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  1. Article ; Online: The presence of interferon affects the progression of non-alcoholic fatty liver disease.

    Møhlenberg, Michelle / Eriksen, Peter Lykke / Laursen, Tea Lund / Nielsen, Mette Bak / Hamilton Dutoit, Stephen Jacques / Grønbæk, Henning / Hartmann, Rune / Thomsen, Karen Louise

    Genes and immunity

    2022  Volume 23, Issue 5, Page(s) 157–165

    Abstract: Inflammation and metabolic dysfunction are hallmarks of the progression of non-alcoholic fatty liver disease (NAFLD), which is the fastest-growing liver disease worldwide. Emerging evidence indicates that innate immune mechanisms are essential drivers of ...

    Abstract Inflammation and metabolic dysfunction are hallmarks of the progression of non-alcoholic fatty liver disease (NAFLD), which is the fastest-growing liver disease worldwide. Emerging evidence indicates that innate immune mechanisms are essential drivers of fibrosis development in chronic inflammatory liver diseases, including NAFLD. In this study, 142 NAFLD patients were genotyped for three IFNL4 single-nucleotide variants in order to investigate the genetic relationship between IFNL4 and fibrosis in NAFLD patients. We observed an overrepresentation of the non-functional IFNL4 allele in patients with significant fibrosis (>F2). Next, we investigated the potential protective role of interferon (IFN) in relation to the development of liver fibrosis in an animal model of non-alcoholic steatohepatitis (NASH). In contradiction to our hypothesis, the results showed an increase in fibrosis in IFN treated animals. Our study clearly indicates that IFN is able to affect the development of liver fibrosis, although our clinical and experimental data are conflicting.
    MeSH term(s) Animals ; Antiviral Agents ; Disease Progression ; Fibrosis ; Interferons/genetics ; Liver/metabolism ; Liver/pathology ; Liver Cirrhosis/genetics ; Liver Cirrhosis/metabolism ; Liver Cirrhosis/pathology ; Non-alcoholic Fatty Liver Disease/genetics
    Chemical Substances Antiviral Agents ; Interferons (9008-11-1)
    Language English
    Publishing date 2022-06-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2060566-3
    ISSN 1476-5470 ; 1466-4879
    ISSN (online) 1476-5470
    ISSN 1466-4879
    DOI 10.1038/s41435-022-00176-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5592: Show issues Location:
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  2. Article ; Online: Severe steroid refractory gastritis induced by Nivolumab: A case report.

    Vindum, Helene Hjorth / Agnholt, Jørgen S / Nielsen, Anders Winther Moelby / Nielsen, Mette Bak / Schmidt, Henrik

    World journal of gastroenterology

    2020  Volume 26, Issue 16, Page(s) 1971–1978

    Abstract: Background: Immune checkpoint inhibitors are widely used for treatment of many advanced malignancies. Lower gastrointestinal (GI) side effects, such as diarrhea and colitis, are common, but upper GI side effects are rarely reported. Consequently, the ... ...

    Abstract Background: Immune checkpoint inhibitors are widely used for treatment of many advanced malignancies. Lower gastrointestinal (GI) side effects, such as diarrhea and colitis, are common, but upper GI side effects are rarely reported. Consequently, the correct treatment of upper GI adverse events has been less frequently described.
    Case summary: We describe a case of a 16-year-old woman with stage IIIb malignant melanoma treated with adjuvant monotherapy using Nivolumab. The patient developed severe gastritis after six series of Nivolumab with weight loss, nausea, and vomiting. There was no effect of intravenous steroids, but the patient´s condition resolved after administration of Infliximab.
    Conclusion: This case report supports the same treatment for gastritis as for colitis, which is in line with current guidelines.
    MeSH term(s) Adolescent ; Chemotherapy, Adjuvant/adverse effects ; Chemotherapy, Adjuvant/methods ; Drug Resistance ; Female ; Gastritis/diagnosis ; Gastritis/drug therapy ; Gastritis/immunology ; Glucocorticoids/pharmacology ; Glucocorticoids/therapeutic use ; Humans ; Immune Checkpoint Inhibitors/adverse effects ; Infliximab/therapeutic use ; Melanoma/immunology ; Melanoma/therapy ; Nivolumab/adverse effects ; Severity of Illness Index ; Skin Neoplasms/immunology ; Skin Neoplasms/therapy ; Treatment Outcome
    Chemical Substances Glucocorticoids ; Immune Checkpoint Inhibitors ; Nivolumab (31YO63LBSN) ; Infliximab (B72HH48FLU)
    Language English
    Publishing date 2020-05-11
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 2185929-2
    ISSN 2219-2840 ; 1007-9327
    ISSN (online) 2219-2840
    ISSN 1007-9327
    DOI 10.3748/wjg.v26.i16.1971
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6039: Show issues Location:
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  3. Article ; Online: Systemic Inflammation Associates With a Myeloid Inflamed Tumor Microenvironment in Primary Resected Colon Cancer-May Cold Tumors Simply Be Too Hot?

    Køstner, Anne Helene / Nielsen, Patricia Switten / Georgsen, Jeanette Baehr / Parner, Erik Thorlund / Nielsen, Mette Bak / Kersten, Christian / Steiniche, Torben

    Frontiers in immunology

    2021  Volume 12, Page(s) 716342

    Abstract: Systemic inflammation measured by the acute-phase protein CRP associates with poor outcome across cancer types. In contrast, local tumor-associated inflammation, primarily evaluated by T-lymphocytes, correlates with favorable prognosis. Yet, little is ... ...

    Abstract Systemic inflammation measured by the acute-phase protein CRP associates with poor outcome across cancer types. In contrast, local tumor-associated inflammation, primarily evaluated by T-lymphocytes, correlates with favorable prognosis. Yet, little is known whether these two responses are related or opposing processes and why elevated CRP in relation to cancer is detrimental for clinical outcome. As proof of concept, we developed a platform combining multiplexed IHC and digital imaging, enabling a virtual readout of both lymphoid and myeloid immune markers and their spatial patterns in the primary tumors of resected stage II and III colon cancer (CC) patients with and without accompanying systemic inflammation. Twenty-one patients with elevated CRP (>30 mg/l) and 15 patients with low CRP (<10 mg/l) were included in the analyses. Whole slides from the primary tumors were stained for markers of adaptive (CD8+, CD4+, foxp3 regulatory T cells, CD20+ B cells) and innate (CD68+ macrophages, CD66b+ neutrophils) immunity and the immune checkpoint molecule PD-L1. Associations between individual immune markers, preoperative CRP values, mismatch repair status (MMR), and risk of recurrence or death were assessed. Unsupervised hierarchical clustering was used to explore whether distinct immune phenotypes were present. Tumors from systemically inflamed patients (CRP >30 mg/l) displayed significantly more myeloid features in terms of higher densities of CD66b+neutrophils (p = 0.001) and CD68+macrophages (p = 0.04) and less lymphoid features (lower CD8 T cell, p = 0.03, and foxp3 regulatory T cell densities, p = 0.03) regardless of MMR status. Additionally, systemically inflamed patients harbored lower mean distances between neutrophils and tumor cells within the TME. Intriguingly, microsatellite instable (MSI) tumor status correlated with systemic inflammation. However, using a combinatorial approach, we found that regardless of an adaptive composite score (compounded CD4+ and CD8+ T cells), a high innate score (CD66b+ neutrophils and CD68+ macrophages) associated significantly with elevated CRP. In conclusion, tumor-associated systemic inflammation correlated with a myeloid-dominated TME in a small cohort of resectable CC patients. Our data highlight the importance of a comprehensive immune classification of tumors including players of innate immunity and support a role for CRP as an informative biomarker of the immune response taking place at the tumor site.
    MeSH term(s) Aged ; Aged, 80 and over ; Biomarkers ; C-Reactive Protein/metabolism ; Colonic Neoplasms/complications ; Colonic Neoplasms/metabolism ; Colonic Neoplasms/pathology ; Colonic Neoplasms/surgery ; Female ; Humans ; Immunohistochemistry ; Inflammation/complications ; Inflammation/etiology ; Inflammation/pathology ; Lymphocytes, Tumor-Infiltrating/immunology ; Lymphocytes, Tumor-Infiltrating/metabolism ; Lymphocytes, Tumor-Infiltrating/pathology ; Male ; Microsatellite Instability ; Middle Aged ; Myeloid Cells/immunology ; Myeloid Cells/metabolism ; Myeloid Cells/pathology ; Neoplasm Staging ; Neutrophil Infiltration/genetics ; Neutrophil Infiltration/immunology ; Recurrence ; Tumor Microenvironment/immunology
    Chemical Substances Biomarkers ; C-Reactive Protein (9007-41-4)
    Language English
    Publishing date 2021-08-31
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.716342
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Oncological results and morbidity following intended curative resection and free jejunal graft reconstruction of cervical esophageal cancer: a retrospective Danish consecutive cohort study.

    Erichsen, Sune Brinck / Slater, Josefine / Kiil, Birgitte Jul / Petersen, Torben Ingemann / Katballe, Niels / Nielsen, Mette Bak / Pikelis, Arunas / Nordsmark, Marianne / Kjaer, Daniel

    Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus

    2021  Volume 35, Issue 3

    Abstract: Background: The role of surgery in treatment of locally advanced cervical esophageal cancer (CEC) remains debated. In the European and American treatment guidelines, definitive chemoradiotherapy (dCRT) is preferred over surgery, while in the Danish ... ...

    Abstract Background: The role of surgery in treatment of locally advanced cervical esophageal cancer (CEC) remains debated. In the European and American treatment guidelines, definitive chemoradiotherapy (dCRT) is preferred over surgery, while in the Danish guidelines, the two treatment modalities are equally recommended. Surgical treatment of CEC is centralized at our center in Denmark. We present our outcomes following neoadjuvant chemoradiotherapy (nCRT) when possible and resection as first-line therapy for CEC and compare with recent published dCRT results.
    Method: We retrospectively reviewed the medical charts of patients treated for cervical esophageal cancer at Aarhus University Hospital from 2001-2018 with nCRT when possible and pharyngolaryngectomy followed by reconstruction with a free jejunal graft.
    Results: Forty consecutive patients were included. About, 45% received nCRT. The median survival was 21 months. The overall, disease-specific and disease-free 5-year survival was 43.6%, 53.2%, and 47.4%, respectively. The rate of microscopically radical resection was 85%. The recurrence rate was 47% and 81% of recurrences were locoregional. The in-hospital and 30-day mortality rate was 0%. Major complications occurred in 27.9%. Anastomotic leakage, graft failure, fistulas and strictures occurred in 10%, 7.5%, 30%, and 30%, respectively.
    Conclusion: Our treatment offers equal oncological results compared to the best internationally published results for dCRT for CEC. Results vary considerably between dCRT studies. Morbidity appears more pronounced following surgery. Future studies are warranted to investigate the Danish national outcomes following dCRT as first-line treatment for curable locally advanced CEC.
    MeSH term(s) Chemoradiotherapy/methods ; Cohort Studies ; Denmark/epidemiology ; Esophageal Neoplasms/drug therapy ; Esophageal Neoplasms/surgery ; Humans ; Morbidity ; Retrospective Studies
    Language English
    Publishing date 2021-07-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 639470-x
    ISSN 1442-2050 ; 1120-8694
    ISSN (online) 1442-2050
    ISSN 1120-8694
    DOI 10.1093/dote/doab048
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2378: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  5. Article ; Online: The association between soluble CD163, disease severity, and ursodiol treatment in patients with primary biliary cholangitis.

    Bossen, Lars / Lau, Tobias Stemann / Nielsen, Mette Bak / Nielsen, Marlene Christina / Andersen, Astrid Højmark / Ott, Peter / Becker, Sabine / Glerup, Henning / Svenningsen, Lise / Eivindson, Martin / Kornerup, Linda / Kjeldsen, Niels Bjørndal / Neumann, Anders / Møller, Holger Jon / Jepsen, Peter / Grønbæk, Henning

    Hepatology communications

    2023  Volume 7, Issue 4

    Abstract: Introduction: The macrophage activation marker soluble (s)CD163 is associated with disease severity and prognosis in patients with primary biliary cholangitis (PBC). Ursodeoxycholic acid (UDCA) treatment attenuates fibrosis progression in PBC patients, ... ...

    Abstract Introduction: The macrophage activation marker soluble (s)CD163 is associated with disease severity and prognosis in patients with primary biliary cholangitis (PBC). Ursodeoxycholic acid (UDCA) treatment attenuates fibrosis progression in PBC patients, but its effect on macrophage activation is unclear. We examined the effect of UDCA on macrophage activation, as determined by sCD163 levels.
    Methods: We included 2 cohorts of PBC patients; 1 cohort with prevalent PBC patients, and 1 cohort of incident PBC patients before start of UDCA treatment and with follow-up after 4 weeks and 6 months. We measured sCD163 and liver stiffness in both cohorts. Further, we measured sCD163 and TNF-α shedding in vitro in monocyte-derived macrophages after UDCA and lipopolysaccharide incubation.
    Results: We included 100 patients with prevalent PBC [93% women, median age 63 y (interquartile range: 51-70)] and 47 patients with incident PBC [77% women, median age 60 y (49-67)]. Prevalent PBC patients had a lower median sCD163 of 3.54 mg/L (2.77-4.72) than incident PBC patients with a median sCD163 of 4.33 mg/L (2.83-5.99) at inclusion. Patients with an incomplete response to UDCA and patients with cirrhosis had higher sCD163 than responders to UDCA and noncirrhosis patients. After 4 weeks and 6 months of UDCA treatment median sCD163 decreased by 4.6% and 9.0%, respectively. In in vitro experiments, UDCA attenuated shedding of TNF-α, but not sCD163, from monocyte-derived macrophages.
    Conclusion: In PBC patients, sCD163 levels correlated with liver disease severity and treatment response to UDCA. Further, after 6 months of UDCA treatment, we observed a decrease in sCD163, which may be related to the treatment.
    MeSH term(s) Female ; Humans ; Male ; Middle Aged ; Cholagogues and Choleretics/therapeutic use ; Liver Cirrhosis, Biliary/drug therapy ; Patient Acuity ; Tumor Necrosis Factor-alpha/therapeutic use ; Ursodeoxycholic Acid/therapeutic use ; Aged
    Chemical Substances CD163 antigen ; Cholagogues and Choleretics ; Tumor Necrosis Factor-alpha ; Ursodeoxycholic Acid (724L30Y2QR)
    Language English
    Publishing date 2023-03-24
    Publishing country United States
    Document type Journal Article
    ISSN 2471-254X
    ISSN (online) 2471-254X
    DOI 10.1097/HC9.0000000000000068
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Clinical outcome of interstitial pulsed dose rate brachytherapy in multimodality treatment of locally advanced primary or recurrent rectal and sigmoid cancer with high risk of incomplete microscopic resection.

    Nielsen, Mette Bak / Rasmussen, Peter Christian / Tanderup, Kari / Nielsen, Søren Kynde / Fokdal, Lars / Laurberg, Søren / Lindegaard, Jacob Christian

    Acta oncologica (Stockholm, Sweden)

    2016  Volume 55, Issue 12, Page(s) 1408–1413

    Abstract: Objective: To evaluate the role of interstitial pulsed dose rate brachytherapy (PDR-BT) in multimodality treatment of locally advanced primary or recurrent rectal and sigmoid cancer with high risk of microscopic incomplete resection (R1).: Methods and ...

    Abstract Objective: To evaluate the role of interstitial pulsed dose rate brachytherapy (PDR-BT) in multimodality treatment of locally advanced primary or recurrent rectal and sigmoid cancer with high risk of microscopic incomplete resection (R1).
    Methods and material: A total of 73 consecutive patients (recurrent/primary: 40/33) were treated with PDR-BT between 2001 and 2010. Patients received preoperative external beam radiotherapy (EBRT) and concomitant chemotherapy. Following resection of the tumor and the involved pelvic organs, a median of four (3-8) catheters were sutured to the tumor bed with a distance of approximately 1 cm between the catheters. A target respecting the catheters with a margin of 5 mm was contoured on computed tomography (CT) and three-dimensional (3D) dose planning with a planning aim for BT of D90 > 30 Gy, (0.6 Gy/pulse, 1 pulse/h) was performed. Previously irradiated patients (27%) underwent surgery that was directly followed by PDR-BT. Postoperative EBRT was then applied to the tumor bed 3-5 weeks after PDR-BT.
    Results: A total of 23 patients (31%) received a radical resection (R0) and 45 patients (62%) received an R1 resection. Five patients (7%) received a macroscopic incomplete resection (R2). The five-year overall survival was 33%. Local control at five years was 67% for patients who received a R0 resection and 32% for patients who received an R1 resection. The five-year actuarial risk of a grade 3-4 BT-related complication was 5%.
    Conclusions: Meaningful disease control and survival can be obtained at an acceptable rate of late morbidity in selected patients with locally advanced primary and recurrent rectal or sigmoid cancer using (chemo) RT, extensive surgery and PDR-BT when a high risk of an R1 resection is expected.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Brachytherapy/mortality ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local/pathology ; Neoplasm Recurrence, Local/therapy ; Neoplasm Staging ; Prognosis ; Prospective Studies ; Radiotherapy Dosage ; Rectal Neoplasms/pathology ; Rectal Neoplasms/therapy ; Sigmoid Neoplasms/pathology ; Sigmoid Neoplasms/therapy ; Survival Rate
    Language English
    Publishing date 2016-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 896449-x
    ISSN 1651-226X ; 0349-652X ; 0284-186X ; 1100-1704
    ISSN (online) 1651-226X
    ISSN 0349-652X ; 0284-186X ; 1100-1704
    DOI 10.1080/0284186X.2016.1213416
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6348: Show issues Location:
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