| 1. |
- Beaumont, Robin N, et al.
(författare)
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Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth.
- 2023
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Ingår i: Nature genetics. - 1546-1718 .- 1061-4036. ; 55:11, s. 1807-19
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Tidskriftsartikel (refereegranskat)abstract
- A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n=65,405), maternal (n=61,228) and paternal (n=52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.
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| 2. |
- Ejlertsen, Bent, et al.
(författare)
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Similar efficacy for ovarian ablation compared with cyclophosphamide, methotrexate, and fluorouracil: from a randomized comparison of premenopausal patients with node-positive, hormone receptor-positive breast cancer
- 2006
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Ingår i: J Clin Oncol. - : American Society of Clinical Oncology (ASCO). - 1527-7755. ; 24:31, s. 4956-4962
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Tidskriftsartikel (refereegranskat)abstract
- To compare the efficacy of ovarian ablation versus chemotherapy in early breast cancer patients with hormone receptor–positive disease. Patients and Methods We conducted an open, randomized, multicenter trial including premenopausal breast cancer patients with hormone receptor–positive tumors and either axillary lymph node metastases or tumors with a size of 5 cm or more. Patients were randomly assigned to ovarian ablation by irradiation or to nine courses of chemotherapy with intravenous cyclophosphamide, methotrexate, and fluorouracil (CMF) administered every 3 weeks. Results Between 1990 and May 1998, 762 patients were randomly assigned, and the present analysis is based on 358 first events. After a median follow-up time of 8.5 years, the unadjusted hazard ratio for disease-free survival in the ovarian ablation group compared with the CMF group was 0.99 (95% CI, 0.81 to 1.22). After a median follow-up time of 10.5 years, overall survival (OS) was similar in the two groups, with a hazard ratio of 1.11 (95% CI, 0.88 to 1.42) for the ovarian ablation group compared with the CMF group. Conclusion In this study, ablation of ovarian function in premenopausal women with hormone receptor–positive breast cancer had a similar effect to CMF on disease-free and OS. No significant interactions were demonstrated between treatment modality and hormone receptor content, age, or any of the well-known prognostic factors.
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| 3. |
- Holm, Paetur M., et al.
(författare)
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Effects of neuromuscular control and strengthening exercises on MRI-measured thigh tissue composition and muscle properties in people with knee osteoarthritis - an exploratory secondary analysis from a randomized controlled trial
- 2024
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Ingår i: SEMINARS IN ARTHRITIS AND RHEUMATISM. - 0049-0172 .- 1532-866X. ; 65
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the effects of adding strength training to neuromuscular control exercises on thigh tissue composition and muscle properties in people with radiographic -symptomatic knee osteoarthritis (KOA). Methods: In this exploratory secondary analysis of a randomized controlled trial, using a complete -case approach, participants performed 12 weeks of twice -weekly neuromuscular control exercise and patient education (NEMEX, n = 34) or NEMEX plus quadriceps strength training (NEMEX+ST, n = 29). Outcomes were MRImeasured inter- and intramuscular adipose tissue (InterMAT, IntraMAT), quadriceps muscle cross-sectional area (CSA), knee -extensor strength, specific strength (strength/lean CSA) and 30 s chair -stands. Betweengroup effects were compared using a mixed model analysis of variance. Results: At 12 weeks, responses to NEMEX+ST overlapped with NEMEX for all outcomes. Both groups reduced InterMAT (NEMEX+ST=25 %, NEMEX=21 %); between -group difference: 0.8cm2 (95 % CI: -0.1, 1.7). NEMEX+ST decreased IntraMAT (2 %) and NEMEX increased IntraMAT (4 %); between -group difference 0.1 %-points (-0.3, 0.5). Both groups increased quadriceps CSA and lean CSA (CSA minus IntraMAT), improved knee -extensor strength and specific strength, and improved chair -stand performance with a trend towards greater effects in NEMEX+ST. Conclusion: Adding strength training to 12 weeks of neuromuscular control exercises provided largely similar effects to neuromuscular control exercises alone in decreasing InterMAT and IntraMAT, in improving kneeextensor strength, CSA and in improving performance -based function in KOA persons, with a trend towards greater effects with additional strength training. Notably, both groups substantially reduced InterMAT and improved specific strength (an index of muscle quality). Our hypothesis -generating work warrants exploration of the roles played by InterMAT and IntraMAT in exercise effects in KOA.
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| 4. |
- Irenaeus, Sandra, et al.
(författare)
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First-in-human study with intratumoral administration of a CD40 agonistic antibody, ADC-1013, in advanced solid malignancies
- 2019
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Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 145:5, s. 1189-1199
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Tidskriftsartikel (refereegranskat)abstract
- Agonistic CD40 antibodies activate dendritic cells and can expand and activate tumor-specific T cells. Our purpose was to assess the CD40 agonistic antibody ADC-1013 in the clinical setting including intratumoral administration since preclinical studies have indicated that intratumoral is better than intravenous administration. A Phase I, open label, multicenter study was conducted in patients with advanced solid tumors who had received established treatments. A modified 3 + 3 dose-escalation was applied (every other week dosing). Twenty-three patients were treated with ADC-1013 intratumorally (dosing from 22.5 mu g/kg up to 400 mu g/kg) or intravenously (dosing at 75 mu g/kg). The pharmacodynamic effects observed in the patients were further verified in an hCD40tg mouse model. Adverse events were mostly Common Terminology Criteria for Adverse Events (CTCAE) Grades 1 or 2 and transient. The serum concentration ADC-1013 and cytokine release (MCP-1, TNF alpha and IL-6) were more pronounced in patients receiving injections in deep metastases compared to patients receiving injections in superficial metastases. Treatment with ADC-1013 resulted in a marked decrease in B cell levels in peripheral blood after 24 h while remaining B cells significantly increased their expression of the cell surface activation marker CD86. Activation of antigen-presenting cells and subsequent activation of T cells were demonstrated in hCD40tg mice. Moreover, ADC-1013 treatment in this mouse model acted synergistically with a PD-1 inhibitor. The results from the first-in-human study of ADC-1013 indicate that intratumoral administration of ADC-1013 into superficial lesions is well tolerated at clinically relevant doses and associated with pharmacodynamic responses.
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| 5. |
- Korsholm, Kasper, et al.
(författare)
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Left Atrial Appendage Occlusion versus Novel Oral Anticoagulation for Stroke Prevention in Atrial Fibrillation: Rationale and Design of the Multicenter Randomized Occlusion-AF Trial.
- 2021
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Ingår i: American heart journal. - : Elsevier BV. - 1097-6744 .- 0002-8703. ; 243, s. 28-38
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of atrial fibrillation (AF) is increasing globally, which is a major clinical and public health concern due to the five-fold increased risk of stroke. Oral anticoagulation with novel oral anticoagulants (NOACs) is the current primary option for stroke prevention in patients with AF, although it increases the risk of major bleeding. Patients with prior ischemic cerebrovascular events are at particularly high risk of both recurrent ischemic events and major bleeding. Left atrial appendage occlusion (LAAO) provides an alternative option for stroke prevention in high-risk patients, however, with currently limited evidence. Thus, randomized trials comparing LAAO to NOACs are needed.The Occlusion-AF trial is designed to assess whether LAAO is non-inferior to NOAC therapy for reduction of the combined endpoint of stroke, systemic embolism, major bleeding (Bleeding Academic Research Consortium ≥ 3) and all-cause mortality in patients with AF and a recent ischemic stroke or transient ischemic attack (TIA).Investigator-initiated multicenter, multinational, randomized open-label non-inferiority trial with blinded outcome evaluation (PROBE design). Patients with documented AF, and an ischemic stroke or TIA within 6 months will be eligible for enrollment. Major exclusion criteria are modified Rankin Scale > 3 at enrollment, glomerular filtration rate < 15 ml/min, and life-expectancy less than 2 years. A total of 750 patients will be randomized 1:1 to receive either a NOAC or LAAO using the Amplatzer Amulet (Abbott, MN, USA) or Watchman FLX (Boston Scientific, MN, USA) with subsequent life-long aspirin 75 mg daily. Follow-up will be based on in-office and telephone follow-up in combination with long-term follow-up (10 years) through national hospital discharge registries in the individual Nordic countries. The primary outcome will be a composite endpoint of stroke, systemic embolism, major bleeding (BARC ≥ 3) and all-cause mortality at 2-year follow-up.The Occlusion-AF trial is designed to compare LAAO to NOAC therapy for secondary stroke prevention in AF patients with a high risk of recurrent thromboembolic events, i.e. with previous ischemic stroke or TIA, and otherwise eligible for anticoagulation. The results are expected to contribute significantly to the understanding of the effects of LAAO compared to the standard contemporary pharmacological treatment in these patients.
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| 6. |
- Kumler, Iben, et al.
(författare)
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Clinical outcome of percutaneous RF-ablation of non-operable patients with liver metastasis from breast cancer
- 2015
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Ingår i: Radiologia Medica. - : Springer Science and Business Media LLC. - 0033-8362 .- 1826-6983. ; 120:6, s. 536-541
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Tidskriftsartikel (refereegranskat)abstract
- Despite improved anti-neoplastic treatment the prognosis for patients with liver metastases from metastatic breast cancer remains poor. Thirty-two consecutive patients with metastatic breast cancer treated with radiofrequency ablation (RFA) at the Department of Oncology, Herlev Hospital, University of Copenhagen, from 1996 to 2010. Time to intrahepatic progression was median 11 months (range 1.6-184 months). Median survival after first RFA was 33.5 months. Survival at 1, 2 and 3 years was 87, 68 and 48 %, respectively. The local recurrence rate was 22 %. In this small, highly selected cohort we found RFA safe and efficacious with a low local recurrence rate and a median survival above that expected with systemic treatment. Our data are in line with previous studies and underscore the need for a large prospective study using optimal chemotherapy regimens and RFA/surgery to clarify whether intense treatment protocols can prolong survival for certain patient groups.
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| 7. |
- McMahon, Colin J, et al.
(författare)
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Adult congenital heart disease training in Europe: current status, disparities and potential solutions.
- 2023
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Ingår i: Open heart. - 2053-3624. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to determine the status of training of adult congenital heart disease (ACHD) cardiologists in Europe.A questionnaire was sent to ACHD cardiologists from 34 European countries.Representatives from 31 of 34 countries (91%) responded. ACHD cardiology was recognised by the respective ministry of Health in two countries (7%) as a subspecialty. Two countries (7%) have formally recognised ACHD training programmes, 15 (48%) have informal (neither accredited nor certified) training and 14 (45%) have very limited or no programme. Twenty-five countries (81%) described training ACHD doctors 'on the job'. The median number of ACHD centres per country was 4 (range 0-28), median number of ACHD surgical centres was 3 (0-26) and the median number of ACHD training centres was 2 (range 0-28). An established exit examination in ACHD was conducted in only one country (3%) and formal certification provided by two countries (7%). ACHD cardiologist number versus gross domestic product Pearson correlation coefficient=0.789 (p<0.001).Formal or accredited training in ACHD is rare among European countries. Many countries have very limited or no training and resort to 'train people on the job'. Few countries provide either an exit examination or certification. Efforts to harmonise training and establish standards in exit examination and certification may improve training and consequently promote the alignment of high-quality patient care.
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| 8. |
- Mogensen, Martin, et al.
(författare)
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Mitochondrial respiration is decreased in skeletal muscle of patients with type 2 diabetes.
- 2007
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 56:6, s. 1592-9
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Tidskriftsartikel (refereegranskat)abstract
- We tested the hypothesis of a lower respiratory capacity per mitochondrion in skeletal muscle of type 2 diabetic patients compared with obese subjects. Muscle biopsies obtained from 10 obese type 2 diabetic and 8 obese nondiabetic male subjects were used for assessment of 3-hydroxy-Acyl-CoA-dehydrogenase (HAD) and citrate synthase activity, uncoupling protein (UCP)3 content, oxidative stress measured as 4-hydroxy-2-nonenal (HNE), fiber type distribution, and respiration in isolated mitochondria. Respiration was normalized to citrate synthase activity (mitochondrial content) in isolated mitochondria. Maximal ADP-stimulated respiration (state 3) with pyruvate plus malate and respiration through the electron transport chain (ETC) were reduced in type 2 diabetic patients, and the proportion of type 2X fibers were higher in type 2 diabetic patients compared with obese subjects (all P < 0.05). There were no differences in respiration with palmitoyl-l-carnitine plus malate, citrate synthase activity, HAD activity, UCP3 content, or oxidative stress measured as HNE between the groups. In the whole group, state 3 respiration with pyruvate plus malate and respiration through ETC were negatively associated with A1C, and the proportion of type 2X fibers correlated with markers of insulin resistance (P < 0.05). In conclusion, we provide evidence for a functional impairment in mitochondrial respiration and increased amount of type 2X fibers in muscle of type 2 diabetic patients. These alterations may contribute to the development of type 2 diabetes in humans with obesity.
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| 9. |
- Mylam, Karen Juul, et al.
(författare)
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F-18-fluorodeoxyglucose-positron emission tomography/computed tomography after one cycle of chemotherapy in patients with diffuse large B-cell lymphoma: results of a Nordic/US intergroup study
- 2015
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Ingår i: Leukemia & Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 56:7, s. 2005-2012
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the predictive value of interim positon emission tomography (I-PET) after one course of chemoimmunotherapy in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). One hundred and twelve patients with DLBCL were enrolled. All patients had PET/computed tomography (CT) scans performed after one course of chemotherapy (PET-1). I-PET scans were categorized according to International Harmonization Project criteria (IHP), Deauville 5-point scale (D 5PS) with scores 1-3 considered negative (D 5PS>3) and D 5PS with scores 1-4 considered negative (D 5PS = 5). Ratios of tumor maximum standardized uptake value (SUVmax) to liver SUVmax were also analyzed. We found no difference in progression-free survival (PFS) between PET-negative and PET-positive patients according to IHP and D 5PS>3. The 2-year PFS using D 5PS = 5 was 50.9% in the PET-positive group and 84.8% in the PET-negative group (p = 0.002). A tumor/liver SUVmax cut-off of 3.1 to distinguish D 5PS scores of 4 and 5 provided the best prognostic value. PET after one course of chemotherapy was not able to safely discriminate PET-positive and PET-negative patients in different prognostic groups.
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| 10. |
- Nielsen-Kudsk, Jens Erik, et al.
(författare)
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Left atrial appendage occlusion versus standard medical care in patients with atrial fibrillation and intracerebral haemorrhage : a propensity score-matched follow-up study
- 2017
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Ingår i: EuroIntervention. - : EUROPA EDITION. - 1774-024X .- 1969-6213. ; 13:3, s. 371-378
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aim of this study was to investigate the prognosis in patients with atrial fibrillation (AF) and intracerebral haemorrhage (ICH) having a left atrial appendage occlusion (LAAO) versus patients receiving standard medical therapy. Methods and results: A total of 151 patients from the Nordic countries with AF and previous ICH who underwent LAAO using the AMPLATZER Cardiac Plug or the AMPLATZER AMULET were compared to a propensity score-matched group of 151 patients receiving standard medical therapy. The two groups were matched so that their risks for stroke and bleeding were similar (CHA2DS2-VASc and HAS-BLED scores). The standard care patients were identified from the Danish Stroke Registry among 787 patients with AF and ICH. The primary endpoint was a composite of all-cause mortality, ischaemic stroke and major bleeding. Patients with AF and a prior ICH treated with LAAO had a lower risk of the composite outcome as compared to patients treated with standard medical care (events/1,000 years [95% confidence interval]: 53.3 [44.3-64.1] vs. 366.7 [298.2-450.9]; hazard ratio 0.16 [0.07-0.37]). Conclusions: LAAO is suggested to be of major clinical benefit in AF patients having sustained an ICH. These results have to be confirmed in a randomised clinical trial.
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| 11. |
- Nielsen, Mie Marie, et al.
(författare)
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Associations between eating difficulties, nutritional status and activity of daily living in acute geriatric patients
- 2018
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Ingår i: Clinical Nutrition ESPEN. - 2405-4577. ; 25, s. 95-99
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Tidskriftsartikel (refereegranskat)abstract
- Background & aimsEating difficulties, having a poor nutritional status, and low activity of daily living are all prevalent issues in the geriatric population. The aim of this study was to explore associations between patients' eating difficulties, their nutritional status and their activity of daily living in patients aged 60 years or older who were admitted to an acute geriatric unit.MethodsA cross-sectional study was conducted between March and September 2016 at the geriatric department of North Denmark Regional Hospital, Hjørring. The inclusion criteria were: ≥ 60years old and hospitalized for a minimum of 24 h. The patients' eating difficulties were assessed using the Minimal Eating Observational Form (MEOF-II), including observations related to ingestion, deglutition and energy/appetite. Eating difficulties were determined on the basis of one or more components of the MEOF-II. Poor nutritional status was defined as an age-specific low body mass index (BMI), <20 kg/m2 if < 70 years, or <22 kg/m2 if ≥ 70 years. Activity of daily living was assessed using the Barthel-100 Index and defined as low (<50) or high (≥50).ResultsA total of 297 geriatric patients were included; the mean age was 83.0 (7.7) years and 56.2% of the patients were female. The prevalence of eating difficulties was 55%. Geriatric patients with eating difficulties had a risk increase of 155% of having poor nutritional status (p = 0.003). Geriatric patients with eating difficulties had a risk increase of 60% of having low activity of daily living (p < 0.001).ConclusionsEating difficulties were highly prevalent in geriatric patients and were associated with poor nutritional status and reduced activity of daily living. The identification of eating difficulties may be important for nutritional interventions and maintenance or improvement of activities of daily living in the geriatric population
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| 12. |
- Nielsen, Mie Marie, et al.
(författare)
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Associations between eating difficulties, nutritional status and activity of daily living in acute geriatric patients
- 2018
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Ingår i: Clinical Nutrition ESPEN. - : Elsevier Ltd.. - 2405-4577. ; 25, s. 95-99
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Tidskriftsartikel (refereegranskat)abstract
- Background & aims Eating difficulties, having a poor nutritional status, and low activity of daily living are all prevalent issues in the geriatric population. The aim of this study was to explore associations between patients' eating difficulties, their nutritional status and their activity of daily living in patients aged 60 years or older who were admitted to an acute geriatric unit. Methods A cross-sectional study was conducted between March and September 2016 at the geriatric department of North Denmark Regional Hospital, Hjørring. The inclusion criteria were: ≥ 60years old and hospitalized for a minimum of 24 h. The patients' eating difficulties were assessed using the Minimal Eating Observational Form (MEOF-II), including observations related to ingestion, deglutition and energy/appetite. Eating difficulties were determined on the basis of one or more components of the MEOF-II. Poor nutritional status was defined as an age-specific low body mass index (BMI), <20 kg/m2 if < 70 years, or <22 kg/m2 if ≥ 70 years. Activity of daily living was assessed using the Barthel-100 Index and defined as low (<50) or high (≥50). Results A total of 297 geriatric patients were included; the mean age was 83.0 (7.7) years and 56.2% of the patients were female. The prevalence of eating difficulties was 55%. Geriatric patients with eating difficulties had a risk increase of 155% of having poor nutritional status (p = 0.003). Geriatric patients with eating difficulties had a risk increase of 60% of having low activity of daily living (p < 0.001). Conclusions Eating difficulties were highly prevalent in geriatric patients and were associated with poor nutritional status and reduced activity of daily living. The identification of eating difficulties may be important for nutritional interventions and maintenance or improvement of activities of daily living in the geriatric population
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| 13. |
- Pedersen, Karl, et al.
(författare)
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Reappearance of Salmonella serovar Choleraesuis var. Kunzendorf in Danish pig herds
- 2015
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Ingår i: Veterinary Microbiology. - : Elsevier. - 0378-1135 .- 1873-2542. ; 176:3-4, s. 282-291
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Tidskriftsartikel (refereegranskat)abstract
- Salmonella enterica serovar Choleraesuis is a porcine adapted serovar which may cause serious outbreaks in pigs. Here we describe outbreaks of salmonellosis due to S. Choleraesuis in four Danish pig farms in 2012-2013 by clinic, serology, and microbiology and compare the isolates to those of a previous outbreak in 1999-2000. The infection was in some herds associated with high mortality and a moderate to high sero-prevalence was found. In 2012-2013 the disease contributed to increased mortality but occurred concomitant with other disease problems in the herds, which likely delayed the diagnosis by up to several months. Nine isolates from the four farms in 2012-2013 and 14 isolates obtained from the outbreak in Denmark in 1999-2000 were subjected to typing using pulsed-field gel electrophoresis (PFGE). Seven isolates were selected for whole genome sequencing (WGS). The PFGE results of 23 isolates displayed five different profiles. The isolates from 2012 to 2013 revealed two distinct profiles, both different from the isolates recovered in 1999-2000. Two of the 2012-2013 farms shared PFGE profiles and had also transported pigs between them. The profile found in the two other 2012-2013 farms was indistinguishable but no epidemiological connection between these farms was found. Analysis of the number of single nucleotide polymorphisms (SNPs) from the WGS data indicated that the isolates from the farms in 2012-2013 were more closely related to each other than to isolates from the outbreak in 1999. It was therefore concluded that the infection was a new introduction and not a persistent infection since the outbreak in 1999. It may further be suggested that there were two or three independent rather than a single introduction. The re-introduction of S. Choleraesuis in Denmark emphasizes the importance of strict hygiene measures in the herds. Further investigations using WGS are now in progress on a larger collection of isolates to study clonality at European level and trace the origin of the infections.
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| 14. |
- Soletormos, Gyorgy, et al.
(författare)
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Design of Tumor Biomarker-Monitoring Trials : A Proposal by the European Group on Tumor Markers
- 2013
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 59:1, s. 52-59
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Tidskriftsartikel (refereegranskat)abstract
- A major application of tumor biomarkers is in serial monitoring of cancer patients, but there are no published guidelines on how to evaluate biomarkers for this purpose. The European Group on Tumor Markers has convened a multidisciplinary panel of scientists to develop guidance on the design of such monitoring trials. The panel proposes a 4-phase model for biomarker-monitoring trials analogous to that in use for the investigation of new drugs. In phase I, biomarker kinetics and correlation with tumor burden are assessed. Phase II evaluates the ability of the biomarker to identify, exclude, and/or predict a change in disease status. In phase III, the effectiveness of tumor biomarker guided intervention is assessed by measuring patient outcome in randomized trials. Phase IV consists of an audit of the long-term effects after biomarker monitoring has been included into standard patient care. Systematic well-designed evaluations of biomarkers for monitoring may provide a stronger evidence base that might enable their earlier use in evaluating responses to cancer therapy.
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