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  • 1.
    Abate Waktola, Ebba Abate
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. EPHI, Ethiopia.
    Blomgran, Robert
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation.
    Verma, Deepti
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation.
    Lerm, Maria
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Belayneh, Meseret
    Univ Addis Abeba, Ethiopia.
    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, Clinical genetics.
    Stendahl, Olle
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation.
    Schön, Thomas
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Kalmar County Hospital, Kalmar, Sweden.
    Polymorphisms in CARD8 and NLRP3 are associated with extrapulmonary TB and poor clinical outcome in active TB in Ethiopia2019In: Scientific Reports, E-ISSN 2045-2322, Vol. 9, article id 3126Article in journal (Refereed)
    Abstract [en]

    Innate immunity is a first line defense against Mycobacterium tuberculosis infection where inflammasome activation and secretion of the pro-inflammatory cytokine IL-1beta, plays a major role. Thus, genetic polymorphisms in innate immunity-related genes such as CARD8 and NLRP3 may contribute to the understanding of why most exposed individuals do not develop infection. Our aim was to investigate the association between polymorphisms in CARD8 and NLRP3 and active tuberculosis (TB) as well as their relationship to treatment outcome in a high-endemic setting for TB. Polymorphisms in CARD8 (C10X) and NLRP3 (Q705K) were analysed in 1190 TB patients and 1990 healthy donors (HD). There was a significant association between homozygotes in the CARD8 polymorphism and extrapulmonary TB (EPTB), which was not the case for pulmonary TB or HDs. Among TB-patients, there was an association between poor treatment outcome and the NLRP3 (Q705K) polymorphism. Our study shows that inflammasome polymorphisms are associated with EPTB and poor clinical outcome in active TB in Ethiopia. The practical implications and determining causal relationships on a mechanistic level needs further study.

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  • 2. Order onlineBuy this publication >>
    Abdalla, Maie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Cancer and reconstructive surgery in Inflammatory bowel disease2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Ulcerative colitis (UC) is a chronic inflammatory disease that affects the colon. According to the literature, some thirty percent of UC patients may require a subtotal colectomy and ileostomy due to failure of medical treatment, acute toxic colitis or dysplasia/cancer diagnosis. Some patients choose to get continence restored with either an ileorectal anastomosis (IRA) or an ileal pouch-anal anastomosis (IPAA). Worldwide most surgeons prefer an IPAA to an IRA, despite reports of pouchitis, impaired fertility and fecundity. Fear of recurring proctitis and fear of rectal cancer in the remaining rectum is contributing to the choice of an IPAA. Little is known regarding the outcomes of IRA compared with IPAA in UC patients. We aimed to investigate the anorectal function, quality of life (QoL), risk of failure and rectal cancer in patients with UC restored with IRA and IPAA respectively.

    Methods: Data about all Inflammatory bowel disease (IBD) patients was obtained from the Swedish National Patient Register (NPR) between 1964-2014 and in one study from the Linköping University Hospital medical records 2006-2012. Patients who developed cancer were identified from the Swedish National Cancer Register. We investigated the risk of cancer and inflammation, functional outcome and failure as well as the quality of life for IRA and IPAA patients. Investigation of risk for cancer in IRA and IPAA compared with the background population was performed using survival analytic techniques: uni-and multivariate regression, Kaplan Meier curves and standardized incidence ratio.

    Results: Twelve percent (7,889 /63,795) of UC patients required colectomy according to the NPR. The relative risk for rectal cancer among patients with an IRA was increased (SIR 8.7). However, the absolute risk was 1.8% after a mean follow up of 8.6 years and the cumulative risk 10- and 20-years after IRA was 1.6% and 5.6%, respectively. Risk factors for rectal cancer were primary sclerosing cholangitis in patients with an IRA (hazard ratio 6.12), and severe dysplasia or cancer of the colon prior to subtotal colectomy in patients with a diverted rectum in place (hazard ratio 3.67). Regarding IPAA, the relative risk to develop rectal cancer was (SIR 0.4) compared with the background population and the absolute risk was only 0.06% after a mean of 12.2 years of follow up. Among patients operated at the Linköping University Hospital: IRA patients reported better overall continence according to the Öresland score with in median3 (IQR 2–5) for IRA (n=38) and 10 (IQR 5–15) for IPAA (n=39, p<0.001). There were no major differences regarding the QoL. According to the NPR, after a median follow up of 12.4 years failure occurred in 265(32%) out of 1112 patients, of which 76 were secondarily reconstructed with an IPAA. Failure of the IPAA occurred in 103 (6%) patients with primary and in 6 (8%) patients after secondary IPAA (log-rank p=0.38).

    Conclusion: IRA is a safe restorative procedure for selected UC patients. Patients should be aware of the annual postoperative endoscopic evaluation with biopsies as well as the need to the use of local anti-inflammatory preparations. However, IRA should not be offered for UC patients with an associated primary sclerosing cholangitis diagnosis due to the increased risk to develop rectal cancer in their rectal mucosa. In such case, IPAA is probably the treatment of choice.  

    List of papers
    1. Risk of Rectal Cancer After Colectomy for Patients With Ulcerative Colitis: A National Cohort Study
    Open this publication in new window or tab >>Risk of Rectal Cancer After Colectomy for Patients With Ulcerative Colitis: A National Cohort Study
    Show others...
    2017 (English)In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 15, no 7, p. 1055-1060, article id e2Article in journal (Refereed) Published
    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.

    Place, publisher, year, edition, pages
    Elsevier, 2017
    Keywords
    SIR; Surgery; IBD Treatment; Patient Management
    National Category
    Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:liu:diva-138873 (URN)10.1016/j.cgh.2016.11.036 (DOI)000403327600022 ()28013111 (PubMedID)
    Note

    Funding Agencies|Medical Research Council of Southeast Sweden; Futurum Academy for Health and Care (Region Jonkoping County, Sweden)

    Available from: 2017-06-27 Created: 2017-06-27 Last updated: 2019-11-04
    2. Survival of ileal pouch anal anastomosis constructed after colectomy or secondary to a previous ileorectal anastomosis in ulcerative colitis patients: a population-based cohort study
    Open this publication in new window or tab >>Survival of ileal pouch anal anastomosis constructed after colectomy or secondary to a previous ileorectal anastomosis in ulcerative colitis patients: a population-based cohort study
    2017 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 5, p. 531-535Article in journal (Refereed) Published
    Abstract [en]

    Objectives: Ileorectal anastomosis (IRA) affects bowel function, sexual function and reproduction less negatively than ileal pouch anal anastomosis (IPAA), the standard reconstruction after colectomy for ulcerative colitis (UC). In younger UC patients, IRA may have a role postponing pelvic surgery and IPAA. The aim of the present study was to investigate the survival of IPAA secondary to IRA compared to IPAA as primary reconstruction, as this has not previously been studied in UC. Patients and methods: All patients with UC diagnosis between 1960 and 2010 in Sweden were identified from the National Patient Registry. From this cohort, colectomized patients reconstructed with primary IPAA and patients reconstructed with IPAA secondary to IRA were identified. The survival of the IPAA was followed up until pouch failure, defined as pouchectomy and ileostomy or a diverting ileostomy alone. Results: Out of 63,796 patients, 1796 were reconstructed with IPAA, either primarily (n=1720) or secondary to a previous IRA (n=76). There were no demographic differences between the groups, including length of follow-up (median 12.6 (IQR 6.7-16.6) years and 10.0 (IQR 3.5-15.9) years, respectively). Failure of the IPAA occurred in 103 (6.0%) patients with primary and in 6 (8%) patients after secondary IPAA (P=0.38 log-rank). The 10-year pouch survival was 94% (95% CI 93-96) for primary IPAA and 92% (81-97) for secondary. Conclusions: Patients choosing IRA as primary reconstruction do not have an increased risk of failure of a later secondary IPAA in comparison with patients with primary IPAA.

    Place, publisher, year, edition, pages
    TAYLOR & FRANCIS LTD, 2017
    Keywords
    Ulcerative colitis; inflammatory bowel disease; ileal pouch anal anastomosis; ileoanal pouches; ileoanal reservoir; pelvic pouches; ileorectal anastomosis; restorative proctocolectomy; pouch failure; pouch survival
    National Category
    Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:liu:diva-136233 (URN)10.1080/00365521.2016.1278457 (DOI)000395746800006 ()28102092 (PubMedID)
    Note

    Funding Agencies|Bengt Ihres Fund; Medical Research Council of Southeast Sweden; Futurum - Academy for Health and Care; Region Jonkoping County, Sweden

    Available from: 2017-03-31 Created: 2017-03-31 Last updated: 2019-11-04
    3. Anorectal Function After Ileo-Rectal Anastomosis Is Better than Pelvic Pouch in Selected Ulcerative Colitis Patients
    Open this publication in new window or tab >>Anorectal Function After Ileo-Rectal Anastomosis Is Better than Pelvic Pouch in Selected Ulcerative Colitis Patients
    Show others...
    2020 (English)In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, p. 250-259Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: With a lifelong perspective, 12% of ulcerative colitis patients will need a colectomy. Further reconstruction via ileo-rectal anastomosis or pouch can be affected by patients' perspective of their quality of life after surgery.

    AIM: To assess the function and quality of life after restorative procedures with either ileo-rectal anastomosis or ileal pouch-anal anastomosis in relation to the inflammatory activity on endoscopy and in biopsies.

    METHOD: A total of 143 UC patients operated with subtotal colectomy and ileo-rectal anastomosis or pouches between 1992 and 2006 at Linköping University Hospital were invited to participate. Those who completed the validated questionnaires (Öresland score, SF-36, Short Health Scale) were offered an endoscopic evaluation including multiple biopsies. Associations between anorectal function and quality of life with type of restorative procedure and severity of endoscopic and histopathologic grading of inflammation were evaluated.

    RESULTS: Some 77 (53.9%) eligible patients completed questionnaires, of these 68 (88.3%) underwent endoscopic evaluation after a median follow-up of 12.5 (range 3.5-19.4) years after restorative procedure. Patients with ileo-rectal anastomosis reported better overall Öresland score: median = 3 (IQR 2-5) for ileo-rectal anastomosis (n = 38) and 10 (IQR 5-15) for pouch patients (n = 39) (p < 0.001). Anorectal function (Öresland score) and endoscopic findings (Baron-Ginsberg score) were positively correlated in pouch patients (tau: 0.28, p = 0.006).

    CONCLUSION: Patients operated with ileo-rectal anastomosis reported better continence compared to pouches. Minor differences were noted regarding the quality of life. Ileo-rectal anastomosis is a valid option for properly selected ulcerative colitis patients if strict postoperative endoscopic surveillance is carried out.

    Place, publisher, year, edition, pages
    Springer-Verlag New York, 2020
    Keywords
    Ileal pouch-anal anastomosis, Ileo-rectal anastomosis, Quality of life, Ulcerative colitis
    National Category
    Surgery Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:liu:diva-160247 (URN)10.1007/s10620-019-05757-6 (DOI)31372911 (PubMedID)2-s2.0-85070104240 (Scopus ID)
    Available from: 2019-09-13 Created: 2019-09-13 Last updated: 2021-12-29Bibliographically approved
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  • 3.
    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.

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  • 4.
    Abdalla, Maie
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Department of General Surgery, Faculty of Medicine, Suez Canal University, Egypt.
    Norblad, Rickard
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Olsson, Malin
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Landerholm, Kalle
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Department of Surgery, Ryhov County Hospital, Jönköping, Sweden.
    Andersson, Peter
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Region Östergötland, Regionledningskontoret, Center for Disaster Medicine and Traumatology.
    Söderholm, Johan D.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    Andersson, Roland
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Department of Surgery, Ryhov County Hospital, Jönköping, Sweden.
    Myrelid, Pär
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    Anorectal Function After Ileo-Rectal Anastomosis Is Better than Pelvic Pouch in Selected Ulcerative Colitis Patients2020In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, p. 250-259Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: With a lifelong perspective, 12% of ulcerative colitis patients will need a colectomy. Further reconstruction via ileo-rectal anastomosis or pouch can be affected by patients' perspective of their quality of life after surgery.

    AIM: To assess the function and quality of life after restorative procedures with either ileo-rectal anastomosis or ileal pouch-anal anastomosis in relation to the inflammatory activity on endoscopy and in biopsies.

    METHOD: A total of 143 UC patients operated with subtotal colectomy and ileo-rectal anastomosis or pouches between 1992 and 2006 at Linköping University Hospital were invited to participate. Those who completed the validated questionnaires (Öresland score, SF-36, Short Health Scale) were offered an endoscopic evaluation including multiple biopsies. Associations between anorectal function and quality of life with type of restorative procedure and severity of endoscopic and histopathologic grading of inflammation were evaluated.

    RESULTS: Some 77 (53.9%) eligible patients completed questionnaires, of these 68 (88.3%) underwent endoscopic evaluation after a median follow-up of 12.5 (range 3.5-19.4) years after restorative procedure. Patients with ileo-rectal anastomosis reported better overall Öresland score: median = 3 (IQR 2-5) for ileo-rectal anastomosis (n = 38) and 10 (IQR 5-15) for pouch patients (n = 39) (p < 0.001). Anorectal function (Öresland score) and endoscopic findings (Baron-Ginsberg score) were positively correlated in pouch patients (tau: 0.28, p = 0.006).

    CONCLUSION: Patients operated with ileo-rectal anastomosis reported better continence compared to pouches. Minor differences were noted regarding the quality of life. Ileo-rectal anastomosis is a valid option for properly selected ulcerative colitis patients if strict postoperative endoscopic surveillance is carried out.

    Download full text (pdf)
    fulltext
  • 5.
    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. Suez Canal Univ, Surg Dept, Plast Surg Unit, Ismailia, Egypt.
    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. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    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, Vol. 42, no 2, p. 1222-1230Article 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.

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  • 6.
    Aberg, Fredrik
    et al.
    Univ Helsinki, Finland; Sahlgrens Univ Hosp, Sweden.
    Danford, Christopher J.
    Beth Israel Deaconess Med Ctr, MA 02215 USA.
    Thiele, Maja
    Odense Univ Hosp, Denmark; Univ Southern Denmark, Denmark.
    Talback, Mats
    Karolinska Inst, Sweden.
    Rasmussen, Ditlev Nytoft
    Odense Univ Hosp, Denmark.
    Jiang, Z. Gordon
    Beth Israel Deaconess Med Ctr, MA 02215 USA.
    Hammar, Niklas
    Karolinska Inst, Sweden.
    Nasr, Patrik
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Ekstedt, Mattias
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    But, Anna
    Univ Helsinki, Finland; Helsinki Univ Hosp, Finland.
    Puukka, Pauli
    Univ Helsinki, Finland.
    Krag, Aleksander
    Odense Univ Hosp, Denmark; Univ Southern Denmark, Denmark.
    Sundvall, Jouko
    Finnish Inst Hlth & Welf, Finland.
    Erlund, Iris
    Finnish Inst Hlth & Welf, Finland.
    Salomaa, Veikko
    Finnish Inst Hlth & Welf, Finland.
    Stal, Per
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Kechagias, Stergios
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Hultcrantz, Rolf
    Karolinska Inst, Sweden.
    Lai, Michelle
    Beth Israel Deaconess Med Ctr, MA 02215 USA.
    Afdhal, Nezam
    Beth Israel Deaconess Med Ctr, MA 02215 USA.
    Jula, Antti
    Finnish Inst Hlth & Welf, Finland.
    Mannisto, Satu
    Finnish Inst Hlth & Welf, Finland.
    Lundqvist, Annamari
    Finnish Inst Hlth & Welf, Finland.
    Perola, Markus
    Finnish Inst Hlth & Welf, Finland.
    Farkkila, Martti
    Univ Helsinki, Finland.
    Hagstrom, Hannes
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    A Dynamic Aspartate-to-Alanine Aminotransferase Ratio Provides Valid Predictions of Incident Severe Liver Disease2021In: HEPATOLOGY COMMUNICATIONS, ISSN 2471-254X, Vol. 5, no 6, p. 1021-1035Article in journal (Refereed)
    Abstract [en]

    The aspartate-to-alanine aminotransferase ratio (AAR) is associated with liver fibrosis, but its predictive performance is suboptimal. We hypothesized that the association between AAR and liver disease depends on absolute transaminase levels and developed and validated a model to predict liver-related outcomes in the general population. A Cox regression model based on age, AAR, and alanine aminotransferase (ALT) level (dynamic AAR [dAAR]) using restricted cubic splines was developed in Finnish population-based health-examination surveys (FINRISK, 2002-2012; n = 18,067) with linked registry data for incident liver-related hospitalizations, hepatocellular carcinoma, or liver death. The model was externally validated for liver-related outcomes in a Swedish population cohort (Swedish Apolipoprotein Mortality Risk [AMORIS] subcohort; n = 126,941) and for predicting outcomes and/or prevalent fibrosis/cirrhosis in biopsied patients with nonalcoholic fatty liver disease (NAFLD), chronic hepatitis C, or alcohol-related liver disease (ALD). The dynamic AAR model predicted liver-related outcomes both overall (optimism-corrected C-statistic, 0.81) and in subgroup analyses of the FINRISK cohort and identified persons with &gt;10% risk for liver-related outcomes within 10 years. In independent cohorts, the C-statistic for predicting liver-related outcomes up to a 10-year follow-up was 0.72 in the AMORIS cohort, 0.81 in NAFLD, and 0.75 in ALD. Area-under-the-curve (AUC) for detecting prevalent cirrhosis was 0.80-0.83 in NAFLD, 0.80 in hepatitis C, but only 0.71 in ALD. In ALD, model performance improved when using aspartate aminotransferase instead of ALT in the model (C-statistic, 0.84 for outcome; AUC, 0.82 for prevalent cirrhosis). Conclusion: A dAAR score provides prospective predictions for the risk of incident severe liver outcomes in the general population and helps detect advanced liver fibrosis/cirrhosis. The dAAR score could potentially be used for screening the unselected general population and as a trigger for further liver evaluations.

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  • 7.
    Adamina, Michel
    et al.
    Cantonal Hosp Winterthur, Switzerland; Univ Basel, Switzerland.
    Bonovas, Stefanos
    Humanitas Univ, Italy; Humanitas Clin and Res Ctr, Italy.
    Raine, Tim
    Cambridge Univ Hosp NHS Fdn Trust, England.
    Spinelli, Antonino
    Humanitas Univ, Italy.
    Warusavitarne, Janindra
    Imperial Coll London, England.
    Armuzzi, Alessandro
    Univ Cattolica Sacro Cuore, Italy.
    Bachmann, Oliver
    Siloah St Trudpert Hosp, Germany.
    Bager, Palle
    Aarhus Univ Hosp, Denmark.
    Biancone, Livia
    Univ Tor Vergata Rome, Italy.
    Bokemeyer, Bernd
    Gastroenterol Practice Minden, Germany.
    Bossuyt, Peter
    Imelda Gen Hosp, Belgium.
    Burisch, Johan
    Univ Copenhagen, Denmark.
    Collins, Paul
    Royal Liverpool Univ Hosp, England.
    Doherty, Glen
    St Vincents Univ Hosp, Ireland; St Vincents Univ Hosp, Ireland.
    El-Hussuna, Alaa
    Aalborg Univ Hosp, Denmark.
    Ellul, Pierre
    Mater Dei Hosp, Malta.
    Fiorino, Gionata
    Humanitas Univ, Italy; Humanitas Clin and Res Ctr, Italy.
    Frei-Lanter, Cornelia
    Hosp Zollikerberg, Switzerland.
    Furfaro, Federica
    Humanitas Clin and Res Ctr, Italy.
    Gingert, Christian
    Cantonal Hosp Winterthur, Switzerland; Univ Witten Herdecke, Germany.
    Gionchetti, Paolo
    Univ Bologna, Italy.
    Gisbert, Javier P.
    Univ Autonoma Madrid, Spain.
    Gomollon, Fernando
    Hosp Cli Univ Lozano Blesa, Spain.
    Lorenzo, Marien Gonzalez
    Humanitas Univ, Italy.
    Gordon, Hannah
    Barts Hlth NHS Trust, England.
    Hlavaty, Tibor
    Comenius Univ, Slovakia; Comenius Univ, Slovakia.
    Juillerat, Pascal
    Univ Hosp Bern, Switzerland.
    Katsanos, Konstantinos
    Univ and Med Sch Ioannina, Greece.
    Kopylov, Uri
    Tel HaShomer Sheba Med Ctr, Israel; Sackler Med Sch, Israel.
    Krustins, Eduards
    Riga Stradins Univ, Latvia.
    Kucharzik, Torsten
    Hosp Luneburg, Germany.
    Lytras, Theodore
    Natl Publ Hlth Org, Greece.
    Maaser, Christian
    Hosp Luneburg, Germany.
    Magro, Fernando
    Dept Pharmacol and Therapeut, Portugal; Univ Porto, Portugal.
    Marshall, John Kenneth
    McMaster Univ, Canada; McMaster Univ, Canada.
    Myrelid, Pär
    Linköping University, Department of Biomedical and Clinical Sciences, 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.
    Pellino, Gianluca
    Univ Campania Luigi Vanvitelli, Italy.
    Rosa, Isadora
    IPOLFG, Portugal.
    Sabino, Joao
    Katholieke Univ Leuven, Belgium.
    Savarino, Edoardo
    Univ Padua, Italy.
    Stassen, Laurents
    Maastricht Univ Med Ctr, Netherlands.
    Torres, Joana
    Hosp Beatriz Angelo, Portugal.
    Uzzan, Mathieu
    Beaujon Hosp, France.
    Vavricka, Stephan
    Univ Hosp, Switzerland.
    Verstockt, Bram
    Katholieke Univ Leuven, Belgium; Katholieke Univ Leuven, Belgium.
    Zmora, Oded
    Shamir Med Ctr Assaf Harofe, Israel.
    ECCO Guidelines on Therapeutics in Crohns Disease: Surgical Treatment2020In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 14, no 2, p. 155-168Article in journal (Refereed)
    Abstract [en]

    This article is the second in a series of two publications relating to the European Crohns and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohns disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohns disease and an update of previous guidelines.

  • 8.
    Adamina, Michel
    et al.
    Cantonal Hosp Winterthur, Switzerland; Univ Basel, Switzerland.
    Feakins, Roger
    Royal Free Hosp, England.
    Iacucci, Marietta
    Univ Birmingham, England; Univ Hosp Birmingham NHS Trust, England.
    Spinelli, Antonino
    Humanitas Clin & Res Ctr, Italy; Humanitas Univ, Italy.
    Cannatelli, Rosanna
    Univ Birmingham, England; Spedali Civili Brescia, Italy.
    DHoore, Andre
    Univ Hosp Leuven, Belgium.
    Driessen, Ann
    Univ Antwerp, Belgium.
    Katsanos, Konstantinos
    Univ Ioannina, Greece; Med Sch Ioannina, Greece.
    Mookhoek, Aart
    Amsterdam UMC, Netherlands.
    Myrelid, Pär
    Linköping University, Department of Biomedical and Clinical Sciences, 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.
    Pellino, Gianluca
    Univ Campania Luigi Vanvitelli, Italy; Vall dHebron Univ Hosp, Spain.
    Peros, Georgios
    Cantonal Hosp Winterthur, Italy; Humanitas Clin & Res Ctr, Italy.
    Tontini, Gian Eugenio
    Fdn IRCCS Ca Granda Osped Maggiore Policlin, Italy; Univ Milan, Italy.
    Tripathi, Monika
    Cambridge Univ Hosp NHS Fdn Trust, England.
    Yanai, Henit
    IBD Ctr, Israel.
    Svrcek, Magali
    Sorbonne Univ, France.
    ECCO Topical Review Optimising Reporting in Surgery, Endoscopy, and Histopathology Collaboration Between S-ECCO, EduCom, H-ECCO2021In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 15, no 7, p. 1089-1105Article, review/survey (Refereed)
    Abstract [en]

    Background and Aims: Diagnosis and management of inflammatory bowel diseases [IBD] requires a lifelong multidisciplinary approach.The quality of medical reporting is crucial in this context.The present topical review addresses the need for optimised reporting in endoscopy, surgery, and histopathology. Methods: A consensus expert panel consisting of gastroenterologists, surgeons, and pathologists, convened by the European Crohns and Colitis Organisation, performed a systematic literature review. The following topics were covered: in endoscopy: [i] general IBD endoscopy; [ii] disease activity and surveillance; [iii] endoscopy treatment in IBD; in surgery: [iv] medical history with surgical relevance, surgical indication, and strategy; [v] operative approach; [vi] intraoperative disease description; [vii] operative steps; in pathology: [viii] macroscopic assessment and interpretation of resection specimens; [ix] IBD histology, including biopsies, surgical resections, and neoplasia; [x] IBD histology conclusion and report. Statements were developed using a Delphi methodology incorporating two consecutive rounds. Current practice positions were set when &gt;= 80% of participants agreed on a recommendation. Results: Thirty practice positions established a standard terminology for optimal reporting in endoscopy, surgery, and histopathology. Assessment of disease activity, surveillance recommendations, advice to surgeons for operative indication and strategies, including margins and extent of resection, and diagnostic criteria of IBD, as well as guidance for the interpretation of dysplasia and cancer, were handled. A standardised report including a core set of items to include in each specialty report, was defined. Conclusions: Interdisciplinary high-quality care requires thorough and standardised reporting across specialties.This topical review offers an actionable framework and practice recommendations to optimise reporting in endoscopy, surgery, and histopathology.

  • 9.
    Ahmad, Awais
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Heijke, R.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Rheumatology.
    Eriksson, Per
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Rheumatology.
    Wirestam, Lina
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Rheumatology.
    Kechagias, Stergios
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Dahle, Charlotte
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Sjöwall, Christopher
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Rheumatology.
    Autoantibodies associated with primary biliary cholangitis are common among patients with systemic lupus erythematosus even in the absence of elevated liver enzymes2021In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 203, no 1, p. 22-31Article in journal (Refereed)
    Abstract [en]

    Knowledge of concomitant autoimmune liver diseases (AILD) is more detailed in primary Sjogrens syndrome (pSS) compared to systemic lupus erythematosus (SLE). Herein, the prevalence of autoantibodies associated with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) was investigated in stored sera from patients with SLE (n = 280) and pSS (n = 114). Antibodies against mitochondria (AMA), liver-kidney microsomal (LKM) antigen, smooth muscle (SMA) and anti-nuclear antibodies (ANA) were analysed with immunofluorescence microscopy. In addition, AILD-associated autoantibodies were tested with immunoblot. Prior to sampling, eight SLE (2 center dot 9%) and three pSS (2 center dot 6%) cases were diagnosed with AILD. Among SLE-cases without known AILD (n = 272), 26 (9 center dot 6%) had PBC-associated autoantibodies, 15 (5 center dot 5%) AIH-associated autoantibodies (excluding ANA) and one serological overlap. Most subjects with PBC-associated autoantibodies had liver enzymes within reference limits (22 of 27, 81%) or mild laboratory cholestasis (two of 27, 7 center dot 4%), while one fulfilled the diagnostic PBC-criteria. AMA-M2 detected by immunoblot was the most common PBC-associated autoantibody in SLE (20 of 272, 7 center dot 4%). The prevalence of SMA (4 center dot 4%) was comparable with a healthy reference population, but associated with elevated liver enzymes in four of 12 (25%), none meeting AIH-criteria. The patient with combined AIH/PBC-serology had liver enzymes within reference limits. Among pSS cases without known AILD (n = 111), nine (8 center dot 1%) had PBC-associated, 12 (10 center dot 8%) AIH-associated autoantibodies and two overlapped. PBC-associated autoantibodies were found as frequently in SLE as in pSS but were, with few exceptions, not associated with laboratory signs of liver disease. Overall, AILD-associated autoantibodies were predominantly detected by immunoblot and no significant difference in liver enzymes was found between AILD autoantibody-negative and -positive patients.

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  • 10.
    Ahrens, Peter
    et al.
    Statens Serum Inst, Denmark.
    Andersen, Lee OBrien
    Statens Serum Inst, Denmark.
    Lilje, Berit
    Statens Serum Inst, Denmark.
    Johannesen, Thor Bech
    Statens Serum Inst, Denmark.
    Gomez Dahl, Ebba
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Dermatology and Venerology. Statens Serum Inst, Denmark; Hlth Ctr Gullviksborg, Sweden.
    Baig, Sharmin
    Statens Serum Inst, Denmark.
    Jensen, Jorgen Skov
    Statens Serum Inst, Denmark.
    Falk, Lars
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Dermatology and Venerology.
    Changes in the vaginal microbiota following antibiotic treatment forMycoplasma genitalium,Chlamydia trachomatisand bacterial vaginosis2020In: PLOS ONE, E-ISSN 1932-6203, Vol. 15, no 7, article id e0236036Article in journal (Refereed)
    Abstract [en]

    The human vagina harbor a rich microbiota. The optimal state is dominated by lactobacilli that help to maintain health and prevent various diseases. However, the microbiota may rapidly change to a polymicrobial state that has been linked to a number of diseases. In the present study, the temporal changes of the vaginal microbiota in patients treated for sexually transmitted diseases or bacterial vaginosis (BV) and in untreated controls were studied for 26 days. The patients included 52 women treated with azithromycin, tetracyclines or moxifloxacin for present or suspected infection withChlamydia trachomatisorMycoplasma genitalium. Women with concurrent BV were also treated with metronidazole. The controls were 10 healthy women of matching age. The microbiota was analyzed by 16S rRNA gene deep sequencing, specific qPCRs and microscopy. There was generally good correlation between Nugent score and community state type (CST) and qPCR confirmed the sequencing results. By sequencing, more than 600 different taxa were found, but only 33 constituted more than 1 parts per thousand of the sequences. In both patients and controls the microbiota could be divided into three different community state types, CST-I, CST-III and CST-IV. Without metronidazole, the microbiota remained relatively stable regarding CST although changes were seen during menstrual periods. Administration of metronidazole changed the microbiota from CST-IV to CST-III in approximately 50% of the treated patients. In contrast, the CST was generally unaffected by azithromycin or tetracyclines. In 30% of the BV patients,Gardnerella vaginaliswas not eradicated by metronidazole. The majority of women colonized withUreaplasma parvumremained positive after azithromycin whileU.urealyticumwas eradicated.

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  • 11.
    Ajmera, Veeral H.
    et al.
    Univ Calif San Diego Hlth, CA USA.
    Cachay, Edward
    Univ Calif San Diego, CA 92103 USA.
    Ramers, Christian
    Family Hlth Ctr, CA USA.
    Vodkin, Irine
    Univ Calif San Diego Hlth, CA USA.
    Bassirian, Shirin
    Univ Calif San Diego Hlth, CA USA.
    Singh, Seema
    Univ Calif San Diego Hlth, CA USA.
    Mangla, Neeraj
    Univ Calif San Diego Hlth, CA USA.
    Bettencourt, Richele
    Univ Calif San Diego Hlth, CA USA.
    Aldous, Jeannette L.
    San Ysidro Hlth, CA USA.
    Park, Daniel
    San Ysidro Hlth, CA USA.
    Lee, Daniel
    Univ Calif San Diego, CA 92103 USA.
    Blanchard, Jennifer
    Univ Calif San Diego, CA 92103 USA.
    Mamidipalli, Adrija
    Univ Calif San Diego, CA 92093 USA.
    Boehringer, Andrew
    Univ Calif San Diego, CA 92093 USA.
    Aslam, Saima
    Univ Calif San Diego, CA 92103 USA.
    Dahlqvist Leinhard, Olof
    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. AMRA Med AB, Linkoping, Sweden.
    Richards, Lisa
    Univ Calif San Diego Hlth, CA USA.
    Sirlin, Claude B.
    Univ Calif San Diego, CA 92093 USA.
    Loomba, Rohit
    Univ Calif San Diego, CA 92093 USA.
    MRI Assessment of Treatment Response in HIV-associated NAFLD: A Randomized Trial of a Stearoyl-Coenzyme-A-Desaturase-1 Inhibitor (ARRIVE Trial)2019In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 70, no 5, p. 1531-1545Article in journal (Refereed)
    Abstract [en]

    Aramchol, an oral stearoyl-coenzyme-A-desaturase-1 inhibitor, has been shown to reduce hepatic fat content in patients with primary nonalcoholic fatty liver disease (NAFLD); however, its effect in patients with human immunodeficiency virus (HIV)-associated NAFLD is unknown. The aramchol for HIV-associated NAFLD and lipodystrophy (ARRIVE) trial was a double-blind, randomized, investigator-initiated, placebo-controlled trial to test the efficacy of 12 weeks of treatment with aramchol versus placebo in HIV-associated NAFLD. Fifty patients with HIV-associated NAFLD, defined by magnetic resonance imaging (MRI)-proton density fat fraction (PDFF) amp;gt;= 5%, were randomized to receive either aramchol 600 mg daily (n = 25) or placebo (n = 25) for 12 weeks. The primary endpoint was a change in hepatic fat as measured by MRI-PDFF in colocalized regions of interest. Secondary endpoints included changes in liver stiffness using magnetic resonance elastography (MRE) and vibration-controlled transient elastography (VCTE), and exploratory endpoints included changes in total-body fat and muscle depots on dual-energy X-ray absorptiometry (DXA), whole-body MRI, and cardiac MRI. The mean (+/- standard deviation) of age and body mass index were 48.2 +/- 10.3 years and 30.7 +/- 4.6 kg/m(2), respectively. There was no difference in the reduction in mean MRI-PDFF between the aramchol group at -1.3% (baseline MRI-PDFF 15.6% versus end-of-treatment MRI-PDFF 14.4%, P = 0.24) and the placebo group at -1.4% (baseline MRI-PDFF 13.3% versus end-of-treatment MRI-PDFF 11.9%, P = 0.26). There was no difference in the relative decline in mean MRI-PDFF between the aramchol and placebo groups (6.8% versus 1.1%, P = 0.68). There were no differences in MRE-derived and VCTE-derived liver stiffness and whole-body (fat and muscle) composition analysis by MRI or DXA. Compared to baseline, end-of-treatment aminotransferases were lower in the aramchol group but not in the placebo arm. There were no significant adverse events. Conclusion: Aramchol, over a 12-week period, did not reduce hepatic fat or change body fat and muscle composition by using MRI-based assessment in patients with HIV-associated NAFLD (clinicaltrials.gov ID:NCT02684591).

  • 12.
    Akbari, Camilla
    et al.
    Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Dodd, Maja
    Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Stål, Per
    Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden; Karolinska University Hospital, Stockholm, Sweden.
    Nasr, Patrik
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken. epartment of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Ekstedt, Mattias
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Kechagias, Stergios
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Vessby, Johan
    Uppsala University Hospital, Uppsala, Sweden.
    Rorsman, Fredrik
    Uppsala University Hospital, Uppsala, Sweden.
    Zhang, Xiao
    Merck & Co., Inc., Rahway, NJ, USA.
    Wang, Tongtong
    Merck & Co., Inc., Rahway, NJ, USA.
    Jemielita, Thomas
    Merck & Co., Inc., Rahway, NJ, USA.
    Fernandes, Gail
    Merck & Co., Inc., Rahway, NJ, USA.
    Engel, Samuel S.
    Merck & Co., Inc., Rahway, NJ, USA.
    Hagström, Hannes
    Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden; Karolinska University Hospital, Stockholm, Sweden.
    Shang, Ying
    Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Long-term major adverse liver outcomes in 1,260 patients with non-cirrhotic NAFLD2024In: JHEP Reports, ISSN 2589-5559, Vol. 6, no 2, article id 100915Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

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  • 13. Order onlineBuy this publication >>
    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, E-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: 2024-01-16
    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: 2022-09-28
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    Staging and tumor biological mechanisms of lymph node metastasis in invasive urinary bladder cancer
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  • 14.
    Alkaissi, Lina Y.
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    Winberg Tinnerfelt, Martin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Heil, Stéphanie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Haapaniemi, Staffan
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Myrelid, Pär
    Linköping University, Department of Biomedical and Clinical Sciences, 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.
    Stange, Eduard F
    Department of Gastroenterology, Dept. Internal Medicine I, University of Tübingen, 72076 Tübingen, Germany.
    Söderholm, Johan D
    Linköping University, Department of Biomedical and Clinical Sciences, 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
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Antagonism of Adherent Invasive E. coli LF82 With Human α-defensin 5 in the Follicle-associated Epithelium of Patients With Ileal Crohn’s Disease2021In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 27, no 7, p. 1116-1127Article in journal (Refereed)
    Abstract [en]

    Background: The first visible signs of Crohns disease (CD) are microscopic erosions over the follicle-associated epithelium (FAE). The aim of the study was to investigate the effects of human alpha-defensin 5 (HD5) on adherent-invasive Escherichia coli LF82 translocation and HD5 secretion after LF82 exposure in an in vitro model of human FAE and in human FAE ex vivo. Methods: An in vitro FAE-model was set up by the coculture of Raji B cells and Caco-2-cl1 cells. Ileal FAE from patients with CD and controls were mounted in Ussing chambers. The effect of HD5 on LF82 translocation was studied by LF82 exposure to the cells or tissues with or without incubation with HD5. The HD5 secretion was measured in human FAE exposed to LF82 or Salmonella typhimurium. The HD5 levels were evaluated by immunofluorescence, immunoblotting, and ELISA. Results: There was an increased LF82 translocation across the FAE-model compared with Caco-2-cl1 (P < 0.05). Incubation of cell/tissues with HD5 before LF82 exposure reduced bacterial passage in both models. Human FAE showed increased LF82 translocation in CD compared with controls and attenuated passage after incubation with sublethal HD5 in both CD and controls (P < 0.05). LF82 exposure resulted in a lower HD5 secretion in CD FAE compared with controls (P < 0.05), whereas Salmonella exposure caused equal secretion on CD and controls. There were significantly lower HD5 levels in CD tissues compared with controls. Conclusions: Sublethal HD5 reduces the ability of LF82 to translocate through FAE. The HD5 is secreted less in CD in response to LF82, despite a normal response to Salmonella. This further implicates the integrated role of antimicrobial factors and barrier function in CD pathogenesis.

  • 15.
    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.

  • 16.
    Almlöv, Karin
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, 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 Norrköping.
    Woisetschläger, Mischa
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Loftås, Per
    Linköping University, Department of Biomedical and Clinical Sciences, 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.
    Hallböök, Olof
    Linköping University, Department of Biomedical and Clinical Sciences, 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.
    Elander, Nils
    Linköping University, Department of Biomedical and Clinical Sciences, 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 Oncology.
    Sandström, Per
    Linköping University, Department of Biomedical and Clinical Sciences, 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.
    MRI Lymph Node Evaluation for Prediction of Metastases in Rectal Cancer2020In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 40, no 5, p. 2757-2763Article in journal (Refereed)
    Abstract [en]

    Aim: To explore whether the size and characteristics of the largest regional lymph node in patients with rectal cancer, based on magnetic resonance imaging (MRI), following neoadjuvant therapy and before surgery, is able to identify patients at high risk of developing metachronous metastases.

    Patients and Methods: A retrospective case–control study with data from the Swedish Colo-Rectal Cancer Registry. Forty patients were identified with metachronous metastases (M+), and 40 patients without metastases (M0) were matched as controls.

    Results: Patients with M+ disease were more likely to have a regional lymph node measuring ≥5 mm than patients with M0. (87% vs. 65%, p=0.02). There was also a significant difference between the groups regarding the presence of an irregular border of the largest lymph node (68% vs. 40%, p=0.01).

    Conclusion: Lymph nodes measuring ≥5 mm with/without displaying irregular borders at MRI performed after neoadjuvant therapy emerged as risk factors for metachronous metastases in patients with rectal cancer. Intensified follow-up programmes may be indicated in these patients.

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  • 17.
    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.

  • 18.
    Andersson, Roland
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Cty Hosp Ryhov, Sweden.
    May fibrine glue play aroleasanadjunct?2019In: Colo-Proctology, ISSN 0174-2442, E-ISSN 1615-6730, Vol. 41, no 3, p. 212-212Article in journal (Other academic)
    Abstract [en]

    n/a

  • 19.
    Andersson, Roland
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Department of Surgery, County Hospital Ryhov, Jönköping, Sweden.
    Doll, Dietrich
    Department of Surgery, St Marienhospital Vechta, Academic Teaching Hospital of the Medical School Hannover, Vechta, Germany.
    Stauffer, Verena K
    Department of Emergency Medicine, Sonnenhofspital, Lindenhofgruppe, Bern, Switzerland.
    Vogt, Andreas P
    Department of Anesthesiology and Pain Medicine, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland.
    Boggs, Steven D
    Department of Anesthesiology, University of Tennessee Health Science Center, Memphis, Tennessee.
    Luedi, Markus M.
    Department of Anesthesiology and Pain Medicine, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland.
    Interdisciplinary Dialogue Is Needed When Defining Perioperative Recommendations: Conflicting Guidelines for Anesthetizing Patients for Pilonidal Surgery2018In: AandA practice, ISSN 2575-3126, Vol. 11, no 8, p. 227-229Article in journal (Refereed)
    Abstract [en]

    National or international guidelines can help surgeons and anesthesiologists make treatment decisions, but the existence of conflicting recommendations can hinder treatment rather than helping. A case in point is the treatment of pilonidal sinus disease, a chronic subcutaneous infection located in the sacrococcygeal area. Its incidence is rising, reaching almost 100/100,000 inhabitants. Three surgical societies have proposed guidelines for treating the disease, but these guidelines vary greatly in their approach to anesthesia. Who should provide input into guidelines? And how can medical disciplines successfully collaborate? Anesthesiologists must be involved in defining perioperative recommendations not only in patients with pilonidal sinus disease.

  • 20.
    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.

  • 21.
    Anstee, Quentin M.
    et al.
    Newcastle Univ, England; Newcastle Upon Tyne Hosp NHS Fdn Trust, England.
    Darlay, Rebecca
    Newcastle Univ, England.
    Cockell, Simon
    Newcastle Univ, England.
    Meroni, Marica
    Univ Milan, Italy.
    Govaere, Olivier
    Newcastle Univ, England.
    Tiniakos, Dina
    Newcastle Univ, England; Natl & Kapodistrian Univ Athens, Greece.
    Burt, Alastair D.
    Newcastle Univ, England; Univ Adelaide, Australia.
    Bedossa, Pierre
    Newcastle Univ, England.
    Palmer, Jeremy
    Newcastle Univ, England.
    Liu, Yang-Lin
    Newcastle Univ, England.
    Aithal, Guruprasad P.
    Nottingham Univ Hosp NHS Trust, England; Univ Nottingham, England.
    Allison, Michael
    Cambridge Univ NHS Fdn Trust, England.
    Yki-Jarvinen, Hannele
    Univ Helsinki, Finland; Helsinki Univ Hosp, Finland.
    Vacca, Michele
    Cambridge Univ NHS Fdn Trust, England; Univ Cambridge, England; Univ Cambridge, England.
    Dufour, Jean-Francois
    Univ Bern, Switzerland.
    Invernizzi, Pietro
    Univ Milano Bicocca, Italy; San Gerardo Hosp, Italy.
    Prati, Daniele
    Univ Milan, Italy.
    Ekstedt, Mattias
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Kechagias, Stergios
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Francque, Sven
    Antwerp Univ Hosp, Belgium.
    Petta, Salvatore
    Univ Palermo, Italy.
    Bugianesi, Elisabetta
    Univ Turin, Italy.
    Clement, Karine
    Sorbonne Univ, France.
    Ratziu, Vlad
    Sorbonne Univ, France.
    Schattenberg, Joern M.
    Johannes Gutenberg Univ Mainz, Germany.
    Valenti, Luca
    Univ Milan, Italy.
    Day, Christopher P.
    Newcastle Univ, England.
    Cordell, Heather J.
    Newcastle Univ, England.
    Daly, Ann K.
    Newcastle Univ, England.
    Genome-wide association study of non-alcoholic fatty liver and steatohepatitis in a histologically characterised cohort2020In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 73, no 3, p. 505-515Article in journal (Refereed)
    Abstract [en]

    Background & Aims: Genetic factors associated with nonalcoholic fatty liver disease (NAFLD) remain incompletely understood. To date, most genome-wide association studies (GWASs) have adopted radiologically assessed hepatic triglyceride content as the reference phenotype and so cannot address steatohepatitis or fibrosis. We describe a GWAS encompassing the full spectrum of histologically characterised NAFLD. Methods: The GWAS involved 1,483 European NAFLD cases and 17,781 genetically matched controls. A replication cohort of 559 NAFLD cases and 945 controls was genotyped to confirm signals showing genome-wide or close to genome-wide significance. Results: Case-control analysis identified signals showing p values &lt;= 5 x 10(-8) at 4 locations (chromosome [chr] 2 GCKR/C2ORF16; chr4 HSD17B13; chr19 TM6SF2; chr22 PNPLA3) together with 2 other signals with p &lt;1 x 10(-7) (chr1 near LEPR and chr8 near IDO2/TC1). Case-only analysis of quantitative traits showed that the PNPLA3 signal (rs738409) had genome-wide significance for steatosis, fibrosis and NAFLD activity score and a new signal (PYGO1 rs62021874) had close to genome-wide significance for steatosis (p = 8.2 x 10(-8)). Subgroup case-control analysis for NASH confirmed the PNPLA3 signal. The chr1 LEPR single nucleotide polymorphism also showed genome-wide significance for this phenotype. Considering the subgroup with advanced fibrosis (&gt;= F3), the signals on chr2, chr19 and chr22 maintained their genome-wide significance. Except for GCKR/C2ORF16, the genome-wide significance signals were replicated. Conclusions: This study confirms PNPLA3 as a risk factor for the full histological spectrum of NAFLD at genome-wide significance levels, with important contributions from TM6SF2 and HSD17B13. PYGO1 is a novel steatosis modifier, suggesting that Wnt signalling pathways may be relevant in NAFLD pathogenesis. Lay summary: Non-alcoholic fatty liver disease is a common disease where excessive fat accumulates in the liver and may result in cirrhosis. To understand who is at risk of developing this disease and suffering liver damage, we undertook a genetic study to compare the genetic profiles of people suffering from fatty liver disease with genetic profiles seen in the general population. We found that particular sequences in 4 different areas of the human genome were seen at different frequencies in the fatty liver disease cases. These sequences may help predict an individuals risk of developing advanced disease. Some genes where these sequences are located may also be good targets for future drug treatments. (C) 2020 European Association for the Study of the Liver. Published by Elsevier B.V.

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  • 22.
    Armandi, Angelo
    et al.
    Univ Turin, Italy; Univ Med Ctr, Germany.
    Sanavia, Tiziana
    Univ Turin, Italy.
    Younes, Ramy
    Boehringer Ingelheim Int GmbH, Germany.
    Caviglia, Gian Paolo
    Univ Turin, Italy.
    Rosso, Chiara
    Univ Turin, Italy.
    Govaere, Olivier
    Newcastle Univ, England.
    Liguori, Antonio
    Fdn Policlin Univ A Gemelli IRCCS, Italy; Fdn Policlin Univ A Gemelli IRCCS, Italy; Univ Cattolica Sacro Cuore, Italy.
    Francione, Paolo
    Fdn IRCCS Ca Granda Osped Maggiore Policlin, Italy.
    Gallego-Duran, Rocio
    Virgen Rocio Univ Hosp, Spain.
    Ampuero, Javier
    Virgen Rocio Univ Hosp, Spain.
    Pennisi, Grazia
    Univ Palermo, Italy.
    Aller, Rocio
    Hosp Clin Valladolid, Spain.
    Tiniakos, Dina
    Newcastle Univ, England; Natl & Kapodistrian Univ Athens, Greece.
    Burt, Alastair
    Newcastle Univ, England.
    David, Ezio
    Univ Turin, Italy.
    Vecchio, Fabio
    Dipartimento Univ Med & Chirurg Traslazionale, Italy.
    Maggioni, Marco
    Ca Granda IRCCS Fdn, Italy.
    Cabibi, Daniela
    Univ Palermo, Italy.
    Mcleod, Duncan
    Westmead Hosp, Australia.
    Pareja, Maria Jesus
    Hosp Univ Valme, Spain.
    Zaki, Marco Y. W.
    Newcastle Univ, England; Minia Univ, Egypt.
    Stal, Per
    Karolinska Univ Hosp, Sweden; Huddinge Karolinska Inst, Sweden.
    Kechagias, Stergios
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Fracanzani, Anna Ludovica
    Fdn IRCCS Ca Granda Osped Maggiore Policlin, Italy; Univ Milan, Italy.
    Valenti, Luca
    Univ Milan, Italy; Fdn IRCCS Ca Granda Osped Maggiore Policlin Milano, Italy.
    Grieco, Antonio
    Dipartimento Univ Med & Chirurg Traslazionale, Italy.
    Miele, Luca
    Fdn Policlin Univ A Gemelli IRCCS, Italy; Fdn Policlin Univ A Gemelli IRCCS, Italy; Univ Cattolica Sacro Cuore, Italy.
    Fariselli, Piero
    Univ Turin, Italy.
    Eslam, Mohammed
    Univ Sydney, Australia.
    Petta, Salvatore
    Univ Palermo, Italy.
    Hagstroem, Hannes
    Karolinska Univ Hosp, Sweden; Huddinge Karolinska Inst, Sweden.
    George, Jacob
    Univ Sydney, Australia.
    Schattenberg, Joern M.
    Univ Med Ctr, Germany; Saarland Univ, Germany.
    Romero-Gomez, Manuel
    Virgen Rocio Univ Hosp, Spain.
    Anstee, Quentin Mark
    Newcastle Univ, England; Newcastle Tyne Hosp NHS Fdn Trust, England.
    Bugianesi, Elisabetta
    Univ Turin, Italy.
    Serum ferritin levels can predict long-term outcomes in patients with metabolic dysfunction-associated steatotic liver disease2024In: Gut, ISSN 0017-5749, E-ISSN 1468-3288Article in journal (Refereed)
    Abstract [en]

    Objective Hyperferritinaemia is associated with liver fibrosis severity in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), but the longitudinal implications have not been thoroughly investigated. We assessed the role of serum ferritin in predicting long-term outcomes or death. Design We evaluated the relationship between baseline serum ferritin and longitudinal events in a multicentre cohort of 1342 patients. Four survival models considering ferritin with confounders or non-invasive scoring systems were applied with repeated five-fold cross-validation schema. Prediction performance was evaluated in terms of Harrell's C-index and its improvement by including ferritin as a covariate. Results Median follow-up time was 96 months. Liver-related events occurred in 7.7%, hepatocellular carcinoma in 1.9%, cardiovascular events in 10.9%, extrahepatic cancers in 8.3% and all-cause mortality in 5.8%. Hyperferritinaemia was associated with a 50% increased risk of liver-related events and 27% of all-cause mortality. A stepwise increase in baseline ferritin thresholds was associated with a statistical increase in C-index, ranging between 0.02 (lasso-penalised Cox regression) and 0.03 (ridge-penalised Cox regression); the risk of developing liver-related events mainly increased from threshold 215.5 mu g/L (median HR=1.71 and C-index=0.71) and the risk of overall mortality from threshold 272 mu g/L (median HR=1.49 and C-index=0.70). The inclusion of serum ferritin thresholds (215.5 mu g/L and 272 mu g/L) in predictive models increased the performance of Fibrosis-4 and Non-Alcoholic Fatty Liver Disease Fibrosis Score in the longitudinal risk assessment of liver-related events (C-indices&gt;0.71) and overall mortality (C-indices&gt;0.65). Conclusions This study supports the potential use of serum ferritin values for predicting the long-term prognosis of patients with MASLD.

  • 23.
    Axelrad, Jordan E.
    et al.
    NYU, NY USA.
    Olen, Ola
    Karolinska Inst, Sweden; Stockholm South Gen Hosp, Sweden; Karolinska Inst, Sweden.
    Soderling, Jonas
    Karolinska Inst, Sweden.
    Roelstraete, Bjorn
    Karolinska Inst, Sweden.
    Khalili, Hamed
    Massachusetts Gen Hosp, MA USA.
    Song, Mingyang
    Faye, Adam
    NYU, NY USA.
    Eberhardson, Michael
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken. Karolinska Inst, Sweden.
    Halfvarson, Jonas
    Orebro Univ, Sweden.
    Ludvigsson, Jonas F.
    Karolinska Inst, Sweden; Orebro Univ Hosp, Sweden; Columbia Univ, NY USA.
    Inflammatory Bowel Disease and Risk of Colorectal Polyps: A Nationwide Population-Based Cohort Study From Sweden2023In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, article id jjad056Article in journal (Refereed)
    Abstract [en]

    Background: Inflammatory bowel disease [IBD] has been linked to an increased risk of colorectal neoplasia. However, the types and risks of specific polyp types in IBD are less clear. Methods: We identified 41 880 individuals with IBD (Crohns disease [CD: n = 12 850]; ulcerative colitis [UC]: n = 29 030]) from Sweden matched with 41 880 reference individuals. Using Cox regression, we calculated adjusted hazard ratios [aHRs] for neoplastic colorectal polyps [tubular, serrated/sessile, advanced and villous] defined by histopathology codes. Results: During follow-up, 1648 [3.9%] IBD patients and 1143 [2.7%] reference individuals had an incident neoplastic colorectal polyp, corresponding to an incidence rate of 46.1 and 34.2 per 10 000 person-years, respectively. This correlated to an aHR of 1.23 (95% confidence interval [CI] 1.12-1.35) with the highest HRs seen for sessile serrated polyps [8.50, 95% CI 1.10-65.90] and traditional serrated adenomas [1.72, 95% CI 1.02-2.91]. aHRs for colorectal polyps were particularly elevated in those diagnosed with IBD at a young age and at 10 years after diagnosis. Both absolute and relative risks of colorectal polyps were higher in UC than in CD [aHRs 1.31 vs 1.06, respectively], with a 20-year cumulative risk difference of 4.4% in UC and 1.5% in CD, corresponding to one extra polyp in 23 patients with UC and one in 67 CD patients during the first 20 years after IBD diagnosis. Conclusions: In this nationwide population-based study, there was an increased risk of neoplastic colorectal polyps in IBD patients. Colonoscopic surveillance in IBD appears important, especially in UC and after 10 years of disease.

  • 24.
    Bakke, Ingunn
    et al.
    NTNU Norwegian Univ Sci & Technol, Norway; St Olavs Univ Hosp, Norway.
    Walaas, Gunnar Andreas
    NTNU Norwegian Univ Sci & Technol, Norway.
    Bruland, Torunn
    NTNU Norwegian Univ Sci & Technol, Norway; St Olavs Univ Hosp, Norway.
    Royset, Elin Synnove
    NTNU Norwegian Univ Sci & Technol, Norway; St Olavs Univ Hosp, Norway; St Olavs Univ Hosp, Norway.
    van Beelen Granlund, Atle
    NTNU Norwegian Univ Sci & Technol, Norway; NTNU Norwegian Univ Sci & Technol, Norway.
    Escudero-Hernández, Celia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences. Christian Albrechts Univ Kiel, Germany; Univ Hosp Schleswig Holstein, Germany.
    Thorsvik, Silje
    NTNU Norwegian Univ Sci & Technol, Norway; St Olavs Univ Hosp, Norway.
    Münch, Andreas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Sandvik, Arne Kristian
    NTNU Norwegian Univ Sci & Technol, Norway; St Olavs Univ Hosp, Norway; NTNU Norwegian Univ Sci & Technol, Norway; St Olavs Univ Hosp, Norway.
    Ostvik, Ann Elisabet
    NTNU Norwegian Univ Sci & Technol, Norway; St Olavs Univ Hosp, Norway; St Olavs Univ Hosp, Norway.
    Mucosal and faecal neutrophil gelatinase-associated lipocalin as potential biomarkers for collagenous colitis2021In: Journal of gastroenterology, ISSN 0944-1174, E-ISSN 1435-5922, Vol. 56, no 10, p. 914-927Article in journal (Refereed)
    Abstract [en]

    Background Collagenous colitis (CC) is an inflammatory bowel disease where chronic diarrhoea is the main symptom. Diagnostic markers distinguishing between CC and other causes of chronic diarrhoea remain elusive. This study explores neutrophil gelatinase-associated lipocalin (NGAL) and its mRNA lipocalin2 (LCN2) as histological and faecal disease markers in CC. Methods NGAL/LCN2 were studied in colonic biopsies from CC patients before and during budesonide treatment using RNA sequencing (n = 9/group), in situ hybridization (ISH) (n = 13-22/group) and immunohistochemistry (IHC) (n = 14-25/group). Faecal samples from CC (n = 3-28/group), irritable bowel syndrome diarrhoea (IBS-D) (n = 14) and healthy controls (HC) (n = 15) were assayed for NGAL and calprotectin. Results NGAL/LCN2 protein and mRNA expression were upregulated in active CC vs HC, and vs paired samples of treated CC in clinical remission. IHC and ISH localized increased NGAL/LCN2 mainly to epithelium of active CC, compared to almost absence in HC and treated CC. In contrast, calprotectin was solely expressed in immune cells. Despite great individual differences, faecal NGAL was significantly increased in active CC compared to HC, IBS-D and treated CC and had high test sensitivity. Faecal calprotectin levels were variably increased in active CC, but the values remained below usual clinical cut-offs. Conclusion NGAL/LCN2 is upregulated in the epithelium of active CC and reduced during budesonide-induced clinical remission to the level of HC and IBD-S. This was reflected in NGAL faecal concentrations. We propose NGAL as an IHC marker for disease activity in CC and a potential faecal biomarker discriminating CC from HC and IBS-D.

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  • 25.
    Balkhed, Wile
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Åberg, Fredrik O.
    Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki University, Helsinki, Finland.
    Nasr, Patrik
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Ekstedt, Mattias
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Kechagias, Stergios
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Repeated measurements of non-invasive fibrosis tests to monitor the progression of non-alcoholic fatty liver disease: A long-term follow-up study2022In: Liver international (Print), ISSN 1478-3223, E-ISSN 1478-3231, Vol. 42, no 7, p. 1546-1556Article in journal (Refereed)
    Abstract [en]

    Background and Aims: The presence of advanced hepatic fibrosis is the prime marker for the prediction of liver-related complications in non-alcoholic fatty liver disease (NAFLD). Blood-based non-invasive tests (NITs) have been developed to evaluate fibrosis and identify patients at risk. Current guidelines propose monitoring the progression of NAFLD using repeated NITs at 2-3-year intervals. The aim of this study was to evaluate the association of changes in NITs measured at two time points with the progression of NAFLD.

    Methods. We retrospectively included NAFLD patients with NIT measurements in whom the baseline hepatic fibrosis stage had been assessed by biopsy or transient elastography (TE). Subjects underwent follow-up visits at least 1 year from baseline to evaluate the progression of NAFLD. NAFLD progression was defined as the development of end-stage liver disease or fibrosis progression according to repeat biopsy or TE. The following NITs were calculated at baseline and follow-up: Fibrosis-4 (FIB-4), NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet ratio index (APRI) and dynamic aspartate-to-alanine aminotransferase ratio (dAAR).

    Results: One hundred and thirty-five patients were included with a mean follow-up of 12.6 +/- 8.5 years. During follow-up, 41 patients (30%) were diagnosed with progressive NAFLD. Change in NIT scores during follow-up was significantly associated with disease progression for all NITs tested except for NFS. However, the diagnostic precision was suboptimal with area under the receiver operating characteristics 0.56-0.64 and positive predictive values of 0.28-0.36 at sensitivity fixed at 90%.

    Conclusions: Change of FIB-4, NFS, APRI, and dAAR scores is only weakly associated with disease progression in NAFLD. Our findings do not support repeated measurements of these NITs for monitoring the course of NAFLD.

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  • 26. 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)
  • 27.
    Barazanji, Nawroz
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Hamilton, Paul J.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Icenhour, Adriane
    Ruhr University Bochum, Bochum, Germany.
    Simon, Rozalyn
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Bednarska, Olga
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Tapper, Sofie
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Tisell, Anders
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine.
    Lundberg, Peter
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Engström, Maria
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Walter, Susanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Irritable bowel syndrome in women: Association between decreased insular subregion volumes and gastrointestinal symptoms2022In: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 35, article id 103128Article in journal (Refereed)
    Abstract [en]

    Irritable bowel syndrome (IBS) is a chronic pain disorder characterized by disturbed interactions between the gut and the brain with depression as a common comorbidity. In both IBS and depression, structural brain alterations of the insular cortices, key structures for pain processing and interoception, have been demonstrated but the specificity of these findings remains unclear. We compared the gray matter volume (GMV) of insular cortex (IC) subregions in IBS women and healthy controls (HC) and examined relations to gastrointestinal (GI) symptoms and glutamate + glutamine (Glx) concentrations. We further analyzed GMV of IC subregions in women with major depression (MDD) compared to HC and addressed possible differences between depression, IBS, IBS with depression and HC.

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  • 28.
    Beamish, Andrew J.
    et al.
    Gothenburg Univ, Sweden; Swansea Bay Univ Hlth Board, Wales.
    Olbers, Torsten
    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 Norrköping. Gothenburg Univ, Sweden.
    Metabolic and bariatric surgery in adolescents2019In: Nature Reviews. Gastroenterology & Hepatology, ISSN 1759-5045, E-ISSN 1759-5053, Vol. 16, no 10, p. 585-587Article in journal (Other academic)
    Abstract [en]

    A new study has added valuable outcome data from adolescents 5 years after undergoing Roux-en-Y gastric bypass. By comparing outcomes from adolescents and adults, the study adds to the existing evidence base, highlighting metabolic and bariatric surgery as an increasingly valuable tool in the multidisciplinary management of adolescents with severe obesity.

  • 29.
    Bednarska, Olga
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Peripheral and Central Mechanisms in Irritable Bowel Syndrome: in search of links2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Irritable bowel syndrome (IBS) is a chronic visceral pain disorder with female predominance, characterized by recurrent abdominal pain and disturbed bowel habits in the absence of an identifiable organic cause. This prevalent and debilitating disease, which accounts for a substantial economic and individual burden, lacks exact diagnostic tools and effective treatment, since its pathophysiology remains uncertain. The bidirectional and multilayered brain-gut axis is a well-established disease model, however, the interactions between central and peripheral mechanisms along the brain-gut axis remain incompletely understood. One of the welldescribed triggering factors, yet accounting for only a fraction of IBS prevalence, is bacterial gastroenteritis that affects mucosal barrier function. Altered gut microbiota composition as well as disturbed intestinal mucosal barrier function and its neuroimmune regulation have been reported in IBS, however, the impact of live bacteria, neither commensal nor pathogenic, on intestinal barrier has not been studied yet. Furthermore, abnormal central processing of visceral sensations and psychological factors such as maladaptive coping have previously been suggested as centrally-mediated pathophysiological mechanisms of importance in IBS. Brain imaging studies have demonstrated an imbalance in descending pain modulatory networks and alterations in brain regions associated with interoceptive awareness and pain processing and modulation, particularly in anterior insula (aINS), although biochemical changes putatively underlying these central alterations remain poorly understood. Most importantly, however, possible associations between these documented changes on central and peripheral levels, which may as complex interactions contribute to disease onset and chronification of symptoms, are widely unknown.

    This thesis aimed to investigate the peripheral and central mechanisms in women with IBS compared to female healthy controls (HC) and to explore possible mutual associations between these mechanisms.

    In Paper I, we studied paracellular permeability and passage of live bacteria, both commensal and pathogenic through colonic biopsies mounted in Ussing chambers. We explored the regulation of the mucosal barrier function by mast cells and the neuropeptide vasoactive intestinal polypeptide (VIP) as well as a correlation between mucosal permeability and gastrointestinal and psychological symptoms. We observed increased paracellular permeability and the passage of commensal and pathogenic live bacteria in patients with IBS compared with HC, which was diminished by blocking the VIP receptors as well as after stabilizing mast cells in both groups. Moreover, higher paracellular permeability was associated with less somatic and psychological symptoms in patients.

    In Paper II, we aimed to determine the association between colonic mucosa paracellular permeability and structural and resting state functional brain connectivity. We demonstrated different patterns of associations between mucosa permeability and functional and structural brain connectivity in IBS patients compared to HC. Specifically, lower paracellular permeability in IBS, similar to the levels detected in HC, was associated with more severe IBS symptoms and increased functional and structural connectivity between intrinsic brain resting state network and descending pain modulation brain regions. Our findings further suggested that this association between mucosa permeability and functional brain connectivity was mainly mediated by coping strategies.

    In Paper III, we investigated putative alterations in excitatory and inhibitory neurotransmission of aINS, as the brain’s key node of the salience network crucially involved in cognitive control, in IBS patients relative to HC and addressed possible connections with both symptoms and psychological factors. We found decreased concentrations of the excitatory neurotransmitter Glx in bilateral aINS in IBS patients compared to HC, while inhibitory neurotransmitter GABA+ levels were comparable. Further, we demonstrated hemisphere-specific associations between abdominal pain, coping and aINS excitatory neurotransmitter concentration.

    In conclusion, this thesis broadens the knowledge on peripheral and central mechanisms in IBS and presents novel findings that bring together the ends of brain-gut axis. Our results depict association between mucosal permeability, IBS symptoms and functional and structural connectivity engaging brain regions involved in emotion and pain modulation as well as underlying neurotransmitter alterations.

    List of papers
    1. Vasoactive Intestinal Polypeptide and Mast Cells Regulate Increased Passage of Colonic Bacteria in Patients With Irritable Bowel Syndrome
    Open this publication in new window or tab >>Vasoactive Intestinal Polypeptide and Mast Cells Regulate Increased Passage of Colonic Bacteria in Patients With Irritable Bowel Syndrome
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    2017 (English)In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 153, no 4, p. 948-+Article in journal (Refereed) Published
    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.

    Place, publisher, year, edition, pages
    W B SAUNDERS CO-ELSEVIER INC, 2017
    Keywords
    Intestinal Permeability; Bacteria; Ketotifen; Inflammation
    National Category
    Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:liu:diva-142158 (URN)10.1053/j.gastro.2017.06.051 (DOI)000411835200024 ()28711627 (PubMedID)
    Note

    Funding Agencies|Stiftelsen Halsofonden, County Council of Ostergotland; Diarrheal Disease Research Centre, Linkoping University; AFA research foundation; Bengt-Ihre fonden, County Council of Ostergotland; Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III, Subdireccion General de Investigacion Sanitaria, Ministerio de Economia y Competitividad [FI12/00254]; NIH [R01 DK048351]; [CP10/00502]; [PI13/00935]; [MV16/00028]; [CIBEREHD CB06/04/0021]

    Available from: 2017-10-24 Created: 2017-10-24 Last updated: 2024-01-10
    2. Interactions between gut permeability and brain structure and function in health and irritable bowel syndrome
    Open this publication in new window or tab >>Interactions between gut permeability and brain structure and function in health and irritable bowel syndrome
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    2019 (English)In: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 21, article id 101602Article in journal (Refereed) Published
    Abstract [en]

    Changes in brain-gut interactions have been implicated in the pathophysiology of chronic visceral pain in irritable bowel syndrome (IBS). Different mechanisms of sensitization of visceral afferent pathways may contribute to the chronic visceral pain reports and associated brain changes that characterize IBS. They include increased gut permeability and gut associated immune system activation, and an imbalance in descending pain inhibitory and facilitatory mechanisms. In order to study the involvement of these mechanisms, correlations between gut epithelial permeability and live bacterial passage, and structural and functional brain connectivity were measured in women with moderate-to-severe IBS and healthy women. The relationships between gut permeability and functional and anatomical connectivity were significantly altered in IBS compared with the healthy women. IBS participants with lower epithelial permeability reported increased IBS symptoms, which was associated with increased functional and structural connectivity in endogenous pain facilitation regions. The findings suggest that relationships between gut permeability and the brain are significantly altered in IBS and suggest the existence of IBS subtypes based on these interactions.

    Place, publisher, year, edition, pages
    Elsevier, 2019
    Keywords
    Irritable bowel syndrome; Gut epithelial permeability; Resting state fMRI; Brain-gut interactions; Default mode network; Coping skills
    National Category
    Neurosciences
    Identifiers
    urn:nbn:se:liu:diva-155612 (URN)10.1016/j.nicl.2018.11.012 (DOI)000460337700015 ()30472166 (PubMedID)2-s2.0-85056893948 (Scopus ID)
    Note

    Funding Agencies|AFA FOrskning [AFA140417]; County Council of Ostergotland [SLS-693541, SLS-503411]; Region Ostergotland [LIO-700871, LIO-606201, LIO-536281, LIO-514271]; Deutsche Forschungsgemeinschaft [DFG IC 81/1-1]; Bengt-Ihre Fonden

    Available from: 2019-03-20 Created: 2019-03-20 Last updated: 2024-01-17Bibliographically approved
    3. Reduced excitatory neurotransmitter levels in anterior insulae are associated with abdominal pain in irritable bowel syndrome
    Open this publication in new window or tab >>Reduced excitatory neurotransmitter levels in anterior insulae are associated with abdominal pain in irritable bowel syndrome
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    2019 (English)In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 160, no 9, p. 2004-2012Article in journal (Refereed) Published
    Abstract [en]

    Irritable bowel syndrome (IBS) is a visceral pain condition with psychological comorbidity. Brain imaging studies in IBS demonstratealtered function in anterior insula (aINS), a key hub for integration of interoceptive, affective, and cognitive processes. However,alterations in aINS excitatory and inhibitory neurotransmission as putative biochemical underpinnings of these functional changesremain elusive. Using quantitative magnetic resonance spectroscopy, we compared women with IBS and healthy women (healthycontrols [HC]) with respect to aINS glutamate 1 glutamine (Glx) and g-aminobutyric acid (GABA1) concentrations and addressedpossible associations with symptoms. Thirty-nine women with IBS and 21 HC underwent quantitative magnetic resonancespectroscopy of bilateral aINS to assess Glx and GABA1 concentrations. Questionnaire data from all participants and prospectivesymptom-diary data from patients were obtained for regression analyses of neurotransmitter concentrations with IBS-related andpsychological parameters. Concentrations of Glx were lower in IBS compared with HC (left aINS P , 0.05, right aINS P , 0.001),whereas no group differences were detected for GABA1concentrations. Lower right-lateralized Glx concentrations in patients weresubstantially predicted by longer pain duration, while less frequent use of adaptive pain‐coping predicted lower Glx in left aINS. Ourfindings provide first evidence for reduced excitatory but unaltered inhibitory neurotransmitter levels in aINS in IBS. The results alsoindicate a functional lateralization of aINS with a stronger involvement of the right hemisphere in perception of abdominal pain and ofthe left aINS in cognitive pain regulation. Our findings suggest that glutaminergic deficiency may play a role in pain processing in IBS.

    Place, publisher, year, edition, pages
    Lippincott Williams & Wilkins, 2019
    Keywords
    Irritable bowel syndrome, Functional magnetic resonance imaging, Quantitative magnetic resonance spectroscopy, Insula, Visceral pain, Coping
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:liu:diva-160012 (URN)10.1097/j.pain.0000000000001589 (DOI)000512903900011 ()31045748 (PubMedID)
    Note

    Funding agencies: NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P41-RR14075, R01 RR16594-01A1, R01 NS052585-01, K08 MH01573, K01 MH01798]; County Council of Ostergotland; AFA research foundation [DNR. 140407]; Bengt-Ihre f

    Available from: 2019-09-02 Created: 2019-09-02 Last updated: 2024-01-10Bibliographically approved
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  • 30.
    Bednarska, Olga
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Biskou, Olga
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Israelsen, Hans
    Nord Rebalance AS, Denmark.
    Tinnerfelt Winberg, Martin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Walter, Susanna
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Keita, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    A postbiotic fermented oat gruel may have a beneficial effect on the colonic mucosal barrier in patients with irritable bowel syndrome2022In: Frontiers in Nutrition, E-ISSN 2296-861X, Vol. 9, article id 1004084Article in journal (Refereed)
    Abstract [en]

    Background: Impaired intestinal permeability and microbial dysbiosis are important pathophysiological mechanisms underlying irritable bowel syndrome (IBS). ReFerm (R)( ), also called Profermin (R), is a postbiotic product of oat gruel fermented with Lactobacillus plantarum 299v. In this study, we investigated whether ReFerm (R) has a beneficial effect on the intestinal epithelial barrier function in patients with IBS.Materials and methods: Thirty patients with moderate to severe IBS-diarrhoea (IBS-D) or IBS-mixed (IBS-M) were treated with enema containing ReFerm (R) or placebo. The patients underwent sigmoidoscopy with biopsies obtained from the distal colon at baseline and after 14 days of treatment with ReFerm (R) or placebo twice daily. The biopsies were mounted in Ussing chambers, and paracellular and transcellular permeabilities were measured for 120 min. In addition, the effects of ReFerm (R) or placebo on the epithelial barrier were investigated in vitro using Caco-2 cells.Results: ReFerm (R) reduced paracellular permeability (p &lt; 0.05) and increased transepithelial resistance (TER) over time (p &lt; 0.01), whereas the placebo had no significant effect in patients. In ReFerm (R)-treated Caco-2 cells, paracellular and transcellular permeabilities were decreased compared to the control (p &lt; 0.05) and placebo (p &lt; 0.01). TER was increased in Caco-2 ReFerm (R)-treated cells, and normalised TER was increased in ReFerm (R)-treated Caco-2 cells compared to control (p &lt; 0.05) and placebo-treated (p &lt; 0.05) cells.Conclusion: ReFerm (R) significantly reduced paracellular permeability and improved TER in colonic biopsies collected from patients with IBS and in a Caco-2 cell model. Our results offer new insights into the potential benefits of ReFerm (R) in IBS management. Further studies are needed to identify the molecular mechanisms underlying the barrier-protective properties of ReFerm (R).

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  • 31.
    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.
    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.

  • 32.
    Beeckmans, Dorien
    et al.
    Katholieke Univ Leuven, Belgium.
    Farre, Ricard
    Katholieke Univ Leuven, Belgium.
    Riethorst, Danny
    Katholieke Univ Leuven, Belgium.
    Keita, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Augustijns, Patrick
    Katholieke Univ Leuven, Belgium.
    Söderholm, Johan D
    Linköping University, Department of Biomedical and Clinical Sciences, 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.
    Vanuytsel, Tim
    Katholieke Univ Leuven, Belgium.
    Vanheel, Hanne
    Katholieke Univ Leuven, Belgium.
    Tack, Jan
    Katholieke Univ Leuven, Belgium.
    Relationship between bile salts, bacterial translocation, and duodenal mucosal integrity in functional dyspepsia2020In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 32, no 5, article id e13788Article in journal (Refereed)
    Abstract [en]

    Background Functional dyspepsia (FD) is a complex disorder, in which multiple mechanisms underlie symptom generation, including impaired duodenal barrier function. Moreover, an altered duodenal bile salt pool was recently discovered in patients with FD. We aimed to evaluate the relationship between bile salts, bacterial translocation, and duodenal mucosal permeability in FD. Methods Duodenal biopsies from patients with FD and healthy volunteers (HV) were mounted in Ussing chambers to measure mucosal resistance and bacterial passage in the absence and presence of fluorescein-conjugated Escherichia coli and glyco-ursodeoxycholic acid (GUDCA) exposure. In parallel, duodenal fluid aspirates were collected from patients and bile salts were analyzed. Key results The transepithelial electrical resistance of duodenal biopsies from patients was lower compared with HV (21.4 +/- 1.3 omega.cm(2) vs. 24.4 +/- 1.2 omega.cm(2); P = .02; N = 21). The ratio of glyco-cholic and glyco-chenodeoxycholic acid (GCDCA) to tauro- and GUDCA correlated positively with transepithelial electrical resistance in patients. Glyco-ursodeoxycholic acid slightly altered the mucosal resistance, resulting in similar values between patient and healthy biopsies (22.1 +/- 1.0 omega.cm(2) vs. 23.0 +/- 1.0 omega.cm(2); P = .5). Bacterial passage after 120 minutes was lower for patient than for healthy biopsies (0.0 [0.0-681.8] vs. 1684.0 [0.0-4773.0] E coli units; P = .02). Glyco-ursodeoxycholic acid increased bacterial passage in patient biopsies (102.1 [0.0-733.0] vs. 638.9 [280.6-2124.0] E coli units; P = .009). No correlation was found between mucosal resistance and bacterial passage. Conclusions amp; inferences Patients with FD displayed decreased duodenal mucosal resistance associated with bile salts, however, not associated with bacterial passage in vitro. In addition, the hydrophilic bile salt glyco-ursodeoxycholic acid abolished differences in mucosal resistance and bacterial passage between patient and control group.

  • 33.
    Bergemalm, Daniel
    et al.
    Orebro Univ, Sweden.
    Andersson, Erik
    Orebro Univ, Sweden.
    Hultdin, Johan
    Umea Univ, Sweden.
    Eriksson, Carl
    Orebro Univ, Sweden.
    Rush, Stephen T.
    Orebro Univ, Sweden.
    Kalla, Rahul
    Univ Edinburgh, Scotland.
    Adams, Alex T.
    Univ Oxford, England.
    Keita, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    DAmato, Mauro
    CIC BioGUNE Basque Res & Technol Alliance & Basqu, Spain; Karolinska Inst, Sweden.
    Gomollon, Fernando
    Hosp Clin Univ Lozano Blesa, Spain.
    Jahnsen, Jorgen
    Akershus Univ Hosp, Norway; Univ Oslo, Norway.
    Ricanek, Petr
    Akershus Univ Hosp, Norway.
    Satsangi, Jack
    Univ Oxford, England; Univ Edinburgh, Scotland.
    Repsilber, Dirk
    Orebro Univ, Sweden; Umea Univ, Sweden.
    Karling, Pontus
    Umea Univ, Sweden.
    Halfvarson, Jonas
    Orebro Univ, Sweden.
    Systemic Inflammation in Preclinical Ulcerative Colitis2021In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 161, no 5, p. 1526-1539Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins. METHODS: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored. RESULTS: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P &lt; .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1 beta, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-kappa B, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naive patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis. CONCLUSIONS: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors.

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  • 34.
    Bergram, Martin
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nasr, Patrik
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Iredahl, Fredrik
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Åby.
    Kechagias, Stergios
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Rådholm, Karin
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Kärna.
    Ekstedt, Mattias
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Low awareness of non-alcoholic fatty liver disease in patients with type 2 diabetes in Swedish Primary Health Care2022In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 57, no 1, p. 60-69Article in journal (Refereed)
    Abstract [en]

    Objectives Non-alcoholic fatty liver disease (NAFLD) is more common in patients with type 2 diabetes mellitus (T2DM) compared to individuals without. Recent guidelines recommend screening for NAFLD in patients with T2DM. Our aim was to investigate the prevalence of NAFLD in patients with T2DM in a Swedish primary health care setting, how they are cared for and assess the risk of biochemical signs of advanced fibrosis. Material and methods In this cohort study, patients with T2DM from five primary health care centers were included. Medical records were retrospectively reviewed and living habits, medical history, results of diagnostic imaging and anthropometric and biochemical features were noted in a standardized form. The risk of steatosis and advanced fibrosis was assessed using commonly used algorithms (FLI, HSI, NAFLD-LFS, NAFLD ridge score, FIB-4 and NFS). Results In total 350 patients were included. Diagnostic imaging had been performed in 132 patients and of these, 34 (26%) had steatosis, which was not noted in the medical records in 16 (47%) patients. One patient with steatosis had been referred to a hepatologist. Of assessable patients, 71-97% had a high to intermediate risk of steatosis and 29-65% had an intermediate to high risk of advanced fibrosis according to the algorithms used. Conclusion This study indicates a high prevalence of NAFLD among T2DM patients in Swedish primary care. Patients with known NAFLD were followed up to a very low extent. Using fibrosis algorithms in primary health care would result in many patients needing further assessment in secondary care.

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  • 35.
    Berryman, Meghan A.
    et al.
    Triplett Laboratory, Institute of Food and Agriculture, Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA.
    Milletich, Patricia L.
    Triplett Laboratory, Institute of Food and Agriculture, Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA.
    Petrone, Joseph R.
    Triplett Laboratory, Institute of Food and Agriculture, Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA.
    Roesch, Luiz FW.
    Roesch Laboratory, Institute of Food and Agriculture, Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA.
    Ilonen, Jorma
    Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland.
    Triplett, Eric W.
    Triplett Laboratory, Institute of Food and Agriculture, Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Autoimmune-associated genetics impact probiotic colonization of the infant gut2022In: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 133, article id 102943Article in journal (Refereed)
    Abstract [en]

    To exemplify autoimmune-associated genetic influence on the colonization of bacteria frequently used in probiotics, microbial composition of stool from 1326 one-year-old infants was analyzed in a prospective general-population cohort, All Babies In Southeast Sweden (ABIS). We show that an individual's HLA haplotype composition has a significant impact on which common Bifidobacterium strains thrive in colonizing the gut. The effect HLA has on the gut microbiome can be more clearly observed when considered in terms of allelic dosage. HLA DR1-DQ5 showed the most significant and most prominent effect on increased Bifidobacterium relative abundance. Therefore, HLA DR1-DQ5 is proposed to act as a protective haplotype in many individuals. Protection-associated HLA haplotypes are more likely to influence the promotion of specific bifidobacteria. In addition, strain-level differences are correlated with colonization proficiency in the gut depending on HLA haplotype makeup. These results demonstrate that HLA genetics should be considered when designing effective probiotics, particularly for those at high genetic risk for autoimmune diseases.

  • 36.
    Biskou, Olga
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Jauregi-Miguel, Amaia
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology.
    Measuring intestinal permeability in celiac disease ex vivo, using Ussing chambers2023In: Methods in Cell Biology, ISSN 0091-679X, Vol. 179, p. 21-38Article in journal (Refereed)
    Abstract [en]

    Multicellular organisms need epithelial barriers to remain compartmentalized and protected from external influences. Although much progress has been made in understanding barrier integrity disruption in Celiac disease (CD), the regulatory and genetic mechanisms underlying the increased intestinal epithelial flux are still unknown. As we learn more about the regulation of permeability in homeostasis and pathogenesis, we will be able to develop strategies to strengthen the epithelial barrier function in intestinal disorders, including CD. For this purpose, Ussing chambers are increasingly used in native tissue, such as gut mucosa or cell monolayers, to assess the integrity of the barrier. In particular, the Ussing chambers allow the measurement of paracellular and transcellular parameters of CD small intestinal biopsies under physiologically specific conditions. In diverse types of diseases, this method is commonly used to determine epithelial barrier defects, but its application to CD has not yet been widely expanded. To provide a great model of barrier ex vivo studies in CD, we facilitate a standard protocol to measure paracellular and transcellular permeability using the Ussing chamber. © 2023 Elsevier Inc.

  • 37.
    Bjorkqvist, Olle
    et al.
    Orebro Univ, Sweden.
    Rangel, Ignacio
    Orebro Univ, Sweden.
    Serrander, Lena
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Magnusson, Cecilia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Reg Jonkoping Cty, Sweden.
    Halfvarson, Jonas
    Orebro Univ, Sweden; Orebro Univ, Sweden.
    Noren, Torbjorn
    Orebro Univ, Sweden.
    Bergman, Malin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Faecalibacterium prausnitzii increases following fecal microbiota transplantation in recurrent Clostridioides difficile infection2021In: PLOS ONE, E-ISSN 1932-6203, Vol. 16, no 4, article id e0249861Article in journal (Refereed)
    Abstract [en]

    Objective Fecal microbiota transplantation (FMT) is a highly effective treatment for Clostridioides difficile infection (CDI). However, the fecal transplants causal components translating into clearance of the CDI are yet to be identified. The commensal bacteria Faecalibacterium prausnitzii may be of great interest in this context, since it is one of the most common species of the healthy gut microbiota and produces metabolites with anti-inflammatory properties. Although there is mounting evidence that F. prausnitzii is an important regulator of intestinal homeostasis, data about its role in CDI and FMT are relatively scarce. Methods Stool samples from patients with recurrent CDI were collected to investigate the relative abundance of F. prausnitzii before and after FMT. Twenty-one patients provided fecal samples before the FMT procedure, at 2 weeks post-FMT, and at 2-4 months post-FMT. The relative abundance of F. prausnitzii was determined using quantitative polymerase chain reaction. Results The abundance of F. prausnitzii was elevated in samples (N = 9) from donors compared to pre-FMT samples (N = 15) from patients (adjusted P&lt;0.001). No significant difference in the abundance of F. prausnitzii between responders (N = 11) and non-responders (N = 4) was found before FMT (P = 0.85). In patients with CDI, the abundance of F. prausnitzii significantly increased in the 2 weeks post-FMT samples (N = 14) compared to the pre-FMT samples (N = 15, adjusted P&lt;0.001). The increase persisted 2-4 months post-FMT (N = 15) compared to pre-FMT samples (N = 15) (adjusted P&lt;0.001). Conclusions FMT increases the relative abundance of F. prausnitzii in patients with recurrent CDI, and this microbial shift remains several months later. The baseline abundance of F. prausnitzii in donors or recipients was not associated with future treatment response, although a true predictive capacity cannot be excluded because of the limited sample size. Further studies are needed to discern whether F. prausnitzii plays an active role in the resolution of CDI.

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  • 38.
    Bjorlykke, Kristin H.
    et al.
    Akershus Univ Hosp, Norway; Univ Oslo, Norway.
    Jahnsen, Jorgen
    Akershus Univ Hosp, Norway; Univ Oslo, Norway.
    Brynskov, Jorn
    Herlev Hosp, Denmark.
    Molander, Pauliina
    Helsinki Univ Hosp, Finland; Univ Helsinki, Finland.
    Eberhardson, Michael
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken. Karolinska Inst, Sweden.
    Davidsdottir, Loa G.
    Univ Hosp Iceland, Iceland.
    Sipponen, Taina
    Helsinki Univ Hosp, Finland; Univ Helsinki, Finland.
    Hjortswang, Henrik
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken. Karolinska Inst, Sweden.
    Goll, Guro Lovik
    Diakonhjemmet Hosp, Norway.
    Syversen, Silje Watterdal
    Diakonhjemmet Hosp, Norway.
    Langholz, Ebbe
    Herlev Hosp, Denmark; Univ Copenhagen, Denmark.
    Jorgensen, Kristin K.
    Akershus Univ Hosp, Norway.
    Steenholdt, Casper
    Herlev Hosp, Denmark.
    Therapeutic drug monitoring in inflammatory bowel disease: implementation, utilization, and barriers in clinical practice in Scandinavia2023In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 58, no 1, p. 25-33Article in journal (Refereed)
    Abstract [en]

    Background and aims Therapeutic drug monitoring (TDM) may optimize biologic and thiopurine therapies in inflammatory bowel disease (IBD). The study aimed to investigate implementation and utilization of TDM in Scandinavia. Methods A web-based questionnaire on the use of TDM was distributed to Scandinavian gastroenterologists via the national societies. Results In total, 297 IBD physicians prescribing biologic therapies, equally distributed between community and university hospitals, were included (response rate 42%) (Norway 118 (40%), Denmark 86 (29%), Sweden 50 (17%), Finland 33 (11%), Iceland 10 (3%)). Overall, TDM was applied during biologic therapies by 87%, and for TNF-inhibitors &gt;90%. Among the users, reactive and proactive TDM were utilized by 90% and 63%, respectively. Danish physicians were significantly less inclined to use TDM compared to other Scandinavian countries; (58% vs 98%); OR 0.03 [0.01-0.09], p &lt; 0.001). Reactive TDM was commonly applied at primary (74%) and secondary (99%) treatment failure. Proactive TDM was used by 80% during maintenance therapy and 56% during induction and more commonly utilized in Norway (p &lt; 0.001), and by physicians managing &gt;10 IBD patients/week (p = 0.005). TDM scenarios were interpreted in accord with available evidence but with discrepancies for proactive TDM. The main barriers to TDM were lack of guidelines (51%) and time lag between sampling and results (49%). TDM of thiopurines was routinely used by 87%. Conclusion TDM of biologic and thiopurine therapies has been broadly implemented into clinical practice in Scandinavia. However, physicians call for TDM guidelines detailing indications and interpretations of test results along with improved test response times.

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  • 39.
    Björk, Dennis
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, 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.
    Delle, Martin
    Karolinska Univ Sjukhuset, Sweden; Karolinska Univ, Sweden.
    Holmquist, Fredrik
    Lund Univ, Sweden.
    Hasselgren, Kristina
    Linköping University, Department of Biomedical and Clinical Sciences, 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.
    Sandström, Per
    Linköping University, Department of Biomedical and Clinical Sciences, 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.
    Lindell, Gert
    Lund Univ, Sweden.
    Sparrelid, Ernesto
    Karolinska Univ Hosp, Sweden.
    Björnsson, Bergthor
    Linköping University, Department of Biomedical and Clinical Sciences, 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.
    Portal vein embolization with N-butyl-cyanoacrylate improves liver hypertrophy compared to microparticles - A Swedish multicenter cohort study2023In: Heliyon, E-ISSN 2405-8440, Vol. 9, no 11, article id e21210Article in journal (Refereed)
    Abstract [en]

    Background: An adequate future liver remnant (FLR) is fundamental for major liver resections. To achieve sufficient FLR, portal vein embolization (PVE) may be used. The most effective material for PVE has yet to be determined. The aim of this study was to investigate the differences in FLR growth between n-butyl-cyanoacrylate glue (NBCA) and microparticles.Material/methodsa: retrospective study was performed at three Swedish hepatobiliary centers and included patients who underwent PVE 2013-2021. Electronic medical records were reviewed, and procedure-related data were collected. Data were analyzed with respect to embolizing material.Results: A total of 265 patients were included: 160 in the NBCA group and 105 in the microparticle group. The NBCA group had a higher degree of hypertrophy (12.1 vs. 9.4 % points, p = 0.003) and a higher resection rate (68 vs. 59 %, p = 0.01) than the microparticle group. Procedurerelated data all indicated the superiority of NBCA. No difference in inducing hypertrophy was observed when comparing patients who received chemotherapy before PVE with those who received chemotherapy before and after PVE within the NBCA group. Discussion/conclusion: This retrospective multicenter study supports the superiority of NBCA compared to microparticles in the setting of PVE. Chemotherapy after PVE does not seem to negatively affect hypertrophy.

  • 40.
    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.

  • 41.
    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.

  • 42. Order onlineBuy this publication >>
    Blomdahl, Julia
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Non-Alcoholic Fatty Liver Disease: Insights into Alcohol Consumption, Genetics, and Proteomics2023Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    NAFLD (Non-Alcoholic Fatty Liver Disease) affects approximately a quarter of the global population and is closely linked to type 2 diabetes mellitus and obesity. The disease spectrum ranges from steatosis and steatohepatitis to fibrosis, cirrhosis, and hepatocellular cancer. However, accurately predicting which patients will experience a progressive disease course remains a significant challenge. The variant gene of PNPLA3 is known to be associated with NAFLD and a more progressive disease, although its precise function remains unclear.   

    Patients with NAFLD typically consume small to moderate amounts of alcohol, with recommended thresholds set at a maximum of 210 gram per week for males and 140 grams per week in females. However, the impact of alcohol consumption on liver disease in NAFLD remains disputed, with conflicting research findings.   

    Liver biopsy is considered the gold standard for diagnosing NAFLD. However, due to its impracticality for such a large population with the condition, various non-invasive methods have been explored for diagnosing and evaluating NAFLD.  

    This thesis aimed to investigate the potential effects of moderate alcohol consumption on NAFLD histology, explore the potential role of variant PNPLA3 in NAFLD, and assess the use of proteomics in classifying fibrosis.  

    In Papers I and II, moderate alcohol consumption was assessed through questionnaires, clinical interviews, and measurement of the direct alcohol biomarker phosphatidylethanol (PEth). Paper I, a cross-sectional study including 86 participants, showed an association between moderate consumption and advanced fibrosis. Moderate consumption was defined as consuming more than 66 grams of ethanol per week or a PEth-value over 50 ng/mL. Notably, individuals with both moderate alcohol consumption and a diagnosis of type 2 diabetes exhibited significantly more advanced fibrosis. Paper II was a cohort study where 82 participants were followed over 17.2 years. Similarly, participants with moderate alcohol consumption displayed significant fibrosis progression. The strongest association was observed in participants with PEth-value of 48 ng/mL or higher, or those with binge drinking.  

    In Paper III, the potential role of variant PNPLA3 was explored, exhibiting impaired autophagic flux and reduced lipophagy in variant PNPLA3 cells. Liver biopsies of NAFLD individuals with variant PNPLA3 displayed an accumulation of lipid droplets positive for both PNPLA3 and LC3 (a common marker of the autophagosome). This suggests that PNPLA3 is part of the lipophagy process, which is impaired in the variant gene and contributes to steatosis.  

    Paper IV examined two independent NAFLD cohorts. In the discovery cohort, 60 participants with biopsy-proven NAFLD were included, while 59 participants were included in the validation cohort. The study evaluated 266 proteins and found that a biomarker model combining ACE2, HGF, and IGFBP-7 distinguished between different fibrosis stages (F0–1 and F2–4) in both cohorts.  

    In summary, measuring phosphatidylethanol is advisable in NAFLD patient evaluations. Elevated PEth-levels (≥48 ng/mL) or alcohol consumption exceeding 66 grams per week should warrant advice to abstain from alcohol. PNPLA3 is implicated in NAFLD pathophysiology, potentially through impaired lipophagy. While its clinical application remains uncertain, genetic profiling for NAFLD risk assessment may become part of future non-invasive approaches. Additionally, proteomics holds promise for non-invasive NAFLD assessment, with the combination of ACE2, HGF, and IGFBP-7 identifying significant fibrosis in two separate cohorts. 

    List of papers
    1. Moderate alcohol consumption is associated with advanced fibrosis in non-alcoholic fatty liver disease and shows a synergistic effect with type 2 diabetes mellitus
    Open this publication in new window or tab >>Moderate alcohol consumption is associated with advanced fibrosis in non-alcoholic fatty liver disease and shows a synergistic effect with type 2 diabetes mellitus
    2021 (English)In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 115, article id 154439Article in journal (Refereed) Published
    Abstract [en]

    Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Whether moderate alcohol consumption plays a role for progression of NAFLD is disputed. Moreover, it is not known which tool is ideal for assessment of alcohol consumption in NAFLD. This study aimed to evaluate if moderate alcohol consumption assessed with different methods, including the biological marker phosphatidylethanol (PEth), is associated with advanced fibrosis in NAFLD. Methods: We conducted a cross-sectional study of patients with biopsy-proven NAFLD. All participants were clinically evaluated with medical history, blood tests, and anthropometric measurements. Alcohol consumption was assessed using PEth in blood, the questionnaire AUDIT-C, and clinical interview. Findings: 86 patients were included of which 17% had advanced fibrosis. All participants reported alcohol consumption &lt; 140 g/week. Average weekly alcohol consumption was higher in the group with advanced fibrosis. Moderate alcohol consumption, independently of the method of assessment, was associated with increased probability of advanced fibrosis (adjusted OR 5.5-9.7, 95% CI 1.05-69.6). Patients with type 2 diabetes mellitus (T2DM) consuming moderate amounts of alcohol had a significantly higher rate of advanced fibrosis compared with those consuming low amounts (50.0-60.0% vs. 33-21.6%, p &lt; 0.05). Conclusions: Moderate alcohol consumption, irrespective of assessment method (clinical interview, AUDIT-C, and PEth), was associated with advanced fibrosis. PEth in blood &gt;= 50 ng/mL may be a biological marker indicating increased risk for advanced fibrosis in NAFLD. Patients with T2DM consuming moderate amounts of alcohol had the highest risk of advanced fibrosis, indicating a synergistic effect of insulin resistance and alcohol on the histopathological progression of NAFLD. (C) 2020 The Author(s). Published by Elsevier Inc.

    Place, publisher, year, edition, pages
    Elsevier, 2021
    Keywords
    Non-alcoholic fatty liver disease; Alcohol drinking; Type 2 diabetes mellitus; Phosphatidylethanol
    National Category
    Surgery
    Identifiers
    urn:nbn:se:liu:diva-173399 (URN)10.1016/j.metabol.2020.154439 (DOI)000608790700005 ()33246008 (PubMedID)2-s2.0-85097192291 (Scopus ID)
    Note

    Funding Agencies|Medical Research Council of Southeast SwedenUK Research & Innovation (UKRI)Medical Research Council UK (MRC)

    Available from: 2021-02-20 Created: 2021-02-20 Last updated: 2023-10-23Bibliographically approved
    2. Moderate alcohol consumption is associated with significant fibrosis progression in NAFLD
    Open this publication in new window or tab >>Moderate alcohol consumption is associated with significant fibrosis progression in NAFLD
    2023 (English)In: HEPATOLOGY COMMUNICATIONS, ISSN 2471-254X, Vol. 7, no 1Article in journal (Refereed) Published
    Abstract [en]

    The effect of moderate alcohol consumption on NAFLD histology is disputed. Assessment of alcohol consumption is commonly performed with interview or questionnaires. Phosphatidylethanol (PEth) in blood is a highly sensitive and specific alcohol biomarker, which only forms in the presence of ethanol. PEth has hitherto not been evaluated in longitudinal NAFLD studies. This study aimed to examine the impact of moderate alcohol consumption on histologic progression and evaluate the utility of PEth in NAFLD. NAFLD patients with serial biopsies were reviewed for inclusion in the study. At baseline, all patients reported alcohol consumption &lt;140 g/week. Anthropometric and biochemical measurements were performed at baseline and follow-up. Alcohol consumption was assessed thoroughly at follow-up with clinical interview, the Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) questionnaire, and analysis of PEth in whole blood. Eighty-two patients were included. Mean follow-up time was 17.2 years (SD & PLUSMN;6.0). Patients with significant fibrosis progression (defined as progression of & GE;2 stages or development of cirrhosis-related complications) reported higher alcohol consumption and had significantly higher PEth. Consumption &gt;66-96 g/week (but &lt;140 g) (i.e. moderate alcohol consumption) was associated with increased risk of significant fibrosis progression compared with no or low consumption. PEth & GE;48 ng/mL and binge drinking showed the highest risk for significant fibrosis progression (aOR: 5.9; 95% CI: 1.6-21.4) and aOR: 5.1; 95% CI: 1.4-18.1, respectively). NAFLD patients consuming moderate amounts of alcohol are at increased risk for significant fibrosis progression and development of cirrhosis-related complications. PEth is a potential biomarker to assess harmful alcohol consumption in NAFLD. Patients reporting moderate consumption or exhibiting PEth & GE;48 ng/mL should be advised to reduce alcohol consumption.

    Place, publisher, year, edition, pages
    LIPPINCOTT WILLIAMS & WILKINS, 2023
    National Category
    Substance Abuse
    Identifiers
    urn:nbn:se:liu:diva-197483 (URN)10.1097/HC9.0000000000000003 (DOI)001038261400003 ()36633482 (PubMedID)
    Note

    Funding Agencies|~ALF Grants; Region Ostergoetland; Medical Research Council of Southeast Sweden [752871]

    Available from: 2023-09-12 Created: 2023-09-12 Last updated: 2024-02-08
    3. PNPLA3 variant M148 causes resistance to starvation-mediated lipid droplet autophagy in human hepatocytes
    Open this publication in new window or tab >>PNPLA3 variant M148 causes resistance to starvation-mediated lipid droplet autophagy in human hepatocytes
    Show others...
    2019 (English)In: Journal of Cellular Biochemistry, ISSN 0730-2312, E-ISSN 1097-4644, Vol. 120, no 1, p. 343-356Article in journal (Refereed) Published
    Abstract [en]

    The mechanism of how patatin-like phospholipase domain-containing protein 3 (PNPLA3) variant M148 is associated with increased risk of development of hepatic steatosis is still debated. Here, we propose a novel role of PNPLA3 as a key player during autophagosome formation in the process of lipophagy. A human hepatocyte cell line, HepG2 cells, expressing recombinant I148 or 148M, was used to study lipophagy under energy deprived conditions, and lipid droplet morphology was investigated using florescence microscopy, image analysis and biochemical assays. Autophagic flux was studied using the golden-standard of LC3-II turnover in combination with the well characterized GFP-RFP-LC3 vector. To discriminate between, perturbed autophagic initiation and lysosome functionality, lysosomes were characterized by Lysotracker staining and LAMP1 protein levels as well as activity and activation of cathepsin B. For validation, human liver biopsies genotyped for I148 and 148M were analyzed for the presence of LC3-II and PNPLA3 on lipid droplets. We show that the M148-PNPLA3 variant is associated with lipid droplets that are resistant to starvation-mediated degradation. M148 expressing hepatocytes reveal decreased autophagic flux and reduced lipophagy. Both I148-PNPLA3 and M148-PNPLA3 colocalize and interact with LC3-II, but the M148-PNPLA3 variant has lower ability to bind LC3-II. Together, our data indicate that PNPLA3 might play an essential role in lipophagy in hepatocytes and furthermore that the M148-PNPLA3 variant appears to display a loss in this activity, leading to decreased lipophagy.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2019
    Keywords
    adiponutrin; lipophagy; liver; steatosis
    National Category
    Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
    Identifiers
    urn:nbn:se:liu:diva-153347 (URN)10.1002/jcb.27378 (DOI)000450823500032 ()30171718 (PubMedID)2-s2.0-85052837166 (Scopus ID)
    Note

    Funding Agencies|Swedish Research Foundation [11284]; Crafoord Foundation; Swedish Diabetes Foundation; Albert Pahlsson Foundation; Dr Per Hakansson Foundation

    Available from: 2018-12-13 Created: 2018-12-13 Last updated: 2023-10-23Bibliographically approved
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  • 43.
    Blomstrand, Hakon
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Adolfsson, Karin
    Ryhov Cty Hosp, Sweden.
    Sandström, Per
    Linköping University, Department of Biomedical and Clinical Sciences, 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.
    Björnsson, Bergthor
    Linköping University, Department of Biomedical and Clinical Sciences, 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.
    Complete Radiologic Response of Metastatic Pancreatic Ductal Adenocarcinoma to Microwave Ablation Combined with Second-Line Palliative Chemotherapy2020In: Case Reports in Gastrointestinal Medicine, ISSN 2090-6528, E-ISSN 2090-6536, Vol. 2020, article id 4138215Article in journal (Refereed)
    Abstract [en]

    Pancreatic ductal adenocarcinoma (PDAC) has a bleak prognosis, especially for the majority of patients diagnosed with metastatic disease. The primary option for palliative treatment is chemotherapy, and responses beyond first-line treatment are rare and typically short. Here, we report a case of a 63-year-old woman with PDAC in the head of the pancreas who was initially successfully treated by pancreaticoduodenectomy followed by adjuvant chemotherapy with gemcitabine. However, disease recurrence with liver and para-aortic lymph node metastases was detected only two months after the completion of adjuvant chemotherapy. First-line palliative chemotherapy with gemcitabine-nab/paclitaxel was commenced. The results were discouraging, with disease progression (liver and lung metastases) detected at the first evaluation; the progression-free survival was just two months (64 days). Surprisingly, the response to second-line palliative chemotherapy with 5-fluorouracil-oxaliplatin was excellent; in combination with the ablation of a liver metastasis, this treatment regimen resulted in a complete radiological response and an 11-month treatment-free interval with a sustained good performance status.

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    fulltext
  • 44.
    Bonfiglio, Ferdinando
    et al.
    School of Biological Sciences, Monash University, Clayton, VIC, Australia; Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Liu, Xingrong
    Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Smillie, Christopher
    Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA.
    Pandit, Anita
    Department of Biostatistics, University of Michigan, School of Public Health, Ann Arbor, MI, USA.
    Kurilshikov, Alexander
    Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
    Bacigalupe, Rodrigo
    Department of Microbiology and Immunology, Rega Instituut, KU Leuven, Leuven, Belgium; Center for Microbiology, VIB, Leuven 3000, Belgium.
    Zheng, Tenghao
    School of Biological Sciences, Monash University, Clayton, VIC, Australia; Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Nim, Hieu
    School of Biological Sciences, Monash University, Clayton, VIC, Australia.
    Garcia-Etxebarria, Koldo
    Department of Gastrointestinal and Liver Diseases, Biodonostia HRI, San Sebastian, Spain.
    Bujanda, Luis
    Department of Gastrointestinal and Liver Diseases, Biodonostia HRI, San Sebastian, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain; Universidad del País Vasco (UPV/EHU), San Sebastian, Spain.
    Andreasson, Anna
    Division of Clinical Medicine, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Agreus, Lars
    Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Walter, Susanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Abecasis, Gonçalo
    Department of Biostatistics, University of Michigan, School of Public Health, Ann Arbor, MI, USA.
    Eijsbouts, Chris
    Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
    Jostins, Luke
    Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK; Christ Church, University of Oxford, Oxford, UK.
    Parkes, Miles
    Division of Gastroenterology, Department of Medicine, University of Cambridge, Cambridge, UK.
    Hughes, David A
    MRC Integrative Epidemiology Unit at University of Bristol, Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
    Timpson, Nicholas
    MRC Integrative Epidemiology Unit at University of Bristol, Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
    Raes, Jeroen
    Department of Microbiology and Immunology, Rega Instituut, KU Leuven, Leuven, Belgium; Center for Microbiology, VIB, Leuven 3000, Belgium.
    Franke, Andre
    Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
    Kennedy, Nicholas A
    IBD Pharmacogenetics, College of Medicine and Health, University of Exeter, Exeter, UK.
    Regev, Aviv
    Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA.
    Zhernakova, Alexandra
    Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
    Simren, Magnus
    Dept of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Camilleri, Michael
    Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER) and Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
    DAmato, Mauro
    School of Biological Sciences, Monash University, Clayton, VIC, Australia; Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Gastrointestinal and Liver Diseases, Biodonostia HRI, San Sebastian, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; Gastrointestinal Genetics Lab, CIC bioGUNE - BRTA, Derio, Spain.
    GWAS of stool frequency provides insights into gastrointestinal motility and irritable bowel syndrome2021In: Cell Genomics, E-ISSN 2666-979X, Vol. 1, no 3, article id 100069Article in journal (Refereed)
    Abstract [en]

    Gut dysmotility is associated with constipation, diarrhea, and functional gastrointestinal disorders like irritable bowel syndrome (IBS), although its molecular underpinnings are poorly characterized. We studied stool frequency (defined by the number of bowel movements per day, based on questionnaire data) as a proxy for gut motility in a GWAS meta-analysis including 167,875 individuals from UK Biobank and four smaller population-based cohorts. We identify 14 loci associated with stool frequency (p = 5.0 × 10-8). Gene set and pathway analyses detected enrichment for genes involved in neurotransmitter/neuropeptide signaling and preferentially expressed in enteric motor neurons controlling peristalsis. PheWAS identified pleiotropic associations with dysmotility syndromes and the response to their pharmacological treatment. The genetic architecture of stool frequency correlates with that of IBS, and UK Biobank participants from the top 1% of stool frequency polygenic score distribution were associated with 5× higher risk of IBS with diarrhea. These findings pave the way for the identification of actionable pathological mechanisms in IBS and the dysmotility syndromes.

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  • 45.
    Bonfiglio, Ferdinando
    et al.
    Biodonostia Hlth Res Inst, Spain; Karolinska Inst, Sweden.
    Zheng, Tenghao
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Garcia-Etxebarria, Koldo
    Biodonostia Hlth Res Inst, Spain; Karolinska Inst, Sweden.
    Hadizadeh, Fatemeh
    Karolinska Inst, Sweden.
    Bujanda, Luis
    Biodonostia Hlth Res Inst, Spain; Univ Basque Country, Spain.
    Bresso, Francesca
    Karolinska Univ Hosp, Sweden.
    Agreus, Lars
    Karolinska Inst, Sweden.
    Andreasson, Anna
    Karolinska Inst, Sweden; Stockholm Univ, Sweden.
    Dlugosz, Aldona
    Karolinska Inst, Sweden.
    Lindberg, Greger
    Karolinska Inst, Sweden.
    Schmidt, Peter T.
    Karolinska Inst, Sweden.
    Karling, Pontus
    Umea Univ, Sweden.
    Ohlsson, Bodil
    Lund Univ, Sweden.
    Simren, Magnus
    Univ Gothenburg, Sweden.
    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.
    Nardone, Gerardo
    Univ Federico II, Italy.
    Cuomo, Rosario
    Federico II Univ Hosp, Italy.
    Usai-Satta, Paolo
    Azienda Osped G Brotzu, Italy.
    Galeazzi, Francesca
    Padova Univ Hosp, Italy.
    Neri, Matteo
    G DAnnunzio Univ and Fdn, Italy; G DAnnunzio Univ and Fdn, Italy.
    Portincasa, Piero
    Univ Bari, Italy.
    Bellini, Massimo
    Univ Pisa, Italy.
    Barbara, Giovanni
    Univ Bologna, Italy.
    Latiano, Anna
    Casa Sollievo Sofferenza Hosp, Italy.
    Huebenthal, Matthias
    Christian Albrechts Univ Kiel, Germany.
    Thijs, Vincent
    Florey Inst Neurosci and Mental Hlth, Australia.
    Netea, Mihai G.
    Radboud Univ Nijmegen, Netherlands; Radboud Univ Nijmegen, Netherlands; Univ Bonn, Germany.
    Jonkers, Daisy
    Maastricht Univ, Netherlands.
    Chang, Lin
    Univ Calif Los Angeles, CA 90095 USA.
    Mayer, Emeran A.
    Univ Calif Los Angeles, CA 90095 USA.
    Wouters, Mira M.
    Katholieke Univ Leuven, Belgium.
    Boeckxstaens, Guy
    Katholieke Univ Leuven, Belgium.
    Camilleri, Michael
    Mayo Clin, MN USA; Mayo Clin, MN USA.
    Franke, Andre
    Christian Albrechts Univ Kiel, Germany.
    Zhernakova, Alexandra
    Univ Med Ctr Groningen, Netherlands.
    DAmato, Mauro
    Biodonostia Hlth Res Inst, Spain; Karolinska Inst, Sweden; Karolinska Inst, Sweden; Ikerbasque, Spain.
    Female-Specific Association Between Variants on Chromosome 9 and Self-Reported Diagnosis of Irritable Bowel Syndrome2018In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 155, no 1, p. 168-179Article in journal (Refereed)
    Abstract [en]

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

  • 46.
    Boursier, Jerome
    et al.
    Ctr Hosp Univ Angers, France; Univ Angers, France.
    Hagstrom, Hannes
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Ekstedt, Mattias
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Moreau, Clemence
    Univ Angers, France.
    Bonacci, Martin
    Intercept Pharmaceut, England; Intercept Pharmaceut Inc, NY USA.
    Cure, Sandrine
    Intercept Pharmaceut, England; Intercept Pharmaceut Inc, NY USA.
    Ampuero, Javier
    Univ Seville, Spain.
    Nasr, Patrik
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Tallab, Lilian
    Karolinska Inst, Sweden.
    Canivet, Clemence M.
    Ctr Hosp Univ Angers, France; Univ Angers, France.
    Kechagias, Stergios
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Mag- tarmmedicinska kliniken.
    Sanchez, Yolanda
    Univ Seville, Spain.
    Dincuff, Eloise
    Ctr Hosp Univ Angers, France.
    Lucena, Ana
    Univ Seville, Spain.
    Roux, Marine
    Univ Angers, France.
    Riou, Jeremie
    Univ Angers, France.
    Trylesinski, Aldo
    Intercept Pharmaceut, England; Intercept Pharmaceut Inc, NY USA.
    Romero-Gomez, Manuel
    Univ Seville, Spain.
    Non-invasive tests accurately stratify patients with NAFLD based on their risk of liver-related events2022In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 76, no 5, p. 1013-1020Article in journal (Refereed)
    Abstract [en]

    Background & Aims: Previous studies on the prognostic significance of non-invasive liver fibrosis tests in non-alcoholic fatty liver disease (NAFLD) lack direct comparison to liver biopsy. We aimed to evaluate the prognostic accuracy of fibrosis-4 (FIB4) and vibration-controlled transient elastography (VCTE), compared to liver biopsy, for the prediction of liver-related events (LREs) in NAFLD. Methods: A total of 1,057 patients with NAFLD and baseline FIB4 and VCTE were included in a multicenter cohort. Of these patients, 594 also had a baseline liver biopsy. The main study outcome during follow-up was occurrence of LREs, a composite endpoint combining cirrhosis complications and/or hepatocellular carcinoma. Discriminative ability was evaluated using Harrells C-index. Results: FIB4 and VCTE showed good accuracy for the prediction of LREs, with Harrells C-indexes &gt;0.80 (0.817 [0.768-0.866] vs. 0.878 [0.835-0.921], respectively, p = 0.059). In the biopsy subgroup, Harrells C-indexes of histological fibrosis staging and VCTE were not significantly different (0.932 [0.910-0.955] vs. 0.881 [0.832-0.931], respectively, p = 0.164), while both significantly outperformed FIB4 for the prediction of LREs. FIB4 and VCTE were independent predictors of LREs in the whole study cohort. The stepwise FIB4-VCTE algorithm accurately stratified the risk of LREs: compared to patients with "FIB4 &lt;1.30", those with "FIB4 &gt;- 1.30 then VCTE &lt;8.0 kPa" had similar risk of LREs (adjusted hazard ratio [aHR] 1.3; 95% CI 0.3-6.8), whereas the risk of LREs significantly increased in patients with "FIB4 &gt;1.30 then VCTE 8.0-12.0 kPa" (aHR 3.8; 95% CI 1.3-10.9), and even more for those with "FIB4 &gt;-1.30 then VCTE &gt;12.0 kPa" (aHR 12.4; 95% CI 5.1- 30.2). Conclusion: VCTE and FIB4 accurately stratify patients with NAFLD based on their risk of LREs. These non-invasive tests are alternatives to liver biopsy for the identification of patients in need of specialized management. Lay summary: The amount of fibrosis in the liver is closely associated with the risk of liver-related complications in nonalcoholic fatty liver disease (NAFLD). Liver biopsy currently remains the reference standard for the evaluation of fibrosis, but its application is limited by its invasiveness. Therefore, we evaluated the ability of non-invasive liver fibrosis tests to predict liver-related complications in NAFLD. Our results show that the blood test FIB4 and transient elastography stratify the risk of liver-related complications in NAFLD, and that transient elastography has similar prognostic accuracy as liver biopsy. These results support the use of non-invasive liver fibrosis tests instead of liver biopsy for the management of patients with NAFLD.(C) 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  • 47.
    Broms, Gabriella
    et al.
    Karolinska Inst, Sweden; Danderyd Hosp, Sweden.
    Soderling, Jonas
    Karolinska Inst, Sweden.
    Sachs, Michael C.
    Karolinska Inst, Sweden.
    Halfvarson, Jonas
    Orebro Univ, Sweden.
    Myrelid, Pär
    Linköping University, Department of Biomedical and Clinical Sciences, 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, Jonas F.
    Karolinska Inst, Sweden; Orebro Univ Hosp, Sweden.
    Everhov, Asa H.
    Karolinska Inst, Sweden; Stockholm South Gen Hosp, Sweden.
    Olen, Ola
    Karolinska Inst, Sweden; Stockholm South Gen Hosp, Sweden; Karolinska Inst, Sweden.
    Capturing biologic treatment for IBD in the Swedish Prescribed Drug Register and the Swedish National Patient Register - a validation study2021In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 56, no 4, p. 410-421Article in journal (Refereed)
    Abstract [en]

    Background It is not known to what extent biologic treatment for IBD is captured in the Swedish Prescribed Drug Register (PDR) and the National Patient Register (NPR). Methods A cross-sectional study from July 2005 until 2017, comparing data on biologic treatment in the PDR and the NPR with medical records. We assessed the proportion of started treatment episodes in the medical records that were found in the PDR/NPR ever, within +/- one year and within +/- three months; for any biologic drug, per specific drug (infliximab, adalimumab, golimumab, vedolizumab, ustekinumab), by calendar period (2005-2008, 2009-2012, and 2013-2017) and by study center. For adalimumab, we assessed the validity of end of treatment episodes. Results Medical records of 1361 patients and 2323 treatment episodes with any biologic were reviewed and 80.1% (95% CI: 78.4-81.7) were ever captured in the PDR/NPR in. A time window of +/- one year or +/- three months reduced the sensitivity to 63.3% (95% CI: 61.3-65.3) and 52.6% (95% CI: 50.5-54.6), respectively. The sensitivity was high (&gt;85%) for the prescribed injection drugs adalimumab, golimumab, and ustekinumab for all time windows and for adalimumab end of treatment, while considerably lower for the infusion drugs infliximab and vedolizumab. Conclusions The PDR and the NPR are reliable data sources on treatment with injection biologics in patients with IBD in Sweden. Infliximab and vedolizumab are poorly captured, why PDR/NPR data should only be used after careful consideration of their limitations or complemented by other data sources, e.g., the disease-specific quality register SWIBREG.

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  • 48.
    Burgueno, Beatriz
    et al.
    Univ Valladolid, Spain.
    Escudero-Hernández, Celia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences. Univ Valladolid, Spain.
    de Pedro, Rodrigo
    Univ Valladolid, Spain.
    Montalvillo, Enrique
    Univ Valladolid, Spain.
    Bernardo, David
    Univ Valladolid, Spain.
    Garcia Lagarto, Elena
    Univ Valladolid, Spain.
    Garrote Adrados, Jose Antonio
    Univ Valladolid, Spain; Hosp Univ Rio Hortega Valladolid, Spain.
    Arranz Sanz, Eduardo
    Univ Valladolid, Spain.
    Fernandez-Salazar, Luis
    Univ Valladolid, Spain.
    Duodenal lymphogram as a complementary tool in the diagnosis of celiac disease in adults2020In: Revista española de enfermedades digestivas, ISSN 1130-0108, E-ISSN 2340-4167, Vol. 112, no 6, p. 434-439Article in journal (Refereed)
    Abstract [en]

    Introduction: celiac disease (CD) patients have a specific pattern of lymphocytic infiltrate in the duodenal mucosa. Flow cytometry is a complementary tool for the diagnosis of CD, which allows the quantification and characterization of intraepithelial lymphocytes (IELs) by what is commonly called a lymphogram. Here we describe our experience with this technique in the diagnosis of CD in adult patients. Methods: lymphograms from 157 patients performed in our center between 2009 and 2017 were retrospectively analyzed. Fourteen patients had a previous diagnosis of CD and followed a gluten-free diet (GFD), 21 had a new diagnosis of CD and the remaining were considered as non-celiac. The association of the lymphogram results (total IELs, CD3- lymphocytes and TcR gamma delta lymphocytes) with the CD diagnosis, compliance with the GFD, time since diagnosis and IgA anti-TG2 titer were determined. Results: the area under the ROC curve of TcR gamma delta lymphocytes for CD patients varied between 0.86 and 0.86. The percentage of TcR gamma delta lymphocytes in GFD-treated patients was lower; 12 (8.5) vs 20.5 (8.7), p = 0.0153. However, it remained high compared to non-CD; 12 (8.5) vs 6.7 (6), p = 0.135. The time since diagnosis and IgA anti-TG2 titer correlated with the lymphogram results. Helicobacter pylori infection and treatment with angiotensin receptor antagonist 2 (ARA2) were associated with differences in the lymphogram results in patients without CD. Conclusions: the duodenal lymphogram is a reliable complementary tool in adults for the diagnosis of CD. However, compliance and duration of the GFD and other factors may condition its diagnostic capacity.

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  • 49.
    Butwicka, Agnieszka
    et al.
    Karolinska Inst, Sweden; Med Univ Warsaw, Poland.
    Sariaslan, Amir
    Karolinska Inst, Sweden.
    Larsson, Henrik
    Karolinska Inst, Sweden.
    Halfvarson, Jonas
    Orebro 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.
    Olen, Ola
    Stockholm South Gen Hosp, Sweden; Karolinska Inst, Sweden.
    Frisen, Louise
    Child and Adolescent Psychiat Res Ctr, Sweden; Karolinska Inst, Sweden.
    Lichtenstein, Paul
    Karolinska Inst, Sweden.
    Ludvigsson, Jonas F.
    Karolinska Inst, Sweden; Orebro Univ, Sweden.
    No association between urbanisation, neighbourhood deprivation and IBD: a population-based study of 4 million individuals2019In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 68, no 5, p. 947-948Article in journal (Other academic)
    Abstract [en]

    n/a

  • 50.
    Buzzetti, Elena
    et al.
    Royal Free Hosp, England; UCL, England.
    Hall, Andrew
    Royal Free Hosp, England; Royal Free Hosp, England.
    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.
    Manuguerra, Roberta
    Royal Free Hosp, England.
    Misas, Marta Guerrero
    Royal Free Hosp, England; UCL, England.
    Covelli, Claudia
    Royal Free Hosp, England.
    Leandro, Gioacchino
    S de Bellis Res Hosp, Italy.
    Luong, TuVinh
    Royal Free Hosp, England.
    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.
    Manesis, Emanuel K.
    Hippokrateion Hosp, Greece.
    Pinzani, Massimo
    Royal Free Hosp, England; UCL, England.
    Dhillon, Amar P.
    Royal Free Hosp, England.
    Tsochatzis, Emmanuel A.
    Royal Free Hosp, England; UCL, England.
    Collagen proportionate area is an independent predictor of long-term outcome in patients with non-alcoholic fatty liver disease2019In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 49, no 9, p. 1214-1222Article in journal (Refereed)
    Abstract [en]

    Background Collagen proportionate area (CPA) measurement is a technique that quantifies fibrous tissue in liver biopsies by measuring the amount of collagen deposition as a proportion of the total biopsy area. CPA predicts clinical outcomes in patients with HCV and can sub-classify cirrhosis. Aim To test the ability of CPA to quantify fibrosis and predict clinical outcomes in patients with NAFLD. Methods We assessed consecutive patients with biopsy-proven NAFLD from three European centres. Clinical and laboratory data were collected at baseline and at the time of the last clinical follow-up or death. CPA was performed at two different objective magnifications, whole biopsy macro and x4 objective magnification, named standard (SM) and high (HM) magnification respectively. The correlation between CPA and liver stiffness was assessed in a sub-group of patients. Results Of 437 patients, 32 (7.3%) decompensated and/or died from liver-related causes during a median follow-up of 103 months. CPA correlated with liver stiffness and liver fibrosis stage across the whole spectrum of fibrosis. HM CPA was significantly higher than SM CPA in stages F0-F3 but similar in cirrhosis, reflecting a higher ability to capture pericellular/perisinusoidal fibrosis at early stages. Age at baseline (HR: 1.04, 95% CI: 1.01-1.08), HM CPA (HR: 1.04 per 1% increase, 95% CI: 1.01-1.08) and presence of advanced fibrosis (HR: 15.4, 95% CI: 5.02-47.84) were independent predictors of liver-related clinical outcomes at standard and competing risk multivariate Cox-regression analysis. Conclusions CPA accurately measures fibrosis and is an independent predictor of clinical outcomes in NAFLD; hence it merits further evaluation as a surrogate endpoint in clinical trials.

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