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- Kjellberg, A., et al.
(author)
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Randomised, controlled, open label, multicentre clinical trial to explore safety and efficacy of hyperbaric oxygen for preventing ICU admission, morbidity and mortality in adult patients with COVID-19
- 2021
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In: BMJ Open. - : BMJ. - 2044-6055. ; 11:7
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Journal article (peer-reviewed)abstract
- Introduction COVID-19 may cause severe pneumonitis and trigger a massive inflammatory response that requires ventilatory support. The intensive care unit (ICU)-mortality has been reported to be as high as 62%. Dexamethasone is the only of all anti-inflammatory drugs that have been tested to date that has shown a positive effect on mortality. We aim to explore if treatment with hyperbaric oxygen (HBO) is safe and effective for patients with severe COVID-19. Our hypothesis is that HBO can prevent ICU admission, morbidity and mortality by attenuating the inflammatory response. The primary objective is to evaluate if HBO reduces the number of ICU admissions compared with best practice treatment for COVID-19, main secondary objectives are to evaluate if HBO reduces the load on ICU resources, morbidity and mortality and to evaluate if HBO mitigates the inflammatory reaction in COVID-19. Methods and analysis A randomised, controlled, phase II, open label, multicentre trial. 200 subjects with severe COVID-19 and at least two risk factors for mortality will be included. Baseline clinical data and blood samples will be collected before randomisation and repeated daily for 7 days, at days 14 and 30. Subjects will be randomised with a computer-based system to HBO, maximum five times during the first 7 days plus best practice treatment or only best practice treatment. The primary endpoint, ICU admission, is defined by criteria for selection for ICU. We will evaluate if HBO mitigates the inflammatory reaction in COVID-19 using molecular analyses. All parameters are recorded in an electronic case report form. An independent Data Safety Monitoring Board will review the safety parameters. Ethics and dissemination The trial is approved by The National Institutional Review Board in Sweden (2020-01705) and the Swedish Medical Product Agency (5.1-2020-36673). Positive, negative and any inconclusive results will be published in peer-reviewed scientific journals with open access.
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- Andersson, A, et al.
(author)
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Effect of nutrient enrichment on the distribution and sedimentation of polychlorinated biphenyls (PCBs) in seawater
- 1998
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In: Hydrobiologia. - 0018-8158 .- 1573-5117. ; 377, s. 45-56
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Journal article (peer-reviewed)abstract
- The effect of nutrient enrichment on the distribution of polychlorinated biphenyl's (PCBs) in the microbial food web and the residence time of PCBs in seawater was studied in an experimental mesocosm system. Two 5 m high temperature and light controlled mesocosm tubes (empty set = 0.5 m) were filled with seawater from the northern Baltic Sea. Inorganic phosphorus and nitrogen were added daily to one mesocosm, while the other served as a control. Experiments were conducted at 5, 10 and 20 degrees C. Three C-14-labelled PCBs of different degree of chlorination were added to subsamples of the mesocosms: 4-chlorobiphenyl (MCB), IUPAC # 3, 2,2',5,5'-tetrachlorobiphenyl (TCB), IUPAC # 52 and 2,2',4,4',5,5'-hexachlorobiphenyl (HCB) IUPAC # 153. The biomasses and growth rates of the microorganisms as well as the sedimentation rate of particulate organic material increased with nutrient enrichment. The size distribution of the microorganisms changed with nutrient status, from dominance of picoplankton (< 2 mu m) in the control towards increased importance of micro (> 10 mu m) and nanoplankton (2-10 mu m) in nutrient enrichment. The specific growth rate of the bacterial community was found to be more temperature dependent than that of the phytoplankton community. The relative proportion of PCBs in the > 2 mu m fraction was observed to be in the order MCB < TCB < HCB, while the opposite distribution prevailed in the < 2 mu m fraction. We hypothesize that this is due to the combined effect of the different K-ow values of the PCBs and a different composition of the particulate organic carbon in the > 2 mu m and < 2 mu m fractions (e.g. different lipid composition). The residence time of the PCBs in the mesocosm generally decreased with nutrient enrichment, but was dependent on the degree of chlorination of the PCB. Our results indicate that the transport of organic pollutants up through the food web is more important in nutrient poor than in nutrient rich waters and that the importance of sedimentation is higher in eutrophic ecosystems.
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- Flinn, Elizabeth M, et al.
(author)
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Recruitment of Gen5-containing complexes during c-Myc-dependent gene activation - Structure and function aspects
- 2002
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In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 277:26, s. 23399-23406
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Journal article (peer-reviewed)abstract
- The N-terminal domain of c-Myc plays a key role in cellular transformation and is involved in both activation and repression of target genes as well as in modulated proteolysis of c-Myc via the proteasome. Given this functional complexity, it has been difficult to clarify the structures within the N terminus that contribute to these different processes as well as the mechanisms by which they function. We have used a simplified yeast model system to identify the primary determinants within the N terminus for W chromatin remodeling of a promoter, (ii) gene activation from a chromatin template in vivo, and (iii) interaction with highly purified Gcn5 complexes as well as other chromatin-remodeling complexes in vitro. The results identify two regions that contain autonomous chromatin opening and gene activation activity, but both regions are required for efficient interaction with chromatin-remodeling complexes in vitro. The conserved Myc boxes do not play a direct role in gene activation, and Myc box II is not generally required for in vitro interactions with remodeling complexes. The yeast SAGA complex, which is orthologous to the human GCN5-TRRAP complex that interacts with Myc in human cells, plays a role in Myc-mediated chromatin opening at the promoter but may also be involved in later steps of gene activation.
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- Mulder, Renée L., et al.
(author)
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Communication and ethical considerations for fertility preservation for patients with childhood, adolescent, and young adult cancer : recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group
- 2021
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In: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 22:2, s. 68-80
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Research review (peer-reviewed)abstract
- Patients with childhood, adolescent, and young adult cancer who will be treated with gonadotoxic therapies are at increased risk for infertility. Many patients and their families desire biological children but effective communication about treatment-related infertility risk and procedures for fertility preservation does not always happen. The PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group reviewed the literature and developed a clinical practice guideline that provides recommendations for ongoing communication methods for fertility preservation for patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger and their families. Moreover, the guideline panel formulated considerations of the ethical implications that are associated with these procedures. Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the evidence and recommendations. In this clinical practice guideline, existing evidence and international expertise are combined to develop transparent recommendations that are easy to use to facilitate ongoing communication between health-care providers and patients with childhood, adolescent, and young adult cancer who might be at high risk for fertility impairment and their families.
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- Ek, L., et al.
(author)
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Randomized phase III trial of low-molecular-weight heparin enoxaparin in addition to standard treatment in small-cell lung cancer : The RASTEN trial
- 2018
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 29:2, s. 398-404
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Journal article (peer-reviewed)abstract
- Background: Coagulation activation and venous thromboembolism (VTE) are hallmarks of malignant disease and represent a major cause of morbidity and mortality in cancer. Coagulation inhibition with low-molecular-weight heparin (LMWH) may improve survival specifically in small-cell lung cancer (SCLC) patients by preventing VTE and tumor progression; however, randomized trials with well-defined patient populations are needed to obtain conclusive data. The aim of RASTEN was to investigate the survival effect of LMWH enoxaparin in a homogenous population of SCLC patients. Patients and methods: We carried out a randomized, multicenter, open-label trial to investigate the addition of enoxaparin at a supraprophylactic dose (1 mg/kg) to standard treatment in patients with newly diagnosed SCLC. The primary outcome was overall survival (OS), and secondary outcomes were progression-free survival (PFS), incidence of VTE and hemorrhagic events. Results: In RASTEN, 390 patients were randomized over an 8-year period (2008-2016), of whom 186 and 191 were included in the final analysis in the LMWH and control arm, respectively. We found no evidence of a difference in OS or PFS by the addition of enoxaparin [hazard ratio (HR), 1.11; 95% confidence interval (CI) 0.89-1.38; P=0.36 and HR, 1.18; 95% CI 0.95-1.46; P=0.14, respectively]. Subgroup analysis of patients with limited and extensive disease did not show reduced mortality by enoxaparin. The incidence of VTE was significantly reduced in the LMWH arm (HR, 0.31; 95% CI 0.11-0.84; P=0.02). Hemorrhagic events were more frequent in the LMWH-treated group but fatal bleedings occurred in both arms. Conclusion: LMWH enoxaparin in addition to standard therapy did not improve OS in SCLC patients despite being administered at a supraprophylactic dose and despite resulting in a significant reduction in VTE incidence. Addition of LMWH cannot be generally recommended in the management of SCLC patients, and predictive biomarkers of VTE and LMWHassociated bleeding in cancer patients are warranted.
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