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Natasja Stæhr Gudmann, Shintaro Hirata, Morten Asser Karsdal, Satoshi Kubo, Anne-Christine Bay-Jensen, Yoshiya Tanaka
OBJECTIVES: This prospective study aimed to use serological biomarkers for evaluation of, connective tissue turnover, in a population of 149 Japanese patients with rheumatoid arthritis (RA). It was aimed to investigate how the connective tissue was affected by treatment at follow-up after 1 year (+/- 6 weeks) with either methotrexate (n=23) alone, or in combination with: adalimumab (n=49), tofacitinib (n=27) or tocilizumab (n=50). METHODS: Clinical characteristics were collected and connective tissue turnover, was evaluated by 4 serological biomarkers: C1M and C3M reflect degradation of types I and III collagen in interstitial tissue; C4M, reflecting degraded type IV collagen of the basement membranes; and CRPM, a marker of degraded C-reactive protein...
February 14, 2018: Clinical and Experimental Rheumatology
Pernille Juhl, Christian S Thudium, Natasja S Gudmann, Morten A Karsdal, Anne-Christine Bay-Jensen, Anne Sofie Siebuhr
OBJECTIVES: The objective of this study was to examine the tissue degradation in response to anti-IL6 receptor treatment in rheumatoid arthritis (RA) patients which are anti-TNF-α inadequate responders. METHODS: RADIATE was a randomised, double-blinded, placebo-controlled, parallel-group, phase III trial. RA patients with previous inadequate response to anti-TNFα therapy (n=299) were randomly assigned to tocilizumab 4 or 8 mg/kg with methotrexate (10-25 mg weekly) or placebo with methotrexate...
January 31, 2018: Clinical and Experimental Rheumatology
Stephanie Downs-Canner, Yongli Shuai, Lekshmi Ramalingam, James F Pingpank, Matthew P Holtzman, Herbert J Zeh, David L Bartlett, Haroon A Choudry
BACKGROUND: To determine if a select subgroup of patients with combined liver and peritoneal colorectal metastases would derive oncologic benefit from surgical resection as a component of multimodality treatment. MATERIALS AND METHODS: We retrospectively compared 32 patients with combined colorectal peritoneal and liver metastases (CRLM) and 173 patients with peritoneal metastases only (CRPM) undergoing cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC)...
November 2017: Journal of Surgical Research
Marketa Husakova, Anne Sofie Siebuhr, Karel Pavelka, Maja Spiritovic, Anne-Christine Bay-Jensen, Andrea Levitova
The objective of this study was to investigate the patient-reported outcomes (PROs) and matrix metalloproteinase (MMP) derived extracellular matrix (ECM) biomarkers in non-radiographic (nr)-axial spondyloarthritis (axSpA) and radiographic (r)-axSpA after exercise intervention. Forty-six axSpA patients with stable disease and treatment underwent 24 weeks long exercise intervention. The clinical and laboratory assessments were performed at baseline and at follow-up. The PROs included evaluation of patient's global disease activity (PGDA), disease activity (DA7), pain (PAIN7) and fatigue during last week and quality of life questionnaires...
August 30, 2017: Clinical Rheumatology
R F Loeser, D P Beavers, A C Bay-Jensen, M A Karsdal, B J Nicklas, A Guermazi, D J Hunter, S P Messier
OBJECTIVE: To examine the effects of dietary weight loss, with and without exercise, on selected soluble biomarkers in overweight and obese older adults with symptomatic knee osteoarthritis (OA). DESIGN: Blood samples were analyzed from 429 participants in the Intensive Diet and Exercise for Arthritis (IDEA) trial randomized to either an 18 month exercise control group (E), weight loss diet (D), or D + E. C1M, C2M, C3M and CRPM biomarkers and interleukin-6 (IL-6) were quantitated using ELISAs...
November 2017: Osteoarthritis and Cartilage
B Hua, E H N Olsen, S Sun, C N Gudme, L Wang, B Vandahl, K Roepstorff, M Kjelgaard-Hansen, B B Sørensen, Y Zhao, M A Karsdal, T Manon-Jensen
INTRODUCTION: Progressive arthropathy caused by recurrent joint bleeds is a severe complication in haemophilia. AIM: We investigated whether biomarkers of cartilage and bone degradation, and inflammation were altered in haemophilia patients and whether these biomarkers could identify haemophilia patients with arthropathy. METHODS: Serum from 35 haemophilia patients with varying degrees of arthropathy and 43 age- and gender-matched control subjects were analysed...
April 24, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
Fatemeh Saberi Hosnijeh, Anne Sofie Siebuhr, Andre G Uitterlinden, Edwin H G Oei, Albert Hofman, Morten A Karsdal, Sita M Bierma-Zeinstra, Anne C Bay-Jensen, Joyce B J van Meurs
BACKGROUND: We aimed to investigate the prognostic value of two biomarkers of tissue inflammation, matrix metalloproteinase-dependent degradation of C-reactive protein (CRPM) and connective tissue type I collagen turnover (C1M), on the incidence and progression of radiographic osteoarthritis (OA) in the Rotterdam Study, a prospective cohort. Moreover, the independent effect of these biomarkers with respect to the established biomarkers of OA progression, like urinary type II collagen degradation (uCTX-II) and serum cartilage oligomeric protein (COMP), was evaluated...
April 1, 2016: Arthritis Research & Therapy
Karen I Maijer, Natasja Stæhr Gudmann, Morten Asser Karsdal, Daniëlle M Gerlag, Paul Peter Tak, Anne Christine Bay-Jensen
OBJECTIVE: Tissue destruction in rheumatoid arthritis (RA) is predominantly mediated by matrix metalloproteinases (MMPs), thereby generating protein fragments. Previous studies have revealed that these fragments include MMP-mediated collagen type I, II, and III degradation, citrullinated and MMP-degraded vimentin and MMP degraded C-reactive protein. We evaluated if biomarkers measuring serum levels of specific sequences of the mentioned fragments would provide further information of diagnostic and/or prognostic processes in early arthritis...
2016: PloS One
Anne C Bay-Jensen, Adam Platt, Anne Sofie Siebuhr, Claus Christiansen, Inger Byrjalsen, Morten A Karsdal
BACKGROUND: Rheumatoid arthritis (RA) is characterized by gradual joint destruction. Tocilizumab (TCZ) significantly suppresses symptoms, however not all patients are protected from joint damage. We investigated whether early measurement of specific biomarkers could predict early joint protection response to tocilizumab. METHOD: Serum biomarkers (CRPM, VICM, C1M, C2M, C3M (MMP-degraded CRP, vimentin type I, II and III collagen), CTX-I/OC (bone turnover), and CRP) were measured in 740 RA patients (the LITHE study) treated with Placebo, or 4 or 8 mg/kg TCZ...
January 20, 2016: Arthritis Research & Therapy
Anne Sofie Siebuhr, Anne C Bay-Jensen, Morten Asser Karsdal, Rik J Lories, Kurt de Vlam
AIM: To investigate if tissue turnover biomarkers were efficacy biomarkers in ankylosing spondylitis and if the biomarkers at baseline predicted a good outcome (BASDAI50). PATIENTS & METHODS: Twenty-two etanercept treated ankylosing spondylitis patients were investigated for inflammation (CRP, ESR, CRPM) and tissue turnover (C1M, C2M, C3M) during the first year of treatment. Biomarkers profiles and treatment response were investigated. RESULTS: ESR, CRP, BASDAI and C1M were decreased with treatment (p ≤ 0...
2016: Biomarkers in Medicine
N J R Lyons, S Pathak, I R Daniels, A Spiers, N J Smart
BACKGROUND: Radiofrequency ablation (RFA) is a well-established treatment modality for colorectal hepatic metastases, the success of which has prompted its use to treat other lesions such as colorectal pulmonary metastases (CRPM). Our aim was to perform a systematic review of the evidence and to assess the safety and effectiveness of ablative techniques in the management of CRPM. METHOD: A literature search was performed using PubMed, Embase, Cochrane Library, CINAHL and Google scholar databases to identify studies, which analysed ablative techniques and their effectiveness in the management of CRPM...
November 2015: European Journal of Surgical Oncology
F Genovese, A S Siebuhr, K Musa, J A Gallagher, A M Milan, M A Karsdal, J Rovensky, A C Bay-Jensen, L R Ranganath
BACKGROUND AND AIM: Alkaptonuria (AKU) clinical manifestations resemble severe arthritis. The Suitability of Nitisinone in Alkaptonuria 1 (SONIA 1) study is a dose-finding trial for nitisinone treatment of AKU patients. We tested a panel of serum and urinary biomarkers reflecting extracellular matrix remodelling (ECMR) of cartilage, bone and connective tissue in SONIA 1 patients to identify non-invasive and diagnostic biomarkers of tissue turnover in AKU. METHODS: Fasted serum and urine were retrieved from 40 SONIA 1 patients and 44 healthy controls...
2015: JIMD Reports
R Gisli Jenkins, Juliet K Simpson, Gauri Saini, Jane H Bentley, Anne-Marie Russell, Rebecca Braybrooke, Philip L Molyneaux, Tricia M McKeever, Athol U Wells, Aiden Flynn, Richard B Hubbard, Diana J Leeming, Richard P Marshall, Morten A Karsdal, Pauline T Lukey, Toby M Maher
BACKGROUND: Idiopathic pulmonary fibrosis, a progressive and inevitably fatal disorder, has a highly variable clinical course. Biomarkers that reflect disease activity are urgently needed to inform patient management and for use as biomarkers of therapeutic response (theragnostic biomarkers) in clinical trials. We aimed to determine whether dynamic change in markers of extracellular matrix (ECM) turnover predicts progression of idiopathic pulmonary fibrosis as determined by change in forced vital capacity and death...
June 2015: Lancet Respiratory Medicine
Line Lindhardt Egsgaard, Thomas Navndrup Eskehave, Anne C Bay-Jensen, Hans Christian Hoeck, Lars Arendt-Nielsen
Biochemical and pain biomarkers can be applied to patients with painful osteoarthritis profiles and may provide more details compared with conventional clinical tools. The aim of this study was to identify an optimal combination of biochemical and pain biomarkers for classification of patients with different degrees of knee pain and joint damage. Such profiling may provide new diagnostic and therapeutic options. A total of 216 patients with different degrees of knee pain (maximal pain during the last 24 hours rated on a visual analog scale [VAS]) (VAS 0-100) and 64 controls (VAS 0-9) were recruited...
January 2015: Pain
Shahid G Farid, Lara Morley, Keith J Roberts, Gareth Morris-Stiff, Andrew M Smith
CONTEXT: Colorectal pancreatic metastases (CRPM) are uncommon, thus the role of surgical resection is unclear. We present our experience of management outcomes of patients with CRPM in a regional pancreatic unit. METHODS: Electronic records of all patients with colorectal cancer (n = 8,228) held by the cancer network were searched for evidence of CRPM. Retrospective analysis of each case was undertaken in relation to diagnosis, management and outcome of CRPM. RESULTS: Four cases of CRPM underwent resection (operative group)...
September 2014: JOP: Journal of the Pancreas
Lars Arendt-Nielsen, Thomas N Eskehave, Line L Egsgaard, Kristian K Petersen, Thomas Graven-Nielsen, Hans C Hoeck, Ole Simonsen, Anne S Siebuhr, Morten Karsdal, Anne C Bay-Jensen
OBJECTIVE: To assess the association between pain mechanisms (sensitization) and biochemical markers for cartilage, bone, and inflammation in patients with knee pain. METHODS: The study group comprised 281 patients with different degrees of knee pain intensity and radiographic findings (using the Kellgren/Lawrence [K/L] scale). The following structurally related serologic biomarkers were measured in serum: high-sensitivity C-reactive protein (hsCRP), matrix metalloproteinase (MMP)-mediated breakdown of CRP (CRPM), MMP-mediated degradation of type I collagen (C1M), C2M, and C3M...
December 2014: Arthritis & Rheumatology
A S Siebuhr, K K Petersen, L Arendt-Nielsen, L L Egsgaard, T Eskehave, C Christiansen, O Simonsen, H C Hoeck, M A Karsdal, A C Bay-Jensen
OBJECTIVES: Osteoarthritis (OA) is a degenerative disease with a subset of patients experiencing joint inflammation, but C-reactive protein (CRP) has shown limited use in OA as a diagnostic marker. The aim was to identify subpopulations of patients with high or low levels of acute (high sensitive CRP (hsCRP)) and/or matrix metalloproteinase (MMP) derived inflammation (CRPM) and investigate the subpopulations' association with biomarkers of collagen degradation and Kellgren-Lawrence (KL) score...
January 2014: Osteoarthritis and Cartilage
D J Leeming, M A Karsdal, I Byrjalsen, F Bendtsen, J Trebicka, M J Nielsen, C Christiansen, S Møller, A Krag
BACKGROUND: The hepatic venous pressure gradient (HVPG) is an invasive, but important diagnostic and prognostic marker in cirrhosis with portal hypertension (PHT). During cirrhosis, remodelling of fibrotic tissue by matrix metalloproteinases (MMPs) is a permanent process generating small fragments of degraded extracellular matrix (ECM) proteins known as neoepitopes, which are then released into the circulation. AIM: To investigate their potential as plasma markers for detection of PHT...
November 2013: Alimentary Pharmacology & Therapeutics
Xiaogang Wang, Daomu Zhao
A nonlinear color and grayscale images cryptosystem based on phase-truncated fractional Fourier transform and optical superposition principle is proposed. In order to realize simultaneous encryption of color and grayscale images, each grayscale image is first converted into two phase masks by using an optical coherent superposition, one of which is treated as a part of input information that will be fractional Fourier transformed while the other in the form of a chaotic random phase mask (CRPM) is used as a decryption key...
September 1, 2013: Applied Optics
Anne C Bay-Jensen, Adam Platt, Inger Byrjalsen, Philippe Vergnoud, Claus Christiansen, Morten A Karsdal
OBJECTIVE: We investigated the effects of tocilizumab (TCZ) on joint tissue remodeling in patients with moderate to severely active RA by measuring tissue-specific biomarker. METHODS: The LITHE biomarker study (n = 740) was a phase III study of 4- and 8-mg/kg TCZ in combination with MTX. Early response was evaluated at week 16 as ±20% improvement in swollen/tender joint counts; and ACR50 was evaluated at week 52. Biomarkers (tissue inflammation: C3M, CRPM, and VICM; cartilage degradation: C2M; and bone turnover: CTx and osteocalcin) were tested in serum from baseline, week 4, 16, 24, and 52, and dose-dependent effect was investigated...
February 2014: Seminars in Arthritis and Rheumatism
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