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Article ; Online: Cell-Free DNA Methylation as Blood-Based Biomarkers for Pancreatic Adenocarcinoma-A Literature Update.

Henriksen, Stine Dam / Thorlacius-Ussing, Ole

Epigenomes

2021 Volume 5, Issue 2

Abstract: Pancreatic adenocarcinoma has a horrible prognosis, which is partly due to difficulties in diagnosing the disease in an early stage. Additional blood-born biomarkers for pancreatic adenocarcinoma are needed. Epigenetic modifications, as changes in DNA ... ...

Abstract	Pancreatic adenocarcinoma has a horrible prognosis, which is partly due to difficulties in diagnosing the disease in an early stage. Additional blood-born biomarkers for pancreatic adenocarcinoma are needed. Epigenetic modifications, as changes in DNA methylation, is a fundamental part of carcinogenesis. The aim of this paper is to do an update on cell-free DNA methylation as blood-based biomarkers for pancreatic adenocarcinoma. The current literature including our studies clearly indicates that cell-free DNA methylation has the potential as blood-based diagnostic and prognostic biomarkers for pancreatic adenocarcinoma. However, still no clinical applicable biomarker for pancreatic adenocarcinoma based on DNA methylation do exist. Further well-designed validation studies are needed.
Language	English
Publishing date	2021-04-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ISSN	2075-4655
ISSN (online)	2075-4655
DOI	10.3390/epigenomes5020008
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Exploring D-Lactate as a Biomarker for Acute Intestinal Necrosis in 2958 Patients: A Prospective Cross-Sectional Study.

Straarup, David / Gotschalck, Kåre A / Christensen, Peter A / Rasmussen, Rikke W / Krarup, Henrik / Lundbye-Christensen, Søren / Handberg, Aase / Thorlacius-Ussing, Ole

The Journal of emergency medicine

2024

Abstract: Background: Timely diagnosis of acute intestinal necrosis (AIN) is lifesaving, but challenging due to unclear clinical presentation. D-lactate has been proposed as an AIN biomarker.: Objectives: We aimed to test the diagnostic performance in a ... ...

Abstract	Background: Timely diagnosis of acute intestinal necrosis (AIN) is lifesaving, but challenging due to unclear clinical presentation. D-lactate has been proposed as an AIN biomarker. Objectives: We aimed to test the diagnostic performance in a clinical setting. Methods: We performed a cross-sectional prospective study, including all adult patients with acute referral to a single tertiary gastrointestinal surgical department during 2015-2016 and supplemented by enrollment of high-risk in-hospital patients suspected of having AIN during 2016-2019. AIN was verified intraoperatively, and D-lactate was analyzed using an automatic spectrophotometric set-up. A D-lactate cut-off for AIN was estimated using the receiver operating characteristic curve. The performance according to patient subgroups was estimated using the area under the receiver operating characteristic curve (AUC). Given the exploratory nature of this study, a formal power calculation was not feasible. Results: Forty-four AIN patients and 2914 controls were enrolled. The D-lactate cut-off was found to be 0.0925 mM. Due to lipemic interference, D-lactate could not be quantified in half of the patients, leaving 23 AIN patients and 1456 controls for analysis. The AUC for the diagnosis of AIN by D-lactate was 0.588 (95% confidence interval 0.475-0.712), with a sensitivity of 0.261 and specificity of 0.892. Analysis of high-risk patients showed similar results (AUC 0.579; 95% confidence interval 0.422-0.736). Conclusion: D-lactate showed low sensitivity for AIN in both average-risk and high-risk patients. Moreover, lipemic interference precluded valid spectrophotometric assessment of D-lactate in half of the patients, further disqualifying the clinical utility of D-lactate as a diagnostic marker for AIN.
Language	English
Publishing date	2024-01-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	605559-x
ISSN	0736-4679
ISSN	0736-4679
DOI	10.1016/j.jemermed.2024.01.001
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Zs.A 1895: Show issues

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Article ; Online: The effect of antithrombotic treatment on the fecal immunochemical test for colorectal cancer screening: a nationwide cross-sectional study.

Rasmussen, Simon Ladefoged / Torp-Pedersen, Christian / Gotschalck, Kåre Andersson / Thorlacius-Ussing, Ole

Endoscopy

2023 Volume 55, Issue 5, Page(s) 444–455

Abstract: BACKGROUND : Screening for colorectal cancer (CRC) using the fecal immunochemical test (FIT) has been widely adopted. The use of antithrombotic treatment is increasing in the Western world. This study aimed to assess the effects of antithrombotic ... ...

Abstract	BACKGROUND : Screening for colorectal cancer (CRC) using the fecal immunochemical test (FIT) has been widely adopted. The use of antithrombotic treatment is increasing in the Western world. This study aimed to assess the effects of antithrombotic treatment on the FIT-based Danish national screening program for CRC. METHODS : This was a cross-sectional study of all individuals returning a FIT from 2014 until 2016. The effect of antithrombotic treatment on FIT positivity and the positive predictive value (PPV) were assessed using proportions and multivariable Poisson regression. RESULTS : Of 884 036 invited individuals, we identified 551 570 participants. A positive FIT was observed in 9052 of 77 007 individuals (11.8 %) receiving antithrombotic treatment compared with 28 387 of 474 587 individuals (6.0 %) receiving no treatment. The adjusted relative risk (RR) for a positive FIT was 1.59 (95 %CI 1.56-1.63) for any treatment. Nonvitamin K oral anticoagulants (NOACs) were associated with the largest increase in FIT positivity (adjusted RR 2.40, 95 %CI 2.48-2.54). The proportion of CRC detected at colonoscopy was slightly lower among patients on antithrombotic treatment (6.0 %, 95 %CI 5.5 %-6.6 %) than among treatment-naïve patients (6.4 %, 95 %CI 6.1 %-6.7 %). The PPV for CRC or high risk adenomas was decreased nearly twofold in patients treated with NOAC (adjusted RR 0.58, 95 %CI 0.51-0.66]). CONCLUSION : Antithrombotic treatment was associated with a decreased PPV in FIT-based CRC screening.
MeSH term(s)	Humans ; Anticoagulants/therapeutic use ; Cross-Sectional Studies ; Fibrinolytic Agents/therapeutic use ; Administration, Oral ; Early Detection of Cancer/methods ; Colorectal Neoplasms/diagnosis ; Colonoscopy ; Mass Screening/methods ; Occult Blood ; Feces
Chemical Substances	Anticoagulants ; Fibrinolytic Agents
Language	English
Publishing date	2023-01-26
Publishing country	Germany
Document type	Journal Article
ZDB-ID	80120-3
ISSN	1438-8812 ; 0013-726X
ISSN (online)	1438-8812
ISSN	0013-726X
DOI	10.1055/a-1992-5598
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Zs.A 669: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 162: Show issues

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Article: Cell-Free DNA Methylation as Blood-Based Biomarkers for Pancreatic Adenocarcinoma—A Literature Update

Henriksen, Stine Dam / Thorlacius-Ussing, Ole

Epigenomes. 2021 Apr. 09, v. 5, no. 2

2021

Abstract	Pancreatic adenocarcinoma has a horrible prognosis, which is partly due to difficulties in diagnosing the disease in an early stage. Additional blood-born biomarkers for pancreatic adenocarcinoma are needed. Epigenetic modifications, as changes in DNA methylation, is a fundamental part of carcinogenesis. The aim of this paper is to do an update on cell-free DNA methylation as blood-based biomarkers for pancreatic adenocarcinoma. The current literature including our studies clearly indicates that cell-free DNA methylation has the potential as blood-based diagnostic and prognostic biomarkers for pancreatic adenocarcinoma. However, still no clinical applicable biomarker for pancreatic adenocarcinoma based on DNA methylation do exist. Further well-designed validation studies are needed.
Keywords	DNA methylation ; adenocarcinoma ; biomarkers ; carcinogenesis ; epigenetics ; prognosis
Language	English
Dates of publication	2021-0409
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ISSN	2075-4655
DOI	10.3390/epigenomes5020008
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Preoperative findings on non-specific CT in patients with primary acute intestinal ischemia: a case-control study.

Straarup, David / Gotschalck, Kåre Andersson / Mikalone, Rasa / Thorlacius-Ussing, Ole

European journal of trauma and emergency surgery : official publication of the European Trauma Society

2021 Volume 48, Issue 4, Page(s) 3025–3032

Abstract: Purpose: Primary acute intestinal ischaemia (AII) is an abdominal catastrophe caused by intravascular obstruction of blood supply. It is difficult to diagnose. Computerized tomography (CT) scan is the modality of choice for diagnostic evaluation. ... ...

Abstract	Purpose: Primary acute intestinal ischaemia (AII) is an abdominal catastrophe caused by intravascular obstruction of blood supply. It is difficult to diagnose. Computerized tomography (CT) scan is the modality of choice for diagnostic evaluation. Majority of previous studies have evaluated CT findings in patients where AII was suspected. However, unveiling the unique radiological findings also in not initially suspected AII patients, might lead to the timely management of AII patients, and is the aim of this study. Methods: In a single-center, retrospective case-control study, preoperative radiological findings from abdominal CT scans in 48 patients with primary AII were compared with 80 non-ischemic controls. Radiological findings were analyzed using multivariable logistical regression with adjustment for age and gender and reported as odds ratios (OR) with 95% confidence intervals (CI) and p values. Results: Thirty-nine (81%) cases with AII were referred to an abdominal CT scan without a specific clinical suspicion of AII. Three main radiological categories (intestinal wall pathology [OR 7.4, CI 2.3-24.0, p value < 0.001], gastrointestinal vessel pathology [OR 19.3, CI 4.6-80.5, p value < 0.001) and intestinal diameter [OR 4.7, CI 1.6-13.4, p value 0.004]) were significantly different in AII patients. Subgroup analysis implied that pneumatosis intestinalis, increased contrast enhancement in the bowel wall, inferior mesenteric artery arteriosclerosis and colonic contraction were predictors of AII. Conclusion: Radiological changes within the intestinal wall, luminal diameter and gastrointestinal vessels are independent predictors of AII. Awareness of these radiological findings, therefore, plays a central role in patients with an indistinct clinical picture in early recognition and treatment of a life-threatening AII. Trial registration number: NCT04361110 (April 24, 2020), retrospectively registered.
MeSH term(s)	Case-Control Studies ; Humans ; Intestinal Obstruction/complications ; Ischemia/diagnostic imaging ; Mesenteric Ischemia/diagnostic imaging ; Mesenteric Ischemia/surgery ; Retrospective Studies ; Tomography, X-Ray Computed/methods
Language	English
Publishing date	2021-07-03
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2275480-5
ISSN	1863-9941 ; 1863-9933
ISSN (online)	1863-9941
ISSN	1863-9933
DOI	10.1007/s00068-021-01741-w
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Zs.A 1221: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 607: Show issues

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Article ; Online: Monocyte recruitment in venous pulmonary embolism at time of cancer diagnosis in upper gastrointestinal cancer patients.

Jakobsen, Sarah S / Frøkjaer, Jens B / Fisker, Rune V / Kristensen, Søren R / Thorlacius-Ussing, Ole / Larsen, Anders C

Journal of thrombosis and thrombolysis

2023 Volume 57, Issue 1, Page(s) 11–20

Abstract: Upper gastrointestinal cancer is frequently complicated by venous thromboembolisms (VTE), especially pulmonary embolisms (PE) increase the mortality rate. Monocytes are a part of the innate immune system and up-regulation may indicate an ongoing ... ...

Abstract	Upper gastrointestinal cancer is frequently complicated by venous thromboembolisms (VTE), especially pulmonary embolisms (PE) increase the mortality rate. Monocytes are a part of the innate immune system and up-regulation may indicate an ongoing inflammatory response or infectious disease and has lately been associated with a moderate risk of suffering from VTE. This prospectively study aims to compare the incidence of pulmonary embolism with markers of coagulation and compare it to the absolute monocyte count. A consecutive cohort of 250 patients with biopsy proven upper gastrointestinal cancer (i.e. pancreas, biliary tract, esophagus and gastric cancer) where included at the time of cancer diagnosis and before treatment. All patients underwent bilateral compression ultrasonography for detection of deep vein thrombosis (DVT). Of these 143 had an additionally pulmonary angiografi (CTPA) with the staging computer tomography. 13 of 250 patients (5.2%) had a DVT and 11 of 143 (7.7%) had CTPA proven PE. PE was significantly more common among patients with elevated D-dimer (OR 11.62, 95%CI: 1.13-119, P = 0.039) and elevated absolute monocyte count (OR 7.59, 95%CI: 1.37-41.98, P = 0.020). Only patients with pancreatic cancer had a significantly higher risk of DVT (OR 11.03, 95%CI: 1.25-97.43, P = 0.031). The sensitivity of absolute monocyte count was 63.6 (95%CI: 30.8-89.1) and specificity 80.3 (95%CI: 72.5-86.7), with a negative predictive value of 96.4 (95%CI: 91-99) in PE. An increased absolute monocyte count was detected in patients suffering from PE but not DVT, suggesting a possible interaction with the innate immune system.
MeSH term(s)	Humans ; Monocytes ; Pancreatic Neoplasms ; Pulmonary Embolism/epidemiology ; Upper Gastrointestinal Tract/pathology ; Venous Thromboembolism/epidemiology ; Prospective Studies ; Incidence ; Biliary Tract Neoplasms ; Esophageal Neoplasms ; Stomach Neoplasms
Language	English
Publishing date	2023-10-04
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article
ZDB-ID	1230645-9
ISSN	1573-742X ; 0929-5305
ISSN (online)	1573-742X
ISSN	0929-5305
DOI	10.1007/s11239-023-02897-5
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Zs.A 4352: Show issues

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Article ; Online: Exploring I-FABP, endothelin-1 and L-lactate as biomarkers of acute intestinal necrosis: a case-control study.

Straarup, David / Gotschalck, Kåre A / Christensen, Peter A / Krarup, Henrik / Lundbye-Christensen, Søren / Handberg, Aase / Thorlacius-Ussing, Ole

Scandinavian journal of gastroenterology

2023 Volume 58, Issue 12, Page(s) 1359–1365

Abstract: Objective: Acute intestinal necrosis (AIN) is a disease with devastating high mortality. AIN due to obstructed arterial blood flow has a blurred clinical presentation. Timely diagnosis is paramount, and a blood-based biomarker is warranted to increase ... ...

Abstract	Objective: Acute intestinal necrosis (AIN) is a disease with devastating high mortality. AIN due to obstructed arterial blood flow has a blurred clinical presentation. Timely diagnosis is paramount, and a blood-based biomarker is warranted to increase patient survival. We aimed to assess intestinal fatty acid binding protein (I-FABP) and endothelin-1 as diagnostic biomarkers for AIN. To our knowledge, this is the first study exploring endothelin-1 in AIN patients from a general surgical population. Design: We conducted a single-centre nested case-control study comparing acutely admitted AIN patients to age- and sex-matched non-AIN patients during 2015-2016. I-FABP and endothelin-1 were analysed using an enzyme-linked immunosorbent assay. L-lactate levels were also measured in all patients. Cut-offs were estimated using receiver operator characteristic curves, and the diagnostic performance was estimated using the area under the receiver operator characteristic curve (AUC). Results: We identified 43 AIN patients and included 225 matched control patients. Median levels of I-FABP, endothelin-1 and L-lactate were 3550 (IQR: 1746-9235) pg/ml, 3.91 (IQR: 3.33-5.19) pg/ml and 0.92 (IQR: 0.74-1.45) mM in AIN patients and 1731 (IQR: 1124-2848) pg/ml, 2.94 (IQR: 2.32-3.82) pg/ml and 0.85 (IQR: 0.64-1.21) mM in control patients, respectively. The diagnostic performances of endothelin-1 and of I-FABP + endothelin-1 combined were moderate. Endothelin-1 alone revealed an AUC of 0.74 (0.67; 0.82). The sensitivity and specificity of endothelin-1 were 0.81 and 0.64, respectively. Conclusion: I-FABP and endothelin-1 are promising biomarkers for AIN, with moderate diagnostic performance compared with the commonly used biomarker L-lactate. Preregistration: ClinicalTrials.gov: NCT05665946.
MeSH term(s)	Humans ; Case-Control Studies ; Endothelin-1 ; Fatty Acid-Binding Proteins/analysis ; Biomarkers ; Vascular Diseases ; Intestinal Diseases ; Necrosis ; Lactates
Chemical Substances	Endothelin-1 ; Fatty Acid-Binding Proteins ; Biomarkers ; Lactates
Language	English
Publishing date	2023-07-04
Publishing country	England
Document type	Journal Article
ZDB-ID	82042-8
ISSN	1502-7708 ; 0036-5521
ISSN (online)	1502-7708
ISSN	0036-5521
DOI	10.1080/00365521.2023.2229930
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Zs.A 567: Show issues

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Article: The effect of antithrombotic treatment on the fecal immunochemical test for colorectal cancer screening: a nationwide cross-sectional study

Rasmussen, Simon Ladefoged / Torp-Pedersen, Christian / Gotschalck, Kåre Andersson / Thorlacius-Ussing, Ole

Endoscopy

2023 Volume 55, Issue 05, Page(s) 444–455

Abstract: Background : Screening for colorectal cancer (CRC) using the fecal immunochemical test (FIT) has been widely adopted. The use of antithrombotic treatment is increasing in the Western world. This study aimed to assess the effects of antithrombotic ... ...

Abstract	Background : Screening for colorectal cancer (CRC) using the fecal immunochemical test (FIT) has been widely adopted. The use of antithrombotic treatment is increasing in the Western world. This study aimed to assess the effects of antithrombotic treatment on the FIT-based Danish national screening program for CRC. Methods : This was a cross-sectional study of all individuals returning a FIT from 2014 until 2016. The effect of antithrombotic treatment on FIT positivity and the positive predictive value (PPV) were assessed using proportions and multivariable Poisson regression. Results : Of 884 036 invited individuals, we identified 551 570 participants. A positive FIT was observed in 9052 of 77 007 individuals (11.8 %) receiving antithrombotic treatment compared with 28 387 of 474 587 individuals (6.0 %) receiving no treatment. The adjusted relative risk (RR) for a positive FIT was 1.59 (95 %CI 1.56–1.63) for any treatment. Nonvitamin K oral anticoagulants (NOACs) were associated with the largest increase in FIT positivity (adjusted RR 2.40, 95 %CI 2.48–2.54). The proportion of CRC detected at colonoscopy was slightly lower among patients on antithrombotic treatment (6.0 %, 95 %CI 5.5 %–6.6 %) than among treatment-naïve patients (6.4 %, 95 %CI 6.1 %–6.7 %). The PPV for CRC or high risk adenomas was decreased nearly twofold in patients treated with NOAC (adjusted RR 0.58, 95 %CI 0.51–0.66]). Conclusion : Antithrombotic treatment was associated with a decreased PPV in FIT-based CRC screening.
Language	English
Publishing date	2023-01-26
Publisher	Georg Thieme Verlag KG
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	80120-3
ISSN	1438-8812 ; 0013-726X
ISSN (online)	1438-8812
ISSN	0013-726X
DOI	10.1055/a-1992-5598
Database	Thieme publisher's database

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Zs.A 669: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 162: Show issues

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Article: Incidental detection of colorectal lesions on

Kousgaard, Sabrina Just / Gade, Michael / Petersen, Lars Jelstrup / Thorlacius-Ussing, Ole

Endoscopy international open

2020 Volume 8, Issue 12, Page(s) E1725–E1731

Abstract: Background and study ... ...

Abstract	Background and study aims
Language	English
Publishing date	2020-11-17
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2761052-4
ISSN	2196-9736 ; 2364-3722
ISSN (online)	2196-9736
ISSN	2364-3722
DOI	10.1055/a-1266-3308
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Article ; Online: Fully automatic d-lactate assay using a modified commercially available method.

Rasmussen, Rikke Wehner / Straarup, David / Thorlacius-Ussing, Ole / Handberg, Aase / Christensen, Peter Astrup

Scandinavian journal of clinical and laboratory investigation

2021 Volume 81, Issue 4, Page(s) 312–317

Abstract: Intestinal infarction is the fast-evolving endpoint of impaired blood perfusion to an intestinal segment which may have fatal outcome. Early diagnosis and treatment within 6 h reduce mortality. Currently, d-lactate is a promising biomarker, however, not ... ...

Abstract	Intestinal infarction is the fast-evolving endpoint of impaired blood perfusion to an intestinal segment which may have fatal outcome. Early diagnosis and treatment within 6 h reduce mortality. Currently, d-lactate is a promising biomarker, however, not available in the acute clinical setting. The aim of this study is implementation of d-lactate analysis in a routine clinical setting. We used a spectrophotometric method, based on enzymatic oxidation of d-lactate by d-lactate dehydrogenase (D-LDH) coupled to the reduction of nicotinamide-adenine dinucleotide (NAD
MeSH term(s)	Automation, Laboratory ; Blood Chemical Analysis/methods ; Emulsions/administration & dosage ; Humans ; Hydrogen-Ion Concentration ; L-Lactate Dehydrogenase/blood ; Lactic Acid/blood ; Limit of Detection ; Mesenteric Ischemia/blood ; NAD/metabolism ; Phospholipids/administration & dosage ; Reagent Kits, Diagnostic ; Reproducibility of Results ; Soybean Oil/administration & dosage ; Spectrophotometry
Chemical Substances	Emulsions ; Phospholipids ; Reagent Kits, Diagnostic ; soybean oil, phospholipid emulsion ; NAD (0U46U6E8UK) ; Lactic Acid (33X04XA5AT) ; Soybean Oil (8001-22-7) ; L-Lactate Dehydrogenase (EC 1.1.1.27)
Language	English
Publishing date	2021-04-20
Publishing country	England
Document type	Journal Article
ZDB-ID	3150-1
ISSN	1502-7686 ; 0036-5513
ISSN (online)	1502-7686
ISSN	0036-5513
DOI	10.1080/00365513.2021.1907859
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