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| 2. |
- Stacchiotti, S., et al.
(author)
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Epithelioid hemangioendothelioma, an ultra-rare cancer : a consensus paper from the community of experts
- 2021
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In: ESMO Open. - : Elsevier BV. - 2059-7029. ; 6:3
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Research review (peer-reviewed)abstract
- Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication.
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| 3. |
- Dahlgard, F, et al.
(author)
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Self reported skin morbidity and ethnicity: a population-based study in a Western community
- 2007
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In: BMC Dermtology. - : Springer Science and Business Media LLC. - 1471-5945. ; 7
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Journal article (peer-reviewed)abstract
- Background Recent studies have shown ethnic differences concerning cardio-vascular disease, diabetes and mental health. Little is known about ethnic differences in skin morbidity. The purpose of this study was to describe possible ethnic differences in self-reported skin morbidity in a Western urban community. Methods The design was cross sectional. 40 888 adults in Oslo, Norway, received a postal questionnaire providing information on socio-demographic factors and self-reported health, including items on skin complaints. Results 18770 individuals answered the questionnaire. In the sample 84% were from Norway. The largest immigrant group was from Western countries (5%) and the Indian Subcontinent (3%). Itch was the most prevalent reported skin symptom (7%), and was significantly more reported by men from East Asia (18%) and Middle East/North Africa (13%). The same observations were seen for reported dry and sore skin. Hair loss was a dominating complaint for men from the Indian Subcontinent and the Middle East/North Africa (23% and 25%) and for women from the same ethnic groups. Women from Sub-Saharan Africa reported significantly more pimples than in the other groups (17%). Conclusion The study showed that there were significant differences in self-reported skin complaints among ethnic groups. Issues concerning the cultural value of some skin symptoms should be examined further. Background
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| 4. |
- Dalgard, F, et al.
(author)
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Self-reported skin complaints: validation of a questionnaire for population surveys
- 2003
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In: British Journal of Dermatology. - : Oxford University Press (OUP). - 1365-2133 .- 0007-0963. ; 149:4, s. 794-800
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Journal article (peer-reviewed)abstract
- Background Estimation of skin diseases in the community is challenging because we do not easily have access to the nonhealthcare-seeking population. A potential tool is a questionnaire asking for self-reported skin complaints. Such an instrument has not yet been developed. Objectives To validate a simple instrument assessing skin morbidity in the general adult population, to predict clinical skin morbidity from self-reported skin complaints. Methods A questionnaire was drawn up in Norwegian and validated against clinical signs in two samples of an urban population, 100 healthcare-seeking adults in a dermatological clinic, and 100 nonhealthcare-seeking adults. A total self-reported score was calculated and validated against severity of clinical signs (no sign, trivial, moderate or severe). The inter-rater agreement was assessed in a small study including 16 patients from a dermatological clinic. Results The participation rate was 98%. The sensitivity was 61%, the specificity 69% and the positive predictive value 82% when the caseness criterion was any clinical sign of skin disease. The agreement was good between the two observers for clinical skin morbidity, with kappa = 0.67. Conclusions This questionnaire is a simple tool to evaluate skin morbidity in an adult population. The use of self-reported complaints to predict clinical morbidity may be of value in quantifying and exploring skin diseases at the population level. Further studies are needed to improve the instrument. It is our intention to demonstrate the potential usefulness of this questionnaire in a forthcoming population survey in Norway.
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| 6. |
- Marina, Neyssa M., et al.
(author)
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Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1) : an open-label, international, randomised controlled trial
- 2016
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In: The Lancet Oncology. - 1470-2045. ; 17:10, s. 1396-1408
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Journal article (peer-reviewed)abstract
- Background We designed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy (≥10% viable tumour) improved event-free survival in patients with high-grade osteosarcoma. Methods EURAMOS-1 was an open-label, international, phase 3 randomised, controlled trial. Consenting patients with newly diagnosed, resectable, high-grade osteosarcoma aged 40 years or younger were eligible for randomisation. Patients were randomly assigned (1:1) to receive either postoperative cisplatin, doxorubicin, and methotrexate (MAP) or MAP plus ifosfamide and etoposide (MAPIE) using concealed permuted blocks with three stratification factors: trial group; location of tumour (proximal femur or proximal humerus vs other limb vs axial skeleton); and presence of metastases (no vs yes or possible). The MAP regimen consisted of cisplatin 120 mg/m2, doxorubicin 37·5 mg/m2 per day on days 1 and 2 (on weeks 1 and 6) followed 3 weeks later by high-dose methotrexate 12 g/m2 over 4 h. The MAPIE regimen consisted of MAP as a base regimen, with the addition of high-dose ifosfamide (14 g/m2) at 2·8 g/m2 per day with equidose mesna uroprotection, followed by etoposide 100 mg/m2 per day over 1 h on days 1–5. The primary outcome measure was event-free survival measured in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00134030. Findings Between April 14, 2005, and June 30, 2011, 2260 patients were registered from 325 sites in 17 countries. 618 patients with poor response were randomly assigned; 310 to receive MAP and 308 to receive MAPIE. Median follow-up was 62·1 months (IQR 46·6–76·6); 62·3 months (IQR 46·9–77·1) for the MAP group and 61·1 months (IQR 46·5–75·3) for the MAPIE group. 307 event-free survival events were reported (153 in the MAP group vs 154 in the MAPIE group). 193 deaths were reported (101 in the MAP group vs 92 in the MAPIE group). Event-free survival did not differ between treatment groups (hazard ratio [HR] 0·98 [95% CI 0·78–1·23]); hazards were non-proportional (p=0·0003). The most common grade 3–4 adverse events were neutropenia (268 [89%] patients in MAP vs 268 [90%] in MAPIE), thrombocytopenia (231 [78% in MAP vs 248 [83%] in MAPIE), and febrile neutropenia without documented infection (149 [50%] in MAP vs 217 [73%] in MAPIE). MAPIE was associated with more frequent grade 4 non-haematological toxicity than MAP (35 [12%] of 301 in the MAP group vs 71 [24%] of 298 in the MAPIE group). Two patients died during postoperative therapy, one from infection (although their absolute neutrophil count was normal), which was definitely related to their MAP treatment (specifically doxorubicin and cisplatin), and one from left ventricular systolic dysfunction, which was probably related to MAPIE treatment (specifically doxorubicin). One suspected unexpected serious adverse reaction was reported in the MAP group: bone marrow infarction due to methotrexate. Interpretation EURAMOS-1 results do not support the addition of ifosfamide and etoposide to postoperative chemotherapy in patients with poorly responding osteosarcoma because its administration was associated with increased toxicity without improving event-free survival. The results define standard of care for this population. New strategies are required to improve outcomes in this setting. Funding UK Medical Research Council, National Cancer Institute, European Science Foundation, St Anna Kinderkrebsforschung, Fonds National de la Recherche Scientifique, Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, Parents Organization, Danish Medical Research Council, Academy of Finland, Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, Federal Ministry of Education and Research, Semmelweis Foundation, ZonMw (Council for Medical Research), Research Council of Norway, Scandinavian Sarcoma Group, Swiss Paediatric Oncology Group, Cancer Research UK, National Institute for Health Research, University College London Hospitals, and Biomedical Research Centre.
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| 8. |
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| 11. |
- Dalgard, F, et al.
(author)
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Self-reported skin morbidity among adults: Associations with quality of life and general health in a Norwegian survey
- 2004
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In: Journal of Investigative Dermatology Symposium Proceedings. - : Elsevier BV. - 1529-1774 .- 1087-0024. ; 9:2, s. 120-125
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Journal article (peer-reviewed)abstract
- Life-quality studies among dermatologic patients have shown that chronic skin diseases have an impact on patients' lives. The purpose of this study was to assess the burden of skin morbidity at a community level. This was presented as prevalence of self-reported skin morbidity and dermatologic life-quality items. The association of skin disease and general health measures like feeling depressed and self-reported general health were measured. The method used was a questionnaire on self-reported skin complaints, including variables such as demographic, psychosocial, general health, dermatologic life-quality items. The design of the study was cross-sectional, with answers from 18,770 adult responders. The results confirmed that skin morbidity is common; itch was the dominating symptom. Younger adults reported more social problems as a result of skin problems than older. The life-quality domain most affected by skin disease was the social one. In a regression model skin disease was as well as rheumatism more strongly associated with feeling depressed than asthma, diabetes, and angina pectoris. Skin disease was also strongly associated with reporting poor general health, although less than other nondermatologic chronic diseases. In conclusion, in this study skin morbidity was strongly associated with general health measures among adults in a population-based setting. To the best of our knowledge these associations have not been described previously at a community level.
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| 12. |
- Dalgard, F, et al.
(author)
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Self-reported skin morbidity and mental health. A population survey among adults in a Norwegian city.
- 2005
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In: British Journal of Dermatology. - : Oxford University Press (OUP). - 1365-2133 .- 0007-0963. ; 153:1, s. 145-149
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Journal article (peer-reviewed)abstract
- Background Several studies among dermatological patients have shown a link between various chronic dermatological diseases and mental morbidity. Objectives To explore the association between self-reported skin morbidity and psychosocial factors in the general population. Methods This population-based cross-sectional study is part of the Oslo Health Study conducted during 2000–2001. All individuals in Oslo County, Norway, born in 1924/25, 1940/41, 1955, 1960 and 1970 received a postal questionnaire, which 18 770 men and women answered. The questionnaire provided information on sociodemographic factors and self-reported health and psychosocial factors. Dichotomous variables for 10 self-reported skin complaints were used. These were previously validated and refer to the most common chronic skin diseases. Mental distress was measured with a validated 10-item instrument, the Hopkins Symptom Check List-10; social support with the number of confidants; and negative life events with a 12-item validated instrument. Results The odds ratio (OR) for mental distress was 1·70 [95% confidence interval (CI) 1·21–2·38] for having itch, 1·64 (95% CI 1·15–2·34) for pimples and 1·72 (95% CI 1·06–2·80) for face rash in an adjusted model. In an adjusted model the OR for skin disease was 1·60 (95% CI 1·39–1·84) when the individual had experienced more than two negative life events; and 2·52 (95% CI 2·12–3·00) for mental distress. Skin morbidity increased for both genders, with poor social support network. There was a significant interaction between social support network and negative life events in the logistic regression model for skin disease when adjusted for sociodemographic factors. Conclusions The study quantifies the association between dermatological problems and psychosocial factors at a population level. It underlines the need to focus on these issues in research and needs assessment in dermatology.
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| 13. |
- Gaspar, Nathalie, et al.
(author)
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Ewing Sarcoma: Current Management and Future Approaches Through Collaboration.
- 2015
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In: Journal of Clinical Oncology. - 1527-7755. ; 33:27, s. 140-3036
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Research review (peer-reviewed)abstract
- Ewing sarcoma (ES) is an aggressive sarcoma of bone and soft tissue occurring at any age with a peak incidence in adolescents and young adults. The treatment of ES relies on a multidisciplinary approach, coupling risk-adapted intensive neoadjuvant and adjuvant chemotherapies with surgery and/or radiotherapy for control of the primary site and possible metastatic disease. The optimization of ES multimodality therapeutic strategies has resulted from the efforts of several national and international groups in Europe and North America and from cooperation between pediatric and medical oncologists. Successive first-line trials addressed the efficacy of various cyclic combinations of drugs incorporating doxorubicin, vincristine, cyclophosphamide, ifosfamide, etoposide, and dactinomycin and identified prognostic factors now used to tailor therapies. The role of high-dose chemotherapy is still debated. Current 5-year overall survival for patients with localized disease is 65% to 75%. Patients with metastases have a 5-year overall survival < 30%, except for those with isolated pulmonary metastasis (approximately 50%). Patients with recurrence have a dismal prognosis. The many insights into the biology of the EWS-FLI1 protein in the initiation and progression of ES remain to be translated into novel therapeutic strategies. Current options and future approaches will be discussed.
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| 14. |
- Joensuu, Heikki, et al.
(author)
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KIT and PDGFRA Mutations and Survival of Gastrointestinal Stromal Tumor Patients Treated with Adjuvant Imatinib in a Randomized Trial
- 2023
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In: Clinical Cancer Research. - 1078-0432. ; 29:17, s. 3313-3319
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Journal article (peer-reviewed)abstract
- Purpose: Limited data are available about the influence of KIT and PDGFRA mutations on overall survival (OS) of patients with gastrointestinal stromal tumor (GIST) treated with adjuvant imatinib. Patients and Methods: The Scandinavian Sarcoma Group XVIII/AIO multicenter trial accrued 400 patients with a high risk for GIST recurrence after macroscopically complete surgery between February 4, 2004, and September 29, 2008. The patients received adjuvant imatinib 400 mg/day for either 1 year or 3 years based on random allocation. We analyzed using conventional sequencing KIT and PDGFRA mutations centrally from 341 (85%) patients who had localized, centrally confirmed GIST, and correlated the results with recurrence-free survival (RFS) and OS in exploratory analyses. Results: During a median follow-up time of 10 years, 164 RFS events and 76 deaths occurred. Most patients were re-treated with imatinib when GIST recurred. Patients with KIT exon 11 deletion or indel mutation treated with 3 years of adjuvant imatinib survived longer than patients treated for 1 year [10-year OS 86% versus 64%, respectively; HR, 0.34; 95% confidence interval (CI), 0.15-0.72; P 0.007], and also had longer RFS (10-year RFS 47% versus 29%; HR, 0.48; 95% CI, 0.31-0.74; P < 0.001). Patients with KIT exon 9 mutation had unfavorable OS regardless of the duration of adjuvant imatinib. Conclusions: Compared with 1 year of imatinib, 3 years of adjuvant imatinib led to 66% reduction in the estimated risk of death and a high 10-year OS rate in the subset of patients with a KIT exon 11 deletion/indel mutation.
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| 15. |
- Joensuu, Heikki, et al.
(author)
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Survival Outcomes Associated with 3 Years vs 1 Year of Adjuvant Imatinib for Patients with High-Risk Gastrointestinal Stromal Tumors : An Analysis of a Randomized Clinical Trial after 10-Year Follow-up
- 2020
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In: JAMA Oncology. - : American Medical Association (AMA). - 2374-2437. ; 6:8, s. 1241-1246
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Journal article (peer-reviewed)abstract
- Importance: Adjuvant imatinib is associated with improved recurrence-free survival (RFS) when administered after surgery to patients with operable gastrointestinal stromal tumor (GIST), but its influence on overall survival (OS) has remained uncertain. Objective: To evaluate the effect of adjuvant imatinib on OS of patients who have a high estimated risk for GIST recurrence after macroscopically complete surgery. Design, Setting, and Participants: In this open-label, randomized (1:1), multicenter phase 3 clinical trial conducted in Finland, Germany, Norway, and Sweden, 400 patients who had undergone macroscopically complete surgery for GIST with a high estimated risk for recurrence according to the modified National Institutes of Health Consensus Criteria were enrolled between February 2004 and September 2008. Data for this follow-up analysis were analyzed from September to November, 2019. Interventions: Imatinib 400 mg/d administered orally for either 12 months or 36 months after surgery. Main Outcomes And Measures: The primary end point was RFS; the secondary objectives included OS and treatment safety. Results: The intention-to-treat cohort consisted of 397 patients (12-month group, 199; 36-month group, 198; 201 men and 196 women; median [IQR] age, 62 (51-69) years and 60 (51-67) years, during a median follow-up time of 119 months after the date of randomization, 194 RFS events and 96 OS events were recorded in the intention-to-treat population. Five-year and 10-year RFS was 71.4% and 52.5%, respectively, in the 36-month group and 53.0% and 41.8% in the 12-month group (hazard ratio [HR], 0.66; 95% CI, 0.49-0.87; P =.003). In the 36-month group, 5-year OS and 10-year OS rates were 92.0% and 79.0%, respectively, and in the 12-month group 85.5% and 65.3% (HR, 0.55; 95% CI, 0.37-0.83; P =.004). The results were similar in the efficacy population, from which 15 patients who did not have GIST in central pathology review and 24 patients who had intra-abdominal metastases removed at surgery were excluded (36-month group, 10-year OS 81.6%; 12-month group, 66.8%; HR, 0.50; 95% CI, 0.32-0.80; P =.003). No new safety signals were detected. Conclusions and Relevance: Three years of adjuvant imatinib is superior in efficacy compared with 1 year of imatinib. Approximately 50% of deaths may be avoided during the first 10 years of follow-up after surgery with longer adjuvant imatinib treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT00116935.
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| 16. |
- Jogestrand, T., et al.
(author)
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Equalis kriterier för karotisdiagnostik – under kontinuerlig uppgradering
- 2012
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In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 109:13, s. 702-703
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Journal article (peer-reviewed)abstract
- Ultraljudsundersökning av karotisartärerna med så kallad duplexteknik har använts i Sverige sedan början av 1980-talet. Equalis expertgrupp för fysiologisk kärldiagnostik har nyligen presenterat sina rekommendationer för karotisdiagnostik med ultraljudsteknik.
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| 17. |
- Rohrs, J., et al.
(author)
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Observation-based evaluation of surface wave effects on currents and trajectory forecasts
- 2012
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In: Ocean Dynamics. - : Springer Science and Business Media LLC. - 1616-7341 .- 1616-7228. ; 62:10-12, s. 1519-1533
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Journal article (peer-reviewed)abstract
- Knowledge of upper ocean currents is needed for trajectory forecasts and is essential for search and rescue operations and oil spill mitigation. This paper addresses effects of surface waves on ocean currents and drifter trajectories using in situ observations. The data set includes colocated measurements of directional wave spectra from a wave rider buoy, ocean currents measured by acoustic Doppler current profilers (ADCPs), as well as data from two types of tracking buoys that sample the currents at two different depths. The ADCP measures the Eulerian current at one point, as modelled by an ocean general circulation model, while the tracking buoys are advected by the Lagrangian current that includes the wave-induced Stokes drift. Based on our observations, we assess the importance of two different wave effects: (a) forcing of the ocean current by wave-induced surface fluxes and the Coriolis-Stokes force, and (b) advection of surface drifters by wave motion, that is the Stokes drift. Recent theoretical developments provide a framework for including these wave effects in ocean model systems. The order of magnitude of the Stokes drift is the same as the Eulerian current judging from the available data. The wave-induced momentum and turbulent kinetic energy fluxes are estimated and shown to be significant. Similarly, the wave-induced Coriolis-Stokes force is significant over time scales related to the inertial period. Surface drifter trajectories were analysed and could be reproduced using the observations of currents, waves and wind. Waves were found to have a significant contribution to the trajectories, and we conclude that adding wave effects in ocean model systems is likely to increase predictability of surface drifter trajectories. The relative importance of the Stokes drift was twice as large as the direct wind drag for the used surface drifter.
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| 18. |
- Rohrs, J., et al.
(author)
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Wave-induced transport and vertical mixing of pelagic eggs and larvae
- 2014
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In: Limnology and Oceanography. - : Wiley. - 0024-3590. ; 59:4, s. 1213-1227
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Journal article (peer-reviewed)abstract
- The transport of pelagic plankton by wind-driven ocean currents and surface gravity waves is investigated for the example of Northeast Arctic cod eggs and larvae on the coast of northern Norway. Previous studies indicate that the wave-induced drift (i.e., Stokes drift) is relevant for the transport of particles in the upper ocean. We use an ocean general circulation model together with a numerical wave prediction model and a Lagrangian particle tracking model to calculate trajectories of fish eggs and larvae. Waves are considered not only for particle drift but also for the air-sea momentum flux, its contribution to the Coriolis force, and vertical mixing. The sample species provides the advantage that many of its physical and behavioral properties are well known (e.g., egg buoyancy), allowing investigation of vertical particle displacement by turbulent mixing in response to wind forcing and wave breaking. The approach accounting for particle mixing by breaking waves enhances agreement between observed and modeled egg profiles. Results also show a general shoreward transport of particles by the Stokes drift. This wave drift exhibits a more constant direction than the Eulerian current and hence stabilizes particle diffusion to favor a dominant direction. For the case of Northeast Arctic cod, waves concentrated model eggs and larvae on average 1.5 km closer to shore, which is 20% of their total distance to the coast. This increases the residence time of first-feeding larvae close to the spawning areas compared to earlier models.
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| 21. |
- Sundby, Cecilia, et al.
(author)
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Conserved methionines in chloroplasts
- 2005
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In: Biochimica et Biophysica Acta - Proteins and Proteomics. - : Elsevier BV. - 1570-9639. ; 1703:2, s. 191-202
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Research review (peer-reviewed)abstract
- Heat shock proteins counteract heat and oxidative stress. In chloroplasts, a small heat shock protein (Hsp21) contains a set of conserved methionines, which date back to early in the emergence of terrestrial plants. Methionines M49, M52, M55, M59, M62, M67 are located on one side of an amphipathic helix, which may fold back over two other conserved methionines (M97 and M101), to form a binding groove lined with methionines, for sequence-independent recognition of peptides with an overall hydrophobic character. The sHsps protect other proteins from aggregation by binding to their hydrophobic surfaces, which become exposed under stress. Data are presented showing that keeping the conserved methionines in Hsp21 in a reduced form is a prerequisite to maintain such binding. The chloroplast generates reactive oxygen species under both stress and unstressed conditions, but this organelle is also a highly reducing cellular compartment. Chloroplasts contain a specialized isoform of the enzyme, peptide methionine sulfoxide reductase, the expression of which is light-induced. Recombinant proteins were used to measure that this reductase can restore Hsp21 methionines after sulfoxidation. This paper also describes how methionine sulfoxidation-reduction can be directly assessed by mass spectrometry, how methionine-to-leucine substitution affects Hsp21, and discusses the possible role for an Hsp21 methionine sulfoxidation-reduction cycle in quenching reactive oxygen species. (C) 2004 Elsevier B.V. All rights reserved.
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