1. |
- Sorbe, Bengt, et al.
(author)
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A population-based series of uterine carcinosarcomas with long-term follow-up.
- 2013
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In: Acta oncologica (Stockholm, Sweden). - : Informa Healthcare. - 1651-226X .- 0284-186X. ; 52:4, s. 759-66
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Journal article (peer-reviewed)abstract
- Background. Carcinosarcomas are a highly malignant type of endometrial carcinomas where extra uterine spread and recurrences are frequent. There is no consensus regarding the best treatment of this group of malignancies. Material and methods. In a complete geographic series of 322 cases of primary uterine carcinosarcomas prophylactic pelvic irradiation and/or chemotherapy was used as postoperative treatment in the majority of the cases. Vaginal brachytherapy was also added as a boost. The primary surgery was extended hysterectomy in 23 cases (10%), and simple hysterectomy in 220 cases (90%). In 46 cases (14%) no major surgery was possible. Results. In the complete series 123 recurrences (38%) were recorded. Locoregional recurrences (11%) and distant recurrences (28%) were most frequent. Type and extent of surgery was not associated with the risk of tumor recurrence. Extended surgery did not reduce the risk of local and regional recurrences. In the complete series, the five-year overall survival rate was 30% and the recurrence-free survival (RFS) rate was 27%. The five-year pelvic disease control was 82% in stage I, 68% in stage II, and 76% for more advanced stages. The five-year locoregional RFS rate was 63% for patients treated with surgery alone, 68% after addition of adjuvant chemotherapy, 86% after adjuvant radiotherapy, and 95% after combined chemotherapy and radiotherapy. Conclusion. Radiotherapy seems to be the most important constituent of the adjuvant therapy. Serious late tissue reactions, requiring surgery, from the bladder and intestine occurred in 2.5% of the irradiated cases. The death of three patients could be related to radiotherapy and of four patients due to the cytotoxic treatment. This population-based series may serve as a baseline for improvements by, e.g. standard care programs and referral to a few specialist centers for this rare and serious disease.
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2. |
- Dreilich, Martin, et al.
(author)
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Telomerase activity is not a key determinant of sensitivity to standard cytotoxic drugs in human esophageal carcinoma cell lines
- 2006
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In: Anti-Cancer Drugs. - 0959-4973 .- 1473-5741. ; 17:5, s. 503-509
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Journal article (peer-reviewed)abstract
- The aim of the present study was to investigate if basal telomerase activity levels may predict sensitivity to cytotoxic drugs in a panel of human esophageal carcinoma cell lines. The TRAPeze telomerase detection assay was used to investigate telomerase activity in the cell lines. Cytotoxic drug sensitivity for 20 standard cytotoxic agents was assessed using the fluorometric microculture cytotoxicity assay (FMCA). Telomerase activity was detected in all cell lines with a broad range of activity levels. Drug sensitivity also varied considerably between the cell lines. Except for a P value towards a correlation between mitoxantrone and telomerase activity (P=0.054), no statistically significant correlation was found between telomerase activity levels and sensitivity to investigated drugs, including key drugs such as cisplatin (P=0.9), 5-fluorouracil (P=0.8) and doxorubicin (P=0.54). We therefore conclude that basal telomerase activity level is not a key determinant of sensitivity to standard cytotoxic drugs in esophageal carcinoma cell lines.
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3. |
- Kader, Rania, et al.
(author)
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Manipulations of Oral Medications in Paediatric Neurology and Oncology Care at a Swedish University Hospital : Health Professionals' Attitudes and Sources of Information
- 2021
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In: Pharmaceutics. - : MDPI. - 1999-4923. ; 13:10
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Journal article (peer-reviewed)abstract
- Oral administration of medications to children requires age-appropriate dosage forms and strengths. In this study, we: (i) assessed the extent of oral dosage form manipulations, (ii) documented how it is carried out, and (iii) examined the attitudes and sources of information regarding the handling from healthcare professionals. Prospective reviews of electronic records, ward observations, and clinician surveys were performed at a paediatric neurology ward and a paediatric oncology ward in Sweden during April to May of 2018. Approximately 15% of oral medications were manipulated for the studied patient group (median age 12.9 years in oncology, 5.8 years in neurology) with approximately 30% of the patients having an enteral feeding tube. Manipulations were performed both to obtain an appropriate dose from, for example, a fraction of the original tablet or to obtain a powder that could be used to prepare a slurry for administration through enteral feeding tubes. Risks identified were related to patient safety such as cross contamination, suboptimal absorption/pharmacokinetics and inaccurate dose. When examining the working environment of nurses, we observed safe handling of hazardous substances but the nurses occasionally experienced stress and a fear of making mistakes due to absence of information. Paediatricians experienced a lack of time to search for proper information on manipulations. As a step towards improving safety in paediatric medication, we suggest the introduction of clinical pharmacists into the team and further evaluating the possibilities of using more ready-to-administer medications with necessary product information and pharmacovigilance support.
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4. |
- Lilljebjörn, Henrik, et al.
(author)
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Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B-cell precursor acute lymphoblastic leukaemia
- 2016
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11790
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Journal article (peer-reviewed)abstract
- Fusion genes are potent driver mutations in cancer. In this study, we delineate the fusion gene landscape in a consecutive series of 195 paediatric B-cell precursor acute lymphoblastic leukaemia (BCP ALL). Using RNA sequencing, we find in-frame fusion genes in 127 (65%) cases, including 27 novel fusions. We describe a subtype characterized by recurrent IGH-DUX4 or ERG-DUX4 fusions, representing 4% of cases, leading to overexpression of DUX4 and frequently co-occurring with intragenic ERG deletions. Furthermore, we identify a subtype characterized by an ETV6-RUNX1-like gene-expression profile and coexisting ETV6 and IKZF1 alterations. Thus, this study provides a detailed overview of fusion genes in paediatric BCP ALL and adds new pathogenetic insights, which may improve risk stratification and provide therapeutic options for this disease.
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5. |
- Lönn, Amanda, 1981-, et al.
(author)
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Lifestyle-related habits and factors before and after cardiovascular diagnosis : a case control study among 2,548 Swedish individuals.
- 2023
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In: International Journal of Behavioral Nutrition and Physical Activity. - : BioMed Central (BMC). - 1479-5868. ; 20:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Healthy lifestyle habits are recommended in prevention of cardiovascular disease (CVD). However, there is limited knowledge concerning the change in lifestyle-related factors from before to after a CVD event. Thus, this study aimed to explore if and how lifestyle habits and other lifestyle-related factors changed between two health assessments in individuals experiencing a CVD event between the assessments, and if changes varied between subgroups of sex, age, educational level, duration from CVD event to second assessment and type of CVD event.METHODS: Among 115,504 Swedish employees with data from two assessments of occupational health screenings between 1992 and 2020, a total of 637 individuals (74% men, mean age 47 ± SD 9 years) were identified having had a CVD event (ischemic heart disease, cardiac arrythmia or stroke) between the assessments. Cases were matched with controls without an event between assessments from the same database (ratio 1:3, matching with replacement) by sex, age, and time between assessment (n = 1911 controls). Lifestyle habits included smoking, active commuting, exercise, diet, alcohol intake, and were self-rated. Lifestyle-related factors included overall stress, overall health (both self-rated), physical capacity (estimated by submaximal cycling), body mass index and resting blood pressure. Differences in lifestyle habits and lifestyle-related factors between cases and controls, and changes over time, were analysed with parametric and non-parametric tests. Multiple logistic regression, OR (95% CI) was used to analyse differences in change between subgroups.RESULTS: Cases had, in general, a higher prevalence of unhealthy lifestyle habits as well as negative life-style related factors prior to the event compared to controls. Nevertheless, cases improved their lifestyle habits and lifestyle factors to a higher degree than controls, especially their amount of active commuting (p = 0.025), exercise (p = 0.009) and non-smoking (p < 0.001). However, BMI and overall health deteriorated to a greater extent (p < 0.001) among cases, while physical capacity (p < 0.001) decreased in both groups.CONCLUSION: The results indicate that a CVD event may increase motivation to improve lifestyle habits. Nonetheless, the prevalence of unhealthy lifestyle habits was still high, emphasizing the need to improve implementation of primary and secondary CVD prevention.
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6. |
- Nilsson, Johan, et al.
(author)
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A randomized study of coronary artery bypass surgery performed with the Resting Heart™ System utilizing a low vs a standard dosage of heparin.
- 2012
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In: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press (OUP). - 1569-9285 .- 1569-9293. ; 15:5, s. 834-839
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Allogeneic blood transfusion and reoperation for postoperative bleeding after the coronary artery bypass grafting have a negative impact on the patient outcome. This study aimed at evaluating the effects of reduced doses of heparin and protamine on the patient outcome, using a heparin-coated mini-cardiopulmonary bypass (CPB) system. METHODS: Sixty patients undergoing elective first-time CPB were prospectively randomized either to have a reduced systemic heparinization [activated clotting time (ACT) = 250 s] or to a control group perfused with a full heparin dose (ACT = 420 s). Blood transfusions, ventilation time, early postoperative bleeding, ICU stay, reoperations for bleeding, postoperative cognitive status and the level of mobilization were registered. RESULTS: Twenty-nine patients were randomized to the control group, 27 patients to the low-dose group and 4 patients were excluded because of protocol violations. Four patients in the control group received a total of 10 units of packed red blood cells, and in the low-dose group, no transfusions were given, P = 0.046. No patient was reoperated because of bleeding. The ICU stay was significantly shorter in the low-dose group (8.4 vs 13.7 h, P = 0.020), less dependent on oxygen on the first postoperative day (78 vs 97%, P = 0.034), better mobilized (89 vs 59%, P = 0.006) and had less pain (visual analogue scale 2.0 vs 3.5, P = 0.019) compared with the control group. CONCLUSIONS: The use of a mini-CPB system combined with a low dose of heparin reduced the need for blood transfusions and may facilitate the faster mobilization of the patients.
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7. |
- Offstad, Jon, et al.
(author)
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The Scandinavian multicenter hemodynamic evaluation of the SJM Regent aortic valve
- 2011
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In: Journal of Cardiothoracic Surgery. - : Springer Science and Business Media LLC. - 1749-8090. ; 6:163
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Journal article (peer-reviewed)abstract
- Background: 112 patients who received small and medium sized St.Jude Regent heart valves (19-25 mm) at 7 Scandinavian centers were studied between January 2003 and February 2005 to obtain non-invasive data regarding the hemodynamic performance at rest and during Dobutamine stress echocardiography (DSE) testing one year after surgery. Material and methods: 46 woman and 66 men, aged 61.8 +/- 9.7 (18-75) years, were operated on for aortic regurgitation (17), stenosis (65), or mixed dysfunction (30). Valve sizes were 19 mm (6), 21 mm (33), 23 mm (41), 25 mm (30). Two patients receiving size 27 valves were excluded from the hemodynamic evaluation. Pledgets were used in 100 patients, everted mattress in 66 and simple interrupted sutures in 21. Valve orientation varied and was dependent on the surgeons' choice. 34 patients (30.4%) underwent concomitant coronary artery surgery. Results: There were two early deaths (1.8%) and three late deaths, one because of pancreatic cancer. Late events during follow-up were: non structural dysfunction (1), bleeding (2), thromboembolism (2). At one year follow up 93% of the patients were in NYHA classes 1-2 versus 47.8% preoperatively. Dobutamine stress echocardiography (DSE) was performed in a total of 66 and maximal peak stress was reached in 61 patients. During DSE testing, the following statistically significant changes took place: Heart rate increased by 73.0%, cardiac output by 85.5%, left ventriclular ejection fraction by 19.6%, and maximal mean prosthetic transvalvular gradient by 133.8%, whereas the effective orifice area index did not change. Left ventricular mass fell during one year from 215 +/- 63 to 197 +/- 62 g (p < 0.05). Conclusion: The Dobutamine test induces a substantial stress, well suitable for echocardiographic assessment of prosthesis valve function and can be performed in the majority of the patients. The changes in pressure gradients add to the hemodynamic characteristics of the various valve sizes. In our patients the St. Jude Regent valve performed satisfactory at rest and under pharmacological stress situation.
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8. |
- Olofsson, P. S., et al.
(author)
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Genetic variants of TNFSF4 and risk for carotid artery disease and stroke
- 2009
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In: Journal of Molecular Medicine. - New York : Springer. - 0946-2716 .- 1432-1440. ; 87:4, s. 337-346
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Journal article (peer-reviewed)abstract
- In two independent human cohorts, the minor allele of SNP rs3850641 in TNFSF4 was significantly more frequent in individuals with myocardial infarction than in controls. In mice, Tnfsf4 expression is associated with increased atherosclerosis. The expression of TNFSF4 in human atherosclerosis and the association between genotype and cerebrovascular disease have not yet been investigated. TNFSF4 messenger RNA (mRNA) levels were significantly higher in human atherosclerotic lesions compared with controls (730â±â30 vs 330â±â65 arbitrary units, pâ<â0.01). TNFSF4 was mainly expressed by macrophages in atherosclerotic lesions. In cell culture, endothelial cells upregulated TNFSF4 in response to tumor necrosis factor alpha (TNF-α; 460â±â110 vs 133â±â8 arbitrary units, pâ<â0.001 after 6 h of stimulation). We analyzed the TNFSF4 gene in 239 patients who had undergone carotid endarterectomy and 138 matching controls from The Biobank of Karolinska Carotid Endarterectomies and Stockholm Heart Epidemiology Program cohorts and 929 patients and 1,382 matching controls from the Sahlgrenska Academy Study on Ischemic Stroke and Case Control Study of Stroke cohorts, limiting inclusion to patients with ischemic stroke. Participants were genotyped for the rs3850641 SNP in TNFSF4. Genotype associations were neither found with TNFSF4 mRNA levels nor with atherosclerosis associated systemic factors or risk for stroke. This study shows that TNFSF4 is expressed on antigen-presenting cells in human carotid atherosclerotic lesions but provides no evidence for an association of TNFSF4 gene variation with the risk for ischemic stroke.
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9. |
- Paulsson, Björn, et al.
(author)
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An overview of wheel–rail interface related research in the European project INNOTRACK including issues in technical and economical validation
- 2009
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In: Proceedings 8th International Conference on Contact Mechanics and Wear of Rail/Wheel Systems. ; , s. 8 pp-
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Conference paper (peer-reviewed)abstract
- The INNOTRACK project (www.innotrack.eu) is a European research project within the 6th Framework Programme. The aim of the INNOTRACK project is to deliver innovative track-related solutions to reduce life cycle costs and improve the reliability, availability, maintainability and safety of the rail sector. The current paper gives an overview of work in INNOTRACK of relevance for the CM2009 conference. The work presented in this paper focuses on innovative processes and methodologies. Topics discussed concern rail selection, installation, inspection and maintenance and also the optimisation of switches and crossings. Finally a discussion on technical, logistical and economical verifications of proposed solutions is presented. Many of the topics included in this overview paper are presented in detail in other contributions to the CM2009 conference.
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10. |
- Paulsson, Gunnar, et al.
(author)
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A Population-based Series of Ovarian Carcinosarcomas with Long-term Follow-up
- 2013
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In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 33:3, s. 1003-1008
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Journal article (peer-reviewed)abstract
- Aim: The aim of the present study was to evaluate a consecutive series of ovarian carcinosarcomas with regard to prognosis, treatment and prognostic factors. Patients and Methods: A consecutive series of 81 ovarian carcinosarcomas from two well-defined geographic regions were studied with regard to survival, type of primary and adjuvant therapy and prognostic factors. All patients but one underwent primary surgery and some patients also received adjuvant chemotherapy (platinum-based) alone or in combination with radiotherapy. Univariate and multivariate Cox proportional regression analysis was used. Survival was analyzed by the Kaplan-Meier technique and differences were assessed by the log-rank test. Results: The mean age of the patients was 73 years. Fifty-one patients received adjuvant chemotherapy and nine patients pelvic irradiation. The 5-year overall survival rate was 10%. Adjuvant therapy (any type) and six completed cycles of chemotherapy were highly significant factors with regard to improved overall survival rate. The only significant tumor-associated prognostic factor was the International Federation of Gynecology and Obstetrics (FIGO) grade of the tumor. FIGO stage, site of metastatic spread, tumor size, histology, DNA ploidy, and tumor necrosis were nonsignificant factors. Therapy was rather well-tolerated and 29 patients (57%) completed at least six cycles of adjuvant chemotherapy. Conclusion: Adjuvant and completed chemotherapy according to the treatment plan were the most important prognostic factors. FIGO grade (grade 3 vs. 1-2) of the epithelial component of the tumor was also a significant prognostic factor in multivariate Cox analysis.
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