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- Ekstrand, Charlotta, et al.
(author)
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Cancer risk in patients with primary immune thrombocytopenia - A Swedish nationwide register study
- 2020
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In: Cancer Epidemiology. - : ELSEVIER SCI LTD. - 1877-7821 .- 1877-783X. ; 69
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Journal article (peer-reviewed)abstract
- Background: Immune thrombocytopenia (ITP) is an autoimmune disease treated with immunosuppressive agents, thrombopoietin receptor agonists, immunomodulation drugs and/or splenectomy. Patients with ITP have been found to have increased risk ofhematological malignancies. Studies investigating stomach/liver cancer are contradictory and the risk of developing other solid tumors is largely unknown. We aimed at estimating risk of overall and organ-specific cancers in patients with primary ITP.Methods: The study population was Swedish patients with at least one ITP diagnosis recorded in the National Patient Register and a 1:10 matched comparison cohort from the population. The study period covers 1997-2016. The Cancer Register and the Cause of Death Register provided data on malignancies and deaths, respectively. Primary ITP was identified using an established algorithm. We used time-split Cox models to estimate hazard ratios (HRs) with 95 % confidence intervals (CIs), adjusted for age, sex, index-year, county, income, education, Charlson score and number of inand outpatient contacts.Results: In total 66,134 individuals were included in the study. Patients with ITP had higher risk of gastrointestinal, skin (all morphologies), lymphoid and hematological cancers. Adjusted HR (95 % CI) for cancer was 1.37 (1.27-1.48), with highest risk during the first year, but with increased risk remaining for up to 20 years for men. For women, the overall risk was increased during the first year, HR (95 % CI) 2.00 (1.55-2.60). A significantly increased liver cancer risk was seen up to 9 years after diagnosis.Conclusion: Patients with primary ITP have higher risk of cancer than the population. The observed increased risk does not seem to be solely due to surveillance bias, but might be associated with ITP or its treatments. Treating hematologists need to have high index of suspicion for cancer.
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| 3. |
- Ekstrand, Charlotta
(author)
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Epidemiological perspective of chronic immune thrombocytopenia
- 2019
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Doctoral thesis (other academic/artistic)abstract
- This thesis deals with different aspects of immune thrombocytopenia disease (ITP), what happens before diagnosis, characteristics of patients at treatment start and outcomes potentially related to the disease and treatment, such as thrombosis and cancer. In study one we investigate the risk of infections prior to the diagnosis of ITP. There are some infections causing secondary ITP and there is an association with infection and risk of autoimmune disease. With information from national health registries we were able to compare the amount of diagnosis of infection and anti-infective drugs within five years before diagnosis of ITP in 1087 patients with primary chronic ITP (cITP) to the general population. Our hypothesis turned out to be right and the patients with ITP were more likely to have had an infection diagnosis, Standardized Incidence Ratio (SIR) 8.74(7.47-10-18) and anti-infective drugs SIR 1.37(1.25-1.50) compared with persons of the same age and sex in the general population. In addition, we estimated the incidence of ITP in Sweden to 2.3 per 100 000. In study two we investigated characteristics at treatment start in patients with (cITP). We wanted to know how the patients’ characteristics influence start and type of treatment. We found that patients start treatment at low platelet counts, median 12(IQR 5-27). This finding supports the recommendation to treat in order to avoid symptoms and not aim for a normal platelet count, in order to avoid unnecessary potential harm from the treatment. Moreover, we confirm that the most common first treatment is corticosteroids followed by diverse treatment used as second line treatment and refractory treatment. During the last four years of the study splenectomy was less common and the time to splenectomy delayed. Comorbidity influenced treatment start and type of treatment. Patients with diabetes were less likely to receive corticosteroids. In the third study underlying risk factors for arterial thrombosis and venous thromboembolism were evaluated. In collaboration with a research group at the university of Toulouse a cohort study was performed using the same variables and analysis in both countries. The incidence rate of arterial thrombosis in France was 15(13.4-16.7) and in Sweden 14.7(12.4-17.5) and for venous thromboembolism in France 6.9(5.9-8.1) and 6.5(5.1-8.1) in Sweden per 1000 person-years, 95% CI. The impact of baseline risk factors was similar as well. In study four we studied the risk of cancer in patients with ITP. Molecular evidence suggests that the dysfunctional immune system related to autoimmune disease may increase the risk of certain cancers. A risk of haematological malignancies has been reported in studies of patients with ITP but the risk of solid tumours warrants further attention and those performed have reported contradictory results. We compared the rate of cancer in patients with ITP to the general population in a matched cohort study. We found a slightly increased risk of overall cancer HR 1.37(1.27-1.48), more pronounced in men, an increased risk of liver cancer 3.83(2.46-5.97) and an increased risk of skin cancer after 10 years of follow up, 1.52(1.05-2.19). We confirmed the increased risk of haematological malignancies. The risk of hematologic malignancies was increased in all time intervals and follow a trend with the highest risk, 9-fold, following the year of diagnosis of ITP to down to twofold higher 10-20 years after diagnosis We conclude that treating clinicians should have a high index of suspicion of cancer when treating these patients.
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| 5. |
- Ekstrand, Charlotta, et al.
(author)
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Patient characteristics when starting treatment and patterns of treatment in adults with chronic immune thrombocytopenia
- 2019
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In: Blood Coagulation and Fibrinolysis. - : LIPPINCOTT WILLIAMS & WILKINS. - 0957-5235 .- 1473-5733. ; 30:7, s. 350-356
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Journal article (peer-reviewed)abstract
- Asymptomatic patients with primary chronic immune thrombocytopenia (ITP) are not recommended treatment if their platelet counts are above 30 x 10(9)/l. Factors such as age and comorbidities may influence clinical manifestations and should be considered for treatment decisions. The aim of this study was to determine the impact of clinical characteristics for initiation of ITP treatment, and the patterns of ITP treatment given. We performed an observational cohort study in Sweden with information from medical records and National Health Registers. Adults diagnosed with incident primary ITP between years 2009 and 2016 were included. Multinomial logistic regression was used to assess the impact of factors predicting treatment start. Out of 858 patients with chronic ITP from 71 hospitals we identified 585 (68%) with a first ITP treatment. For 537 (92%) corticosteroids were the first choice. The median platelet counts at start of treatment was 12 x 10(9)/l (interquartile range 5-27 x 10(9)/l). The variables predicting treatment start were platelet counts below 20 x 10(9)/l and treatment with antihypertensive drugs. Patients with diabetes were less likely to receive corticosteroids. Severe bleeding occurred in 75 (13%) of the patients. Platelet counts below 20 x 10(9)/l, antihypertensive treatment and bleedings were the strongest predictors of treatment start, diabetes yielded lower odds to start corticosteroid treatment. The majority of the patients had corticosteroids as first treatment while second treatment was diverse. Asymptomatic thrombocytopenia is not considered a reason as such for initiating treatment. In the latter years, splenectomy seemed to occur later in the course of treatment.
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| 7. |
- Ekstrand, Jimmy, et al.
(author)
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Breast density and estradiol are associated with distinct different expression patterns of metabolic proteins in normal human breast tissue in vivo
- 2023
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In: Frontiers in Oncology. - : FRONTIERS MEDIA SA. - 2234-943X. ; 13
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Journal article (peer-reviewed)abstract
- BackgroundBreast density and exposure to sex steroids are major risk factors for breast cancer. The local microenvironment plays an essential role in progression of breast cancer. Metabolic adaption is a major hallmark of cancer. Whether proteins from the extracellular space regulating metabolism are affected in breast cancer, dense breasts or by estrogen exposure are not yet fully elucidated. MethodsWomen with breast cancer, postmenopausal women with normal breast tissue with varying breast density or premenopausal women with breasts exposed to high levels of estradiol were included in the study. Microdialysis was used to collect proteins from the extracellular space in vivo in 73 women; 12 with breast cancer, 42 healthy postmenopausal women with different breast densities, and 19 healthy premenopausal women. Breast density was determined as lean tissue fraction (LTF) using magnetic resonance imaging. Data were evaluated in a murine breast cancer model. We quantified a panel of 92 key proteins regulating metabolism using proximity extension assay. ResultsWe report that 29 proteins were upregulated in human breast cancer. In dense breasts 37 proteins were upregulated and 17 of these were similarly regulated as in breast cancer. 32 proteins correlated with LTF. In premenopausal breasts 19 proteins were up-regulated and 9 down-regulated. Of these, 27 correlated to estradiol, a result that was confirmed for most proteins in experimental breast cancer. Only two proteins, pro-cathepsin H and galanin peptide, were similarly regulated in breast cancer, dense- and estrogen exposed breasts. ConclusionsMetabolic proteins may be targetable for breast cancer prevention. Depending on risk factor, this may, however, require different approaches as breast density and estradiol induce distinct different expression patterns in the breast. Additionally, metabolic proteins from the extracellular space may indeed be further explored as therapeutic targets for breast cancer treatment.
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| 8. |
- Ekstrand, Jimmy, et al.
(author)
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Breast Density and Estradiol Are Major Determinants for Soluble TNF-TNF-R Proteins in vivo in Human Breast Tissue
- 2022
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In: Frontiers in Immunology. - Lausanne, Switzerland : Frontiers Media S.A.. - 1664-3224. ; 13
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Journal article (peer-reviewed)abstract
- High mammographic density and exposure to sex steroids are independent risk factors for breast cancer by yet unknown mechanisms. Inflammation is one hallmark of cancer and the tumor necrosis factor family of proteins (TNFSFs) and receptors (TNFRSFs) are key determinants of tissue inflammation. The relationship between TNFSFs/TNFRSFs and breast tissue density or local breast estradiol levels is unknown. We investigated whether TNFSFs and soluble TNFRSFs (sTNFRSFs) are dysregulated in vivo in human breast cancer and dense breast tissue of postmenopausal women. We explored TNFSF/TNFRSF correlations with breast density and estradiol, both locally in the breast and in abdominal subcutaneous (s.c.) fat as a measure of systemic effects. Microdialysis was used for local sampling of in vivo proteins and estradiol in a total of 73 women; 12 with breast cancer, 42 healthy postmenopausal women with different breast densities, and 19 healthy premenopausal women. Breast density was determined as lean tissue fraction (LTF) using magnetic resonance imaging. Microdialysis was also performed in estrogen receptor (ER) positive breast cancer in mice treated with the pure anti-estrogen fulvestrant and tumor tissue was subjected to immunohistochemistry. 23 members of the TNFSF/sTNFRSF families were quantified using proximity extension assay.Our data revealed upregulation of TNFSF10, 13 and 13B, TNFRSF6, 6B, 9, 11A, 11B, 13B, 14, and 19, and TNFR-1 and -2 in ER+ breast cancer in women. In dense breast tissue TNFSF10, 13, and 14, TNFRSF3, 6, 9, 10B, 13B, 14, 19, and TNFR-1 and -2 were upregulated. Certain TNFSFs/TNFRSFs were increased in premenopausal breasts relative to postmenopausal breasts. Furthermore, estradiol correlated with most of the TNFSF/sTNFRSF members, though LTF only correlated with some of the proteins. Several of these associations were breast tissue-specific, as very few correlated with estradiol in abdominal s.c. fat. Estrogen dependent regulations of TNFSF2 (TNF-alpha) and TNF-R2 were corroborated in ER+ breast cancer in mice. Taken together, our data indicate TNFSFs/sTNFRSFs may represent potential targetable pathways for treatment of breast cancer patients and in prevention of breast cancer development in women with dense breasts.
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| 9. |
- Ekstrand, Per, et al.
(author)
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The meaning of health among newly arrived immigrants : A qualitative study from stakeholders’ perspectives
- 2022
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In: Nordic journal of nursing research. - : Sage Publications. - 2057-1585 .- 2057-1593. ; 43:1
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Journal article (peer-reviewed)abstract
- Good health is a prerequisite for individuals to function in everyday life. The same applies to newly arrived immigrants, where good health is crucial for successful establishment. The aim of this study was to describe stakeholders’ experiences of how newly arrived immigrants’ health affects their opportunities to establish themselves in society. The study had a qualitative design where open-ended questions were analysed following Braun and Clarke’s guidelines for conducting a qualitative thematic analysis. The results consist of three themes: Mental health problems, disabilities, and tormenting concerns about absent family members; A precarious life situation related to housing, education, and income; and Deficiencies in responding to health challenges in organisations and in society. Stakeholders face health problems among newly arrived immigrants that they do not have the right skills to deal with. We argue for the presence of nurses in organisations working with newly arrived immigrants, and that nurses’ competence is necessary to capture their needs.
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| 10. |
- Eriksson, Ronnie, et al.
(author)
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Multiplex and quantifiable detection of nucleic acid from pathogenic fungi using padlock probes, generic real time PCR and specific suspension array readout
- 2009
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In: Journal of Microbiological Methods. - : Elsevier BV. - 0167-7012 .- 1872-8359. ; 78:2, s. 195-202
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Journal article (peer-reviewed)abstract
- A new concept for multiplex detection and quantification of microbes is here demonstrated on a range of infectious fungal species. Padlock probe methodology in conjunction with qPCR and Luminex technology was used for simultaneous detection of ten fungal species in one single experiment. By combining the multiplexing properties of padlock probes and Luminex detection with the well established quantitative characteristics of qPCR, quantitative microbe detection was done in 10-plex mode. A padlock probe is an oligonucleotide that via a ligation reaction forms circular DNA when hybridizing to specific target DNA. The region of the padlock probe that does not participate in target DNA hybridization contains generic primer sequences for amplification and a tag sequence for Luminex detection. This was the fundament for well performing multiplexing. Circularized padlock probes were initially amplified by rolling circle amplification (RCA), followed by a SybrGreen real time PCR which allowed an additive quantitative assessment of target DNA in the sample. Detection and quantification of amplified padlock probes were then done on color coded Luminex microspheres carrying anti-tag sequences. A novel technique, using labeled oligonucleotides to prevent reannealing of amplimers by covering the flanks of the address sequence, improved the signal to noise ratio in the detection step considerably. The method correctly detected fungi in a variety of clinical samples and offered quantitative information on fungal nucleic acid.
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