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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.
    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.  

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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.

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  • 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.
    Abusabeib, Alyaa
    et al.
    Department of Bariatric Surgery/Bariatric Medicine, Hamad General Hospital, Doha, Qatar.
    El Ansari, Walid
    University of Skövde, School of Health Sciences. University of Skövde, Digital Health Research (DHEAR). Department of Surgery, Hamad General Hospital, Doha, Qatar / College of Medicine, Qatar University, Doha, Qatar.
    Alobaidan, Jassim
    Department of Bariatric Surgery/Bariatric Medicine, Hamad General Hospital, Doha, Qatar.
    Elhag, Wahiba
    Department of Bariatric Surgery/Bariatric Medicine, Hamad General Hospital, Doha, Qatar.
    First Case Report of Fulminant Hepatitis After Laparoscopic Sleeve Gastrectomy Associated with Concomitant Maximal Therapeutic Dose of Acetaminophen Use, Protein Calorie Malnutrition, and Vitamins A and D, Selenium, and Glutathione Deficiencies2021In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 31, no 2, p. 899-903Article in journal (Refereed)
    Abstract [en]

    Nonalcoholic fatty liver disease (NAFLD) is increasingly being linked to obesity. Although laparoscopic sleeve gastrectomy (LSG) is effective for weight loss that can ultimately resolve NAFLD, an initial transient deterioration of liver functions could be observed during the first few months post-operatively, after which a subsequent improvement of the liver functions might occur. Rapid weight loss, nutritional deficiencies, and protein malnutrition can all contribute to hepatic dysfunction and can affect the metabolism of medications such as acetaminophen leading to more insult to a compromised liver. We report acute liver failure after LSG associated with protein calorie malnutrition, multiple nutritional deficiencies in addition to concomitant use of therapeutic doses of acetaminophen. Treatment with N-acetylcysteine, and replacement of deficient multivitamins and trace elements resulted in significant improvement in liver functions. 

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  • 8.
    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.

  • 9.
    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.

  • 10.
    Adams, A.
    et al.
    Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Kalla, R.
    Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Vatn, S.
    Institute of Clinical Medicine, EpiGen, University of Oslo, Oslo, Norway.
    Bonfiglio, F.
    BioCruces Health Research Institue, Bilbao, Spain.
    Nimmo, E.
    Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Kennedy, N.
    Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Ventham, N.
    Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Vatn, M.
    Institute of Clinical Medicine, EpiGen, University of Oslo, Oslo, Norway.
    Ricanek, P.
    Department of Gastroenterology, Akershus University, Akershus, Norway.
    Bergemalm, Daniel
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Söderholm, J.
    Department of Surgery, Linköping University Hospital, Linköping, Sweden;.
    Pierik, M.
    Department of Gastroenterology and Hepatology, Maastricht University Medical Center (MUMC), Maastricht, Netherlands.
    Törkvist, L.
    Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden.
    Gomollon, F.
    University Hospital Clinic Lozano Blesa, Zaragoza, Spain.
    Gut, I.
    CNAG-CRG Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain.
    Jahnsen, J.
    Institute of Clinical Medicine, EpiGen, University of Oslo, Oslo, Norway.
    Satsangi, J.
    Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Epigenetic alterations at diagnosis predict susceptibility, prognosis and treatment escalation in inflammatory bowel disease - IBD Character2017In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 11, no Suppl. 1, p. S108-S108Article in journal (Refereed)
  • 11.
    Adori, Csaba
    et al.
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Daraio, Teresa
    Karolinska Inst, Rolf Luft Res Ctr Diabet & Endocrinol, Dept Mol Med & Surg, S-17176 Stockholm, Sweden..
    Kuiper, Raoul
    Karolinska Inst, Dept Lab Med, S-17177 Stockholm, Sweden..
    Barde, Swapnali
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Horvathova, Lubica
    Slovak Acad Sci, Biomed Res Ctr, Inst Expt Endocrinol, Bratislava, Slovakia..
    Yoshitake, Takashi
    Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden..
    Ihnatko, Robert
    Linköping Univ, Dept Clin Chem, S-58285 Linköping, Sweden.;Linköping Univ, Dept Clin & Expt Med, S-58285 Linköping, Sweden.;Georg August Univ Gottingen, Univ Med Ctr, Inst Pathol, Gottingen, Germany..
    Valladolid-Acebes, Ismael
    Karolinska Inst, Rolf Luft Res Ctr Diabet & Endocrinol, Dept Mol Med & Surg, S-17176 Stockholm, Sweden..
    Vercruysse, Pauline
    Karolinska Inst, Rolf Luft Res Ctr Diabet & Endocrinol, Dept Mol Med & Surg, S-17176 Stockholm, Sweden..
    Wellendorf, Ashley M.
    Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA..
    Gramignoli, Roberto
    Karolinska Inst, Dept Lab Med, S-17177 Stockholm, Sweden..
    Bozoky, Bela
    Karolinska Univ Hosp, Dept Clin Pathol Cytol, Huddinge, Sweden..
    Kehr, Jan
    Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden..
    Theodorsson, Elvar
    Linköping Univ, Dept Clin Chem, S-58285 Linköping, Sweden.;Linköping Univ, Dept Clin & Expt Med, S-58285 Linköping, Sweden..
    Cancelas, Jose A.
    Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.;Univ Cincinnati, Hoxworth Blood Ctr, Coll Med, Cincinnati, OH 45267 USA..
    Mravec, Boris
    Slovak Acad Sci, Biomed Res Ctr, Inst Expt Endocrinol, Bratislava, Slovakia.;Comenius Univ, Fac Med, Inst Physiol, Bratislava, Slovakia..
    Jorns, Carl
    Karolinska Univ Hosp Huddinge, PO Transplantat, S-14152 Stockholm, Sweden..
    Ellis, Ewa
    Karolinska Inst, Karolinska Univ Hosp, Dept Transplantat Surg, S-17177 Stockholm, Sweden.;Karolinska Inst, Karolinska Univ Hosp, Dept Clin Sci Intervent & Technol CLINTEC, S-17177 Stockholm, Sweden..
    Mulder, Jan
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Uhlén, Mathias
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology. Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden.;Royal Inst Technol, Sci Life Lab, S-10691 Stockholm, Sweden..
    Bark, Christina
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Hokfelt, Tomas
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Disorganization and degeneration of liver sympathetic innervations in nonalcoholic fatty liver disease revealed by 3D imaging2021In: Science Advances, E-ISSN 2375-2548, Vol. 7, no 30, article id eabg5733Article in journal (Refereed)
    Abstract [en]

    Hepatic nerves have a complex role in synchronizing liver metabolism. Here, we used three-dimensional (3D) immunoimaging to explore the integrity of the hepatic nervous system in experimental and human nonalcoholic fatty liver disease (NAFLD). We demonstrate parallel signs of mild degeneration and axonal sprouting of sympathetic innervations in early stages of experimental NAFLD and a collapse of sympathetic arborization in steatohepatitis. Human fatty livers display a similar pattern of sympathetic nerve degeneration, correlating with the severity of NAFLD pathology. We show that chronic sympathetic hyperexcitation is a key factor in the axonal degeneration, here genetically phenocopied in mice deficient of the Rac-1 activator Vav3. In experimental steatohepatitis, 3D imaging reveals a severe portal vein contraction, spatially correlated with the extension of the remaining nerves around the portal vein, enlightening a potential intrahepatic neuronal mechanism of portal hypertension. These fundamental alterations in liver innervation and vasculature uncover previously unidentified neuronal components in NAFLD pathomechanisms.

  • 12. Adori, Monika
    et al.
    Bhat, Sadam
    Gramignoli, Roberto
    Valladolid-Acebes, Ismael
    Bengtsson, Tore
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Uhlèn, Mathias
    Adori, Csaba
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Karolinska Institutet, Sweden.
    Hepatic Innervations and Nonalcoholic Fatty Liver Disease2023In: Seminars in liver disease (Print), ISSN 0272-8087, E-ISSN 1098-8971, Vol. 43, no 02, p. 149-162Article, review/survey (Refereed)
    Abstract [en]

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder. Increased sympathetic (noradrenergic) nerve tone has a complex role in the etiopathomechanism of NAFLD, affecting the development/progression of steatosis, inflammation, fibrosis, and liver hemodynamical alterations. Also, lipid sensing by vagal afferent fibers is an important player in the development of hepatic steatosis. Moreover, disorganization and progressive degeneration of liver sympathetic nerves were recently described in human and experimental NAFLD. These structural alterations likely come along with impaired liver sympathetic nerve functionality and lack of adequate hepatic noradrenergic signaling. Here, we first overview the anatomy and physiology of liver nerves. Then, we discuss the nerve impairments in NAFLD and their pathophysiological consequences in hepatic metabolism, inflammation, fibrosis, and hemodynamics. We conclude that further studies considering the spatial-temporal dynamics of structural and functional changes in the hepatic nervous system may lead to more targeted pharmacotherapeutic advances in NAFLD.

  • 13.
    Adori, Monika
    et al.
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Bhat, Sadam
    Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
    Gramignoli, Roberto
    Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Valladolid-Acebes, Ismael
    Department of Molecular Medicine and Surgery, The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden.
    Bengtsson, Tore
    Department of Molecular Biosciences, The Wenner-Gren Institute (MBW), Stockholm University, Stockholm, Sweden.
    Uhlén, Mathias
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Adori, Csaba
    Department of Molecular Biosciences, The Wenner-Gren Institute (MBW), Stockholm University, Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hepatic Innervations and Nonalcoholic Fatty Liver Disease2023In: Seminars in liver disease (Print), ISSN 0272-8087, E-ISSN 1098-8971, Vol. 43, no 2, p. 149-162Article in journal (Refereed)
    Abstract [en]

    Abbreviations: VMN/PVN, hypothalamic ventromedial nucleus/paraventricular nucleus; VLM/VMM, ventrolateral medulla/ventromedial medulla; SMG/CG, superior mesenteric ganglion/caeliac ganglia; NTS, nucleus of the solitary tract; NG, nodose ganglion. Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder. Increased sympathetic (noradrenergic) nerve tone has a complex role in the etiopathomechanism of NAFLD, affecting the development/progression of steatosis, inflammation, fibrosis, and liver hemodynamical alterations. Also, lipid sensing by vagal afferent fibers is an important player in the development of hepatic steatosis. Moreover, disorganization and progressive degeneration of liver sympathetic nerves were recently described in human and experimental NAFLD. These structural alterations likely come along with impaired liver sympathetic nerve functionality and lack of adequate hepatic noradrenergic signaling. Here, we first overview the anatomy and physiology of liver nerves. Then, we discuss the nerve impairments in NAFLD and their pathophysiological consequences in hepatic metabolism, inflammation, fibrosis, and hemodynamics. We conclude that further studies considering the spatial-temporal dynamics of structural and functional changes in the hepatic nervous system may lead to more targeted pharmacotherapeutic advances in NAFLD.

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

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

  • 15.
    Agrawal, M.
    et al.
    The Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, USA.
    Shrestha, Sarita
    Örebro University, School of Medical Sciences.
    Corn, G.
    Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark.
    Nielsen, N. M.
    Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark.
    Frisch, M.
    Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark.
    Colombel, J. F.
    The Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, USA.
    Jess, T.
    Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark.
    The epidemiology of inflammatory bowel diseases among immigrants to Denmark: A population-based cohort study2020In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 14, no Suppl. 1, p. S006-S007Article in journal (Other academic)
  • 16.
    Agrawal, Manasi
    et al.
    The Dr Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
    Corn, Giulia
    Department of Epidemiology Research, Statens Serum Institut, Kobenhavn, Denmark.
    Shrestha, Sarita
    Örebro University, School of Medical Sciences.
    Nielsen, Nete Munk
    Department of Epidemiology Research, Statens Serum Institut, Kobenhavn, Denmark.
    Frisch, Morten
    Department of Epidemiology Research, Statens Serum Institut, Kobenhavn, Denmark.
    Colombel, Jean-Frederic
    The Dr Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
    Jess, Tine
    Department of Epidemiology Research, Statens Serum Institut, Kobenhavn, Denmark.
    Inflammatory bowel diseases among first-generation and second-generation immigrants in Denmark: a population-based cohort study2021In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 70, no 6, p. 1037-1043Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Our objective was to estimate the relative risk of IBD among first-generation and second-generation immigrants in Denmark compared with native Danes.

    DESIGN: Using national registries, we established a cohort of Danish residents between 1977 and 2018. Cohort members with known country of birth were followed for Crohn's disease (CD) and ulcerative colitis (UC) diagnoses. Incidence rate ratios (IRRs) served as measures of relative risk and were calculated by log-linear Poisson regression, using rates among native Danes as reference, stratified by IBD risk in parental country of birth, and among first-generation immigrants by age at immigration and duration of stay in Denmark.

    RESULTS: Among 8.7 million Danes, 4156 first-generation and 898 second-generation immigrants were diagnosed with CD or UC. Overall, comparing first-generation immigrants with native Danes, the IRR was 0.80 (95% CI 0.76 to 0.84) for CD and 0.74 (95% CI 0.71 to 0.77) for UC. The IRR of IBD increased with ≥20 years stay in Denmark. The IRR of CD increased with immigration at ≥40 years of age. Comparing second-generation immigrants with native Danes, the IRR of IBD was 0.97 (95% CI 0.91 to 1.04). There was significant interaction with sex, with higher IRR of IBD in male than in female immigrants.

    CONCLUSION: Relative to native Danish men and women, IBD risk among first-generation immigrants was lower, reflected the risk in their parental country of birth and increased with ≥20 years stay in Denmark. For second-generation immigrants, relative risk of IBD was lower only among women. These complex patterns suggest the role of environmental IBD risk factors.

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

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

  • 18. Agréus, Lars
    et al.
    Hellström, Per M.
    Talley, Nicholas J.
    Wallner, Bengt
    Forsberg, Anna
    Vieth, Michael
    Veits, Lothar
    Björkegren, Karin
    Engstrand, Lars
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Towards a healthy stomach? Helicobacter pylori prevalence has dramatically decreased over 23 years in adults in a Swedish community2016In: United European Gastroenterology journal, ISSN 2050-6406, E-ISSN 2050-6414, Vol. 4, no 5, p. 686-696Article in journal (Refereed)
    Abstract [en]

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

  • 19.
    Ahlman, B.
    et al.
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden; Metabolic Research Laboratory, St Göran's Hospital, Stockholm, Sweden.
    Andersson, K.
    Metabolic Research Laboratory, St Göran's Hospital, Stockholm, Sweden.
    Leijonmarck, C. E.
    Department of Surgery, St Göran's Hospital, Stockholm, Sweden.
    Ljungqvist, Olle
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Hedenborg, L.
    Department of Pathology, St Göran's Hospital, Stockholm, Sweden.
    Wernerman, J.
    St Göran's Hospital, Stockholm, Sweden.
    Short-term starvation alters the free amino acid content of human intestinal mucosa1994In: Clinical Science, ISSN 0143-5221, E-ISSN 1470-8736, Vol. 86, no 6, p. 653-662Article in journal (Refereed)
    Abstract [en]

    1. The effects of short-term starvation and refeeding on the free amino acid concentrations of the intestinal mucosa were characterized in male subjects (n=6), using endoscopically obtained biopsy specimens from the duodenum and from all four segments of the colon.

    2. The alterations in the amino acid concentrations in response to short-term starvation were overall uniform in both duodenal and colonic mucosa as well as in plasma. Most amino acids decreased, whereas branched-chain amino acids increased.

    3. In the colon, glutamic acid and glutamine decreased during the starvation period, whereas they remained unaltered in the duodenum. This was the major difference in response to short-term starvation between the amino acid concentrations in the intestinal mucosa of the duodenum and colon.

    4. Refeeding for 3 days normalized the amino acid concentrations except for glutamic acid, asparagine and histidine, which remained low in the colon, and threonine, which showed an overshoot in both parts of the intestine. S. The changes in mucosal amino acid concentrations seen in response to starvation and refeeding were uniform in the four segments of the colon. This suggests that sampling from the rectum/sigmoid colon will give representative values for the free amino acid concentrations of the entire large intestine.

  • 20.
    Ahmad, Awais
    et al.
    Linköping Univ, Dept Biomed & Clin Sci, Div Inflammat & Infect, Clin Immunol & Transfus Med, SE-58183 Linköping, Sweden..
    Dahle, Charlotte
    Linköping Univ, Dept Biomed & Clin Sci, Div Inflammat & Infect, Clin Immunol & Transfus Med, SE-58183 Linköping, Sweden..
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Sjowall, Christopher
    Linköping Univ, Dept Biomed & Clin Sci, Div Inflammat & Infect Rheumatol, SE-58183 Linköping, Sweden..
    Kechagias, Stergios
    Linköping Univ, Dept Hlth Med & Caring Sci, Div Diagnost & Specialist Med Gastroenterol & Hep, SE-58183 Linköping, Sweden..
    Autoantibodies Associated with Autoimmune Liver Diseases in a Healthy Population: Evaluation of a Commercial Immunoblot Test2022In: Diagnostics, ISSN 2075-4418, Vol. 12, no 7, article id 1572Article in journal (Refereed)
    Abstract [en]

    Autoantibodies constitute important tools for diagnosing the autoimmune liver diseases (AILD) autoimmune hepatitis and primary biliary cholangitis. The EUROLINE immunoblot assay, detecting multiple specificities, is widely used, but the clinical importance of weakly positive findings is unclear. The manufacturer's recommended cut-off was evaluated by investigating AILD-associated autoantibodies in 825 blood donors and 60 confirmed AILD cases. Positive findings were followed up with immunofluorescence microscopy on rat tissue, anti-M2-ELISA, alternative immunoblot assay, and liver function tests. Thirty-six (4.4%) blood donors were positive with EUROLINE. The most common specificities were LC-1 (1.6%), gp210 (1.3%), and AMA-M2 (1.1%). In general, the positive results were higher in patients than in blood donors, whereas anti-LC-1 was higher in blood donors. The liver function tests were slightly elevated in 2 of the 36 immunoblot positive blood donors. The majority of the positive EUROLINE findings could not be confirmed with the follow-up tests. The EUROLINE-Autoimmune Liver Diseases-(IgG) immunoblot detected autoantibodies in 4.4% of blood donors without signs of AILD. Our findings indicate that the recommended cut-off can be raised for most specificities without loss of diagnostic sensitivity. The prevalence of anti-LC-1 among blood donors indicates a problem with the antigen source.

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  • 21.
    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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  • 22.
    Ahmad, Shafqat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Carrasquilla, Germán
    Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Langner, Taro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Menzel, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Malmberg, Filip
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hammar, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Censin, Jenny C.
    Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK; 7Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
    Sayols-Baixeras, Sergi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nguyen, Diem
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Mora, Andrés Martínez
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Jan W.
    Clinical Diabetes and Metabolism, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Genetics of liver fat and volume associate with altered metabolism and whole body magnetic resonance imaging2022In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 77, p. S40-S40Article in journal (Other academic)
  • 23.
    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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  • 24.
    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).

  • 25.
    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. Department 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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  • 26.
    Akbari, Camilla
    et al.
    Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden..
    Dodd, Maja
    Karolinska Univ Hosp, Dept Upper GI, Div Hepatol, Stockholm, Sweden..
    Stål, Per
    Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Upper GI, Div Hepatol, Stockholm, Sweden..
    Nasr, Patrik
    Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden.;Linköping Univ, Dept Gastroenterol & Hepatol, Div Internal Med, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Ekstedt, Mattias
    Kechagias, Stergios
    Linköping Univ, Dept Gastroenterol & Hepatol, Div Internal Med, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Vessby, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    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
    Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Upper GI, Div Hepatol, Stockholm, Sweden.;Karolinska Univ Hosp, Div Hepatol, C1 77, S-14186 Stockholm, Sweden..
    Shang, Ying
    Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden..
    Long-term major adverse liver outcomes in 1,260 patients with non-cirrhotic NAFLD2024In: JHEP Reports, E-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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  • 27.
    Al Zoubi, Mohammad
    et al.
    Department of General Surgery, Hamad Medical Corporation, Doha, Qatar.
    El Ansari, Walid
    University of Skövde, School of Health Sciences. University of Skövde, Digital Health Research (DHEAR). Department of Surgery, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar / College of Medicine, Qatar University, Doha, Qatar.
    Al Moudaris, Ahmed A.
    Department of General Surgery, Hamad Medical Corporation, Doha, Qatar.
    Abdelaal, Abdelrahman
    Department of General Surgery, Hamad Medical Corporation, Doha, Qatar.
    Largest case series of giant gallstones ever reported, and review of the literature2020In: International Journal of Surgery Case Reports, E-ISSN 2210-2612, Vol. 72, p. 454-459Article in journal (Refereed)
    Abstract [en]

    Introduction: Giant/large gallstones have high risk of complications, and technical difficulties during surgery. This case series is the largest ever reported. Presentation of cases: Case 1: Female (44 years), with one year intermittent right upper quadrant colicky pain. Ultrasound: large gallstone (normal gallbladder). Elective laparoscopic cholecystectomy (LC): 6 × 4 × 3.3 cm gallstone. Case 2: Female (41 years), presented to emergency room with 3 days right upper quadrant pain/tenderness, vomiting, and positive murphy's sign. Ultrasound: large gallstone, calculus cholecystitis. Emergency LC: 4.5 × 3.1 × 3.5 cm gallstone. Case 3: Male (38 years), with history of gallstones and acute cholecystitis presented with intermittent right upper quadrant pain (2 months) and vomiting. Normal abdominal examination. Ultrasound: large gallstone. Elective LC: 4.1 × 4 × 3.6 cm gallstone. Conclusions: Gallstones >5 cm are very rare, with higher risk of complications. Gallbladder should be removed even if asymptomatic. Gallstones >3 cm have increased risk for gallbladder cancer, biliary enteric fistula and ileus. LC has challenges that include grasping the gallbladder wall, exposure of Calot's triangle, and retrieval of gallbladder out of the abdomen. LC appears to be procedure of choice and should be performed by an experienced surgeon, considering the possibility of conversion to open cholecystectomy in case of inability to expose the anatomy or intraoperative difficulties. © 2020 The Author(s)

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  • 28.
    Alaedini, Armin
    et al.
    Institute of Human Nutrition, Columbia University Medical Center, New York NY, USA; Department of Medicine, Celiac Disease Center, Columbia University Medical Center, New York NY, USA .
    Lebwohl, Benjamin
    Department of Medicine, Celiac Disease Center, Columbia University Medical Center, New York NY, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Wormser, Gary P.
    Division of Infectious Diseases, Department of Medicine, New York Medical College, Valhalla NY, United States.
    Green, Peter H.
    Department of Medicine, Celiac Disease Center, Columbia University Medical Center, Columbia University, New York NY, USA.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; School of Medicine, Division of Epidemiology and Public Health, University of Nottingham, Nottingham, United Kingdom.
    Borrelia infection and risk of celiac disease2017In: BMC Medicine, E-ISSN 1741-7015, Vol. 15, article id 169Article in journal (Refereed)
    Abstract [en]

    Background: Environmental factors, including infectious agents, are speculated to play a role in the rising prevalence and the geographic distribution of celiac disease, an autoimmune disorder. In the USA and Sweden where the regional variation in the frequency of celiac disease has been studied, a similarity with the geographic distribution of Lyme disease, an emerging multisystemic infection caused by Borrelia burgdorferi spirochetes, has been found, thus raising the possibility of a link. We aimed to determine if infection with Borrelia contributes to an increased risk of celiac disease.

    Methods: Biopsy reports from all of Sweden's pathology departments were used to identify 15,769 individuals with celiac disease. Through linkage to the nationwide Patient Register, we compared the rate of earlier occurrence of Lyme disease in the patients with celiac disease to that in 78,331 matched controls. To further assess the temporal relationship between Borrelia infection and celiac disease, we also examined the risk of subsequent Lyme disease in patients with a diagnosis of celiac disease.

    Results: Twenty-five individuals (0.16%) with celiac disease had a prior diagnosis of Lyme disease, whereas 79 (0.5%) had a subsequent diagnosis of Lyme disease. A modest association between Lyme disease and celiac disease was seen both before (odds ratio, 1.61; 95% confidence interval (CI), 1.06-2.47) and after the diagnosis of celiac disease (hazard ratio, 1.82; 95% CI, 1.40-2.35), with the risk of disease being highest in the first year of follow-up.

    Conclusions: Only a minor fraction of the celiac disease patient population had a prior diagnosis of Lyme disease. The similar association between Lyme disease and celiac disease both before and after the diagnosis of celiac disease is strongly suggestive of surveillance bias as a likely contributor. Taken together, the data indicate that Borrelia infection is not a substantive risk factor in the development of celiac disease.

  • 29.
    Alaish, Ram
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundgren, David
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Safety of azathioprine and 6-mercaptopurine in patients with inflammatory bowel disease naive to thiopurine treatment2017In: International journal of clinical pharmacology and therapeutics, ISSN 0946-1965, Vol. 55, no 7, p. 594-600Article in journal (Refereed)
    Abstract [en]

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

  • 30.
    Al-Bluwi, Ghada S. M.
    et al.
    Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
    AlNababteh, Asma H.
    Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
    Östlundh, Linda
    National Medical Library, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
    Al-Shamsi, Saif
    Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
    Al-Rifai, Rami H.
    Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
    Prevalence of Celiac Disease in Patients With Turner Syndrome: Systematic Review and Meta-Analysis2021In: Frontiers in Medicine, E-ISSN 2296-858X, Vol. 8, article id 674896Article, review/survey (Refereed)
    Abstract [en]

    Introduction: Celiac disease (CD) is a multifactorial autoimmune disorder, and studies have reported that patients with Turner syndrome (TS) are at risk for CD. This systematic review and meta-analysis aimed to quantify the weighted prevalence of CD among patients with TS and determine the weighted strength of association between TS and CD.

    Methods: Studies published between January 1991 and December 2019 were retrieved from four electronic databases: PubMed, Scopus, Web of Science, and Embase. Eligible studies were identified and relevant data were extracted by two independent reviewers following specific eligibility criteria and a data extraction plan. Using the random-effects model, the pooled, overall and subgroup CD prevalence rates were determined, and sources of heterogeneity were investigated using meta-regression.

    Results: Among a total of 1,116 screened citations, 36 eligible studies were included in the quantitative synthesis. Nearly two-thirds of the studies (61.1%) were from European countries. Of the 6,291 patients with TS who were tested for CD, 241 were diagnosed with CD, with a crude CD prevalence of 3.8%. The highest and lowest CD prevalence rates of 20.0 and 0.0% were reported in Sweden and Germany, respectively. The estimated overall weighted CD prevalence was 4.5% (95% confidence interval [CI], 3.3-5.9, I-2, 67.4%). The weighted serology-based CD prevalence in patients with TS (3.4%, 95% CI, 1.0-6.6) was similar to the weighted biopsy-based CD prevalence (4.8%; 95% CI, 3.4-6.5). The strength of association between TS and CD was estimated in only four studies (odds ratio 18.1, 95% CI, 1.82-180; odds ratio 4.34, 95% CI, 1.48-12.75; rate ratio 14, 95% CI, 1.48-12.75; rate ratio 42.5, 95% CI, 12.4-144.8). Given the lack of uniformity in the type of reported measures of association and study design, producing a weighted effect measure to evaluate the strength of association between TS and CD was unfeasible.

    Conclusion: Nearly 1 in every 22 patients with TS had CD. Regular screening for CD in patients with TS might facilitate early diagnosis and therapeutic management to prevent adverse effects of CD such as being underweight and osteoporosis.

  • 31.
    Albshesh, Ahmad
    et al.
    Sheba Medical Center, Department of Gastroenterology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
    Taylor, Joshua
    Department of Gastroenterology, Montreal General Hospital, Montreal QC, Canada.
    Savarino, Edoardo, V
    Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
    Truyens, Marie
    IBD Unit, Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium.
    Armuzzi, Alessandro
    IBD Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
    Ribaldone, Davide G.
    Division of Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy.
    Shitrit, Ariella Bar-Gil
    Shaare Zedek Medical Center, Faculty of Medicine, Digestive Diseases Institute, Hebrew University of Jerusalem, Jerusalem, Israel.
    Fibelman, Morine
    Tel Aviv Medical Center, Department of Gastroenterology and Liver Diseases, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
    Molander, Pauliina
    Abdominal Center, Department of Gastroenterology, Helsinki University Hospital, Helsinki, Finland.
    Liefferinckx, Claire
    Department of Gastroenterology, Erasme University Hopital, Brussels, Belgium.
    Nancey, Stephane
    Department of Gastroenterology, Hospices Civils de Lyon, University Claude Bernard Lyon, Lyon, France; INSERM, U1111, CIRI, Lyon, France.
    Korani, Mohamed
    Division of Gastroenterology, The Pennine Acute Hospitals NHS Trust, Manchester, UK; Manchester Academic Health Sciences, University of Manchester, Manchester, UK.
    Rutka, Mariann
    First Department of Medicine, University of Szeged, Szeged, Hungary.
    Barreiro-de Acosta, Manuel
    IBD Unit, Gastroenterology Department, University Hospital of Santiago de Compostela, Santiago, Spain.
    Domislovic, Viktor
    Department of Gastroenterology, Hepatology, and Nutrition, University Hospital Centre Zagreb, Zagreb, Croatia.
    Suris, Gerard
    Digestive System Service, Bellvitge University Hospital, Catalan Institute of Health, Barcelona, Spain.
    Eriksson, Carl
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Alves, Catarina
    Department of Gastroenterology, Centro Hospitalar São João, Porto, Portugal.
    Mpitouli, Afroditi
    Department of Gastroenterology, Venizeleion General Hospital, Heraklion, Crete, Greece.
    di Jiang, Caroline
    Department of Gastroenterology, Addenbrooke’s Hospital, Cambridge University Hospitals, Cambridge, UK.
    Tepes, Katja
    University Medical Centre Ljubljana, Department of Gastroenterology, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.
    Coletta, Marina
    Department of Hepatology and Clinical Gastroenterology, ASST Santi Paolo e Carlo-Ospedale San Polo Universitario Milano Mariabeatrice, Milan, Italy.
    Foteinogiannopoulou, Kalliopi
    Department of Gastroenterology, University Hospital of Heraklion, Crete, Greece.
    Gisbert, Javier P.
    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Madrid, Spain.
    Amir-Barak, Hadar
    IBD Center, Division of Gastroenterology, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel and the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
    Attauabi, Mohamed
    Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark.
    Seidelin, Jakob
    Department of Gastroenterology, Herlev University Hospital, Copenhagen, Denmark.
    Afif, Waqqas
    Department of Gastroenterology, Montreal General Hospital, Montreal QC, Canada.
    Marinelli, Carla
    Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
    Lobaton, Triana
    IBD Unit, Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium.
    Pugliese, Daniela
    IBD Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
    Maharshak, Nitsan
    Tel Aviv Medical Center, Department of Gastroenterology and Liver Diseases, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
    Cremer, Anneline
    Department of Gastroenterology, Erasme University Hopital, Brussels, Belgium.
    Limdi, Jimmy K.
    Division of Gastroenterology, The Pennine Acute Hospitals NHS Trust, Manchester, UK; Manchester Academic Health Sciences, University of Manchester, Manchester, UK.
    Molnár, Tamás
    First Department of Medicine, University of Szeged, Szeged, Hungary.
    Otero-Alvarin, Borja
    IBD Unit, Gastroenterology Department, University Hospital of Santiago de Compostela, Santiago, Spain.
    Krznaric, Zeljko
    Department of Gastroenterology, Hepatology, and Nutrition, University Hospital Centre Zagreb, Zagreb, Croatia.
    Magro, Fernando
    Department of Gastroenterology, Centro Hospitalar São João, Porto, Portugal.
    Karmiris, Konstantinos
    Department of Gastroenterology, Venizeleion General Hospital, Heraklion, Crete, Greece.
    Raine, Tim
    Department of Gastroenterology, Addenbrooke’s Hospital, Cambridge University Hospitals, Cambridge, UK.
    Drobne, David
    University Medical Centre Ljubljana, Department of Gastroenterology, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.
    Koutroubakis, Ioannis
    Department of Gastroenterology, University Hospital of Heraklion, Crete, Greece.
    Chaparro, Maria
    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Madrid, Spain.
    Yanai, Henit
    IBD Center, Division of Gastroenterology, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel and the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
    Burisch, Johan
    Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark.
    Kopylov, Uri
    Sheba Medical Center, Department of Gastroenterology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
    Effectiveness of Third-Class Biologic Treatment in Crohn's Disease: A Multi-Center Retrospective Cohort Study2021In: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 10, no 13, article id 2914Article in journal (Refereed)
    Abstract [en]

    Background: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn's disease (CD) failing anti- Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described.

    Aims and Methods: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD.

    Results: Two-hundred and four patients were included; 156/204 (76%) patients received VDZ as a second- and UST as a third-class therapy (group A); the remaining 48/204 (24%) patients received UST as a second- and VDZ as a third-class therapy (group B). At week 16-22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9); 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission (p = 0.5). At week 52; 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9); 31/103 (30%) and 47/29 (24.1%) were in clinical remission (p = 0.5).

    Conclusion: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent.

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

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

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  • 33.
    Alexander, Tobias
    et al.
    Charite Univ Med Berlin, Dept Rheumatol & Clin Immunol, Berlin, Germany.;Free Univ Berlin, Berlin, Germany.;Humboldt Univ, Berlin, Germany.;Berlin Inst Hlth BIH, Berlin, Germany.;Deutsch Rheuma Forschungszentrum DRFZ Berlin, Berlin, Germany..
    Snowden, John A.
    Sheffield Teaching Hospitals Fdn NHS Trust, Dept Haematol, Sheffield, S Yorkshire, England.;Univ Sheffield, Dept Oncol & Metab, Sheffield, S Yorkshire, England..
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Landtblom: Neurology.
    Chang, Hyun-Dong
    Deutsch Rheuma Forschungszentrum DRFZ Berlin, Berlin, Germany.;Tech Univ Berlin, Inst Biotechnol, Berlin, Germany..
    Del Papa, Nicoletta
    ASST G PiniCTO, Dip Reumatol, Scleroderma Clin, Milan, Italy..
    Farge, Dominique
    CRMR MATHEC, Malad AutoImmunes & Therapie Cellulaire, Unite Med Interne UF 04, Paris, France.;Univ Paris, IRSL, Rech Clin Appl Hematol, Paris, France.;McGill Univ, Dept Med, Montreal, PQ, Canada..
    Lindsay, James O.
    Queen Mary Univ London, Blizard Inst, Ctr Immunobiol, Barts & London Sch Med, London, England..
    Malard, Florent
    Sorbonne Univ, Serv Hematol Clin & Therapie Cellulaire, Hop St Antoine, AP HP,INSERM,UMRs 938, Paris, France..
    Muraro, Paolo A.
    Imperial Coll London, Dept Brain Sci, London, England..
    Nitti, Rosamaria
    Univ Vita Salute San Raffaele, IRCCS San Raffaele Sci Inst, Unit Hematol & Bone Marrow Transplantat, Milan, Italy..
    Salas, Azucena
    IDIBAPS, CIBER, EHD, Barcelona, Spain..
    Sharrack, Basil
    Sheffield Teaching Hosp NHS, Dept Neurosci, Fdn Trust, Sheffield, S Yorkshire, England.;Univ Sheffield, NIHR Neurosci BioMed Res Ctr, Sheffield, S Yorkshire, England..
    Mohty, Mohamad
    Sorbonne Univ, Serv Hematol Clin & Therapie Cellulaire, Hop St Antoine, AP HP,INSERM,UMRs 938, Paris, France..
    Greco, Raffaella
    Univ Vita Salute San Raffaele, IRCCS San Raffaele Sci Inst, Unit Hematol & Bone Marrow Transplantat, Milan, Italy..
    Intestinal Microbiome in Hematopoietic Stem Cell Transplantation For Autoimmune Diseases: Considerations and Perspectives on Behalf of Autoimmune Diseases Working Party (ADWP) of the EBMT2021In: Frontiers in Oncology, E-ISSN 2234-943X, Vol. 11, article id 722436Article in journal (Refereed)
    Abstract [en]

    Over the past decades, hematopoietic stem cell transplantation (HSCT) has been evolving as specific treatment for patients with severe and refractory autoimmune diseases (ADs), where mechanistic studies have provided evidence for a profound immune renewal facilitating the observed beneficial responses. The intestinal microbiome plays an important role in host physiology including shaping the immune repertoire. The relationships between intestinal microbiota composition and outcomes after HSCT for hematologic diseases have been identified, particularly for predicting the mortality from infectious and non-infectious causes. Furthermore, therapeutic manipulations of the gut microbiota, such as fecal microbiota transplant (FMT), have emerged as promising therapeutic approaches for restoring the functional and anatomical integrity of the intestinal microbiota post-transplantation. Although changes in the intestinal microbiome have been linked to various ADs, studies investigating the effect of intestinal dysbiosis on HSCT outcomes for ADs are scarce and require further attention. Herein, we describe some of the landmark microbiome studies in HSCT recipients and patients with chronic ADs, and discuss the challenges and opportunities of microbiome research for diagnostic and therapeutic purposes in the context of HSCT for ADs.

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  • 34. Alexandersson, Bjarki
    et al.
    Hamad, Yousef
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Stress Research Institute. Karolinska University Hospital, Sweden; Macquarie University, Australia.
    Rubio, Carlos A.
    Ando, Yugo
    Tanaka, Kyosuke
    Ichiya, Tamaki
    Rezaie, Reza
    Schmidt, Peter T.
    High-Definition Chromoendoscopy Superior to High-Definition White-Light Endoscopy in Surveillance of Inflammatory Bowel Diseases in a Randomized Trial2020In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 18, no 9, p. 2101-2107Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: There is debate over the optimal method for colonoscopic surveillance of patients with inflammatory bowel diseases. Guidelines recommend chromoendoscopy, but the value of chromoendoscopy in high-definition colonoscopy has not been proven. Furthermore, the value of random biopsies is controversial. METHODS: We performed a prospective study of 305 patients with ulcerative colitis or Crohn's colitis referred for surveillance colonoscopy at a university hospital in Sweden, from March 2011 through April 2016. Patients randomly assigned to a group that received high-definition chromoendoscopy with indigo carmine (HD-CE; n=152), collection of 32 random biopsies, and targeted biopsies or polypectomies or to a group that received high-definition white light endoscopy (HD-WLE; n=153), collection of 32 random biopsies, and targeted biopsies or polypectomies. The primary endpoint was number of patients with dysplastic lesions. RESULTS: Dysplastic lesions were detected in 17 patients with HD-CE and 7 patients with HD-WLE (P=.032). Dysplasias in random biopsies (n=9760) were detected in 9 patients: 6 (3.9%) in the HD-CE group and 3 (2.0%) in the HD-WLE group (P=.72). Of the 9 patients with dysplasia, 3 patients (33%) had primary sclerosing cholangitis-only 18% of patients (54/305) included in the study had primary sclerosing cholangitis. The number of dysplastic lesions per 10 min of withdrawal time was 0.066 with HD-CE and 0.027 with HD-WLE (P=.056). CONCLUSIONS: In a randomized trial, we found HD-CE with collection of random biopsies to be superior to HD-WLE with random biopsies for detection of dysplasia per colonoscopy. These results support the use of chromoendoscopy for surveillance of patients with inflammatory bowel diseases. ClinicalTrials.gov no: NCT01505842.

  • 35. Alexandersson, Bjarki T.
    et al.
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Stress Research Institute. Karolinska Institutet, Sweden; Macquarie University, North Ryde, Australia.
    Hedin, Charlotte
    Broms, Gabriella
    Schmidt, Peter T.
    Forsberg, Anna
    Inflammatory Bowel Disease Is not Linked to a Higher Rate of Adverse Events in Colonoscopy: a Nationwide Population-based Study in Sweden2023In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 17, no 12, p. 1962-1967Article in journal (Refereed)
    Abstract [en]

    Background and Aims: Inflammatory bowel disease may cause long-standing inflammation and fibrosis and may increase the risk of adverse events in colonoscopy. We evaluated whether inflammatory bowel disease and other potential risk factors are associated with bleeding or perforation in a nationwide, population-based, Swedish study.

    Methods: Data from 969 532 colonoscopies, including 164 012 [17%] on inflammatory bowel disease patients, between 2003 and 2019, were retrieved from the National Patient Registers. ICD-10 codes for bleeding [T810] and perforation [T812] within 30 days of the colonoscopy were recorded. Multivariable logistic regression was used to test if inflammatory bowel disease status, inpatient setting, time period, general anaesthesia, age, sex, endoscopic procedures, and antithrombotic treatment were associated with higher odds for bleeding and perforation.

    Results: Bleeding and perforation were reported in 0.19% and 0.11% of all colonoscopies, respectively. Bleeding [odds ratio 0.66, p <0.001] and perforation [odds ratio 0.79, p <0.033] were less likely in colonoscopies in individuals with inflammatory bowel disease status. Bleeding and perforation were more common in inpatient than in outpatient inflammatory bowel disease colonoscopies. The odds for bleeding but not perforation increased between 2003 to 2019. General anaesthesia was associated with double the odds for perforation.

    Conclusions: Individuals with inflammatory bowel disease did not have more adverse events compared with individuals without inflammatory bowel disease status. However, the inpatient setting was associated with more adverse events, particularly in inflammatory bowel disease status. General anaesthesia was associated with a greater risk of perforation.

  • 36.
    Alexandersson, Bjarki T.
    et al.
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden..
    Hugerth, Luisa W.
    Karolinska Inst, Tumour & Cell Biol MTC, Dept Microbiol, Sci Life Lab,CTMR, Solna, Sweden..
    Hedin, Charlotte
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Gastroenterol Dermatovenereol & Rheumatol, Gastroenterol Unit, Stockholm, Sweden..
    Forsberg, Anna
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden..
    Talley, Nicholas J.
    Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW, Australia..
    Agreus, Lars
    Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden..
    Jarbrink-Sehgal, Ellionore
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden.;Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Sect Gastroenterol & Hepatol, Houston, TX USA..
    Engstrand, Lars
    Karolinska Inst, Tumour & Cell Biol MTC, Dept Microbiol, Sci Life Lab,CTMR, Solna, Sweden..
    Andreasson, Anna
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden.;Stockholm Univ, Stress Res Inst, Stockholm, Sweden.;Macquarie Univ, Dept Psychol, N Ryde, NSW, Australia..
    Schmidt, Peter T.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology. Karolinska Inst, Dept Med Solna, Stockholm, Sweden..
    Diverticulosis is not associated with altered gut microbiota nor is it predictive of future diverticulitis: a population-based colonoscopy study2023In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 58, no 10, p. 1131-1138, article id 2194010Article in journal (Refereed)
    Abstract [en]

    Background: The etiopathogenesis of diverticular disease is unknown. Objective: To compare the fecal and mucosa-associated microbiota between participants with and without diverticulosis and participants who later developed diverticulitis versus those that did not from a population-based study. Methods: The PopCol study, conducted in Stockholm, Sweden, invited a random sample of 3556 adults to participate, of which 745 underwent colonoscopy. Overall, 130 participants (17.5%) had diverticulosis. 16S rRNA gene sequencing was conducted on available sigmoid biopsy samples from 529 and fecal samples from 251 individuals. We identified individuals who subsequently developed acute diverticulitis up to 13 years after sample collection. In a case-control design matching for gender, age (+/-5 years), smoking and antibiotic exposure, we compared taxonomic composition, richness and diversity of the microbiota between participants with or without diverticulosis, and between participants who later developed acute diverticulitis versus those who did not. Results: No differences in microbiota richness or diversity were observed between participants with or without diverticulosis, nor for those who developed diverticulitis compared with those who did not. No bacterial taxa were significantly different between participants with diverticulosis compared with those without diverticulosis. Individuals who later developed acute diverticulitis (2.8%) had a higher abundance of genus Comamonas than those who did not (p =.027). Conclusions: In a population-based cohort study the only significant difference was that those who later develop diverticulitis had more abundance of genus Comamonas. The significance of Comamonas is unclear, suggesting a limited role for the gut microbiota in the etiopathogenesis of diverticular disease.

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  • 37. Alexandersson, Bjarki T.
    et al.
    Hugerth, Luisa W.
    Hedin, Charlotte
    Forsberg, Anna
    Talley, Nicholas J.
    Agreus, Lars
    Järbrink-Sehgal, Ellionore
    Engstrand, Lars
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Stress Research Institute. Stockholm University, Faculty of Social Sciences, Department of Psychology, Biological psychology. Karolinska Institutet, Sweden; Macquarie University, Australia.
    Schmidt, Peter T.
    Diverticulosis is not associated with altered gut microbiota nor is it predictive of future diverticulitis: a population-based colonoscopy study2023In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 58, no 10, p. 1131-1138Article in journal (Refereed)
    Abstract [en]

    Background: The etiopathogenesis of diverticular disease is unknown.

    Objective: To compare the fecal and mucosa-associated microbiota between participants with and without diverticulosis and participants who later developed diverticulitis versus those that did not from a population-based study.

    Methods: The PopCol study, conducted in Stockholm, Sweden, invited a random sample of 3556 adults to participate, of which 745 underwent colonoscopy. Overall, 130 participants (17.5%) had diverticulosis. 16S rRNA gene sequencing was conducted on available sigmoid biopsy samples from 529 and fecal samples from 251 individuals. We identified individuals who subsequently developed acute diverticulitis up to 13 years after sample collection. In a case-control design matching for gender, age (+/−5 years), smoking and antibiotic exposure, we compared taxonomic composition, richness and diversity of the microbiota between participants with or without diverticulosis, and between participants who later developed acute diverticulitis versus those who did not.

    Results: No differences in microbiota richness or diversity were observed between participants with or without diverticulosis, nor for those who developed diverticulitis compared with those who did not. No bacterial taxa were significantly different between participants with diverticulosis compared with those without diverticulosis. Individuals who later developed acute diverticulitis (2.8%) had a higher abundance of genus Comamonas than those who did not (p = .027).

    Conclusions: In a population-based cohort study the only significant difference was that those who later develop diverticulitis had more abundance of genus Comamonas. The significance of Comamonas is unclear, suggesting a limited role for the gut microbiota in the etiopathogenesis of diverticular disease.

  • 38.
    Alfonsson, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Weineland-Strandskov, Sandra
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Self-Reported Hedonism Predicts 12-Month Weight Loss After Roux-en-Y Gastric Bypass2017In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 27, no 8, p. 2073-2078Article in journal (Refereed)
    Abstract [en]

    Introduction Research regarding psychological risk factors for reduced weight loss after bariatric surgery has yielded mixed results, especially for variables measured prior to surgery. More profound personality factors have shown better promise and one such factor that may be relevant in this context is time perspective, i.e., the tendency to focus on present or future consequences. The aim of this study was to investigate the predictive value of time perspective for 12-month weight loss after Roux-en-Y gastric bypass surgery.

    Methods A total of 158 patients were included and completed self-report instruments prior to surgery. Weight loss was measured after 12 months by medical staff. Background variables as well as self-reported disordered eating, psychological distress, and time perspective were analyzed with regression analysis to identify significant predictors for 12-month weight loss.

    Results The mean BMI loss at 12 months was 14 units, from 45 to 30 kg/m(2). Age, sex, and time perspective could significantly predict weight loss but only male sex and self-reported hedonism were independent risk factors for reduced weight loss in the final regression model.

    Conclusion In this study, self-reported hedonistic time perspective proved to be a better predictor for 12-month weight loss than symptoms of disordered eating and psychological distress. It is possible that a hedonistic tendency of focusing on immediate consequences and rewards is analogous to the impaired delay discounting seen in previous studies of bariatric surgery candidates. Further studies are needed to identify whether these patients may benefit from extended care and support after surgery.

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  • 39.
    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.

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    Staging and tumor biological mechanisms of lymph node metastasis in invasive urinary bladder cancer
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  • 40.
    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.

  • 41.
    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.

  • 42.
    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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  • 43.
    Almon, Ricardo
    et al.
    Örebro University, School of Health and Medical Sciences.
    Engfeldt, Peter
    Örebro University, School of Health and Medical Sciences.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Sjöström, Michael
    Nilsson, Torbjörn K.
    Örebro University, School of Health and Medical Sciences.
    Prevalence and trends in adult-type hypolactasia in different age cohorts in Central Sweden diagnosed by genotyping for the adult-type hypolactasia-linked LCT -13910C > T mutation2007In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 42, no 2, p. 165-170Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Adult-type hypolactasia (AtH) can be diagnosed by genotyping in addition to functional tests or intestinal biopsy. The aims of this study were to estimate the prevalence of AtH by genotyping and to investigate whether AtH prevalence has changed in Sweden during the 20th century. MATERIAL AND METHODS: Schoolchildren (n=690) born in 1983 and 1989, and elderly individuals (n=392) born between 1920 and 1932 were genotyped for AtH using Pyrosequencing technology. RESULTS: The overall prevalence of AtH among children was 14.1%. The majority of children (92%, n=635) were Caucasians with genotype prevalences: CC, 61 (10%); CT, 259 (41%); TT, 307 (49%). The frequency of the mutated allele q was 0.300 in this cohort. The prevalence of AtH estimated from the Hardy-Weinberg equilibrium (HWE) (q 2), was 9.0% (95% CI: 6.7-11.2%). Eight percent (n=55) of the children were non-Caucasian; genotype prevalences were CC, 36 (66%); CT, 15 (27%); TT, 4 (7%). The prevalence of AtH in these children estimated from HWE was 62.5% (95% CI: 49.7-75.3%). The elderly subjects were all Caucasians. Their genotype prevalences were: CC, 20 (5%); CT, 166 (42%); TT, 206 (53%); the frequency of the mutated allele q was 0.262 and their AtH prevalence estimated from HWE was 6.8% (95% CI: 4.3-9.2%). CONCLUSIONS: The overall prevalence of AtH in children (14%) was higher than previously thought. Among Caucasians, higher figures were seen in children than in the elderly (9% versus 6.8%). The prevalence thus seems to be increasing and this may be due to the immigration of both non-Caucasian and Caucasian groups with a higher prevalence of AtH.

  • 44.
    Alonso-Cotoner, Carmen
    et al.
    Servei de Aparell Digestiu, Vall d'Hebron Hospital Universitari, Passeig Vall d'Hebron, Barcelona, Spain; Grup de Neuro-Inmuno-Gastroenterología, Unitat de Fisiología I Fisiopatología Digestiva, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain; Universitat Autònoma de Barcelona, Facultat de Medicina, Bellaterra, Barcelona, Spain; CIBER de Enfermedades Hepaticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain.
    Abril-Gil, Mar
    Grup de Neuro-Inmuno-Gastroenterología, Unitat de Fisiología I Fisiopatología Digestiva, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
    Albert-Bayo, Mercé
    Grup de Neuro-Inmuno-Gastroenterología, Unitat de Fisiología I Fisiopatología Digestiva, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
    Ganda Mall, John Peter
    Grup de Neuro-Inmuno-Gastroenterología, Unitat de Fisiología I Fisiopatología Digestiva, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain; Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Expósito, Elba
    Grup de Neuro-Inmuno-Gastroenterología, Unitat de Fisiología I Fisiopatología Digestiva, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
    González-Castro, Ana M.
    Grup de Neuro-Inmuno-Gastroenterología, Unitat de Fisiología I Fisiopatología Digestiva, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
    Lobo, Beatriz
    Servei de Aparell Digestiu, Vall d'Hebron Hospital Universitari, Passeig Vall d'Hebron, Barcelona, Spain; Grup de Neuro-Inmuno-Gastroenterología, Unitat de Fisiología I Fisiopatología Digestiva, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain; Universitat Autònoma de Barcelona, Facultat de Medicina, Bellaterra, Barcelona, Spain.
    Santos, Javier
    Servei de Aparell Digestiu, Vall d'Hebron Hospital Universitari, Barcelona, Spain; Grup de Neuro-Inmuno-Gastroenterología, Unitat de Fisiología I Fisiopatología Digestiva, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain; Universitat Autònoma de Barcelona, Facultat de Medicina, Bellaterra, Barcelona, Spain; CIBER de Enfermedades Hepaticas y Digestivas (CIBERHED), Instituto de Salud Carlos III, Madrid, Spain.
    The Role of Purported Mucoprotectants in Dealing with Irritable Bowel Syndrome, Functional Diarrhea, and Other Chronic Diarrheal Disorders in Adults2021In: Advances in Therapy, ISSN 0741-238X, E-ISSN 1865-8652, Vol. 38, no 5, p. 2054-2076Article, review/survey (Refereed)
    Abstract [en]

    Chronic diarrhea is a frequent presenting symptom, both in primary care medicine and in specialized gastroenterology units. It is estimated that more than 5% of the global population suffers from chronic diarrhea. and that about 40% of these subjects are older than 60 years. The clinician is frequently faced with the need to decide which is the best therapeutic approach for these patients. While the origin of chronic diarrhea is diverse, impairment of intestinal barrier function, dysbiosis. and mucosal micro-inflammation are being increasingly recognized as underlying phenomena characterizing a variety of chronic diarrheal diseases. In addition to current pharmacological therapies, there is growing interest in alternative products such as mucoprotectants, which form a mucoadhesive film over the epithelium to reduce and protect against the development of altered intestinal permeability, dysbiosis, and mucosal micro-inflammation. This manuscript focuses on chronic diarrhea in adults, and we will review recent evidence on the ability of these natural compounds to improve symptoms associated with chronic diarrhea and to exert protective effects for the intestinal barrier. 

  • 45.
    Al-Saffar, Ahmad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Takemi, Shota
    Saitama Univ, Grad Sch Sci & Engn, Div Life Sci, Area Regulatory Biol,Sakura Ku, 255 Shimo Ohkubo, Saitama 3388570, Japan.
    Saaed, Hiwa K.
    Univ Sulaimani, Coll Pharm, Dept Pharmacol & Toxicol, Sulaymaniyah, Iraq.
    Sakata, Ichiro
    Saitama Univ, Grad Sch Sci & Engn, Div Life Sci, Area Regulatory Biol,Sakura Ku, 255 Shimo Ohkubo, Saitama 3388570, Japan.
    Sakai, Takafumi
    Saitama Univ, Grad Sch Sci & Engn, Div Life Sci, Area Regulatory Biol,Sakura Ku, 255 Shimo Ohkubo, Saitama 3388570, Japan;Saitama Univ, Grad Sch Sci & Engn, Div Strategy Res, Area Life NanoBio,Sakura Ku, 255 Shimo Ohkubo, Saitama 3388570, Japan.
    Utility of animal gastrointestinal motility and transit models in functional gastrointestinal disorders2019In: Baillière's Best Practice & Research: Clinical Gastroenterology, ISSN 1521-6918, E-ISSN 1532-1916, Vol. 40-41, article id 101633Article, review/survey (Refereed)
    Abstract [en]

    Alteration in the gastrointestinal (GI) motility and transit comprises an important component of the functional gastrointestinal disorders (FGID). Available animal GI motility and transit models are to study symptoms (delayed gastric emptying, constipation, diarrhea) rather than biological markers to develop an effective treatment that targets the underlying mechanism of altered GI motility in patients. Animal data generated from commonly used methods in human like scintigraphy, breath test and wireless motility capsule may directly translate to the clinic. However, species differences in the control mechanism or pharmacological responses of GI motility may compromise the predictive and translational value of the preclinical data to human. In this review we aim to provide a summary on animal models used to mimic GI motility alteration in FGID, and the impact of the species differences in the physiological and pharmacological responses on the translation of animal GI motility and transit data to human. 

  • 46.
    Al-Saffar, Anas K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology. Baghdad Univ, Coll Vet Medicine, Dept Surg & Obstet, Baghdad, Iraq..
    Halim, Md Abdul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Hall, G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Hellström, Per M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Webb, Dominic-Luc
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Small intestinal lactulose and sucralose hyper-permeability in inflammatory bowel disease2018In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, p. S124-S124Article in journal (Other academic)
  • 47.
    Al-Saffar, Anas Kh.
    et al.
    Baghdad University/ College of Veterinary Medicine.
    Halim, Abdul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Hellström, Per M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Webb, Dominic-Luc
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Concurrent small and large intestinal permeability in inflammatory bowel disease: Hyper-permeability in IBDManuscript (preprint) (Other (popular science, discussion, etc.))
    Abstract [en]

    Hyper-permeability in inflammatory bowel disease (IBD) has mostly been explored in the colon, where symptomatic inflammation is prevalent. Relationships between small and large intestine barrier function were examined. Fasted (4h) IBD (19 ulcerative colitis, 11 Crohn's disease) and 25 healthy control subjects’ were investigated. Lactulose (10g), mannitol (5g), riboflavin (0.05g) and sucralose (5g) were ingested with 500 mL water. Urine lactulose and mannitol were measured by enzyme assays, riboflavin by intrinsic fluorescence and sucralose by HPLC. CRP was measured by nephelometry. In IBD, small intestine lactulose and sucralose % recoveries were 1.77 and 2.73 fold higher than controls; combined data revealed the two probes were correlated (R2=0.6). In IBD, large intestine sucralose % recovery was 2.6 fold higher than controls and correlated with small intestine sucralose % recovery (R2=0.6). Conclusions: Sucralose yields similar result as lactulose for small intestine permeability, while having higher S:N, implying sucralose is more sensitive. No evidence was found for riboflavin malabsorption in IBD. There is concurrent small and large intestine hyper-permeability in IBD. Small intestine hyper-permeability is presumably related to inflammation in the large intestine, but without obvious deficiency in transporter mediated micronutrient absorption (i.e., riboflavin) in the small intestine.

  • 48.
    Al-Saffar, Anas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Meijer, Carl Hampus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Gannavarapu, Venkata Ram
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Hall, Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Li, Yichen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Diaz Tartera, Hetzel O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Lördal, Mikael
    Department of Medicine, Division of Gastroenterology and Hepatology, Danderyds Sjukhus, Danderyd, Sweden.
    Ljung, Tryggve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology. Abbvie, Solna, Sweden.
    Hellström, Per M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Webb, Dominic-Luc
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Parallel Changes in Harvey-Bradshaw Index, TNFα, and Intestinal Fatty Acid Binding Protein  in Response to Infliximab in Crohn’s Disease2017In: Gastroenterology Research and Practice, ISSN 1687-6121, E-ISSN 1687-630X, p. 1-8, article id 1745918Article in journal (Refereed)
    Abstract [en]

    Intestinal fatty acid binding protein (I-FABP) indicates barrier integrity. Aims: determine if I-FABP is elevated in active Crohn's disease (CD) and if I-FABP parallels anti-TNF alpha antibody (infliximab) induced lowering of TNF alpha and Harvey-Bradshaw Index (HBI) as potential indicator of mucosal healing. I-FABP distribution along human gut was determined. Serum from 10 CD patients collected during first three consecutive infliximab treatments with matched pretreatment and follow-up samples one week after each treatment and corresponding HBI data were analyzed. I-FABP reference interval was established from 31 healthy subjects with normal gut permeability. I-FABP and TNF alpha were measured by ELISA; CRP was measured by nephelometry. Healthy tissue was used for I-FABP immunohistochemistry. Pretreatment CD patient TNF alpha was 1.6-fold higher than in-house reference interval, while I-FABP was 2.5-fold higher, which lowered at follow-ups. Combining all 30 infusion/follow-up pairs also revealed changes in I-FABP. HBI followed this pattern; CRP declined gradually. I-FABP was expressed in epithelium of stomach, jejunum, ileum, and colon, with the highest expression in jejunum and ileum. I-FABP is elevated in active CD with a magnitude comparable to TNF alpha. Parallel infliximab effects on TNF alpha, HBI, and I-FABP were found. I-FABP may be useful as an intestine selective prognostic marker in CD.

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  • 49.
    Alsaqal, Salem
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hockings, Paul
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical, Mölndal, Sweden.
    Gummesson, Anders
    Hedström, Anders
    Hulthe, Johannes
    Johansson, Lars
    Niessen, Heiko G
    Schoelch, Corinna
    Schultheis, Christian
    Vessby, Johan
    Wanders, Alkwin
    Rorsman, Fredrik
    Ebeling Barbier, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    The Combination of MR Elastography and Proton Density Fat Fraction Improves Diagnosis of Nonalcoholic Steatohepatitis.2022In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 56, no 2, p. -379Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is rapidly increasing worldwide. It is subdivided into nonalcoholic fatty liver (NAFL) and the more aggressive form, nonalcoholic steatohepatitis (NASH), which carries a higher risk of developing fibrosis and cirrhosis. There is currently no reliable non-invasive method for differentiating NASH from NAFL.

    PURPOSE: To investigate the ability of magnetic resonance imaging (MRI)-based imaging biomarkers to diagnose NASH and moderate fibrosis as well as assess their repeatability.

    STUDY TYPE: Prospective.

    SUBJECTS: Sixty-eight participants (41% women) with biopsy-proven NAFLD (53 NASH and 15 NAFL). Thirty participants underwent a second MRI in order to assess repeatability.

    FIELD STRENGTH/SEQUENCE: 3.0 T; MR elastography (MRE) (a spin-echo echo-planar imaging [SE-EPI] sequence with motion-encoding gradients), MR proton density fat fraction (PDFF) and R2* mapping (a multi-echo three-dimensional gradient-echo sequence), T1 mapping (a single-point saturation-recovery technique), and diffusion-weighted imaging (SE-EPI sequence).

    ASSESSMENT: Quantitative MRI measurements were obtained and assessed alone and in combination with biochemical markers (cytokeratin-18 [CK18] M30, alanine transaminase [ALT], and aspartate transaminase [AST]) using logistic regression models. Models that could differentiate between NASH and NAFL and between moderate to advanced fibrosis (F2-4) and no or mild fibrosis (F0-1), based on the histopathological results, were identified.

    STATISTICAL TESTS: Independent samples t-test, Pearson's chi-squared test, area under the receiver operating characteristic curve (AUROC), Spearman's correlation, intra-individual coefficient of variation, and intraclass correlation coefficient (ICC). Statistical significance was set at P < 0.05.

    RESULTS: There was a significant difference between the NASH and NAFL groups with liver stiffness assessed with MRE, CK18 M30, and ALT, with an AUROC of 0.74, 0.76, and 0.70, respectively. Both MRE and PDFF contributed significantly to a bivariate model for diagnosing NASH (AUROC = 0.84). MRE could significantly differentiate between F2-4 and F0-1 (AUROC = 0.74). A model combining MRE with AST improved the diagnosis of F2-4 (AUROC = 0.83). The ICC for repeatability was 0.94 and 0.99 for MRE and PDFF, respectively.

    DATA CONCLUSION: MRE can potentially diagnose NASH and differentiate between fibrosis stages. Combining MRE with PDFF improves the diagnosis of NASH.

    LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

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  • 50.
    Amcoff, K.
    et al.
    Orebro Univ, Dept Gastroenterol, Fac Med & Hlth, Orebro, Sweden..
    Cao, Y.
    Univ Orebro, Sch Med Sci, Clin Epidemiol & Biostat, Orebro, Sweden..
    Zhulina, Y.
    Orebro Univ, Dept Gastroenterol, Fac Med & Hlth, Orebro, Sweden..
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Halfvarson, J.
    Orebro Univ, Dept Gastroenterol, Fac Med & Hlth, Orebro, Sweden..
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Prognostic significance of eosinophil granule proteins in inflammatory bowel disease2018In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, p. S181-S182Article in journal (Other academic)
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