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Slagelse, Denmark

Glintborg B.,Gentofte University Hospital | Ostergaard M.,Copenhagen University | Krogh N.S.,Zitelab Aps | Dreyer L.,Rigshospitalet | And 2 more authors.
Annals of the Rheumatic Diseases | Year: 2010

Objectives: To use prospectively registered data from the Danish nationwide rheumatological database (DANBIO) to describe disease activity, clinical response, treatment duration and predictors of drug survival (ie, number of days individual patients maintained treatment) and clinical response among patients with ankylosing spondylitis (AS) receiving their first treatment series with a tumour necrosis factor α (TNFα) inhibitor. Methods: 842 TNFα inhibitor naive patients with AS were identified in DANBIO. Clinical response, drug survival and predictors thereof were investigated. 'Clinical response' was defined as a 50% or 20 mm reduction in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) within 6 months compared with baseline. Achievement of a BASDAI <40 mm within 6 months was used as a second response parameter. Results: 603 patients (72%) were men, disease duration 5 (1-13) years (median (IQR), age 41 (32-50) years. 445 (53%) received infliximab, 247 (29%) adalimumab and 150 (18%) etanercept. Parameters at baseline/1-year follow-up were: C-reactive protein (CRP): 14 (7-27)/5 (2-10) mg/l, BASDAI 59 (44-72)/21 (8-39) mm, Bath Ankylosing Spondylitis Functional Index (BASFI) 50 (34-67)/24 (9-45) mm, Bath Ankylosing Spondylitis Metrology Index 40 (20-50)/20 (10-40) mm. Within 6 months, 407/644 patients (63%) achieved a clinical response. Median drug survival was 4.3 years. One- and 2-year survival rates were 74% and 63%, respectively. Baseline characteristics associated with longer drug survival were male gender, CRP >14 mg/l and low visual analogue scale fatigue (Cox regression analysis). Age, TNFα inhibitor and methotrexate use were insignificant. CRP >14 mg/l, lower BASFI and younger age at baseline was associated with clinical response and achievement of a BASDAI <40 mm (logistic regression analysis). Conclusion: TNFα inhibitors provide a rapid and sustained decrease of disease activity among patients with AS in clinical practice. Factors associated with continued treatment, clinical response and achievement of a BASDAI <40 mm were identified. Source

Two assays (Liaison, Diasorin; IDEIA, Oxoid) for detection of Borrelia-specific antibodies were compared. A case-control design using patients with neuroborreliosis (n = 48), laboratory defined by a positive Borrelia-specific antibody index in the spinal fluid, was available and was intended to represent the serological response of disseminated early Lyme borreliosis in general. Serum samples were obtained from 216 Danish blood donors as controls. By comparing sensitivity and specificity using pre-specified cut-off values, significant differences were found. However, using receiver operating characteristic (ROC) curves to optimize and standardize test interpretation, it was shown that testing with both IDEIA IgG and IgM was comparable to testing with Liaison IgG alone by comparing the area under the curve of the diagnostically relevant 25 % partial ROC curve (P = 0.1). When using the Liaison OspC/VlsE IgM assay, the specificity was decreased without a gain in sensitivity. This study proposes standardizing of reporting by using a control population as the reference and choosing decision thresholds guided by the risk of false-positive results at 2 and 8 %. The sensitivities for IDEIA (IgG and IgM combined) were 85 and 95 % and for the Liaison (VlsE IgG) method were 67 and 96 %, respectively. Methods for test evaluation, test interpretation and statistical testing are presented and discussed. In conclusion, Liaison VlsE IgG alone and IDEIA IgG/IgM combined showed a high and comparable discriminatory ability to distinguish serum samples from patients with neuroborreliosis from blood donor controls. However, cut-off values should be adjusted for a proper comparison. © 2013 SGM. Source

Elias D.,University of Southern Denmark | Vever H.,University of Southern Denmark | Laenkholm A.-V.,Slagelse Hospital | Gjerstorff M.F.,University of Southern Denmark | And 3 more authors.
Oncogene | Year: 2015

To elucidate the molecular mechanisms of tamoxifen resistance in breast cancer, we performed gene array analyses and identified 366 genes with altered expression in four unique tamoxifen-resistant (TamR) cell lines vs the parental tamoxifen-sensitive MCF-7/S0.5 cell line. Most of these genes were functionally linked to cell proliferation, death and control of gene expression, and include FYN, PRKCA, ITPR1, DPYD, DACH1, LYN, GBP1 and PRLR. Treatment with FYN-specific small interfering RNA or a SRC family kinase inhibitor reduced cell growth of TamR cell lines while exerting no significant effect on MCF-7/S0.5 cells. Moreover, overexpression of FYN in parental tamoxifen-sensitive MCF-7/S0.5 cells resulted in reduced sensitivity to tamoxifen treatment, whereas knockdown of FYN in the FYN-overexpressing MCF-7/S0.5 cells restored sensitivity to tamoxifen, demonstrating growth- and survival-promoting function of FYN in MCF-7 cells. FYN knockdown in TamR cells led to reduced phosphorylation of 14-3-3 and Cdc25A, suggesting that FYN, by activation of important cell cycle-associated proteins, may overcome the anti-proliferative effects of tamoxifen. Evaluation of the subcellular localization of FYN in primary breast tumors from two cohorts of endocrine-treated ER+ breast cancer patients, one with advanced disease (N=47) and the other with early disease (N=76), showed that in the former, plasma membrane-associated FYN expression strongly correlated with longer progression-free survival (P<0.0002). Similarly, in early breast cancer patients, membrane-associated expression of FYN in the primary breast tumor was significantly associated with increased metastasis-free (P<0.04) and overall (P<0.004) survival independent of tumor size, grade or lymph node status. Our results indicate that FYN has an important role in tamoxifen resistance, and its subcellular localization in breast tumor cells may be an important novel biomarker of response to endocrine therapy in breast cancer. © 2015 Macmillan Publishers Limited. All rights reserved. Source

Nielsen H.L.,Aarhus University Hospital | Engberg J.,Slagelse Hospital | Ejlertsen T.,Aarhus University Hospital | Bucker R.,Charite - Medical University of Berlin | Nielsen H.,Aarhus University Hospital
Clinical Microbiology and Infection | Year: 2012

There are only sparse data on the short-term and medium-term clinical impacts of Campylobacter concisus infection. A clinical study was performed during a 2-year period to determine the clinical manifestations in C. concisus-positive adult patients. A case patient was defined as an adult patient (≥18 years) with a C. concisus-positive stool sample during the study period. Clinical data were obtained with use of a questionnaire supplemented with the patients' medical records, if any. The short-term and medium-term clinical manifestations in these patients were compared with those of patients with Campylobacter jejuni/Campylobacter coli infection. One hundred and seventy-four C. concisus patients and 196 C. jejuni/C. coli patients participated in the study. Patients with pre-existing inflammatory bowel disease or microscopic colitis or enteric co-infection were excluded from review of the clinical manifestations. Comparison of the short-term clinical manifestations in 139 C. concisus patients with those in 187 C. jejuni/C. coli patients showed a significantly lower prevalence of fever, chills, mucus and blood in stools, and weight loss. However, 80% of C. concisus patients, but only 32% of C. jejuni/C. coli patients, had diarrhoea for >2 weeks. After a 6-month follow-up period, 12% of C. concisus patients were diagnosed with microscopic colitis, whereas no C. jejuni/C. coli patients were diagnosed with non-infective colitis. Irritable bowel symptoms were common in both groups at follow-up. C. concisus infection seems to cause a milder course of acute gastroenteritis than C. jejuni/C. coli infection, but is associated with more prolonged diarrhoea. © 2012 European Society of Clinical Microbiology and Infectious Diseases. Source

Jensen J.D.,University of Southern Denmark | Knoop A.,University of Southern Denmark | Laenkholm A.V.,Slagelse Hospital | Grauslund M.,Copenhagen University | And 4 more authors.
Annals of Oncology | Year: 2012

Background: This study was conducted to determine the frequency of PIK3CA mutations and human epidermal growth factor receptor-2 (HER2) phosphorylation status (pHER2-Tyr1221/1222) and if PIK3CA, phosphatase and tensin homolog (PTEN), or pHER2 has an impact on outcome in HER2-positive early-stage breast cancer patients treated with adjuvant chemotherapy and trastuzumab. Patients and methods: Two hundred and forty HER2-positive early-stage breast cancer patients receiving adjuvant treatment (cyclophosphamide 600 mg/m2, epirubicin 60 mg/m2, and fluorouracil 600 mg/m2) before administration of 1 year trastuzumab were assessable. PTEN and pHER2 expression were assessed by immunohistochemistry. PIK3CA mutations (exons 9 and 20) were determined by pyrosequencing. Results: Five-year overall survival (OS) and invasive disease-free survival were 87.8% and 81.0%, respectively. Twenty-six percent of patients had a PIK3CA mutation, 24% were PTEN low, 45% pHER2 high, and 47% patients had increased PI3K pathway activation (PTEN low and/or PIK3CA mutation). No significant correlations were observed between the clinicopathological variables and PIK3CA, PTEN, and pHER2 status. In both univariate and multivariate analyses, patients with PIK3CA mutations or high PI3K pathway activity had a significant worse OS [multivariate: hazard ratio (HR) 2.14, 95% confidence interval (CI) 1.01-4.51, P = 0.046; and HR 2.35, 95% CI 1.10-5.04, P = 0.03]. Conclusion: Patients with PIK3CA mutations or increased PI3K pathway activity had a significantly poorer survival despite adequate treatment with adjuvant chemotherapy and trastuzumab. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. Source

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