteroides but was enriched in Proteobacteria, Streptococcus, Mycoplasma, and mtDNA (P < 0.001); the latter increased in the same patients with heightened innate immunity and stress markers in their blood (P < 0.05). These data describe vitiligo-specific cutaneous and gut microbiota and a link between skin dysbiosis, mitochondrial damage, and immunity in patients with vitiligo.

  • 50. 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.

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