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  • 1.
    Abdalla, Maie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Suez Canal University, Egypt.
    Landerholm, Kalle
    Ryhov County Hospital, Sweden.
    Andersson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Andersson, Roland
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov County Hospital, Sweden.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Risk of Rectal Cancer After Colectomy for Patients With Ulcerative Colitis: A National Cohort Study2017In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 15, no 7, p. 1055-1060, article id e2Article in journal (Refereed)
    Abstract [en]

    BACKGROUND amp; AIMS: Patients with ulcerative colitis (UC) have an increased risk of rectal cancer, therefore reconstruction with an ileal pouch-anal anastomosis (IPAA) generally is preferred to an ileorectal anastomosis (IRA) after subtotal colectomy. Similarly, completion proctectomy is recommended for patients with ileostomy and a diverted rectum, although this approach has been questioned because anti-inflammatory agents might reduce cancer risk. We performed a national cohort study in Sweden to assess the risk of rectal cancer in patients with UC who have an IRA, IPAA, or diverted rectum after subtotal colectomy.

    METHODS: We collected data from the Swedish National Patient Register for a cohort of 5886 patients with UC who underwent subtotal colectomy with an IRA, IPAA, or diverted rectum from 1964 through 2010. Patients who developed rectal cancer were identified from the Swedish National Cancer Register. The risk of rectal cancer was compared between this cohort and the general population by standardized incidence ratio analysis.

    RESULTS: Rectal cancer occurred in 20 of 1112 patients (1.8%) who received IRA, 1 of 1796 patients (0.06%) who received an IPAA, and 25 of 4358 patients (0.6%) with a diverted rectum. Standardized incidence ratios for rectal cancer were 8.7 in patients with an IRA, 0.4 in patients with an IPAA, and 3.8 in patients with a diverted rectum. Risk factors for rectal cancer were primary sclerosing cholangitis in patients with an IRA (hazard ratio, 6.12), and colonic severe dysplasia or cancer before subtotal colectomy in patients with a diverted rectum (hazard ratio, 3.67).

    CONCLUSIONS: In an analysis of the Swedish National Patient Register, we found that the risk for rectal cancer after colectomy in patients with UC is low, in relative and absolute terms, after reconstruction with an IPAA. An IRA and diverted rectum are associated with an increased risk of rectal cancer, compared with the general population, but the absolute risk is low. Patients and their health care providers should consider these findings in making decisions to leave the rectum intact, perform completion proctectomy, or reconstruct the colon with an IRA or IPAA.

  • 2.
    Abdelrahman, Islam
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Mossaad, Bassem
    Plastic Surgery Unit, Surgery Department Suez, Canal University, Ismailia, Egypt.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Elmasry, Moustafa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Evaluation of Glandular Liposculpture as a Single Treatment for Grades I and II Gynaecomastia2018In: Aesthetic Plastic Surgery, ISSN 0364-216X, E-ISSN 1432-5241, p. 1-9Article in journal (Refereed)
    Abstract [en]

    Background

    Gynaecomastia is a benign enlargement of the male breast, of which the psychological burden on the patient can be considerable, with the increased risk of disorders such as depression, anxiety, and social phobia. Minimal scarring can be achieved by liposuction alone, though it is known to have a limited effect on the dense glandular and fibroconnective tissues. We know of few studies published on “liposuction alone”, so we designed this study to evaluate the outcome of combining liposuction with glandular liposculpturing through two axillary incisions as a single treatment for the management of grades I and II gynaecomastia.

    Methods

    We made a retrospective analysis of 18 patients with grade I or II gynaecomastia who were operated on by combined liposuction and glandular liposculpturing using a fat disruptor cannula, without glandular excision, during the period 2014–2016. Patient satisfaction was assessed using the Breast Evaluation Questionnaire (BEQ), which is a 5-point Likert scale (1 = very dissatisfied; 2 = dissatisfied; 3 = neither; 4 = satisfied; 5 = very satisfied). The post-operative aesthetic appearance of the chest was evaluated by five independent observers on a scale from 1 to 5 (5 = considerable improvement).

    Results

    The patient mean (SD) overall satisfaction score was 4.7 (0.7), in which 92% of the responders were “satisfied” to “very satisfied”. The mean (SD) BEQ for all questions answered increased from 2.1 (0.2) “dissatisfied” preoperatively to 4.1 (0.2) “satisfied” post-operatively. The observers’ mean (SD) rate for the improvement in the shape of the front chest wall was 4.1 (0.7). No haematomas were recorded, one patient developed a wound infection, and two patients complained of remnants of tissue. The median (IQR) body mass index was 27.4 (26.7–29.4), 11 patients had gynaecomastia grade I, and 7 patients grade II. The median (IQR) volume of aspirated fat was 700 ml (650–800), operating time was 67 (65–75) minutes, 14 patients had general anaesthesia, and hospital charges were US$ 538 (481–594).

    Conclusions

    Combined liposuction and liposculpturing using the fat disruptor cannula resulted in satisfied patients and acceptable outcomes according to the observers’ ratings. It could be a useful alternative with an outcome that corresponds to that of more expensive methods.

  • 3.
    Aljabery, Firas
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Staging and tumor biological mechanisms of lymph node metastasis in invasive urinary bladder cancer2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Aim: To study the possibility of detecting lymph node metastasis in locally advanced urinary bladder cancer (UBC) treated with radical cystectomy (RC) by using preoperative positron emission tomography/computed tomography (PET/CT) and peroperative sentinel node biopsy (SNB) technique. We also investigate the clinical significance of macrophage traits expression by cancer cells, M2-macrophage infiltration (MI) in tumor stroma and the immunohistochemical expression of biomarkers in cancer cells in relation to clinicopathologic data.

    Patients and Methods: We studied prospectively 122 patients with UBC, pathological stage pT1–pT4 treated with RC and pelvic lymph node dissection (PLND) during 2005–2011 at the Department of Urology, Linköping University Hospital. In the first study, we compared the results of preoperative PET/CT and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes (LNs). In the second study we investigated the value of SNB technique for detecting pathological LNs during RC in patients with UBC. W also examined the significance of the primary tumor location in the bladder in predicting the site of LN metastases, and the prognostic significance of lympho-vascular invasion (LVI) and lymph node metastasis density (LNMD) on survival. In the third study, we investigate the clinical significance of macrophage infiltration (MI) in tumor stroma and macrophage-traits expression by tumor cells. In the fourth study, we investigate the cell cycle suppression proteins p53, p21, pRb, p16, p14 ARF as well as tumors proliferative protein Ki67 and DNA repair protein ERCC1 expression in cancer cells. The results were compared with clinical and pathological characteristics and outcome.

    Results: Prior to RC, PET/CT was used to detect LN metastasis in 54 patients. PET/CT had 41% sensitivity, 86% specificity, 58% PPV, and 76% NPV, whereas the corresponding figures for conventional CT were 41%, 89%, 64%, and 77%. SNB was performed during RC in 103 patients. A median number of 29 (range 7–68) nodes per patient were examined. SNs were detected in 83 out of 103 patients (81%). The sensitivity and specificity for detecting metastatic disease by SNB varied among LN stations, with average values of 67% -90%. LNMD or ≥8% and LVI were significantly related to shorter survival. In 103 patients, MI was high in 33% of cases, while moderate and low infiltration occurred in 42% and 25% of tumors respectively. Patients with tumors containing high and moderate compared to low MI had low rate of LN metastases (P=0.06) and improved survival (P=0.06), although not at significant level. The expression of different tumor suppression proteins was altered in 47-91% of the patients. There were no significant association between cancer specific survival (CSS) and any of the studied biomarkers. In case of altered p14ARF, ERCC1 or p21, CSS was low in case of low p53 immunostaining but increased in case of p53 accumulation, although not at a significant level, indicating a possible protective effect of p53 accumulation in these cases.

    Conclusion: PET/ CT provided no improvement over conventional CT in detection and localization of regional LN metastases in bladder cancer. It is possible to detect the SN but the technique is not a reliable for perioperative localization of LN metastases; however, LVI and LNMD at a cut-off level of 8% had significant prognostic values. MI in the tumor microenvironment but not CD163 expression in tumor cells seems to be synergistic with the immune response against urinary bladder cancer. Our results further indicate that altered p53 might have protective effect on survival in case of altered p14ARF, p21, or ERCC1 indicating an interaction between these biomarkers.

    List of papers
    1. PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.
    Open this publication in new window or tab >>PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.
    Show others...
    2015 (English)In: BMC urology, ISSN 1471-2490, Vol. 15, no 1, p. 87-Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: We studied patients treated with radical cystectomy for locally advanced bladder cancer to compare the results of both preoperative positron emission tomography/computed tomography (PET/CT) and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes.

    METHODS: Patients who had bladder cancer and were candidates for cystectomy underwent preoperative PET/CT using 18-fluorodeoxyglucose (FDG) and conventional CT. The results regarding lymph node involvement were independently evaluated by two experienced radiologists and were subsequently compared with histopathology results, the latter of which were reassessed by an experienced uropathologist (HO).

    RESULTS: There were 54 evaluable patients (mean age 68 years, 47 [85 %] males and 7 [15 %] females) with pT and pN status as follows: < pT2-14 (26 %), pT2-10 (18 %), and > pT2-30 (56 %); pN0 37 (69 %) and pN+ 17 (31 %). PET/CT showed positive lymph nodes in 12 patients (22 %), and 7 of those cases were confirmed by histopathology; the corresponding results for conventional CT were 11 (20 %) and 7 patients (13 %), respectively. PET/CT had 41 % sensitivity, 86 % specificity, 58 % PPV, and 76 % NPV, whereas the corresponding figures for conventional CT were 41 %, 89 %, 64 %, and 77 %. Additional analyses of the right and left side of the body or in specified anatomical regions gave similar results.

    CONCLUSIONS: In this study, PET/CT and conventional CT had similar low sensitivity in detecting and localizing regional lymph node metastasis in bladder cancer.

    National Category
    Urology and Nephrology Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-120796 (URN)10.1186/s12894-015-0080-z (DOI)000359832000001 ()26294219 (PubMedID)
    Available from: 2015-08-25 Created: 2015-08-25 Last updated: 2017-05-17
    2. Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study.
    Open this publication in new window or tab >>Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study.
    Show others...
    2017 (English)In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 120, no 3, p. 329-336Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES: To investigate the possibility of detecting sentinel lymph nodes (SNs) in patients with urinary bladder cancer (BCa) intra-operatively and whether the histopathological status of the identified SNs reflected that of the lymphatic field.

    PATIENTS AND METHODS: We studied 103 patients with BCa pathological stage T1-T4 who were treated with cystectomy and pelvic lymph node (LN) dissection during 2005-2011 at the Department of Urology, Linköping University Hospital. Radioactive tracer Nanocoll 70 MBq and blue dye were injected into the bladder wall around the primary tumour before surgery. SNs were detected ex vivo during the operation with a handheld Geiger probe (Gamma Detection System; Neoprobe Corp., Dublin, OH, USA). All LNs were formalin-fixed, sectioned three times, mounted on slides and stained with haematoxylin and eosin. An experienced uropathologist evaluated the slides.

    RESULTS: The mean age of the patients was 69 years, and 80 (77%) were male. Pathological staging was T1-12 (12%), T2-20 (19%), T3-48 (47%) and T4-23 (22%). A mean (range) number of 31 (7-68) nodes per patient were examined, totalling 3 253 nodes. LN metastases were found in 41 patients (40%). SNs were detected in 83 of the 103 patients (80%). Sensitivity and specificity for detecting metastatic disease by SN biopsy (SNB) varied between LN stations, with average values of 67% and 90%, respectively. LN metastatic density (LNMD) had a significant prognostic impact; a value of ≥8% was significantly related to shorter survival. Lymphovascular invasion (LVI) occurred in 65% of patients (n = 67) and was significantly associated with shorter cancer-specific survival (P < 0.001).

    CONCLUSION: We conclude that SNB is not a reliable technique for peri-operative localization of LN metastases during cystectomy for BCa; however, LNMD has a significant prognostic value in BCa and may be useful in the clinical context and in BCa oncological and surgical research. LVI was also found to be a prognostic factor.

    Place, publisher, year, edition, pages
    Wiley-Blackwell Publishing Inc., 2017
    Keywords
    #BladderCancer, #blcsm, cystectomy, lymph node metastasis, prognostic factors, sentinel node
    National Category
    Surgery
    Identifiers
    urn:nbn:se:liu:diva-136947 (URN)10.1111/bju.13700 (DOI)000407781500011 ()27797436 (PubMedID)
    Note

    Funding agencies: County Council of Ostergotland, Linkoping, Sweden

    Available from: 2017-05-01 Created: 2017-05-01 Last updated: 2018-05-03
  • 4.
    Almer, Sven
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Befrits, R.
    Gastrocentrum medicin, Karolinska universitetssjukhuset, Solna, Sweden.
    Eriksson, A.S.
    Medicinkliniken, Sahlgrenska universitetssjukhuset/Östra, Göteborg, Sweden.
    Halfvarson, J.
    Sektionen för gastroenterologi, Medicinska kliniken, Universitetssjukhuset, Örebro, Sweden.
    Hindorf, U.
    VO gastroenterologi, Universitetssjukhuset i Lund, Sweden.
    Lofberg, R.
    IBD-enheten, Sophiahemmet, Stockholm, Sweden.
    Modern läkemedelsterapi vid crohn - Nationella riktlinjer2009In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, no 45, p. 2988-2993Article in journal (Refereed)
    Abstract [sv]

    Lättanvända begrepp och definitioner på sjukdomsaktivitet och behandlingseffekt bör få ökad spridning inom sjukvården.

    Majoriteten av patienter med Crohns sjukdom behöver långvarig läkemedelsbehandling, och ungefär hälften genomgår en eller flera operationer någon gång under sjukdomstiden.

    Det är viktigt att tidigt i sjukdomsförloppet identifiera riskfaktorer för utveckling av komplicerad och aggressiv sjukdom och behandla intensivt i dessa fall.

    En aktiv strategi med regelbundet övervägande av tillgängliga behandlingsalternativ medför att de flesta patienter med Crohns sjukdom behåller en god livskvalitet.

  • 5.
    Andersson, Peter
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Norblad, Rickard
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Ileorectal anastomosis in comparison with ileal pouch anal anastomosis in reconstructive surgery for ulcerative colitis - a single institution experience2014In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 8, no 7, p. 582-589Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    Ileal pouch anal anastomosis (IPAA) is the standard procedure for reconstruction after colectomy for ulcerative colitis (UC). However, ileorectal anastomosis (IRA) as an alternative has, recently experienced a revival. This study from a single center compares the clinical outcomes of these procedures.

    METHODS:

    From 1992 to 2006, 253 patients consecutively underwent either IRA (n=105) or IPAA (n=148). Selection to either procedure was determined on the basis of rectal inflammation, presence of dysplasia/cancer or patient preferences. Patient-records were retrospectively evaluated. Mean follow-up time was 5.4 and 6.3 years respectively.

    RESULTS:

    Major postoperative complications occurred in 12.4% of patients after IRA and in 12.8% after IPAA (ns). Complications of any kind after IRA or IPAA, even including subsequent stoma-closure, occurred in 23.8% and 39.9% respectively (p<0.01). Estimated cumulative failure rates after 5 and 10 years were 10.1% and 24.1% for IRA and 6.1% and 18.6% for IPAA respectively (ns). The most common cause for failure was intractable proctitis (4.8%) and unspecified dysfunction (4.8%) respectively. At follow-up 76.9% of patients with IRA had proctitis and 34.1% with IPAA had pouchitis. Estimated cumulative cancer-risk after 10, 20 and 25 year duration of disease was 0.0%, 2.1% and 8.7% for IRA. Figures for IPAA were 0.7%, 1.8% and 1.8% (ns).

    CONCLUSION:

    Failure-rates did not significantly differ between patients operated with IRA or IPAA. Patients operated with IPAA had a higher cumulative number of postoperative complications. The high long-term cancer-risk after IRA indicates that this procedure should be an interim solution in younger patients.

  • 6.
    Angelison, L.
    et al.
    Helsingborg Hospital, Sweden.
    Almer, S.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Eriksson, A.
    Sahlgrenska University Hospital Östra, Sweden.
    Karling, P.
    Umeå University, Sweden.
    Fagerberg, U.
    Västmanlands Hospital, Sweden; Karolinska Institute, Sweden.
    Halfvarson, J.
    University of Örebro, Sweden.
    Thorn, M.
    Uppsala University, Sweden.
    Björk, J.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Hindorf, U.
    Lund University, Sweden.
    Löfberg, R.
    Karolinska Institute, Sweden.
    Bajor, A.
    Södera Älvsborgs sjukhus, Borås, Sweden.
    Hjortswang, Henrik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Hammarlund, P.
    Ängelholm Hospital, Sweden.
    Grip, O.
    Skåne University Hospital, Sweden.
    Torp, J.
    Kristianstad Central Hospital, Sweden.
    Marsal, J.
    Skåne University Hospital, Sweden.
    Hertervig, E.
    Skåne University Hospital, Sweden.
    Long-term outcome of infliximab treatment in chronic active ulcerative colitis: a Swedish multicentre study of 250 patients2017In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 45, no 4, p. 519-532Article in journal (Refereed)
    Abstract [en]

    Background Real-life long-term data on infliximab treatment in ulcerative colitis are limited. Aim To study the long-term efficacy and safety of infliximab in chronic active ulcerative colitis and possible predictors of colectomy and response were also examined. Methods A retrospective multi-centre study of infliximab treatment in 250 patients with chronic active ulcerative colitis with inclusion criteria: age 18 years, ambulatory treated, steroid-dependent or intolerant and/or immunomodulator refractory or intolerant. Results Steroid-free clinical remission was achieved by 123/250 patients (49.2%) at 12 months and in 126/250 patients at a median follow-up of 2.9 years (50.4%). Primary response at 3 months was achieved by 190/250 (76.0%) patients and associated with a high probability of response 168/190 (88.4%) at 12 months and 143/190 (75.3%) at follow-up. Long-term rate of colectomy in primary responders was 6/190 (3.2%) at 12 months and 27/190 (14.2%) at last follow-up. Failure to achieve response at 3 months was associated with a high risk of subsequent colectomy, 29/60 (48.3%) at 12 months and 41/60 (68.3%) at follow-up. Response at 12 months was associated with a low risk of subsequent colectomy, 14/181 (7.7%) compared with non-response 19/34 (55.9%) (P amp;lt; 0.0001). Non-response at 3 months was an independent predictor of subsequent colectomy (HR = 9.40, 95% CI = 5.10-17.35, P amp;lt; 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.

  • 7. Bantel, H.
    et al.
    Berg, C.
    Vieth, M. W.
    Stolte, M.
    Kruis, W.
    Luegering, N.
    Domschke, W.
    Los, Marek Jan
    Department of Immunology and Cell Biology, University of Münster, Münster, Germany.
    Schulze-Osthoff, Klaus
    Department of Immunology and Cell Biology, University of Münster, Münster, Germany .
    Mesalazine inhibits activation of transcription factor NF-KB in inflamed mucosa of patients with ulcerative colitis.2000In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 118, no 4, p. A1116-A1116Article in journal (Refereed)
  • 8.
    Bednarska, Olga
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Casado-Bedmar, Maite
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Salvo-Romero, Eloisa
    University of Autonoma Barcelona, Spain.
    Vicario, Maria
    University of Autonoma Barcelona, Spain.
    Mayer, Emeran A.
    University of Calif Los Angeles, CA 90095 USA.
    Keita, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Vasoactive Intestinal Polypeptide and Mast Cells Regulate Increased Passage of Colonic Bacteria in Patients With Irritable Bowel Syndrome2017In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 153, no 4, p. 948-+Article in journal (Refereed)
    Abstract [en]

    BACKGROUND amp; AIMS: Irritable bowel syndrome (IBS) is associated with intestinal dysbiosis and symptoms of IBS develop following gastroenteritis. We aimed to study the passage of live bacteria through the colonic epithelium, and determine the role of mast cells (MCs) and vasoactive intestinal polypeptide (VIP) in barrier regulation in IBS and healthy individuals. METHODS: Colon biopsies from 32 women with IBS and 15 age-matched healthy women (controls) were mounted in Ussing chambers; we measured numbers of fluorescently labeled Escherichia coli HS and Salmonella typhimurium that passed through from the mucosal side to the serosal side of the tissue. Some biopsies were exposed to agents that block the VIP receptors (VPAC1 and VPAC2) or MCs. Levels of VIP and tryptase were measured in plasma and biopsy lysates. Number of MCs and MCs that express VIP or VIP receptors were quantified by immunofluorescence. Biopsies from an additional 5 patients with IBS and 4 controls were mounted in chambers and Salmonella were added; we studied passage routes through the epithelium by transmission electron microscopy and expression of tight junctions by confocal microscopy. RESULTS: In colon biopsies from patients with IBS, larger numbers of E coli HS and S typhimurium passed through the epithelium than in biopsies from controls (P amp;lt;.0005). In transmission electron microscopy analyses, bacteria were found to cross the epithelium via only the transcellular route. Bacterial passage was reduced in biopsies from patients with IBS and controls after addition of antibodies against VPACs or ketotifen, which inhibits MCs. Plasma samples from patients with IBS had higher levels of VIP than plasma samples from controls. Biopsies from patients with IBS had higher levels of tryptase, larger numbers of MCs, and a higher percentage of MCs that express VPAC1 than biopsies from controls. In biopsies from patients with IBS, addition of Salmonella significantly reduced levels of occludin; subsequent addition of ketotifen significantly reversed this effect. CONCLUSIONS: We found that colonic epithelium tissues from patients with IBS have increased translocation of commensal and pathogenic live bacteria compared with controls. The mechanisms of increased translocation include MCs and VIP.

  • 9.
    Björnsson, Bergthor
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Bojmar, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Nitrite, a novel method to decrease ischemia/reperfusion injury in the rat liver2015In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 6, p. 1775-1783Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate whether nitrite administered prior to ischemia/reperfusion (I/R) reduces liver injury.

    METHODS: Thirty-six male Sprague-Dawley rats were randomized to 3 groups, including sham operated (n = 8), 45-min segmental ischemia of the left liver lobe (IR, n = 14) and ischemia/reperfusion (I/R) preceded by the administration of 480 nmol of nitrite (n = 14). Serum transaminases were measured after 4 h of reperfusion. Liver microdialysate (MD) was sampled in 30-min intervals and analyzed for glucose, lactate, pyruvate and glycerol as well as the total nitrite and nitrate (NOx). The NOx was measured in serum.

    RESULTS: Aspartate aminotransferase (AST) at the end of reperfusion was higher in the IR group than in the nitrite group (40 ± 6.8 μkat/L vs 22 ± 2.6 μkat/L, P = 0.022). Similarly, alanine aminotransferase (ALT) was also higher in the I/R group than in the nitrite group (34 ± 6 μkat vs 14 ± 1.5 μkat, P = 0.0045). The NOx in MD was significantly higher in the nitrite group than in the I/R group (10.1 ± 2.9 μM vs 3.2 ± 0.9 μM, P = 0.031) after the administration of nitrite. During ischemia, the levels decreased in both groups and then increased again during reperfusion. At the end of reperfusion, there was a tendency towards a higher NOx in the I/R group than in the nitrite group (11.6 ± 0.7 μM vs 9.2 ± 1.1 μM, P = 0.067). Lactate in MD was significantly higher in the IR group than in the nitrite group (3.37 ± 0.18 mM vs 2.8 ± 0.12 mM, P = 0.01) during ischemia and the first 30 min of reperfusion. During the same period, glycerol was also higher in the IRI group than in the nitrite group (464 ± 38 μM vs 367 ± 31 μM, P = 0.049). With respect to histology, there were more signs of tissue damage in the I/R group than in the nitrite group, and 29% of the animals in the I/R group exhibited necrosis compared with none in the nitrite group. Inducible nitric oxide synthase (iNOS) transcription increased between early ischemia (t = 15) and the end of reperfusion in both groups.

    CONCLUSION: Nitrite administered before liver ischemia in the rat liver reduces anaerobic metabolism and cell necrosis, which could be important in the clinical setting.

  • 10.
    Björnsson, Bergthor
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Winbladh, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Bojmar, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Gullstrand, Per
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Conventional, but not remote ischemic preconditioning, reduces iNOS transcription in liver ischemia/reperfusion2014In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 20, no 28, p. 9506-9512Article in journal (Refereed)
    Abstract [en]

    AIM: To study the effects of preconditioning on inducible nitric oxide synthase (iNOS) and interleukin 1 (IL-1) receptor transcription in rat liver ischemia/reperfusion injury (IRI). METHODS: Seventy-two male rats were randomized into 3 groups: the one-hour segmental ischemia (IRI, n = 24) group, the ischemic preconditioning (IPC, n = 24) group or the remote ischemic preconditioning (R-IPC, n = 24) group. The IPC and R-IPC were performed as 10 min of ischemia and 10 min of reperfusion. The iNOS and the IL-1 receptor mRNA in the liver tissue was analyzed with real time PCR. The total Nitrite and Nitrate (NOx) in continuously sampled microdialysate (MD) from the liver was analyzed. In addition, the NOx levels in the serum were analyzed. RESULTS: After 4 h of reperfusion, the iNOS mRNA was significantly higher in the R-IPC (Delta Ct: 3.44 +/- 0.57) group than in the IPC (Delta Ct: 5.86 +/- 0.82) group (P = 0.025). The IL-1 receptor transcription activity was reduced in the IPC group (Delta Ct: 1.88 +/- 0.53 to 4.81 +/- 0.21), but not in the R-IPC group, during reperfusion (P = 0.027). In the MD, a significant drop in the NOx levels was noted in the R-IPC group (12.3 +/- 2.2 to 4.7 +/- 1.2 mu mol/L) at the end of ischemia compared with the levels in early ischemia (P = 0.008). A similar trend was observed in the IPC group (11.8 +/- 2.1 to 6.4 +/- 1.5 mu mol/L), although this difference was not statistically significant. The levels of NOx rose quickly during reperfusion in both groups. CONCLUSION: IPC, but not R-IPC, reduces iNOS and IL-1 receptor transcription during early reperfusion, indicating a lower inflammatory reaction. NOx is consumed in the ischemic liver lobe.

  • 11.
    da Silva, Stéphanie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Conséquences d’un stress chronique sur la barrière de mucus intestinal chez le rat: effet du probiotique Lactobacillus farciminis2013Doctoral thesis, monograph (Other academic)
    Abstract [en]

    Background. Despite a large body of literature incriminating mucus alterations in the pathogenesis of Intestinal Bowel Diseases (IBD), structural and physical changes in the mucus layer remain poorly understood in the micro-inflammatory context of Irritable Bowel Syndrome (IBS). Moreover, some probiotic treatments prevent stress-induced intestinal epithelial barrier impairment but little is known about their influence on intestinal mucin structural modifications and mucus properties induced by stress. Thereby, this study aimed at evaluating whether (i) a chronic stress modified the number of gut goblet cells and Muc2 expression and O-glycosylation, (ii) L. farciminis (LF) treatment prevented these alterations and (iii) observed effects were related to the in vivo colonization capacity of LF.

    Main results and conclusions. Water Avoidance Stress (WAS) did not modify neither the number of intestinal goblet cells nor Muc2 expression. Mass Spectrometry analysis demonstrated that O-glycosylation of mucins was strongly affected by WAS, and confirmed in another model of IBS (maternal deprivation model). Under stress conditions, the mucus layer, showed a flattened morphology, probably indicative of a loss in its cohesive properties. The mucus layer alteration was, thus, in relation with epithelial barrier impairment and visceral hypersensitivity. LF administration prevented WAS-induced functional, biochemical and physical changes of mucus. The presence of LF in the ileum and colon was confirmed and we observed that Segmented Filamentous Bacteria (SFB) population was reduced by LF.

    Chronic stress induced functional changes in rats, as well as a shift in mucin O-glycosylation rather than changes in mucin expression, resulting in a loss of mucus layer cohesive properties. These results confirm that LF is a valuable probiotic in the IBS management.

    Methods. IBS Animal model (WAS and maternal deprivation), histological, Mass Spectrometry, Microscopy (Fluorescence, AFM, SEM and TEM), bacterial localization by Fluorescence In Situ Hybridization (FISH), qPCR, intestinal paracellular permeability, visceral sensitivity.

  • 12. DA SILVA, Stéphanie
    Spatial localization and binding of the probiotic Lactobacillus farciminis to the rat intestinal mucosa: influence of chronic stress2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203Article in journal (Refereed)
  • 13. DA SILVA, Stéphanie
    Stress disrupts intestinal mucus barrier in rats via mucin O-glycosylation shift: prevention by a probiotic treatment.2014In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547Article in journal (Refereed)
  • 14.
    Da Silva, Stéphanie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Keita, Åsa V.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Mohlin, Sofie
    Translational Cancer Research, Cancer Center at Medicon Village, Lund University, Lund, Sweden.
    Påhlman, Sven
    Translational Cancer Research, Cancer Center at Medicon Village, Lund University, Lund, Sweden.
    Théodorou, Vassilia
    Toxalim UMR 1331 INRA/INP/UPS Neuro-Gastroenterology and Nutrition Unit, Toulouse, France.
    Påhlman, Ingrid
    Albireo AB, Arvid Wallgrens Backe, Gothenburg, Sweden.
    Mattson, Jan P.
    Albireo AB, Arvid Wallgrens Backe, Gothenburg, Sweden.
    Söderholm, Johan D.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    A novel topical PPARγ agonist induces PPARγ-activity in ulcerative colitis mucosa and prevents and reverses inflammation in induced-colitis models2018In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 24, no 4, p. 792-805Article in journal (Refereed)
    Abstract [en]

    Background: Peroxisome proliferator-activated receptor-gamma (PPARγ) exerts anti-inflammatory effects and is therefore a potential target in ulcerative colitis (UC). A novel PPARγ agonist (AS002) developed for local action was evaluated ex vivo in biopsies from UC patients and in vivo in mice with low-grade dextran sodium sulfate (DSS)- and trinitrobenzene sulfonic acid (TNBS)-induced colitis.Methods: Colonic biopsies from UC patients (n = 18) and healthy controls (n = 6) were incubated with AS002 or rosiglitazone (positive control) to measure mRNA expression of the PPARγ-responsive gene ADIPOPHILIN and protein levels of UC-related cytokines (enzyme-linked immunosorbent assay). AS002 absorption was determined in the colonic mucosa of UC patients. DSS-colitis mice received PPARγ agonists or vehicle daily by intrarectal administration starting 2 days before induction of colitis (preventive) or from days 3 to 8 (curative). Myeloperoxidase (MPO) and cytokine levels in colonic mucosa were determined. In addition, AS002 effects were studied in TNBS colitis.Results: AS002 displayed an absorption pattern of a lipophilic drug totally metabolized in the mucosa. AS002 and rosiglitazone increased ADIPOPHILIN mRNA expression (3-fold) and decreased TNF-α, IL-1β, and IL-13 levels in human UC biopsies. In DSS, in both preventive and curative treatment and in TNBS colitis, AS002 protected against macroscopic and histological damage and lowered MPO and TNF-α, IL-1β, and IL-13 levels.Conclusions: AS002 triggers anti-inflammatory PPARγ activity in the human colonic mucosa of UC patients and prevents and reverses colitis in mice. Our data suggest that AS002 has potential for topical maintenance treatment of UC, which warrants further studies in vivo in patients.

  • 15. Daferera, Niki
    et al.
    Kumar Kumawat, Ashok
    University of Örebro, Sweden.
    Hultgren-Hornquist, Elisabeth
    University of Örebro, Sweden.
    Ignatova, Simone
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Faculty of Medicine and Health Sciences.
    Münch, Andreas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Fecal stream diversion and mucosal cytokine levels in collagenous colitis: A case report2015In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 19, p. 6065-6071Article in journal (Refereed)
    Abstract [en]

    In this case report, we examined the levels of cytokines expressed before and during fecal stream diversion and after intestinal continuity was restored in a patient with collagenous colitis. We report the case of a 46-year-old woman with chronic, active collagenous colitis who either failed to achieve clinical remission or experienced adverse effects with the following drugs: loperamide, cholestyramine, budesonide, methotrexate and adalimumab. Due to the intractable nature of the disease and because the patient was having up to 15 watery bowel movements per day, she underwent a temporary ileostomy. Colonic biopsies were analyzed for mucosal cytokine protein levels before and during fecal stream diversion and after intestinal continuity was restored. Mucosal protein levels of interleukin (IL)-1 beta, IL-2, IL-6, IL-12, IL-17 A, IL-23, TNF, IFN-gamma, IL-4, IL-5, IL-10 and IL-13 were all higher during active disease and decreased to non-detectable or considerably lower levels during fecal stream diversion. One month after the restoration of bowel continuity, when the patient experienced a relapse of symptoms, IL-2, IL-23 and IL-21 levels were again increased. Our results indicate that fecal stream diversion in this patient suppressed the levels of all cytokines analyzed in colonic biopsies. With the recurrence of clinical symptoms and histological changes after bowel reconstruction, the levels of primarily proinflammatory cytokines increased. Our findings support the hypothesis that a luminal factor triggers the inflammation observed in collagenous colitis.

  • 16.
    Danielsson Borssen, Åsa
    et al.
    Umeå University, Sweden.
    Marschall, Hanns-Ulrich
    University of Gothenburg, Sweden.
    Bergquist, Annika
    Karolinska University Hospital Huddinge, Sweden.
    Rorsman, Fredrik
    Uppsala University, Sweden.
    Weiland, Ola
    Karolinska University Hospital Huddinge, Sweden.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Nyhlin, Nils
    Örebro University, Sweden.
    Verbaan, Hans
    Lund University, Sweden.
    Nilsson, Emma
    Lund University, Sweden.
    Werner, Marten
    Umeå University, Sweden.
    Epidemiology and causes of death in a Swedish cohort of patients with autoimmune hepatitis2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 9, p. 1022-1028Article in journal (Refereed)
    Abstract [en]

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

  • 17.
    Drewes, Asbjørn M.
    et al.
    Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Denmark.
    Munkholm, Pia
    NOH (Nordsjællands Hospital) Gastroenterology, Denmark.
    Simrén, Magnus
    Department of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Breivik, Harald
    Department of Pain Management and Research, Oslo University Hospital and University of Oslo, Norway.
    Kongsgaard, Ulf E.
    Department of Anaesthesiology, Division of Emergencies and Critical Care, Oslo University Hospital, Norway and Medical Faculty, University of Oslo, Norway.
    Hatlebakk, Jan G.
    Department of Clinical Medicine, Haukeland University Hospital, Bergen, Norway.
    Agreus, Lars
    Division of Family Medicine, Karolinska Institute, Stockholm, Sweden.
    Friedrichsen, Maria
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Region Östergötland, Local Health Care Services in East Östergötland, Center of Palliative Care.
    Christrup, Lona L.
    Department of Drug Design and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Denmark.
    Definition, diagnosis and treatment strategies for opioid-induced bowel dysfunction—: Recommendations of the Nordic Working Group2016In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 11, p. 111-122Article, review/survey (Refereed)
    Abstract [en]

    Background and aims: Opioid-induced bowel dysfunction (OIBD) is an increasing problem due to the common use of opioids for pain worldwide. It manifests with different symptoms, such as dry mouth,gastro-oesophageal reflux, vomiting, bloating, abdominal pain, anorexia, hard stools, constipation and incomplete evacuation. Opioid-induced constipation (OIC) is one of its many symptoms and probably the most prevalent. The current review describes the pathophysiology, clinical implications, and treatment of OIBD.Methods: The Nordic Working Group was formed to provide input for Scandinavian specialists in multiple, relevant areas. Seven main topics with associated statements were defined. The working plan provided a structured format for systematic reviews and included instructions on how to evaluate the level of evidence according to the GRADE guidelines. The quality of evidence supporting the different statements was rated as high, moderate or low. At a second meeting, the group discussed and voted on each section with recommendations (weak and strong) for the statements.Results: The literature review supported the fact that opioid receptors are expressed throughout the gastrointestinal tract. When blocked by exogenous opioids, there are changes in motility, secretion and absorption of fluids, and sphincter function that are reflected in clinical symptoms. The group supported a recent consensus statement for OIC, which takes into account the change in bowel habits for at least one week rather than focusing on the frequency of bowel movements. Many patients with pain received opioid therapy and concomitant constipation is associated with increased morbidity and utilization of healthcare resources. Opioid treatment for acute postoperative pain will prolong the postoperative ileus.

  • 18.
    Dulai, Parambir S
    et al.
    University of California at San Diego, La Jolla, CA..
    Singh, Siddharth
    University of California at San Diego, La Jolla, CA.
    Patel, Janki
    University of California at San Diego, La Jolla, CA.
    Soni, Meera
    University of California at San Diego, La Jolla, CA.
    Prokop, Larry J
    Mayo Clinic, Rochester, Minnesota.
    Younossi, Zobair
    Department of Medicine, Inova Fairfax Hospital, Falls Church, VA.
    Sebastiani, Giada
    McGill University Health Centre, Montreal, Quebec, Canada.
    Ekstedt, Mattias
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Hagstrom, Hannes
    Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Nasr, Patrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Stal, Per
    Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Wong, Vincent Wai-Sun
    Chinese University of Hong Kong, Hong Kong.
    Kechagias, Stergios
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Hultcrantz, Rolf
    Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Loomba, Rohit
    University of California at San Diego, La Jolla, CA.
    Increased risk of mortality by fibrosis stage in non-alcoholic fatty liver disease: Systematic Review and Meta-analysis.2017In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 65, no 5, p. 1557-1565Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND: Liver fibrosis is the most important predictor of mortality in nonalcoholic fatty liver disease (NAFLD). Quantitative risk of mortality by fibrosis stage has not been systematically evaluated. We aimed to quantify the fibrosis stage-specific risk of all-cause and liver-related mortality in NAFLD.

    METHODS: Through a systematic review and meta-analysis, we identified 5 adult NAFLD cohort studies reporting fibrosis stage specific mortality (0-4). Using fibrosis stage 0 as a reference population, fibrosis stage-specific mortality rate ratios (MRR) with 95% confidence intervals (CI), for all-cause and liver-related mortality, were estimated. The study is reported according to the PRISMA statement.

    RESULTS: 1,495 NAFLD patients with 17,452 patient years of follow-up were included. Compared to NAFLD patients with no fibrosis (stage 0), NAFLD patients with fibrosis were at an increased risk for all-cause mortality and this risk increased with increase in the stage of fibrosis: stage 1, MRR, 1.58 (95% CI 1.19-2.11); stage 2, MRR, 2.52 (95% CI 1.85-3.42); stage 3, MRR, 3.48 (95% CI 2.51-4.83), and stage 4, MRR, 6.40 (95% CI 4.11-9.95). The results were more pronounced as the risk of liver-related mortality increased exponentially with increase in the stage of fibrosis: stage 1, MRR, 1.41 (95% CI 0.17-11.95); stage 2, MRR, 9.57 (95% CI 1.67-54.93); stage 3, MRR, 16.69 (95% CI 2.92-95.36); and stage 4, MRR, 42.30 (95% CI 3.51-510.34).

    LIMITATIONS: Inability to adjust for co-morbid conditions or demographics known to impact fibrosis progression in NAFLD, and the inclusion of patients with simple steatosis and NASH without fibrosis in the reference comparison group.

    CONCLUSION: The risk of liver-related mortality increases exponentially with increase in fibrosis stage. These data have important implications in assessing utility of each stage and benefits of regression of fibrosis from one stage to another. This article is protected by copyright. All rights reserved.

  • 19.
    Dutta, Ravi Kumar
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Genetics of primary hyperaldosteronism2016In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 23, no 10, p. R437-R454Article, review/survey (Refereed)
    Abstract [en]

    Hypertension is a common medical condition and affects approximately 20% of the population in developed countries. Primary aldosteronism is the most common form of secondary hypertension and affects 8-13% of patients with hypertension. The two most common causes of primary aldosteronism are aldosterone-producing adenoma and bilateral adrenal hyperplasia. Familial hyperaldosteronism types I, II and III are the known genetic syndromes, in which both adrenal glands produce excessive amounts of aldosterone. However, only a minority of patients with primary aldosteronism have one of these syndromes. Several novel susceptibility genes have been found to be mutated in aldosterone-producing adenomas: KCNJ5, ATP1A1, ATP2B3, CTNNB1, CACNA1D, CACNA1H and ARMC5. This review describes the genes currently known to be responsible for primary aldosteronism, discusses the origin of aldosterone-producing adenomas and considers the future clinical implications based on these novel insights.

  • 20.
    Eberhardson, M.
    et al.
    Danderyd Hospital, Sweden; Karolinska Institute, Sweden.
    Soderling, J. K.
    Karolinska Institute, Sweden.
    Neovius, M.
    Karolinska Institute, Sweden.
    Cars, T.
    Public Healthcare Serv, Sweden; Uppsala University, Sweden.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Ludvigsson, J. F.
    Karolinska Institute, Sweden; Örebro University Hospital, Sweden.
    Askling, J.
    Karolinska Institute, Sweden.
    Ekbom, A.
    Karolinska Institute, Sweden.
    Olen, O.
    Karolinska Institute, Sweden; Sachs Childrens Hospital, Sweden.
    Anti-TNF treatment in Crohns disease and risk of bowel resection-a population based cohort study2017In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 46, no 6, p. 589-598Article in journal (Refereed)
    Abstract [en]

    Background: TNF inhibitors (TNFi) have been shown to reduce the need for surgery in Crohns disease, but few studies have examined their effect beyond the first year of treatment. Aim: To conduct a register-based observational cohort study in Sweden 2006-2014 to investigate the risk of bowel resection in bowel surgery naive TNFi-treated Crohns disease patients and whether patients on TNFi amp;gt;= 12 months are less likely to undergo bowel resection than patients discontinuing treatment before 12 months. Methods: We identified all individuals in Sweden with Crohns disease through the Swedish National Patient Register 1987-2014 and evaluated the incidence of bowel resection after first ever dispensation of adalimumab or infliximab from 2006 and up to 7 years follow-up. Results: We identified 1856 Crohns disease patients who had received TNFi. Among these patients, 90% treatment retention was observed at 6 months after start of TNFi and 65% remained on the drug after 12 months. The cumulative rates of surgery in Crohns disease patients exposed to TNFi years 1-7 were 7%, 13%, 17%, 20%, 23%, 25% and 28%. Rates of bowel resection were similar between patients with TNFi survival amp;lt; 12 months and amp;gt;= 12 months respectively (P=.27). No predictors (eg, sex, age, extension or duration of disease) for bowel resection were identified. Conclusions: The risk of bowel resection after start of anti-TNF treatment is higher in regular health care than in published RCTs. Patients on sustained TNFi treatment beyond 12 months have bowel resection rates similar to those who discontinue TNFi treatment earlier.

  • 21.
    Ek, Weronica E
    et al.
    Karolinska Institutet, Stockholm .
    Reznichenko, Anna
    Karolinska Institutet, Stockholm.
    Ripke, Stephan
    Massachusetts General Hospital Boston, Cambridge Massachussetts, USA .
    Niesler, Beate
    University of Heidelberg, Germany .
    Zucchelli, Marco
    Karolinska Institutet, Stockholm.
    Rivera, Natalia V
    Karolinska Institutet, Stockholm.
    Schmidt, Peter T
    University Hospital, Karolinska institutet, Stockholm .
    Pedersen, Nancy L
    Karolinska Institutet, Stockholm.
    Magnusson, Patrik
    Karolinska Institutet, Stockholm.
    Talley, Nicholas J
    University of Newcastle, Australia .
    Holliday, Elizabeth G
    University of Newcastle, Australia .
    Houghton, Lesley
    University of Manchester UK and Mayo Clinic, Jacksonville USA.
    Gazouli, Maria
    University of Athens, Greece .
    Karamanolis, George
    University of Athens, Greece .
    Rappold, Gudrun
    University of Heidelberg, Germany.
    Burwinkel, Barbara
    University Women's Clinic, University of Heidelberg, Germany.
    Surowy, Harald
    University Women's Clinic, University of Heidelberg, Germany.
    Rafter, Joseph
    Karolinska Institutet, Stockholm .
    Assadi, Ghazaleh
    Karolinska Institutet, Stockholm .
    Li, Ling
    Karolinska Institutet, Stockholm .
    Papadaki, Evangelia
    Karolinska Institutet, Stockholm .
    Gambaccini, Dario
    University of Pisa, Pisa Italy .
    Marchi, Santino
    University of Pisa, Pisa Italy .
    Colucci, Rocchina
    Department of Clinical and Experimental Medicine University of Pisa, Italy .
    Blandizzi, Corrado
    Department of Clinical and Experimental Medicine University of Pisa, Italy .
    Barbaro, Raffaella
    University of Bologna, Italy .
    Karling, Pontus
    Umeå University .
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Ohlsson, Bodil
    Skånes University Hospital, Malmö .
    Tornblom, Hans
    Sahlgrenska Academy, University of Gothenburg, Göteborg.
    Bresso, Francesca
    Karolinska University Hospital, Stockholm .
    Andreasson, Anna
    Sweden Stress Research Institute, Stockholm University.
    Dlugosz, Aldona
    Karolinska Instituet, Stockholm .
    Simren, Magnus
    Sahlgrenska Academy, University of Gothenburg, Göteborg.
    Agreus, Lars
    Karolinska Institutet Stockholm .
    Lindberg, Greger
    Karolinska University Hospital, Karolinska Institutet, Stockholm.
    Boeckxstaens, Guy
    Leuven University, Leuven, Belgium .
    Bellini, Massimo
    University of Pisa, Italy .
    Stanghellini, Vincenzo
    University of Bologna, Italy .
    Barbara, Giovanni
    University of Bologna, Italy .
    Daly, Mark J
    Massachusetts General Hospital Boston, Cambridge Massachussetts, USA .
    Camilleri, Michael
    Mayo Clinic, Rochester, Minnesota, USA .
    Wouters, Mira M
    Leuven University, Belgium .
    D'Amato, Mauro
    Karolinska Institutet, Stockholm .
    Exploring the genetics of irritable bowel syndrome: a GWA study in the general population and replication in multinational case-control cohorts.2015In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 64, p. 1774-1782Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so far. We sought to identify true IBS genetic risk factors by means of genome-wide association (GWA) and independent replication studies.

    DESIGN: We conducted a GWA study (GWAS) of IBS in a general population sample of 11 326 Swedish twins. IBS cases (N=534) and asymptomatic controls (N=4932) were identified based on questionnaire data. Suggestive association signals were followed-up in 3511 individuals from six case-control cohorts. We sought genotype-gene expression correlations through single nucleotide polymorphism (SNP)-expression quantitative trait loci interactions testing, and performed in silico prediction of gene function. We compared candidate gene expression by real-time qPCR in rectal mucosal biopsies of patients with IBS and controls.

    RESULTS: One locus at 7p22.1, which includes the genes KDELR2 (KDEL endoplasmic reticulum protein retention receptor 2) and GRID2IP (glutamate receptor, ionotropic, delta 2 (Grid2) interacting protein), showed consistent IBS risk effects in the index GWAS and all replication cohorts and reached p=9.31×10(-6) in a meta-analysis of all datasets. Several SNPs in this region are associated with cis effects on KDELR2 expression, and a trend for increased mucosal KDLER2 mRNA expression was observed in IBS cases compared with controls.

    CONCLUSIONS: Our results demonstrate that general population-based studies combined with analyses of patient cohorts provide good opportunities for gene discovery in IBS. The 7p22.1 and other risk signals detected in this study constitute a good starting platform for hypothesis testing in future functional investigations.

  • 22.
    Ekstedt, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology.
    Non-Alcoholic Fatty Liver Disease: A clinical and histopathological study2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Fatty liver has previously often been associated with excessive alcohol consumption. During the last two decades, the interest in fatty liver occurring in non-drinkers i.e. non-alcoholic fatty liver disease (NAFLD) has increased dramatically. Today, NAFLD is considered as the most common liver disease in the developed world. It is strongly associated with obesity, insulin resistance, and hypertension. Thus, NAFLD is considered as the hepatic manifestation of the metabolic syndrome.

    The spectrum of NAFLD includes: simple fatty liver without necroinflammatory activity; non-alcoholic steatohepatitis (NASH), a condition characterised by hepatocellular injury, inflammation, and fibrosis; cirrhosis; and in some individuals hepatocellular carcinoma.

    The degree of steatosis in liver biopsies is usually assessed by a morphological semiquantitative approach in which the pathologist uses a four-graded scale: 0–3 or none, slight, moderate and severe. In this thesis we show that there is a considerable inter- and intraindividual variation in such scoring methods and that a more standardised and quantitative approach is preferable. The area/volume of fat in liver biopsies is greatly overestimated when assessed semiquantitatively. Moreover, the point counting technique has a better reproducibility than visual evaluation and should be preferred in estimates of liver steatosis.

    The long-term clinical and histopathological course of 129 consecutively enrolled NAFLD patients was studied. Mean follow-up (SD) was 13.7 (1.3) years. Survival of NASH patients was reduced compared with a matched reference population. These subjects more often died from cardiovascular and liver-related causes. Seven patients (5.4%) developed end-stage liver disease, including 3 patients with hepatocellular carcinoma. Most NAFLD patients will develop diabetes or impaired glucose tolerance in the long term. Progression of liver fibrosis is associated with more pronounced insulin resistance and significant weight gain.

    During follow-up, 17 patients had been prescribed a statin. At follow-up, patients on medication with statins had significantly higher BMI. Diabetes was significantly more common among patients on medication with statins and they had significantly more pronounced insulin resistance. However, they exhibited a significant reduction of liver steatosis at follow-up as opposed to patients not taking statins. Although patients under statin treatment exhibited a high risk profile for progression of liver fibrosis, only four patients on statin treatment progressed in fibrosis stage. It is concluded that statins can be prescribed safely in patients with elevated liver enzymes because of NAFLD.

    Alcohol consumption was evaluated with a validated questionnaire combined with an oral interview. In a multivariate analysis moderate alcohol consumption, particularly when frequency of heavy episodic drinking was analysed, consistent with the diagnosis of NAFLD to be set, was independently associated with fibrosis progression in NAFLD.

    The NAFLD activity score (NAS) is a newly proposed system to grade the necroinflammatory activity in liver biopsies of NAFLD patients. We evaluated the usefulness of the NAS in predicting clinical deterioration and fibrosis progression in our cohort of NAFLD patients. Although the NAS was independently associated with future risk of progressive fibrosis in NAFLD, the clinical usefulness of the score was limited due to significant overlap in clinical development between NAS-score groups.

    List of papers
    1. Semiquantitative evaluation overestimates the degree of steatosis in liver biopsies: a comparison to stereological point counting.
    Open this publication in new window or tab >>Semiquantitative evaluation overestimates the degree of steatosis in liver biopsies: a comparison to stereological point counting.
    2005 (English)In: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 18, no 7, p. 912-916Article in journal (Refereed) Published
    Abstract [en]

    The degree of steatosis in liver biopsies is usually assessed by a morphological semiquantitative approach in which the histopathologist uses a four-graded scale: 0-3 or none, slight, moderate and severe. Scores 1-3 are considered to correspond to fat deposition in <33, 33-66 and >66% of the hepatocytes. There is a considerable inter- and intra-individual variation in such scoring methods and a more standardized and quantitative approach is preferable. In the present study, we compare the semiquantitative technique with the stereological point counting method in the assessment of hepatic steatosis. A total of 75 archived liver needle biopsies were used. They were selected according to the original routine diagnosis of slight, moderate or severe steatosis. In all, 10 randomly selected images from each biopsy were digitized into a computer, a point grid lattice was superimposed and the number of hits on fat globules was counted. A pathologist scored the specimens in a four-graded scale as described above. The mean liver biopsy area (volume) with fat in hepatocytes was 2.2% for grade 1, 9.2% for grade 2 and 23.1% for grade 3. The kappa value for the semiquantitative estimates was 0.71 for the unweigthed kappa and 0.87 for weighted kappa. The intraclass correlation coefficient (ICC) was 0.99 for images counted twice and 0.95 when two sets of images were captured from the same biopsy. These ICCs indicate excellent agreement and above that of the semiquantitative estimates. In conclusion, the area/volume of fat content of the hepatocytes is greatly overemphasized in semiquantitative estimation. Furthermore, the point counting technique has a better reproducibility than visual evaluation and should be preferred in estimates of liver steatosis in scientific studies and in clinical contexts when the amount of steatosis is important for treatment and prognosis, such as liver transplantation.

    Keywords
    Liver, quantification, steatosis
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-17322 (URN)10.1038/modpathol.3800370 (DOI)15920560 (PubMedID)
    Available from: 2009-03-18 Created: 2009-03-18 Last updated: 2017-12-13Bibliographically approved
    2. Long-term follow-up of patients with NAFLD and elevated liver enzymes.
    Open this publication in new window or tab >>Long-term follow-up of patients with NAFLD and elevated liver enzymes.
    Show others...
    2006 (English)In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 44, no 4, p. 865-873Article in journal (Refereed) Published
    Abstract [en]

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of elevated liver enzymes in patients of developed countries. We determined the long-term clinical and histological courses of such patients. In a cohort study, 129 consecutively enrolled patients diagnosed with biopsy-proven NAFLD were reevaluated. Survival and causes of death were compared with a matched reference population. Living NAFLD patients were offered repeat liver biopsy and clinical and biochemical investigation. Mean follow-up (SD) was 13.7 (1.3) years. Mortality was not increased in patients with steatosis. Survival of patients with nonalcoholic steatohepatitis (NASH) was reduced (P = .01). These subjects more often died from cardiovascular (P = .04) and liver-related (P = .04) causes. Seven patients (5.4%) developed end-stage liver disease, including 3 patients with hepatocellular carcinoma. The absence of periportal fibrosis at baseline had a negative predictive value of 100% in predicting liver-related complications. At follow-up, 69 of 88 patients had diabetes or impaired glucose tolerance. Progression of liver fibrosis occurred in 41%. These subjects more often had a weight gain exceeding 5 kg (P = .02), they were more insulin resistant (P = .04), and they exhibited more pronounced hepatic fatty infiltration (P = .03) at follow-up. In conclusion, NAFLD with elevated liver enzymes is associated with a clinically significant risk of developing end-stage liver disease. Survival is lower in patients with NASH. Most NAFLD patients will develop diabetes or impaired glucose tolerance in the long term. Progression of liver fibrosis is associated with more pronounced insulin resistance and significant weight gain.

    Keywords
    Liver, quantification, steatosis
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-17323 (URN)10.1002/hep.21327 (DOI)17006923 (PubMedID)
    Available from: 2009-03-18 Created: 2009-03-18 Last updated: 2017-12-13Bibliographically approved
    3. Statins in non-alcoholic fatty liver disease and chronically elevated liver enzymes: a histopathological follow-up study.
    Open this publication in new window or tab >>Statins in non-alcoholic fatty liver disease and chronically elevated liver enzymes: a histopathological follow-up study.
    Show others...
    2007 (English)In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 47, no 1, p. 135-141Article in journal (Refereed) Published
    Abstract [en]

    Background/Aims: The effect of statins on hepatic histology in non-alcoholic fatty liver disease (NAFLD) is not known. This study explores hepatic histology in NAFLD patients before and after initiation of statin therapy and compares histological outcome with NAFLD patients who had not been prescribed statins.

    Methods: Sixty-eight NAFLD patients were re-evaluated. Follow-up ranged from 10.3 to 16.3 years. Subjects were clinically investigated and a repeat liver biopsy was obtained. No patient was taking statins at baseline while 17 patients were treated with statins at follow-up.

    Results: At baseline, patients that later were prescribed statins had significantly higher BMI and more pronounced hepatic steatosis. At follow-up patients on medication with statins continued to have significantly higher BMI. Diabetes was significantly more common among patients on medication with statins and they had significantly more pronounced insulin resistance. However, they exhibited a significant reduction of liver steatosis at follow-up as opposed to patients not taking statins. Despite exhibiting a high risk profile for progression of liver fibrosis, only four patients on statin treatment progressed in fibrosis stage.

    Conclusions: Statins can be prescribed in patients with elevated liver enzymes because of NAFLD.

    Keywords
    Non-alcoholic fatty liver disease, Histology, Statin, Metabolic syndrome
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-17324 (URN)10.1016/j.jhep.2007.02.013 (DOI)17400325 (PubMedID)
    Available from: 2009-03-18 Created: 2009-03-18 Last updated: 2017-12-13Bibliographically approved
    4. Alcohol consumption is associated with progression of hepatic fibrosis in non-alcoholic fatty liver disease
    Open this publication in new window or tab >>Alcohol consumption is associated with progression of hepatic fibrosis in non-alcoholic fatty liver disease
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    2009 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 44, no 3, p. 366-374Article in journal (Refereed) Published
    Abstract [en]

    Objective: Moderate alcohol consumption has been reported to be inversely associated with cardiovascular disease and total mortality. The importance of non-alcoholic fatty liver disease (NAFLD) is increasing and many NAFLD patients suffer from cardiovascular disease. In these patients, moderate alcohol consumption could be beneficial. The aim of this study was to investigate whether low alcohol intake, consistent with the diagnosis of NAFLD, is associated with fibrosis progression in established NAFLD.

    Material and methods: Seventy-one patients originally referred because of chronically elevated liver enzymes and diagnosed with biopsy-proven NAFLD were re-evaluated. A validated questionnaire combined with an oral interview was used to assess weekly alcohol consumption and the frequency of episodic drinking. Significant fibrosis progression in NAFLD was defined as progression of more than one fibrosis stage or development of endstage liver disease during follow-up.

    Results: Mean follow-up (SD) was 13.8 (1.2) years between liver biopsies. At follow-up, 17 patients (24%) fulfilled the criteria for significant fibrosis progression. The proportion of patients reporting heavy episodic drinking at least once a month was higher among those with significant fibrosis progression (p=0.003) and a trend towards higher weekly alcohol consumption was also seen (p=0.061). In a multivariate binary logistic regression analysis, heavy episodic drinking (p0.001) and insulin resistance (p0.01) were independently associated with significant fibrosis progression.

    Conclusions: Moderate alcohol consumption, consistent with the diagnosis of NAFLD to be set, is associated with fibrosis progression in NAFLD. These patients should be advised to refrain from heavy episodic drinking.

    Keywords
    Alcoholic liver disease, fatty liver, histopathology, liver fibrosis, non-alcoholic fatty liver disease
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-17133 (URN)10.1080/00365520802555991 (DOI)
    Available from: 2009-03-07 Created: 2009-03-07 Last updated: 2017-12-13Bibliographically approved
    5. The clinical relevance of the Nonalcoholic Fatty Liver Disease Activity Score (NAS) in predicting fibrosis progression
    Open this publication in new window or tab >>The clinical relevance of the Nonalcoholic Fatty Liver Disease Activity Score (NAS) in predicting fibrosis progression
    Show others...
    2008 (English)Article in journal (Other academic) Submitted
    Abstract [en]

    Objective: The NAFLD activity score (NAS) is a newly proposed system to grade the necroinflammatory activity in liver biopsies of NAFLD patients. This study evaluates the usefulness of the NAS in predicting clinical deterioration and fibrosis progression in NAFLD.

    Methods: One hundred and twenty-nine patients with biopsy proven NAFLD were included in a long-term histological follow-up study. Clinical and histological course were compared between NASH, “borderline NASH”, and “not NASH” patients. Significant fibrosis progression in NAFLD was defined as progression of more than one fibrosis stage or development of end-stage liver disease during follow-up.

    Results: Eighty-eight patients accepted re-evaluation and 68 underwent repeat liver biopsy. Mean time between biopsies was 13.8 ± 1.2 years (range 10.3-16.3). At baseline, NASH was diagnosed in 2 (1.6%) patients, and at follow-up, in 1 (1.5%) patient. A trend towards higher baseline NAS was seen in patients (n = 7) that developed end-stage liver disease (3.1 ± 0.9 vs. 2.4 ± 1.0; P = 0.062). Baseline NAS was significantly higher in patients with progressive fibrosis (2.9 ± 0.9 vs. 2.2 ± 0.9; P = 0.017), and NAS was independently associated with significant fibrosis progression tested in a multivariate analysis (P = 0.023). However, 18% of patients without NASH progressed significantly in fibrosis stage.

    Conclusion: Although the NAS is independently associated with future risk of progressive fibrosis in NAFLD, the clinical usefulness of the score is limited due to the significant overlap in clinical development between NAS-score groups.

    Keywords
    Steatohepatitis, Fatty liver, Fibrosis progression, Clinical follow-up, Histopathology
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-17325 (URN)
    Available from: 2009-03-18 Created: 2009-03-18 Last updated: 2009-08-17Bibliographically approved
  • 23.
    Ekstedt, Mattias
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Hagström, Hannes
    Unit of Gastroenterology and Hepatology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm .
    Nasr, Patrik
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Stal, Per
    Unit of Gastroenterology and Hepatology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm .
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Gastroentorology.
    Hultcrantz, Rolf
    Unit of Gastroenterology and Hepatology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm.
    Nonalcoholic Fatty Liver Disease Activity Score and Mortality: Imperfect But Not Insignificant REPLY2016In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 64, no 1, p. 310-311Article in journal (Refereed)
  • 24.
    Ekstedt, Mattias
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Hagström, Hannes
    Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Nasr, Patrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Stål, Per
    Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Hultcrantz, Rolf
    Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up2015In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 61, no 5, p. 1547-1554Article in journal (Refereed)
    Abstract [en]

    Background and rationale for the study: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, strongly associated with insulin resistance and the metabolic syndrome. Nonalcoholic steatohepatitis, i.e. fatty liver accompanied by necroinflammatory changes, is mostly defined by the NAFLD activity score (NAS). The aim of the current study was to determine disease-specific mortality in NAFLD, and evaluate the NAS and fibrosis stage as prognostic markers for overall and disease-specific mortality. Methods: In a cohort study, data from 229 well-characterized patients with biopsy-proven NAFLD were collected. Mean follow-up was 26.4 (± 5.6, range 6-33) years. A reference population was obtained from the National Registry of Population, and information on time and cause of death were obtained from the Registry of Causes of Death. Main results: NAFLD patients had an increased mortality compared with the reference population (HR 1.29, CI 1.04-1.59, p=0.020), with increased risk of cardiovascular disease (HR 1.55, CI 1.11-2.15, p=0.01), hepatocellular carcinoma (HR 6.55, CI 2.14-20.03, p=0.001), infectious disease (HR 2.71, CI 1.02-7.26, p=0.046), and cirrhosis (HR 3.2, CI 1.05-9.81, p=0.041). Overall mortality was not increased in patients with NAS 5-8 and fibrosis stage 0-2 (HR 1.41, CI 0.97-2.06, p=0.07), whereas patients with fibrosis stage 3-4, irrespective of NAS, had increased mortality (HR 3.3, CI 2.27-4.76, p<0.001). Conclusions: NAFLD patients have increased risk of death, with a high risk of death from cardiovascular disease and liver-related disease. The NAS was not able to predict overall mortality, whereas fibrosis stage predicted both overall and disease-specific mortality.

  • 25.
    El Serafi, Ibrahim
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Remberger, Mats
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    El-Serafi, Ahmed
    Karolinska Inst, Sweden; Univ Sharjah, U Arab Emirates.
    Benkessou, Fadwa
    Karolinska Inst, Sweden.
    Zheng, Wenyi
    Karolinska Inst, Sweden.
    Martell, Eva
    Karolinska Univ Hosp, Sweden.
    Ljungman, Per
    Karolinska Univ Hosp, Sweden.
    Mattsson, Jonas
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Hassan, Moustapha
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    The effect of N-acetyl-l-cysteine (NAC) on liver toxicity and clinical outcome after hematopoietic stem cell transplantation2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 8293Article in journal (Refereed)
    Abstract [en]

    Busulphan (Bu) is a myeloablative drug used for conditioning prior to hematopoietic stem cell transplantation. Bu is predominantly metabolized through glutathione conjugation, a reaction that consumes the hepatic glutathione. N-acetyl-l-cysteine (NAC) is a glutathione precursor used in the treatment of acetaminophen hepatotoxicity. NAC does not interfere with the busulphan myeloablative effect. We investigated the effect of NAC concomitant treatment during busulphan conditioning on the liver enzymes as well as the clinical outcome. Prophylactic NAC treatment was given to 54 patients upon the start of busulphan conditioning. These patients were compared with 54 historical matched controls who did not receive NAC treatment. In patients treated with NAC, aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were significantly (P amp;lt; 0.05) decreased after conditioning compared to their start values. Within the NAC-group, liver enzymes were normalized in those patients (30%) who had significantly high start values. No significant decrease in enzyme levels was observed in the control group. Furthermore, NAC affected neither Bu kinetics nor clinical outcome (sinusoidal obstruction syndrome incidence, graft-versus-host disease and/or graft failure). In conclusion: NAC is a potential prophylactic treatment for hepatotoxicity during busulphan conditioning. NAC therapy did not alter busulphan kinetics or affect clinical outcome.

  • 26.
    Eriksson, Carl
    et al.
    Örebro University, Sweden.
    Marsal, Jan
    Lund University, Sweden; Skåne University Hospital, Sweden.
    Bergemalm, Daniel
    Örebro University, Sweden.
    Vigren, Lina
    Ystad Hospital, Sweden.
    Bjork, Jan
    Karolinska Institute, Sweden.
    Eberhardson, Michael
    Karolinska Institute, Sweden.
    Karling, Pontus
    Umeå University, Sweden.
    Soderman, Charlotte
    St Goran Hospital, Sweden.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Cao, Yang
    Örebro University, Sweden; Karolinska Institute, Sweden.
    Sjöberg, Daniel
    Uppsala University, Sweden.
    Thorn, Mari
    Uppsala University, Sweden.
    Karlen, Per
    Danderyd Hospital, Sweden.
    Hertervig, Erik
    Skåne University Hospital, Sweden.
    Strid, Hans
    Södra Älvsborgs Sjukhus, Sweden.
    Ludvigsson, Jonas F.
    Karolinska Institute, Sweden; Örebro University Hospital, Sweden.
    Almer, Sven
    Karolinska Institute, Sweden.
    Halfvarson, Jonas
    Örebro University, Sweden.
    Long-term effectiveness of vedolizumab in inflammatory bowel disease: a national study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG)2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 6-7, p. 722-729Article in journal (Refereed)
    Abstract [en]

    Objectives: Clinical trials have demonstrated the efficacy of vedolizumab in inflammatory bowel disease (IBD). However, these findings may not reflect the clinical practice. Therefore, we aimed to describe a vedolizumab-treated patient population and assess long-term effectiveness.Materials and methods: Patients initiating vedolizumab between 1 June 2014 and 30 May 2015 were identified through the Swedish National Quality Registry for IBD. Prospectively collected data on treatment and disease activity were extracted. Clinical remission was defined as Patient Harvey Bradshaw indexamp;lt;5 in Crohns disease (CD) and Patient Simple Clinical Colitis Activity indexamp;lt;3 in ulcerative colitis (UC).Results: Two-hundred forty-six patients (147CD, 92 UC and 7 IBD-Unclassified) were included. On study entry, 86% had failed TNF-antagonist and 48% of the CD patients had undergone1 surgical resection. After a median follow-up of 17 (IQR: 14-20) months, 142 (58%) patients remained on vedolizumab. In total, 54% of the CD- and 64% of the UC patients were in clinical remission at the end of follow-up, with the clinical activity decreasing (pamp;lt;.0001 in both groups). Faecal-calprotectin decreased in CD (pamp;lt;.0001) and in UC (p=.001), whereas CRP decreased in CD (p=.002) but not in UC (p=.11). Previous anti-TNF exposure (adjusted HR: 4.03; 95% CI: 0.96-16.75) and elevated CRP at baseline (adjusted HR: 2.22; 95% CI: 1.10-4.35) seemed to be associated with discontinuation because of lack of response. Female sex was associated with termination because of intolerance (adjusted HR: 2.75; 95% CI: 1.16-6.48).Conclusion: Vedolizumab-treated patients represent a treatment-refractory group. A long-term effect can be achieved, even beyond 1 year of treatment.

  • 27.
    Everhov, Asa H.
    et al.
    Karolinska Inst, Sweden.
    Halfvarson, Jonas
    Örebro Univ, Sweden.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Sachs, Michael C.
    Karolinska Inst, Sweden.
    Nordenvall, Caroline
    Karolinska Univ Hosp, Sweden.
    Söderling, Jonas
    Karolinska Inst, Sweden.
    Ekbom, Anders
    Karolinska Inst, Sweden.
    Neovius, Martin
    Karolinska Inst, Sweden.
    Ludvigsson, Jonas F.
    Karolinska Inst, Sweden; Orebro Univ, Sweden; Univ Nottingham, England; Columbia Univ Coll Phys and Surg, NY USA.
    Askling, Johan
    Karolinska Inst, Sweden.
    Olen, Ola
    Karolinska Inst, Sweden; Sachs Children and Youth Hosp, Sweden.
    Incidence and Treatment of Patients Diagnosed With Inflammatory Bowel Diseases at 60 Years or Older in Sweden2018In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 154, no 3, p. 518-+Article in journal (Refereed)
    Abstract [en]

    BACKGROUND amp; AIMS: Diagnosis of inflammatory bowel diseases (IBD) is increasing among elderly persons (60 years or older). We performed a nationwide population-based study to estimate incidence and treatment of IBD. METHODS: We identified all incident IBD cases in Sweden from 2006 through 2013 using national registers and up to 10 matched population comparator subjects. We collected data on the patients health care contacts and estimated incidence rates, health service burden, pharmacologic treatments, extra-intestinal manifestations, and surgeries in relation to age of IBD onset (pediatric, amp;lt;18 years; adults, 18-59 years; elderly, amp;gt;= 60 years). RESULTS: Of 27,834 persons diagnosed with incident IBD, 6443 (23%) had a first diagnosis of IBD at 60 years or older, corresponding to an incidence rate of 35/100,000 person-years (10/100,000 person-years for Crohns disease, 19/100,000 person-years for ulcerative colitis, and 5/100,000 person-years for IBD unclassified). During a median follow-up period of 4.2 years (range, 0-9 years), elderly patients had less IBD-specific outpatient health care but more IBD-related hospitalizations and overall health care use than adult patients with IBD. Compared with patients with pediatric or adult-onset IBD, elderly patients used fewer biologics and immunomodulators but more systemic corticosteroids. Occurrence of extra-intestinal manifestations was similar in elderly and adult patients, but bowel surgery was more common in the elderly (13% after 5 years vs 10% in adults) (Pamp;lt;.001). The absolute risk of bowel surgery was higher in the elderly than in the general population, but in relative terms, the risk increase was larger in younger age groups. CONCLUSIONS: In a nationwide cohort study in Sweden, we associated diagnosis of IBD at age 60 years or older with a lower use of biologics and immunomodulators but higher absolute risk of bowel surgery, compared with diagnosis at a younger age. The large differences in pharmacologic treatment of adults and elderly patients are not necessarily because of a milder course of disease and warrant further investigation.

  • 28.
    Forsgren, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    The Non-Invasive Liver Biopsy: Determining Hepatic Function in Diffuse and Focal LiverDisease2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The liver is one of the largest organs within the human body and it handles many vital tasks such as nutrient processing, toxin removal, and synthesis of important proteins. The number of people suffering from chronic liver disease is on the rise, likely due to the present ‘western’ lifestyle. As disease develops in the liver there are pathophysiological manifestations within the liver parenchyma that are both common and important to monitor. These manifestations include inflammation, fatty infiltration (steatosis), excessive scar tissue formation (fibrosis and cirrhosis), and iron loading. Importantly, as the disease progresses there is concurrent loss of liver function. Furthermore, postoperative liver function insufficiency is an important concern when planning surgical treatment of the liver, because it is associated with both morbidity and mortality. Liver function can also be hampered due to drug-induced injuries, an important aspect to consider in drug-development.

    Currently, an invasive liver needle biopsy is required to determine the aetiology and to stage or grade the pathophysiological manifestations. There are important limitations with the biopsy, which include, risk of serious complications, mortality, morbidity, inter- and intra-observer variability, sampling error, and sampling variability. Cleary, it would be beneficial to be able investigate the pathophysiological manifestations accurately, non-invasively, and on regional level.

    Current available laboratory liver function blood panels are typically insufficient and often only indicate damage at a late stage. Thus, it would be beneficial to have access to biomarkers that are both sensitive and responds to early changes in liver function in both clinical settings and for the pharmaceutical industry and regulatory agencies.

    The main aim of this thesis was to develop and evaluate methods that can be used for a ‘non-invasive liver biopsy’ using magnetic resonance (MR). We also aimed to develop sensitive methods for measure liver function based on gadoxetate-enhanced MR imaging (MRI).

    The presented work is primarily based on a prospective study on c. 100 patients suffering from chronic liver disease of varying aetiologies recruited due to elevated liver enzyme levels, without clear signs of decompensated cirrhosis. Our results show that the commonly used liver fat cut-off for diagnosing steatosis should be lowered from 5% to 3% when using MR proton-density fat fraction (PDFF). We also show that MR elastography (MRE) is superior in staging fibrosis.

    Finally we presented a framework for quantifying liver function based on gadoxetate-enhanced MRI. The method is based on clinical images and a clinical approved contrast agent (gadoxetate). The framework consists of; state-of the-art image reconstruction and correction methods, a mathematical model, and a precise model parametrization method. The model was developed and validated on healthy subjects. Thereafter the model was found applicable on the chronic liver disease cohort as well as validated using gadoxetate levels in biopsy samples and blood samples. The liver function parameters correlated with clinical markers for liver function and liver fibrosis (used as a surrogate marker for liver function).

    In summary, it should be possible to perform a non-invasive liver biopsy using: MRI-PDFF for liver fat and iron loading, MRE for liver fibrosis and possibly also inflammation, and measure liver function using the presented framework for analysing gadoxetate-enhanced MRI. With the exception of an MREtransducer no additional hardware is required on the MR scanner. The liver function method is likely to be useful both in a clinical setting and in pharmaceutical trials.

    List of papers
    1. Separation of advanced from mild hepatic fibrosis by quantification of the hepatobiliary uptake of Gd-EOB-DTPA
    Open this publication in new window or tab >>Separation of advanced from mild hepatic fibrosis by quantification of the hepatobiliary uptake of Gd-EOB-DTPA
    Show others...
    2013 (English)In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 23, no 1, p. 174-181Article in journal (Refereed) Published
    Abstract [en]

    Objectives

    To apply dynamic contrast-enhanced (DCE) MRI on patients presenting with elevated liver enzymes without clinical signs of hepatic decompensation in order to quantitatively compare the hepatocyte-specific uptake of Gd-EOB-DTPA with histopathological fibrosis stage.

    Methods

    A total of 38 patients were prospectively examined using 1.5-T MRI. Data were acquired from regions of interest in the liver and spleen by using time series of single-breath-hold symmetrically sampled two-point Dixon 3D images (non-enhanced, arterial and venous portal phase; 3, 10, 20 and 30 min) following a bolus injection of Gd-EOB-DTPA (0.025 mmol/kg). The signal intensity (SI) values were reconstructed using a phase-sensitive technique and normalised using multiscale adaptive normalising averaging (MANA). Liver-to-spleen contrast ratios (LSC_N) and the contrast uptake rate (KHep) were calculated. Liver biopsy was performed and classified according to the Batts and Ludwig system.

    Results

    Area under the receiver-operating characteristic curve (AUROC) values of 0.71, 0.80 and 0.78, respectively, were found for KHep, LSC_N10 and LSC_N20 with regard to severe versus mild fibrosis. Significant group differences were found for KHep (borderline), LSC_N10 and LSC_N20.

    Conclusions

    Liver fibrosis stage strongly influences the hepatocyte-specific uptake of Gd-EOB-DTPA. Potentially the normalisation technique and KHep will reduce patient and system bias, yielding a robust approach to non-invasive liver function determination.

    Place, publisher, year, edition, pages
    Springer, 2013
    Keywords
    Quantification, Gd-EOB-DTPA, Dynamic contrast-enhanced MRI, Pharmacokinetics, Liver
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-87242 (URN)10.1007/s00330-012-2583-2 (DOI)000312324500022 ()
    Projects
    NILB
    Note

    Funding Agencies|Swedish Research Council|VR/M 2007-2884|Medical Research Council of South-east Sweden|FORSS 12621|Linkoping University, Linkoping University Hospital Research Foundations||County Council of Ostergotland||

    Available from: 2013-01-14 Created: 2013-01-14 Last updated: 2017-12-06
    2. Physiologically Realistic and Validated Mathematical Liver Model Revels Hepatobiliary Transfer Rates for Gd-EOB-DTPA Using Human DCE-MRI Data
    Open this publication in new window or tab >>Physiologically Realistic and Validated Mathematical Liver Model Revels Hepatobiliary Transfer Rates for Gd-EOB-DTPA Using Human DCE-MRI Data
    Show others...
    2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 4, p. 0095700-Article in journal (Refereed) Published
    Abstract [en]

    Objectives: Diffuse liver disease (DLD), such as non-alcoholic fatty liver disease (NASH) and cirrhosis, is a rapidly growing problem throughout the Westernized world. Magnetic resonance imaging (MRI), based on uptake of the hepatocyte-specific contrast agent (CA) Gd-EOB-DTPA, is a promising non-invasive approach for diagnosing DLD. However, to fully utilize the potential of such dynamic measurements for clinical or research purposes, more advanced methods for data analysis are required. Methods: A mathematical model that can be used for such data-analysis was developed. Data was obtained from healthy human subjects using a clinical protocol with high spatial resolution. The model is based on ordinary differential equations and goes beyond local diffusion modeling, taking into account the complete system accessible to the CA. Results: The presented model can describe the data accurately, which was confirmed using chi-square statistics. Furthermore, the model is minimal and identifiable, meaning that all parameters were determined with small degree of uncertainty. The model was also validated using independent data. Conclusions: We have developed a novel approach for determining previously undescribed physiological hepatic parameters in humans, associated with CA transport across the liver. The method has a potential for assessing regional liver function in clinical examinations of patients that are suffering of DLD and compromised hepatic function.

    Place, publisher, year, edition, pages
    Public Library of Science, 2014
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-106962 (URN)10.1371/journal.pone.0095700 (DOI)000335226500139 ()
    Available from: 2014-06-04 Created: 2014-06-02 Last updated: 2017-12-05
    3. Using a 3% Proton Density Fat Fraction as a Cut-off Value Increases Sensitivity of Detection of Hepatic Steatosis, Based on Results from Histopathology Analysis
    Open this publication in new window or tab >>Using a 3% Proton Density Fat Fraction as a Cut-off Value Increases Sensitivity of Detection of Hepatic Steatosis, Based on Results from Histopathology Analysis
    Show others...
    2017 (English)In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 153, no 1, p. 53-+Article in journal (Refereed) Published
    Abstract [en]

    It is possible to estimate hepatic triglyceride content by calculating the proton density fat fraction (PDFF), using proton magnetic resonance spectroscopy (less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS), instead of collecting and analyzing liver biopsies to detect steatosis. However, the current PDFF cut-off value (5%) used to define steatosis by magnetic resonance was derived from studies that did not use histopathology as the reference standard. We performed a prospective study to determine the accuracy of less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF in measurement of steatosis using histopathology analysis as the standard. We collected clinical, serologic, less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF, and liver biopsy data from 94 adult patients with increased levels of liver enzymes (6 months or more) referred to the Department of Gastroenterology and Hepatology at Linköping University Hospital in Sweden from 2007 through 2014. Steatosis was graded using the conventional histopathology method and fat content was quantified in biopsy samples using stereological point counts (SPCs). We correlated less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF findings with SPCs (r = 0.92; P less than.001). less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF results correlated with histopathology results (ρ = 0.87; P less than.001), and SPCs correlated with histopathology results (ρ = 0.88; P less than.001). All 25 subjects with PDFF values of 5.0% or more had steatosis based on histopathology findings (100% specificity for PDFF). However, of 69 subjects with PDFF values below 5.0% (negative result), 22 were determined to have steatosis based on histopathology findings (53% sensitivity for PDFF). Reducing the PDFF cut-off value to 3.0% identified patients with steatosis with 100% specificity and 79% sensitivity; a PDFF cut-off value of 2.0% identified patients with steatosis with 94% specificity and 87% sensitivity. These findings might be used to improve non-invasive detection of steatosis.

    Place, publisher, year, edition, pages
    Elsevier, 2017
    National Category
    Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:liu:diva-136544 (URN)10.1053/j.gastro.2017.03.005 (DOI)000403918300022 ()
    Note

    Funding agencies: Swedish Research Council/Medicine and Health [VR/M 2007-2884, VR/M 2012-3199]; Swedish Research Council/Natural and Engineering Sciences [VR/NT 2014-6157]; Swedish Innovation Agency VINNOVA [2013-01314]; Region Ostergotland (ALF)

    Available from: 2017-04-19 Created: 2017-04-19 Last updated: 2018-04-18Bibliographically approved
  • 29.
    Fostad, Ida G.
    et al.
    University of Oslo, Norway; Norwegian Dry Eye Clin, Norway.
    Eidet, Jon R.
    Norwegian Dry Eye Clin, Norway; Oslo University Hospital, Norway.
    Utheim, Tor P.
    University of Oslo, Norway; Norwegian Dry Eye Clin, Norway; Oslo University Hospital, Norway; Vestre Viken Hospital Trust, Norway; Buskerud and Vestfold University of Coll, Norway.
    Raeder, Sten
    Norwegian Dry Eye Clin, Norway.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Messelt, Edvard B.
    University of Oslo, Norway.
    Dartt, Darlene A.
    Harvard University, MA USA.
    Dry Eye Disease Patients with Xerostomia Report Higher Symptom Load and Have Poorer Meibum Expressibility2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 5, p. e0155214-Article in journal (Refereed)
    Abstract [en]

    The purpose of the study was to investigate if xerostomia (dry mouth) is associated with symptoms and signs of dry eye disease (DED). At the Norwegian Dry Eye Clinic, patients with symptomatic DED with different etiologies were consecutively included in the study. The patients underwent a comprehensive ophthalmological work-up and completed self-questionnaires on symptoms of ocular dryness (Ocular Surface Disease Index [OSDI] and McMonnies Dry Eye Questionnaire) and the Sjogrens syndrome (SS) questionnaire (SSQ). Three hundred and eighteen patients (52% women and 48% men) with DED were included. Patient demographics were: 0 to 19 years (1%), 20 to 39 (25%), 40 to 59 (34%), 60 to 79 (35%) and 80 to 99 (5%). Xerostomia, defined as "daily symptoms of dry mouth the last three months" (as presented in SSQ) was reported by 23% of the patients. Female sex was more common among patients with xerostomia (81%) than among non-xerostomia patients (44%; Pamp;lt; 0.001). Patients with xerostomia (60 +/- 15 years) were older than those without xerostomia (51 +/- 17; Pamp;lt; 0.001). The use of prescription drugs was more prevalent among xerostomia patients (65%) than among non-xerostomia patients (35%; Pamp;lt; 0.021; adjusted for age and sex). Patients with xerostomia had a higher OSDI score (19.0 +/- 10.0) than those without xerostomia (12.9 +/- 8.0; Pamp;lt; 0.001). Moreover, xerostomia patients had more pathological meibum expressibility (0.9 +/- 0.7) than those without xerostomia (0.7 +/- 0.8; P = 0.046). Comparisons of OSDI and ocular signs were performed after controlling for the effects of sex, age and the number of systemic prescription drugs used. In conclusion, xerostomia patients demonstrated a higher DED symptom load and had poorer meibum expressibility than non-xerostomia patients.

  • 30.
    Ganda Mall, John-Peter
    et al.
    School of Medical Sciences, Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    Casado-Bedmar, Maite
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Winberg, Martin E.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Brummer, Robert J.
    School of Medical Sciences, Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    Schoultz, Ida
    School of Medical Sciences, Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    Keita, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. School of Medical Sciences, Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    A ß-Glucan-Based Dietary Fiber Reduces Mast Cell-Induced Hyperpermeability in Ileum From Patients With Crohns Disease and Control Subjects2018In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 24, no 1, p. 166-178Article in journal (Refereed)
    Abstract [en]

    Administration of ß-glucan has shown immune-enhancing effects. Our aim was to investigate whether ß-glucan could attenuate mast cell (MC)-induced hyperpermeability in follicle-associated epithelium (FAE) and villus epithelium (VE) of patients with Crohns disease (CD) and in noninflammatory bowel disease (IBD)-controls. Further, we studied mechanisms of ß-glucan uptake and effects on MCs in vitro.

  • 31.
    Gerdin, Linda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Department of Surgery, Höglandssjukhuset, Eksjö, Sweden.
    Eriksson, Anders S.
    Sahlgrens University Hospital, Sweden.
    Olaison, Gunnar
    Northern Hospital Zeeland, Denmark.
    Sjödahl, Rune
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Faculty of Medicine and Health Sciences.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    The Swedish Crohn Trial: A Prematurely Terminated Randomized Controlled Trial of Thiopurines or Open Surgery for Primary Treatment of Ileocaecal Crohns Disease2016In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no 1, p. 50-54Article in journal (Refereed)
    Abstract [en]

    Background and aims: The importance of efficient and safe treatment of Crohns disease is highlighted by its chronicity. Both medical and surgical treatments have shown good results in the symptomatic control of limited ileocaecal Crohns disease. The aim of this study was to compare medical treatment with surgical treatment of ileocaecal Crohns disease. Methods: Thirty-six patients from seven hospitals with primary ileocaecal Crohns disease were randomized to either medical or surgical treatment. The medical treatment was induction of remission with budesonide and thereafter maintenance treatment with azathioprine. The surgical treatment was open ileocaecal resection. Crohns disease activity index over time, expressed as area under the curve at 1, 3 and 5 years, was the primary endpoint. Subjective health measured with the 36-item Short Form Survey Instrument (SF36) and a visual analogue scale (VAS) were secondary endpoints. Results: There were no differences between the treatment groups in Crohns disease activity index over time. General health, measured as SF36 score, was higher in patients receiving surgical treatment than in those receiving medical treatment at 1 year, but there was no corresponding difference in VAS. Due to the slow inclusion rate and changes in clinical practice, the study was t = erminated prematurely. Conclusion: The study ended up being underpowered and should be interpreted with caution, but there was no clinically significant difference between the two treatment arms. Further studies are needed to address this important clinical question.

  • 32.
    Grodzinsky, Ewa
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Viktorsson, Lisa
    Carlsson, Ann-Kristin
    Jones, Michael P.
    Macquarie University, Australia.
    Olsen Faresjö, Ashild
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    More negative self-esteem and inferior coping strategies among patients diagnosed with IBS compared with patients without IBS - a case-control study in primary care2015In: BMC Family Practice, ISSN 1471-2296, E-ISSN 1471-2296, Vol. 16, no 6Article in journal (Refereed)
    Abstract [en]

    Background

    Irritable Bowel Syndrome (IBS) is a chronic, relapsing gastrointestinal disorder,that affects approximately 10% of the general population and the majority are diagnosed  in primary care. IBS has been reported to be associated with altered psychological and cognitive functioning such as mood disturbances, somatization, catastrophizing or altered visceral interoception by negative emotions and stress. The aim was to  investigate the psychosocial constructs of self-esteem and sense of coherence among IBS patients compared to non-IBS patients in primary care.     

    Methods

    A case–control study in primary care setting among IBS patients meeting the ROME III         criteria (n = 140) compared to controls i.e. non-IBS patients (n = 213) without any         present or previous gastrointestinal complaints. The data were collected through self-reportedquestionnaires of psychosocial factors.     

    Results

    IBS-patients reported significantly more negative self-esteem (p < 0.001), lower scores         for positive self-esteem (p < 0.001), and lower sense of coherence (p < 0.001) than the controls. The IBS-cases were also less likely to report ‘good’ health status (p < 0.001) and less likely to report a positive belief in the future (p < 0.001). After controlling for relevant confounding factors in multiple regressions, the elevation  in negative self-esteem among IBS patients remained statistically significant (p =0.02), as did the lower scores for sense of coherence among IBS cases (p = 0.04).     

    Conclusions

    The more frequently reported negative self-esteem and inferior coping strategies among         IBS patients found in this study suggest the possibility that psychological therapies         might be helpful for these patients. However these data do not indicate the causal         direction of the observed associations. More research is therefore warranted to determine whether these psychosocial constructs are more frequent in IBS patients.

  • 33.
    Hadizadeh, Fatemeh
    et al.
    Karolinska Inst, Sweden; Isfahan Univ Med Sci, Iran.
    Bonfiglio, Ferdinando
    Karolinska Inst, Sweden; BioDonostia Hlth Res Inst, Spain.
    Belheouane, Meriem
    Christian Albrechts Univ Kiel, Germany; Max Planck Inst Evolutionary Biol, Germany.
    Vallier, Marie
    Christian Albrechts Univ Kiel, Germany; Max Planck Inst Evolutionary Biol, Germany.
    Sauer, Sascha
    Max Delbruck Ctr Mol Med BIMSB BIH, Germany.
    Bang, Corinna
    Christian Albrechts Univ Kiel, Germany.
    Bujanda, Luis
    BioDonostia Hlth Res Inst, Spain; Univ Pais Vasco UPV EHU, Spain.
    Andreasson, Anna
    Karolinska Inst, Sweden; Stockholm Univ, Sweden.
    Agreus, Lars
    Karolinska Inst, Sweden.
    Engstrand, Lars
    Karolinska Inst, Sweden; Sci Life Lab, Sweden.
    Talley, Nicholas J.
    Karolinska Inst, Sweden; Univ Newcastle, Australia; Mayo Clin, MN USA; AGIRA, Australia.
    Rafter, Joseph
    Karolinska Inst, Sweden.
    Baines, John F.
    Christian Albrechts Univ Kiel, Germany; Max Planck Inst Evolutionary Biol, Germany.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Franke, Andre
    Christian Albrechts Univ Kiel, Germany.
    DAmato, Mauro
    BioDonostia Hlth Res Inst, Spain; Karolinska Inst, Sweden; Basque Sci Fdn, Spain.
    Faecal microbiota composition associates with abdominal pain in the general population2018In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 67, no 4, p. 778-+Article in journal (Other academic)
    Abstract [en]

    n/a

  • 34.
    Hadizadeh, Fatemeh
    et al.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; School of Nutrition, Isfahan University of Medical Sciences, Isfahan, Iran.
    Walter, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. susanne.walter@liu.se.
    Belheouane, Meriem
    Max Planck Institute for Evolutionary Biology, Plön, Germany; Institute for Experimental Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany.
    Bonfiglio, Ferdinando
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Heinsen, Femke-Anouska
    Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany.
    Andreasson, Anna
    Division for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Stress Research Institute, Stockholm University, Stockholm, Sweden.
    Agreus, Lars
    Division for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Engstrand, Lars
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Clinical Genomics Facility, Science for Life Laboratory, Stockholm, Sweden.
    Baines, John F
    Max Planck Institute for Evolutionary Biology, Plön, Germany; Institute for Experimental Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany.
    Rafter, Joseph
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Franke, Andre
    Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany.
    DAmato, Mauro
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; BioCruces Health Research Institute and IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
    Stool frequency is associated with gut microbiota composition2017In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 66, no 3, p. 559-560Article in journal (Other academic)
  • 35.
    Hagström, Hannes
    et al.
    Center for Digestive Diseases, Unit of Hepatology, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Nasr, Patrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Bottai, Matteo
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Ekstedt, Mattias
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Hultcrantz, Rolf
    Center for Digestive Diseases, Unit of Hepatology, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Stål, Per
    Center for Digestive Diseases, Unit of Hepatology, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Elevated serum ferritin is associated with increased mortality in non-alcoholic fatty liver disease after 16 years of follow-up2016In: Liver international (Print), ISSN 1478-3223, E-ISSN 1478-3231, Vol. 36, no 11, p. 1688-1695Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: High levels of ferritin in patients with non-alcoholic fatty liver disease (NAFLD) are associated with significant fibrosis and higher NAFLD activity score (NAS). It is unclear if this association has an impact on mortality. We investigated if high levels of ferritin, with or without iron overload, were associated with an increased mortality in NAFLD.

    METHODS: We included 222 patients between 1979 and 2009 with biopsy-proven NAFLD and available serum ferritin concentrations. The cohort was divided into "high" (n = 89) and "normal" (n = 133) ferritin values, using a cut-point of 350 μg/L in males, and 150 μg/L in females, and stratified upon iron overload status. Data on mortality was obtained from a national, population based register. Poisson regression was used to estimate hazard ratios for mortality. The estimates were adjusted for age at biopsy, sex, smoking, BMI, diabetes, hypertension, cardiovascular disease and fibrosis stage at the time of biopsy.

    RESULTS: The median follow-up time was 15.6 years (range: 0.5-34.2). Patients with high ferritin had more advanced fibrosis and higher NAS than patients with normal ferritin (p < 0.05). Fifteen years after diagnosis, and after adjusting for confounders, the high-ferritin group showed an increasingly higher mortality that was statistically significant (Hazard ratio = 1.10 per year, 95% Confidence interval 1.01-1.21, p < 0.05). There was no difference in mortality between patients with different iron overload patterns.

    CONCLUSIONS: High levels of ferritin are associated with a long-term increased risk of death. This article is protected by copyright. All rights reserved.

  • 36.
    Hagström, Hannes
    et al.
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden; Karolinska Institute, Sweden.
    Nasr, Patrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Ekstedt, Mattias
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Hammar, Ulf
    Karolinska Institute, Sweden.
    Stal, Per
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden; Karolinska Institute, Sweden.
    Hultcrantz, Rolf
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden; Karolinska Institute, Sweden.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD2017In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 67, no 6, p. 1265-1273Article in journal (Refereed)
    Abstract [en]

    Background amp; Aims: Non-alcoholic fatty liver disease (NAFLD) is very common in the general population, but identifying patients with increased risk of mortality and liver-specific morbidity remains a challenge. Non-alcoholic steatohepatitis (NASH) is thought to enhance this risk; therefore, resolution of NASH is a major endpoint in current pharmacologic studies. Herein, we aim to investigate the long-term prognosis of a large cohort of NAFLD patients, and to study the specific effect of NASH and fibrosis stage on prognosis. Methods: We conducted a retrospective cohort study of 646 biopsy-proven NAFLD patients. Each case was matched for age, sex and municipality to ten controls. Outcomes on mortality and severe liver disease, defined as cirrhosis, liver decompensation/failure or hepatocellular carcinoma, were evaluated using population-based registers. Cox regression models adjusted for age, sex and type 2 diabetes were used to examine the long-term risk according to fibrosis stage. Likelihood ratio tests were used to assess whether adding NASH to these models increased the predictive capacity. Laplace regression was used to estimate the time to severe liver disease according to stage of fibrosis. Results: During a follow-up of mean 20 years (range 0-40) equivalent to 139,163 person-years, 12% of NAFLD patients and 2.2% of controls developed severe liver disease (p amp;lt; 0.001). Compared to controls, the risk of severe liver disease increased per stage of fibrosis (hazard ratio ranging from 1.9 in F0 to 104.9 in F4). Accounting for the presence of NASH did not change these estimates significantly (likelihood ratio test amp;gt; 0.05 for all stages of fibrosis). Similar results were seen for overall mortality. The lower end of the 95% confidence interval for the 10th percentile of time to development of severe liver disease was 22-26 years in F0-1, 9.3 years in F2, 2.3 years in F3, and 0.9 years to liver decompensation in F4. Conclusions: In this, the largest ever study of biopsy-proven NAFLD, the presence of NASH did not increase the risk of liver-specific morbidity or overall mortality. Knowledge of time to development of severe liver disease according to fibrosis stage can be used in individual patient counselling and for public health decisions. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  • 37.
    Hagström, Hannes
    et al.
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Nasr, Patrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Ekstedt, Mattias
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Stal, Per
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Bedossa, Pierre
    University of Paris Diderot, France.
    Hultcrantz, Rolf
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    SAF score and mortality in NAFLD after up to 41 years of follow-up2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 1, p. 87-91Article in journal (Refereed)
    Abstract [en]

    Background and aims: A new score for the histological severity of nonalcoholic fatty liver disease (NAFLD), called SAF (Steatosis, Activity and Fibrosis) has been developed. We aimed to evaluate the impact of this score on overall mortality. Methods: We used data from 139 patients with biopsy-proven NAFLD. All biopsies were graded according to the SAF scoring system and disease severity was classified as mild, moderate or severe. Causes of death were extracted from a national, population-based register. A Cox regression model, adjusted for sex, body mass index (BMI) and diabetes mellitus type 2, was applied. Results: At baseline 35 patients presented with mild or moderate disease respectively, and 69 patients with severe disease. During follow-up (median 25.3 years, range 1.7-40.8) 74 patients died, 11 in the mild group (31%), 18 in the moderate group (51%) and 45 in the severe group (65%), p=.002. Compared to patients with mild disease, patients with moderate disease did not have a significant increase in overall mortality (HR 1.83, 95% CI 0.89-3.77, p=.10). Patients with severe disease had a significant increase in mortality (HR 2.65, 95% CI 1.19-5.93, p=.017). However, when adjusting for fibrosis stage, significance was lost (HR 1.85, 95% CI 0.76-4.54, p=.18). NASH, defined as per the FLIP algorithm, was not associated with mortality compared to not having NASH (HR 1.46, 95% CI 0.74-2.90, p=.28). Conclusions: After adjustment for fibrosis, the SAF score was not associated with increased mortality in NAFLD. This finding should be corroborated in larger cohorts with similar follow-up time.

  • 38.
    Hahn, Katharina
    et al.
    Christian Albrechts University of Kiel, Germany.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Hammarström, Per
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Urban, Peter
    Institute Pathol and Dermatopathol, Germany.
    Ruediger Meliss, Rolf
    Institute Dermatopathol, Germany.
    Behrens, Hans-Michael
    Christian Albrechts University of Kiel, Germany.
    Krueger, Sandra
    Christian Albrechts University of Kiel, Germany.
    Roecken, Christoph
    Christian Albrechts University of Kiel, Germany.
    Establishing and validating the fluorescent amyloid ligand h-FTAA (heptamer formyl thiophene acetic acid) to identify transthyretin amyloid deposits in carpal tunnel syndrome2017In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 24, no 2, p. 78-86Article in journal (Refereed)
    Abstract [en]

    Transthyretin-derived (ATTR) amyloidosis is a frequent finding in carpal tunnel syndrome. We tested the following hypotheses: the novel fluorescent amyloid ligand heptameric formic thiophene acetic acid (h-FTAA) has a superior sensitivity for the detection of amyloid compared with Congo red-staining; Amyloid load correlates with patient gender and/or patient age. We retrieved 208 resection specimens obtained from 184 patients with ATTR amyloid in the carpal tunnel. Serial sections were stained with Congo red, h-FTAA and an antibody directed against transthyretin (TTR). Stained sections were digitalized and forwarded to computational analyses. The amount of amyloid was correlated with patient demographics. Amyloid stained intensely with h-FTAA and an anti-TTR-antibody. Congo red-staining combined with fluorescence microscopy was significantly less sensitive than h-FTAA-fluorescence and TTR-immunostaining: the highest percentage area was found in TTR-immunostained sections, followed by h-FTAA and Congo red. The Pearson correlation coefficient was .8 (Congo red vs. h-FTAA) and .9 (TTR vs. h-FTAA). Amyloid load correlated with patient gender, anatomical site and patient age. h-FTAA is a highly sensitive method to detect even small amounts of ATTR amyloid in the carpal tunnel. The staining protocol is easy and h-FTAA may be a much more sensitive procedure to detect amyloid at an earlier stage.

  • 39.
    Hallert, Claes
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Swedish oats is superior to usual diet in maintaining ulcerative colitis patients in remission2010In: J Crohn’s & Colitis, 2010Conference paper (Refereed)
  • 40.
    Hallert, Claes
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Women with coeliac disease living on a gluten-free diet for years continue to seek more health-care2009In: Gut 2009;58 (suppl II) A262., 2009Conference paper (Refereed)
  • 41.
    Hallert, Claes
    et al.
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Svensson, M.
    Värnamo Hospital.
    Tholstrup, J.
    Eksjö Hospital .
    Hultberg, B.
    Lund University Hospital.
    B vitamins improve health in patients with coeliac disease living on a gluten-free diet2009In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 29, no 8, p. 811-816Article in journal (Refereed)
    Abstract [en]

    Background Patients with coeliac disease living on a gluten-free diet show vitamin deficiency and reduced subjective health status.

    Aim To study the biochemical and clinical effects of B vitamin supplementation in adults with longstanding coeliac disease.

    Methods In a double blind placebo controlled multicentre trial, 65 coeliac patients (61% women) aged 45–64 years on a strict gluten-free diet for several years were randomized to a daily dose of 0.8 mg folic acid,0.5 mg cyanocobalamin and 3 mg pyridoxine or placebo for 6 months. The outcome measures were psychological general well-being (PGWB) and the plasma total homocysteine (tHcy) level, marker of B vitamin status.

    Results Fifty-seven patients (88%) completed the trial. The tHcy level was baseline median 11.7 μmol/L (7.4–23.0), significantly higher than in matched population controls [10.2 μmol/L (6.7–22.6) (P < 0.01)]. Following vitamin supplementation, tHcy dropped a median of 34% (P < 0.001), accompanied by significant improvement in well-being (P < 0.01), notably Anxiety (P < 0.05) and Depressed Mood (P < 0.05) for patients with poor well-being.

    Conclusions Adults with longstanding coeliac disease taking extra B vitamins for 6 months showed normalized tHcy and significant improvement in general well-being, suggesting that B vitamins should be considered in people advised to follow a gluten-free diet.

  • 42.
    Hallert, Claes
    et al.
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Sverker, Annette
    Nordiska folkhälsohögskolan, Göteborg.
    Fridell, Karin
    Må bra med glutenintolerans: fakta, råd, recept2009 (ed. 1)Book (Other academic)
    Abstract [sv]

    Må bra med glutenintolerans är för dig som inte tål gluten, oavsett om du varit glutenintolerant under en lång tid eller om du nyligen fått diagnosen celiaki. Skriften är författad av docent Claes Hallert som är en av Sveriges mest namnkunniga läkare inom området. Claes ger en pedagogisk förklaring av sjukdomen, orsak, symtom och behandling samt aktuell forskning.Aukt socionom Annette Sverker, verksam på Nordiska folkhälsohögskolan i Göteborg, ger tips och råd hur du kan hantera vardagen som glutenintolerant, när du ska handla glutenfritt, äta på restaurang, fika på arbetet, äta middag hos vänner eller åka på utlandssemester.Dietisten Karin Fridell berättar vad man kan äta och vad man måste undvika som glutenintolerant. Karin redogör även för de nya EU-reglerna kring livsmedelsmärkning, ger baktips och en rad nya glutenfria recept.Skriften är rikligt illustrerad med inspirerande foton. Den är faktagranskad av leg. dietist Carina Lunneryd, Lunds universitetssjukhus, Iréne Jonson, Svenska celiakiförbundet och leg. läkare Ann Österman som själv är

  • 43.
    Hellström Ängerud, Karin
    et al.
    Institutionen för omvårdnad, Umeå Universitet.
    Ericsson, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Isaksson, R-M
    Norrbotten County Council, Department of Research, Luleå.
    Sederholm Lawesson, Sofia
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Thylén, Ingela
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Differences in symptoms in relation to myocardial infarction.2016Conference paper (Other academic)
    Abstract [en]

    Background: In myocardial infarction (MI) rapid diagnosis and treatment is crucial for the prognosis. Previous research has found that symptom presentation influence pre hospital delay times but studies about differences in MI symptoms between patients with ST-elevation myocardial infarction (STEMI) and non ST-elevation myocardial infarction (NSTEMI) are sparse and inconclusive. To enhance the understanding of symptom presentation in regard to MI type, we aimed to describe symptoms in relation to MI type and to find predictors of STEMI versus NSTEMI in patients with MI.

    Methods: Patients with MI (n=694) from the SymTime study were included. SymTime was a multicentre cross-sectional study of symptoms and actions in the prehospital phase of MI and data were collected using a previously validated questionnaire administered to MI patients within 24 h of admission to hospital.

    Results: Patients with STEMI were younger, more often men and smokers. Patients with NSTEMI were more likely to have a history of hypertension, MI and stroke. Chest pain was the most common symptom in both groups. Pain, discomfort, or pressure located in the jaw or teeth, vertigo/pre-syncope, cold sweat and nausea/vomiting were significantly more frequent in patients with STEMI (Table 1). In a multivariate logistic regression model patients with STEMI were more likely to present with cold sweat (OR 4.13, 95% CI 2.71–6.29) jaw pain (OR 2.14, 95% CI 1.02–4.50), and nausea (OR 2.01, 95% CI 1.20–3.33), and less likely to have a history of stroke (OR 0.35, 95% CI 0.15–0.84), fluctuating symptoms (OR 0.54, 95% CI 0.36–0.83) and anxiety (OR 0.54, 95% CI 0.32–0.92) compared to patients with NSTEMI.

    Conclusion: Patients with STEMI differed significantly from those with NSTEMI regarding symptom presentation. This knowledge is important for health care personnel to recognize symptoms alarming for STEMI when evaluating patients with MI symptoms.

  • 44.
    Högberg, Lotta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Stenhammar, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Diagnosis criteria in young children2009In: Nature Reviews Gastroenterology & Hepatology, ISSN 1759-5045, E-ISSN 1759-5053, Vol. 6, no 8, p. 447-448Article in journal (Other academic)
    Abstract [en]

    n/a

  • 45.
    Högberg, Lotta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Stenhammar, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Pediatric celiac disease-is a diagnostic biopsy necessary?2012In: Nature Reviews Gastroenterology & Hepatology, ISSN 1759-5045, E-ISSN 1759-5053, Vol. 9, no 3, p. 127-128Article in journal (Other academic)
    Abstract [en]

    A small-bowel biopsy is currently required in the diagnosis of celiac disease in children. The European Society for Pediatric Gastroenterology, Hepatology and Nutrition has now presented new guidelines for the diagnosis of celiac disease, which indicate that small-bowel biopsy could be avoided in certain cases.

  • 46.
    Isaksson, Sofi
    et al.
    Lund University, Sweden.
    Jonsson, Per
    Lund University, Sweden.
    Monsef, Nastaran
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Brunnstrom, Hans
    Lund University, Sweden.
    Bendahl, Par-Ola
    Lund University, Sweden.
    Jonsson, Mats
    Lund University, Sweden.
    Staaf, Johan
    Lund University, Sweden.
    Planck, Maria
    Lund University, Sweden.
    CA 19-9 and CA 125 as potential predictors of disease recurrence in resectable lung adenocarcinoma2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 10, article id e186284Article in journal (Refereed)
    Abstract [en]

    Objectives Among patients who underwent primary surgery for non-small cell lung cancer (NSCLC), recurrent disease is frequent and cannot be accurately predicted solely from TNM stage and histopathological features. The aim of this study was to examine the association of tumor markers in pre-operative serum with recurrent disease. Material and methods Blood samples were collected prior to lung cancer surgery from 107 patients with stage I-III lung adenocarcinoma surgically treated at Lund University hospital, Lund, Sweden, between 2005 and 2011. The serum tumor markers Carcinoembryonic antigen (CEA), Neuron-specific enolase (NSE), Cancer antigen 125 (CA 125), Human epididymis protein 4 (HE4) and Carbohydrate antigen (CA 19-9) were analyzed retrospectively and clinical follow-up data were collected from patient charts. Forty (37%) patients were diagnosed with recurrent disease. Results Sixty-eight (64%) patients had at least one elevated tumor marker prior to surgery. In analysis of disease-free survival (DFS), CA 125 and/or CA 19-9 were significantly associated with recurrent disease adjusted to stage and adjuvant treatment (hazard ratio 2.8, 95% confidence interval 1.4-5.7, p = 0.006). Conclusion High pre-operative serum CA 19-9 and/or CA 125 might indicate an increased incidence of recurrent disease in resectable lung adenocarcinomas.

  • 47.
    Jakobsson, Gustav L.
    et al.
    Karolinska Institute, Sweden.
    Sternegard, Emil
    Karolinska Institute, Sweden.
    Olen, Ola
    Sachs Childrens Hospital, Sweden; Karolinska Institute, Sweden.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Ljung, Rickard
    Karolinska Institute, Sweden.
    Strid, Hans
    Södra Älvsborgs Sjukhus, Sweden; University of Gothenburg, Sweden.
    Halfvarson, Jonas
    University of Örebro, Sweden.
    Ludvigsson, Jonas F.
    Karolinska Institute, Sweden; Oregon University Hospital, Sweden; University of Nottingham, England; Columbia University, NY USA.
    Validating inflammatory bowel disease (IBD) in the Swedish National Patient Register and the Swedish Quality Register for IBD (SWIBREG)2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 2, p. 216-221Article in journal (Refereed)
    Abstract [en]

    Background: Both the Swedish National Patient Register (NPR) and the Swedish Quality Register for inflammatory bowel disease (IBD, SWIBREG) are important sources of research data and information. However, the validity of a diagnosis of IBD in these registers is unknown. Methods: Medical charts of 129 randomly selected patients from the NPR and 165 patients registered both in SWIBREG and the NPR were reviewed. Patients were classified according to standardized criteria for ulcerative colitis (UC), Crohns disease (CD), or IBD unclassified (IBD-U). Positive predictive values (PPVs) for UC, CD, IBD-U (only SWIBREG), or having any form of IBD were then calculated. Results: For cases with amp;gt;= 2 diagnoses of IBD in the NPR (hospitalizations or non-primary care outpatient visits), the PPV was 93% (95% CI: 87-97) for any IBD, 79% (66-88) for UC and 72% (60-82) for CD. In UC patients with amp;gt;= 2 UC diagnoses but never a CD diagnosis, the PPV increased to 90% (77-97). The PPV for CD in patients with amp;gt;= 2 CD diagnoses but never a UC diagnosis was 81% (67-91)). Combining data from SWIBREG (amp;gt;= 1 record) and the NPR (amp;gt;= 1 record), the PPV was 99% for any IBD (97-100), 96% (89-99) for UC, and 90% (82-96) for CD. Conclusion: The validity of the UC, CD, and IBD diagnoses is high in the NPR but even higher when cases were identified both in SWIBREG and the NPR. These results underline the need for a well-functioning Swedish Quality Register for IBD as a complement to the NPR.

  • 48.
    Johansson, Joel
    et al.
    Linköping University, Faculty of Health Sciences, Faculty of Health Sciences, Medical Programme.
    Ignatova, Simone
    Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Ekstedt, Mattias
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Gastroentorology.
    Pinworm infestation mimicking crohns' disease2013In: Case Reports in Gastrointestinal Medicine, ISSN 2090-6528, E-ISSN 2090-6536, Vol. 2013, article id 706197Article in journal (Refereed)
    Abstract [en]

    We here report a case of a young man who presented to his general practitioner with diarrhea. Inflammatory bowel disease was suspected and a colonoscopy showed aphthous lesions suggestive of Crohns' disease but biopsies revealed eggs of Enterobius vermicularis. When treated for this parasite, his symptoms were alleviated and a followup colonoscopy revealed a normal colon and distal ileum. Enterobius vermicularis is the most common parasite worldwide and has been attributed with many different presentations and pathologies. It is therefore necessary to maintain vigilance, even in high-income countries, in order to diagnose patients with one of the many atypical presentations of pinworms.

  • 49.
    Johansson, Joel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Sahin, Christofer
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Pestoff, Rebecka
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Ignatova, Simone
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Edsjö, Anders
    Sahlgrenska University Hospital Göteborg .
    Ekstedt, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Stenmark Askmalm, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    A Novel SMAD4 Mutation Causing Severe Juvenile Polyposis Syndrome with Protein Losing Enteropathy, Immunodeficiency, and Hereditary Haemorrhagic Telangiectasia.2015In: Case Reports in Gastrointestinal Medicine, ISSN 2090-6528, E-ISSN 2090-6536, Vol. 2015, p. 1-5, article id 140616Article in journal (Refereed)
    Abstract [en]

    Juvenile polyposis syndrome (JPS) is a rare genetic disorder characterized by juvenile polyps of the gastrointestinal tract. We present a new pathogenic mutation of the SMAD4 gene and illustrate the need for a multidisciplinary health care approach to facilitate the correct diagnosis. The patient, a 47-year-old Caucasian woman, was diagnosed with anaemia at the age of 12. During the following 30 years, she developed numerous gastrointestinal polyps. The patient underwent several operations, and suffered chronic abdominal pain, malnutrition, and multiple infections. Screening of the SMAD4 gene revealed a novel, disease-causing mutation. In 2012, the patient suffered hypoalbuminemia and a large polyp in the small bowel was found. Gamma globulin was given but the patient responded with fever and influenza-like symptoms and refused more treatment. The patient underwent surgery in 2014 and made an uneventful recovery. At follow-up two months later albumin was 38 g/L and IgG was 6.9 g/L. Accurate diagnosis is essential for medical care. For patients with complex symptomatology, often with rare diseases, this is best provided by multidisciplinary teams including representatives from clinical genetics. Patients with a SMAD4 mutation should be followed up both for JPS and haemorrhagic hereditary telangiectasia and may develop protein loosing enteropathy and immunodeficiency.

  • 50.
    Jonsson, Åsa
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    How to create and analyze a Heart Failure Registry with emphasis on Anemia and Quality of Life2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background and aims

    Heart failure (HF) is a major cause of serious morbidity and death in the population and one of the leading medical causes of hospitalization among people older than 60 years. The aim of this thesis was to describe how to create and how to analyze a Heart Failure Registry with emphasis on Anemia and Quality of Life. (Paper I) We described the creation of the Swedish Heart Failure Registry (SwedeHF) as an instrument, which may help to optimize the handling of HF patients and show how the registry can be used to improve the management of patients with HF. (Paper II) In order to show how to analyze a HF registry we investigated the prevalence of anemia, its predictors, and its association with mortality and morbidity in a large cohort of unselected patients with HFrEF included in the SwedeHF, and to explore if there are subgroups of HF patients identifying high--‐risk patients in need of treatment. (Paper III) In order to show another way of analyzing a HF registry we assessed the prevalence of, associations with, and prognostic impact of anemia in patients with HFmrEF and HFpEF. (Paper IV) Finally we examined the usefulness of EQ--‐ 5D as a measure of patient--‐reported outcomes among HF patients using different analytical models and data from the SwedeHF, and comparing results about HRQoL for patients with HFpEF and HFrEF.

    Methods

    An observational study based on the SwedeHF database, consisting of about 70 variables, was undertaken to describe how a registry is created and can be used (Paper I). One comorbidity (anemia) was applied to different types of HF patients, HFrEF (EF <40%) (II) and HFmrEF (EF 40--‐49% ) or HFpEF (> 50%) (III) analyzing the data with different statistical methods. The usefulness of EQ--‐5D as measure of patient--‐ reported outcomes was studied and the results about HRQoL were compared for patients with HFpEF and HFrEF (IV).

    Results

    In the first paper (Paper I) we showed how to create a HF registry and presented some characteristics of the patients included, however not adjusted since this was not the purpose of the study. In the second paper (Paper II) we studied anemia in patients with HFrEF and found that the prevalence of anemia in HFrEF were 34 % and the most important independent predictors were higher age, male gender and renal dysfunction. One--‐year survival was 75 % with anemia vs. 81 % without (p<0,001). In the matched cohort after propensity score the hazard ratio associated with anemia was for all--‐cause death 1.34. Anemia was associated with greater risk with lower age, male gender, EF 30--‐39%, and NYHA--‐class I--‐II. In the third paper (Paper III) we studied anemia in other types of HF patients and found that the prevalence in the overall cohort in patients with EF > 40% was 42 %, in HFmrEF 38 % and in HFpEF (45%). Independent associations with anemia were HFpEF, male sex, higher age, worse New York Heart Association class and renal function, systolic blood pressure <100 mmHg, heart rate ≥70 bpm, diabetes, and absence of atrial fibrillation. One--‐year survival with vs. without anemia was 74% vs. 89% in HFmrEF and 71% vs. 84% in HFpEF (p<0.001 for all). Thus very similar results in paper II and III but in different types of HF patients. In the fourth paper (Paper IV) we studied the usefulness of EQ--‐5D in two groups of patients with HF (HFpEF and HFrEF)) and found that the mean EQ--‐5D index showed small reductions in both groups at follow--‐up. The patients in the HFpEF group reported worsening in all five dimensions, while those in the HFrEF group reported worsening in only three. The Paretian classification showed that 24% of the patients in the HFpEF group and 34% of those in the HFrEF group reported overall improvement while 43% and 39% reported overall worsening. Multiple logistic regressions showed that treatment in a cardiology clinic affected outcome in the HFrEF group but not in the HFpEF group (Paper IV).

    Conclusions

    The SwedeHF is a valuable tool for improving the management of patients with HF, since it enables participating centers to focus on their own potential for improving diagnoses and medical treatment, through the online reports (Paper I). Anemia is associated with higher age, male gender and renal dysfunction and increased risk of mortality and morbidity (II, III). The influence of anemia on mortality was significantly greater in younger patients in men and in those with more stable HF (Paper II, III). The usefulness of EQ--‐5D is dependent on the analytical method used. While the index showed minor differences between groups, analyses of specific dimensions showed different patterns of change in the two groups of patients (HFpEF and HFrEF). The Paretian classification identified subgroups that improved or worsened, and can therefore help to identify needs for improvement in health services (Paper IV).

    List of papers
    1. Heart failure registry: a valuable tool for improving the management of patients with heart failure
    Open this publication in new window or tab >>Heart failure registry: a valuable tool for improving the management of patients with heart failure
    2010 (English)In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 12, no 1, p. 25-31Article in journal (Refereed) Published
    Abstract [en]

    Guidelines on how to diagnose and treat patients with heart failure (HF) are published regularly. However, many patients do not fulfil the diagnostic criteria and are not treated with recommended drugs. The Swedish Heart Failure Registry (S-HFR) is an instrument which may help to optimize the handling of HF patients. The S-HFR is an Internet-based registry in which participating centres (units) can record details of their HF patients directly online and transfer data from standardized forms or from computerized patient documentation. Up to December 2007, 16 117 patients from 78 units had been included in the S-HFR. Of these, 10 229 patients had been followed for at least 1 year, and 2133 deaths were recorded. Online reports from the registry showed that electrocardiograms were available for 97% of the patients. Sinus rhythm was found in 51% of patients and atrial fibrillation in 38%. Echocardiography was performed in 83% of the patients. Overall, 77% of patients were treated with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, 80% were on beta-blockers, 34% on aldosterone antagonists, and 83% on diuretics. The S-HFR is a valuable tool for improving the management of patients with HF, since it enables participating centres to focus on their own potential for improving diagnoses and medical treatment, through the online reports provided.

    Keywords
    Heart failure; Registry; Diagnostics; Medical treatment
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-52877 (URN)10.1093/eurjhf/hfp175 (DOI)
    Available from: 2010-01-13 Created: 2010-01-12 Last updated: 2017-12-12
    2. A comprehensive assessment of the association between anemia, clinical covariates and outcomes in a population-wide heart failure registry
    Open this publication in new window or tab >>A comprehensive assessment of the association between anemia, clinical covariates and outcomes in a population-wide heart failure registry
    Show others...
    2016 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 211, p. 124-131Article in journal (Refereed) Published
    Abstract [en]

    Background: The aim was to investigate the prevalence of, predictors of, and association with mortality and morbidity of anemia in a large unselected cohort of patients with heart failure (HF) and reduced ejection fraction (HFrEF) and to explore if there were specific subgroups of high risk. Methods: In patients with HFrEF in the Swedish Heart Failure Registry, we assessed hemoglobin levels and associations between baseline characteristics and anemia with logistic regression. Using propensity scores for anemia, we assessed the association between anemia and outcomes with Cox regression, and performed interaction and sub-group analyses. Results: There were 24 511 patients with HFrEF (8303 with anemia). Most important independent predictors of anemia were higher age, male gender and renal dysfunction. One-year survival was 75% with anemia vs. 81% without (p &lt; 0.001). In the matched cohort after propensity score the hazard ratio associated with anemia was for all-cause death 1.34 (1.28-1.40; p &lt; 0.0001), CV mortality 1.28 (1.20-1.36; p &lt; 0.0001), and combined CV mortality or HF hospitalization 1.24 (1.18-1.30; p &lt; 0.0001). In interaction analyses, anemia was associated with greater risk with lower age, male gender, EF 30-39%, and NYHA-class I-II. Conclusion: In HFrEF, anemia is associated with higher age, male gender and renal dysfunction and increased risk of mortality and morbidity. The influence of anemia on mortality was significantly greater in younger patients, in men, and in those with more stable HF. The clinical implication of these findings might be in the future to perform targeted treatment studies. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

    Place, publisher, year, edition, pages
    ELSEVIER IRELAND LTD, 2016
    Keywords
    Heart failure; Reduced ejection fraction; Anemia; Outcomes; Observational study
    National Category
    Mathematics Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-127741 (URN)10.1016/j.ijcard.2016.02.144 (DOI)000373918100029 ()26999301 (PubMedID)
    Note

    Funding Agencies|Swedish National Board of Health and Welfare; Swedish Association of Local Authorities and Regions; Swedish Society of Cardiology; Linkoping University; Swedish HF Registry foundation

    Available from: 2016-05-12 Created: 2016-05-12 Last updated: 2017-11-30
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