| 1. |
- Hatschek, T., et al.
(författare)
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PREDIX HER2 trial : Event-free survival and pathologic complete response in clinical subgroups and stromal TILs levels
- 2020
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Ingår i: Annals of Oncology. - : Elsevier. - 0923-7534 .- 1569-8041. ; 31:Suppl. 2, s. S49-S49
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Neoadjuvant treatment with Trastuzumab-emtansine was associated with similar rates of pathological complete remission (pCR) as standard therapy withd ocetaxel, trastuzumab and pertuzumab in the PREDIX HER2 trial. Here, results of event-free survival (EFS), and pCR rates in key clinical-pathological subgroups and biomarkers including the abundance of stromal tumor infiltrating lymphocytes (TILs) are presented.Methods: PREDIX HER2 is a randomized, multicenter, open-label, phase 2 study involving 9 Swedish sites. Patients with HER2 positive breast cancer, verified by ISH, T>20 mm and/or verified lymph node metastases were randomized to six three-weekly courses of either docetaxel, trastuzumab SC and pertuzumab (group A), or trastuzumab emtansine (T-DM1, group B). Switch of treatment to the opposite arm was allowed in case of lack of response or severe toxicity. Radiological evaluation included 18F-FDG PET/CT. Patients in both groups received adjuvant chemotherapy with epirubicin and cyclophosphamide. TILs were evaluated using standard methodology, median 10%.Results: In total 197 pts. were evaluable, 99 in group A, and 98 in group B. pCR (ypT0/is ypN0) was achieved in 90 pts, 45.7%, with no significant difference between the two treatment groups. pCR rates were lower in the group of patients with hormone receptor (HR)epositive compared with HR-negative tumors but similar in both treatment groups. pCR rates did not differ between the two treatments in subgroups defined by age, menopausal status, tumor grade, T size, node status, HR-status, HER2 status and Ki67. Progressive disease was observed in 3 pts. (3%) during treatment with T-DM1, none in group A. After a median follow-up of 2.4 years 13 EFS events occurred, with no significant differences between the treatment groups. The presence of 10% TILs predicted pCR significantly (p¼0.009), similar in both treatment groups. We also found that a decrease of SUVmax by more than 80% was highly predictive of pCR. HRQoL was significantly better in pts. receiving T-DM1.Conclusions: Our data suggest that neoadjuvant T-DM1 may be as effective as standard neoadjuvant treatment in all clinical subgroups evaluated. Both TILs and PET/CT showed potential to predict pCR.Clinical trial identification: NCT02568839.
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| 2. |
- Hedayati, E., et al.
(författare)
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Outcome and presentation of heart failure in breast cancer patients : Findings from a Swedish register-based study
- 2020
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Ingår i: European Heart Journal - Quality of Care and Clinical Outcomes. - : Oxford University Press. - 2058-5225 .- 2058-1742. ; 6:2, s. 147-155
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Heart failure (HF) patients diagnosed with breast cancer (BC) may have a higher risk of death, and different HF presentation and treatment than patients without BC.Methods and results: A total of 14 998 women with incident HF (iHF) or prevalent HF (pHF) enrolled in the Swedish HF Registry within and after 1 month since HF diagnosis, respectively, between 2008 and 2013. Patients were linked with the National Patient-, Cancer-, and Cause-of-Death Registry. Two hundred and ninety-four iHF and 338 pHF patients with BC were age-matched to 1470 iHF and 1690 pHF patients without BC. Comorbidity and treatment characteristics were compared using the χ2 tests for categories. Cox proportional hazard models assessed the hazard ratio (HR) and 95% confidence intervals (95% CIs) of all-cause and cardiovascular mortality among HF patients with and without BC. In the pHF group, BC patients had less often myocardial infarction (21.6% vs. 28.6%, P < 0.01) and received less often aspirin (47.6% vs. 55.1%, P = 0.01), coronary revascularization (11.8% vs. 16.2%, P < 0.01), or device therapy (0.9% vs. 3.0%, P = 0.03). After median follow-up of 2 years, risk of all-cause mortality (iHF: HR = 1.04, 95% CI = 0.83-1.29 and pHF: HR = 0.94, 95% CI = 0.79-1.12), cardiovascular mortality (iHF: HR = 0.94, 95% CI = 0.71-1.24 and pHF: HR = 0.89, 95% CI = 0.71-1.10), and HF mortality (iHF: HR = 0.80, 95% CI = 0.34-1.90 and pHF: HR = 0.75, 95% CI = 0.43-1.29) were similar for patients with and without BC in the iHF and pHF groups.Conclusion: Risk of all-cause and cardiovascular mortality in HF patients did not differ by BC status. Differences in pre-existing myocardial infarction and HF treatment among pHF patients with and without BC may suggest differences in pathogenesis of HF.
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| 3. |
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| 4. |
- Bergh, Cecilia, 1972-, et al.
(författare)
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Under the weather : acute myocardial infarction and subsequent case fatality with influenza burden - a nationwide observational study
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 40:Suppl. 1, s. 3994-3994
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Influenza may precipitate cardiovascular disease but influenza typically peaks in winter coinciding with other triggers of myocardial infarction (MI) such as low air temperature, high wind velocity, low air pressure and short sunshine duration. We aimed to study week-to-week variation in influenza cases and acute MI after meteorological confounder adjustment in a nationwide setting.Methods: Weekly laboratory-confirmed influenza case reports were obtained from the Public Health Agency of Sweden from 2009 to 2016 and merged with the nationwide SWEDEHEART MI registry. Weekly counts of MI were studied with regard to influenza cases stratified into tertiles, 0–16, 17–164 and>164 influenza cases/week. Incidence rate ratios were calculated for each category and compared to a reference period of the year with no influenza. A negative binomial regression model was applied to adjust for weather parameters.Results: A total of 133 562 MIs were reported to the registry during the study period of which 44 055 were ST-elevation MIs. Weeks with influenza cases were associated with higher risk of MI. For 0–16 influenza cases/week the unadjusted incidence rate ratio (IRR) for MI was 1.04 (95% confidence interval [CI] 1.01–1.07, p=0.007); for 17–163 cases/week the IRR=1.07 (95% CI 1.04–1.10, p≤0.001) and for≥164 cases/week the IRR=1.08 (95% CI 1.05–1.11, p≤0.001). Results were consistent across a large range of subgroups and after adjusting for confounders. In addition, all-cause mortality was higher in weeks with highest reported rates of influenza cases.Conclusion: In this nationwide observational study, we found an association between occurrence of MI and number of influenza cases beyond what could be explained by meteorological factors.
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| 5. |
- Klapwijk, Maartje, et al.
(författare)
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Capturing complexity : Forests, decision-making and climate change mitigation action
- 2018
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Ingår i: Global Environmental Change. - : Elsevier. - 0959-3780 .- 1872-9495. ; 52, s. 238-247
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Tidskriftsartikel (refereegranskat)abstract
- Managed forests can play an important role in climate change mitigation due to their capacity to sequester carbon. However, it has proven difficult to harness their full potential for climate change mitigation. Managed forests are often referred to as socio-ecological systems as the human dimension is an integral part of the system. When attempting to change systems that are influenced by factors such as collective knowledge, social organization, understanding of the situation and values represented in society, initial intentions often shift due to the complexity of political, social and scientific interactions. Currently, the scientific literature is dispersed over the different factors related to the socio-ecological system. To examine the level of dispersion and to obtain a holistic view, we review climate change mitigation in the context of Swedish forest research. We introduce a heuristic framework to understand decision-making connected to climate change mitigation. We apply our framework to two themes which span different dimensions in the socio-ecological system: carbon accounting and bioenergy. A key finding in the literature was the perception that current uncertainties regarding the reliability of different methods of carbon accounting inhibits international agreement on the use of forests for climate change mitigation. This feeds into a strategic obstacle affecting the willingness of individual countries to implement forest-related carbon emission reduction policies. Decisions on the utilization of forests for bioenergy are impeded by a lack of knowledge regarding the resultant biophysical and social consequences. This interacts negatively with the development of institutional incentives regarding the production of bioenergy using forest products. Normative disagreement about acceptable forest use further affects these scientific discussions and therefore is an over-arching influence on decision-making. With our framework, we capture this complexity and make obstacles to decision-making more transparent to enable their more effective resolution. We have identified the main research areas concerned with the use of managed forest in climate change mitigation and the obstacles that are connected to decision making.
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| 6. |
- Laudette, Marion, et al.
(författare)
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Cardiomyocyte-specific PCSK9 deficiency compromises mitochondrial bioenergetics and heart function
- 2023
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Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 119:7, s. 1537-1552
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Tidskriftsartikel (refereegranskat)abstract
- Aims Pro-protein convertase subtilisin-kexin type 9 (PCSK9), which is expressed mainly in the liver and at low levels in the heart, regulates cholesterol levels by directing low-density lipoprotein receptors to degradation. Studies to determine the role of PCSK9 in the heart are complicated by the close link between cardiac function and systemic lipid metabolism. Here, we sought to elucidate the function of PCSK9 specifically in the heart by generating and analysing mice with cardiomyocyte-specific Pcsk9 deficiency (CMPcsk9−/− mice) and by silencing Pcsk9 acutely in a cell culture model of adult cardiomyocyte-like cells. Methods and results Mice with cardiomyocyte-specific deletion of Pcsk9 had reduced contractile capacity, impaired cardiac function, and left ventricular dilatation at 28 weeks of age and died prematurely. Transcriptomic analyses revealed alterations of signalling pathways linked to cardiomyopathy and energy metabolism in hearts from CM-Pcsk9−/− mice vs. wild-type littermates. In agreement, levels of genes and proteins involved in mitochondrial metabolism were reduced in CM-Pcsk9−/− hearts. By using a Seahorse flux analyser, we showed that mitochondrial but not glycolytic function was impaired in cardiomyocytes from CM-Pcsk9−/− mice. We further showed that assembly and activity of electron transport chain (ETC) complexes were altered in isolated mitochondria from CM-Pcsk9−/− mice. Circulating lipid levels were unchanged in CM-Pcsk9−/− mice, but the lipid composition of mitochondrial membranes was altered. In addition, cardiomyocytes from CM-Pcsk9−/− mice had an increased number of mitochondria–endoplasmic reticulum contacts and alterations in the morphology of cristae, the physical location of the ETC complexes. We also showed that acute Pcsk9 silencing in adult cardiomyocyte-like cells reduced the activity of ETC complexes and impaired mitochondrial metabolism. Conclusion PCSK9, despite its low expression in cardiomyocytes, contributes to cardiac metabolic function, and PCSK9 deficiency in cardiomyocytes is linked to cardiomyopathy, impaired heart function, and compromised energy production.
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| 7. |
- Wengström, Yvonne, 1959-, et al.
(författare)
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Quantitative assessment of skin erythema following breast cancer RT
- 2003
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Ingår i: Radiotherapy and Oncology. - 0167-8140 .- 1879-0887. ; 68, s. S20-S20
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Tidskriftsartikel (refereegranskat)abstract
- Visual assessment is the most common clinical investigation of skin reactions in radiotherapy. Due to the unquantitative and subjective nature of this method additional non-invasive methods are needed for more accurate evaluation of the visible acute adverse skin reactions due to radiotherapy• The purpose of this study was to evaluate a new objective measure with regard to reliability and validity and compare it with an established objective measure and a visual assessment.Material and Methods: A sample of fifty-three consecutive patients commencing curative tangential radiation therapy to the breast parenchyma was included in the study• The skin area of the treated breast was divided into five sections and assessed individually at 0 Gy, 24 Gy and 50 Gy. The RTOG scoring system was used for the visual assessment of the skin reactions. The first objective measure included reflectance spectrometry (DermaSpectrometer) measures at fixed points within the treatment area. For the second objective measure digital images were taken with a system using a digital camera and software. The images were analyzed using the Adobe Photoshop 5•0 software program•Results: The results provided significant evidence of the test-retest reliability of the camera• The correlation between the objective measures proved to be significant as the treatment progressed• The results suggest that the Camera may be used in a reliable and valid way to measure skin erythema due to radiotherapy•
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| 8. |
- Wennerholm, U. B., et al.
(författare)
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Induction of labour at 41 weeks versus expectant management and induction of labour at 42 weeks (SWEdish Post-term Induction Study, SWEPIS) : multicentre, open label, randomised, superiority trial
- 2020
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Ingår i: Geburtshilfe und Frauenheilkunde. - : Georg Thieme Verlag KG. - 0016-5751 .- 1438-8804. ; 80:10, s. E76-E76
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To evaluate if induction of labour at 41 weeks improves perinatal and maternal outcomes in women with low risk pregnancies compared with expectant management and induction at 42 weeks.Methods: A multicenter, randomised controlled superiority trial.Women with low risk singleton pregnanies (n = 2760) were randomised to either induction or expectant management group. The primary outcome was a composite perinatal outcome including one or more of stillbirth, neonatal mortality, Apgar score < 7 at five minutes, pH < 7.00 or metabolic acidosis (pH < 7.05 and base deficit >12 mmol/L) in the umbilical artery, hypoxic ischaemic encephalopathy, intracranial haemorrhage, convulsions, meconium aspiration syndrome, mechanical ventilation within 72 hours, obstetric brachial plexus injury. Primary analysis was by intention to treat.Results: The study was stopped early owing to a significantly higher rate of perinatal mortality in the expectant management group (no deaths compared to six deaths, p = 0.03). The primary outcome did not differ: 2.4 % (33/1381) in the induction group and 2.2 % (31/1379) in the expectant management group (RR 1.06, 95 %CI 0.65 to 1.73; p = 0.90). The proportion of caesarean delivery, instrumental vaginal delivery, or any major maternal morbidity did not differ between the groups.Conclusions: There was no significant difference in the primary composite outcome when comparing induction at 41 weeks with expectant management and induction at 42. However, a reduction of the secondary outcome perinatal mortality was observed without increasing adverse maternal outcomes. To offer induction at 41 weeks could be one of few interventions that reduces the rate of stillbirths.
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