| 1. |
- Irenaeus, Sandra, et al.
(författare)
-
First-in-human study with intratumoral administration of a CD40 agonistic antibody, ADC-1013, in advanced solid malignancies
- 2019
-
Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 145:5, s. 1189-1199
-
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.
|
|
| 2. |
- Kumler, Iben, et al.
(författare)
-
Clinical outcome of percutaneous RF-ablation of non-operable patients with liver metastasis from breast cancer
- 2015
-
Ingår i: Radiologia Medica. - : Springer Science and Business Media LLC. - 0033-8362 .- 1826-6983. ; 120:6, s. 536-541
-
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.
|
|
| 3. |
- Mylam, Karen Juul, et al.
(författare)
-
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
-
Ingår i: Leukemia & Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 56:7, s. 2005-2012
-
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.
|
|
| 4. |
- Nielsen-Kudsk, Jens Erik, et al.
(författare)
-
Left atrial appendage occlusion versus standard medical care in patients with atrial fibrillation and intracerebral haemorrhage : a propensity score-matched follow-up study
- 2017
-
Ingår i: EuroIntervention. - : EUROPA EDITION. - 1774-024X .- 1969-6213. ; 13:3, s. 371-378
-
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.
|
|
| 5. |
- Nielsen, Mie Marie, et al.
(författare)
-
Associations between eating difficulties, nutritional status and activity of daily living in acute geriatric patients
- 2018
-
Ingår i: Clinical Nutrition ESPEN. - 2405-4577. ; 25, s. 95-99
-
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
|
|
| 6. |
- Nielsen, Mie Marie, et al.
(författare)
-
Associations between eating difficulties, nutritional status and activity of daily living in acute geriatric patients
- 2018
-
Ingår i: Clinical Nutrition ESPEN. - : Elsevier Ltd.. - 2405-4577. ; 25, s. 95-99
-
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
|
|
| 7. |
- Pedersen, Karl, et al.
(författare)
-
Reappearance of Salmonella serovar Choleraesuis var. Kunzendorf in Danish pig herds
- 2015
-
Ingår i: Veterinary Microbiology. - : Elsevier. - 0378-1135 .- 1873-2542. ; 176:3-4, s. 282-291
-
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.
|
|
