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Sökning: WFRF:(Hardell E)

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  • Domeij-Arverud, Erica, et al. (författare)
  • Ageing, deep vein thrombosis and male gender predict poor outcome after acute Achilles tendon rupture
  • 2016
  • Ingår i: Bone and Joint Journal. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 2049-4394. ; 98B98-B:12, s. 1635-1641
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Patients with acute Achilles tendon rupture (ATR) exhibit prolonged healing, high incidence of deep venous thrombosis (DVT) and a wide variation of functional outcome. This extensive discrepancy in outcome may be explained by a lack of knowledge of detrimental factors, and subsequent shortage of adequate interventions. Methods: A total of 111 patients (84 men, 16 women; mean age 40.3±8.4) with acute total ATR were prospectively assessed. At one year post-operatively a uniform outcome score, Achilles Combined Outcome Score (ACOS), was obtained by combining three validated, independent, outcome measures: Achilles tendon Total Rupture Score, heel-rise height test, and limb symmetry heel-rise height. Candidate predictors of ACOS included; treatment, sex, age, smoking, body mass index (BMI), time to surgery, physical activity level pre- and post-injury, symptoms, quality of life and DVT-incidence. Results: Three independent variables correlated significantly with the dichotomized outcome score ACOS, while the other factors demonstrated no correlation. Low age (40 or less=0; above 40=1) was the strongest independent predictor of developing a good outcome at one year after ATR (OR= 0.20, 95 % C.I. 0.08 – 0.51), followed by female gender (Man= 1; Woman= 2) (OR= 4.18, 95 % C.I. 1.01 – 17.24). Notably, patients without a DVT (No=0, Yes=1) during post-operative immobilization experienced a better outcome (OR= 0.31, 95 % C.I. 0.12 – 0.80). Conclusion: DVT during leg immobilization, aging and male gender are independent negative predictors of outcome in patients with acute ATR. Age and gender should be further studied as to pinpoint the underlying causes leading to poor outcome. To enhance the outcome after ATR the first clinical focus should be on DVT-prevention during immobilization, possibly by usage of mechanical compression therapy and early weight bearing and mobilization.
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  • Binzer-Panchal, Amrei, et al. (författare)
  • Integrated molecular analysis of undifferentiated uterine sarcomas reveals clinically relevant molecular subtypes
  • 2019
  • Ingår i: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 25:7, s. 2155-2165
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Undifferentiated uterine sarcomas (UUS) are rare, extremely deadly, sarcomas with no effective treatment. The goal of this study was to identify novel intrinsic molecular UUS subtypes using integrated clinical, histopathologic, and molecular evaluation of a large, fully annotated, patient cohort. Experimental Design: Fifty cases of UUS with full clinicopathologic annotation were analyzed for gene expression (n ¼ 50), copy-number variation (CNV, n ¼ 40), cell morphometry (n ¼ 39), and protein expression (n ¼ 22). Gene ontology and network enrichment analysis were used to relate over- and underexpressed genes to pathways and further to clinicopathologic and phenotypic findings. Results: Gene expression identified four distinct groups of tumors, which varied in their clinicopathologic parameters. Gene ontology analysis revealed differential activation of pathways related to genital tract development, extracellular matrix (ECM), muscle function, and proliferation. A multi-variable, adjusted Cox proportional hazard model demonstrated that RNA group, mitotic index, and hormone receptor expression influence patient overall survival (OS). CNV arrays revealed characteristic chromosomal changes for each group. Morphometry demonstrated that the ECM group, the most aggressive, exhibited a decreased cell density and increased nuclear area. A cell density cutoff of 4,300 tumor cells per mm 2 could separate ECM tumors from the remaining cases with a sensitivity of 83% and a specificity of 94%. IHC staining of MMP-14, Collagens 1 and 6, and Fibronectin proteins revealed differential expression of these ECM-related proteins, identifying potential new biomarkers for this aggressive sarcoma subgroup. Conclusions: Molecular evaluation of UUS provides novel insights into the biology, prognosis, phenotype, and possible treatment of these tumors.
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  • Gabrielson, Marike, et al. (författare)
  • Hormonal determinants of mammographic density and density change
  • 2020
  • Ingår i: Breast Cancer Research. - : BMC. - 1465-5411 .- 1465-542X. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Mammographic density (MD) is a strong risk factor for breast cancer. We examined how endogenous plasma hormones are associated with average MD area (cm(2)) and annual MD change (cm(2)/year). Methods This study within the prospective KARMA cohort included analyses of plasma hormones of 1040 women. Hormones from the progestogen (n = 3), androgen (n = 7), oestrogen (n = 2) and corticoid (n = 5) pathways were analysed by ultra-performance supercritical fluid chromatography-tandem mass spectrometry (UPSFC-MS/MS), as well as peptide hormones and proteins (n = 2). MD was measured as a dense area using the STRATUS method (mean over the left and right breasts) and mean annual MD change over time. Results Greater baseline mean MD was associated with overall higher concentrations of progesterone (average + 1.29 cm(2)per doubling of hormone concentration), 17OH-progesterone (+ 1.09 cm(2)), oesterone sulphate (+ 1.42 cm(2)), prolactin (+ 2.11 cm(2)) and SHBG (+ 4.18 cm(2)), and inversely associated with 11-deoxycortisol (- 1.33 cm(2)). The association between MD and progesterone was confined to the premenopausal women only. The overall annual MD change was - 0.8 cm(2). Hormones from the androgen pathway were statistically significantly associated with MD change. The annual MD change was - 0.96 cm(2)and - 1.16 cm(2)lesser, for women in the highest quartile concentrations of testosterone and free testosterone, respectively, compared to those with the lowest concentrations. Conclusions Our results suggest that, whereas hormones from the progestogen, oestrogen and corticoid pathways drive baseline MD, MD change over time is mainly driven by androgens. This study emphasises the complexity of risk factors for breast cancer and their mechanisms of action.
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  • Gremel, Gabriela, et al. (författare)
  • A prognosis based classification of undifferentiated uterine sarcomas : Identification of mitotic index, hormone receptors and YWHAE-FAM22 translocation status as predictors of survival
  • 2015
  • Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 136:7, s. 1608-1618
  • Tidskriftsartikel (refereegranskat)abstract
    • Undifferentiated uterine sarcomas (UUS) are rare tumors with a heterologous biology and a poor prognosis. The goal of this study was to examine clinicopathology, biomarkers and YWHAE-FAM22 translocation status, in the prognosis of these tumors. Twenty-six cases of UUS were included. All original slides were rereviewed and age at diagnosis, tumor stage, Kurihara diagnosis, mitotic index, presence of necrosis and grade of nuclear atypia were recorded. Additionally, a tissue microarray was constructed from 22 of the cases, and the protein biomarkers P53, P16, Ki-67, Cyclin-D1, ER, PR and ANLN were evaluated by immunohistochemistry. All tumors were evaluated for the presence of a YWHAE-FAM translocation; the translocation was demonstrated in the three Cyclin-D1 positive tumors. Follow-up data in the form of overall survival were available on all patients. These tumors could be divided into two prognostic groups, a high mitotic index group (10 cases, M=36.8, SD=5.4) and a low mitotic index group (16 cases, M=8.7, SD=5.8). These two groups showed a statistically significant difference in prognosis. The expression of ER, PR or presence of the YWHAE-FAM22 translocation correlated with low mitotic index and an additionally improved prognosis, although the number of cases was small. These results indicate that UUS can be divided into two prognostic groups using mitotic index as a primary criteria, followed by expression of either ER, PR or the presence of a YWHAE-FAM22 translocation as a secondary criteria. This study demonstrates the presence of statistically significant prognostic subgroups within UUS, and provides treatment insights.
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  • Hardell, Elin, et al. (författare)
  • Validation of a Mitotic Index Cutoff as a Prognostic Marker in Undifferentiated Uterine Sarcomas
  • Ingår i: American Journal of Surgical Pathology. - : Lippincott Williams & Wilkins. - 0147-5185 .- 1532-0979. ; 41:9, s. 1231-1237
  • Tidskriftsartikel (refereegranskat)abstract
    • Undifferentiated uterine sarcomas (UUS) are a heterogenous group of high-grade mesenchymal tumors. Although these tumors are highly aggressive, a subset of patients may experience long-term survival. These tumors have previously been divided morphologically into uniform and pleomorphic types. A previous study demonstrated that a mitotic index cutoff of 25 mitoses/10 high-power fields (corresponding to 11.16 mitotic figures/mm) could successfully divide tumors into 2 prognostic groups with significantly different overall survival. The goals of the current study were to (1) validate this mitotic index cutoff in an independent, multicenter cohort and (2) explore the prognostic value of the mitotic index groups in relation to other clinicopathologic variables. Cases were included from 3 independent institutions: The Norwegian Radium Hospital, The Mayo Clinic, and Skåne University Hospital. A total of 40 tumors were included after central review. All cases were negative for the YWHAE-FAM22A/B and JAZF1-JJAZ1 translocations. Survival data were available on all patients. In this study, one-third of patients with UUS survived beyond 5 years. The crude (unadjusted) Cox Proportional Hazards model revealed a number of parameters that significantly impacted overall survival, including mitotic index group, patient age, stage, and the presence of tumor necrosis. Classification into the uniform and pleomorphic types was not prognostic. Combining these parameters into an adjusted model revealed that only the mitotic index group and stage were prognostic. On the basis of these findings, it is proposed that UUS be subdivided into “mitogenic” and “not otherwise specified” types.
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  • Hardell, L., et al. (författare)
  • Malignant lymphoma and exposure to chemicals, especially organic solvents, chlorophenols and phenoxy acids : A case-control study
  • Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920. ; 43:2, s. 169-176
  • Tidskriftsartikel (refereegranskat)abstract
    • A number of men with malignant lymphoma of the histiocytic type and previous exposure to phenoxy acids or chlorophenols were observed and reported in 1979. A matched case-control study has therefore been performed with cases of malignant lymphoma (Hodgkin's disease and non-Hodgkin lymphoma). This study included 169 cases and 338 controls. The results indicate that exposure to phenoxy acids, chlorophenols, and organic solvents may be a causative factor in malignant lymphoma. Combined exposure of these chemicals seemed to increase the risk. Exposure to various other agents was not obviously different in cases and in controls.
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