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- Hjorth-Hansen, H., et al.
(author)
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Safety and efficacy of the combination of pegylated interferon-alpha 2b and dasatinib in newly diagnosed chronic-phase chronic myeloid leukemia patients
- 2016
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In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 30:9, s. 1853-1860
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Journal article (peer-reviewed)abstract
- Dasatinib (DAS) and interferon-a have antileukemic and immunostimulatory effects and induce deep responses in chronic myeloid leukemia (CML). We assigned 40 newly diagnosed chronic-phase CML patients to receive DAS 100 mg o.d. followed by addition of pegylated interferon-alpha 2b (PegIFN) after 3 months (M3). The starting dose of PegIFN was 15 mu g/week and it increased to 25 mu g/week at M6 until M15. The combination was well tolerated with manageable toxicity. Of the patients, 84% remained on PegIFN at M12 and 91% (DAS) and 73% (PegIFN) of assigned dose was given. Only one patient had a pleural effusion during first year, and three more during the second year. After introduction of PegIFN we observed a steep increase in response rates. Major molecular response was achieved in 10%, 57%, 84% and 89% of patients at M3, M6, M12 and M18, respectively. At M12, MR4 was achieved by 46% and MR4.5 by 27% of patients. No patients progressed to advanced phase. In conclusion, the combination treatment appeared safe with very promising efficacy. A randomized comparison of DAS +/- PegIFN is warranted.
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- Kontro, M, et al.
(author)
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HOX gene expression predicts response to BCL-2 inhibition in acute myeloid leukemia
- 2017
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In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 31:2, s. 301-309
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Journal article (peer-reviewed)abstract
- Inhibitors of B-cell lymphoma-2 (BCL-2) such as venetoclax (ABT-199) and navitoclax (ABT-263) are clinically explored in several cancer types, including acute myeloid leukemia (AML), to selectively induce apoptosis in cancer cells. To identify robust biomarkers for BCL-2 inhibitor sensitivity, we evaluated the ex vivo sensitivity of fresh leukemic cells from 73 diagnosed and relapsed/refractory AML patients, and then comprehensively assessed whether the responses correlated to specific mutations or gene expression signatures. Compared with samples from healthy donor controls (nonsensitive) and chronic lymphocytic leukemia (CLL) patients (highly sensitive), AML samples exhibited variable responses to BCL-2 inhibition. Strongest CLL-like responses were observed in 15% of the AML patient samples, whereas 32% were resistant, and the remaining exhibited intermediate responses to venetoclax. BCL-2 inhibitor sensitivity was associated with genetic aberrations in chromatin modifiers, WT1 and IDH1/IDH2. A striking selective overexpression of specific HOXA and HOXB gene transcripts were detected in highly BCL-2 inhibitor sensitive samples. Ex vivo responses to venetoclax showed significant inverse correlation to β2-microglobulin expression and to a lesser degree to BCL-XL and BAX expression. As new therapy options for AML are urgently needed, the specific HOX gene expression pattern can potentially be used as a biomarker to identify venetoclax-sensitive AML patients for clinical trials.Leukemia advance online publication, 2 September 2016; doi:10.1038/leu.2016.222.
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- Yamamoto, Shinji, et al.
(author)
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Liver transplantation for familial amyloidotic polyneuropathy (FAP) : a single-center experience over 16 years
- 2007
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In: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 7:11, s. 2597-2604
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Journal article (peer-reviewed)abstract
- Orthotopic liver transplantation (LTx) is currently the only available treatment that has been proven to halt the progress of familial amyloidotic polyneuropathy (FAP). The aim of this study was to assess mortality and symptomatic response to LTx for FAP. All 86 FAP patients transplanted at our hospital between April 1990 and November 2005 were included in the study. Five patients underwent retransplantation. The 1-, 3- and 5-year patient survival rates in patients transplanted during 1996-2005 were 94.6%, 92.3% and 92.3%, respectively, a significant difference from the rates of 76.7%, 66.7% and 66.7%, respectively, during 1990-1995 (p = 0.0003). Multivariate analysis revealed that the age at the time of LTx (>or=40 years), duration of the disease (>or=7 years) and modified body mass index (mBMI) (<600) were independent prognostic factors for patient survival. A halt in the progress of symptoms was noted in most patients, but only a minority experienced an improvement after LTx. To optimize the posttransplant prognosis, LTx should be performed in the early stages of the disease, and close post-LTx monitoring of heart function by echocardiography and of heart arrhythmia by Holter ECG is mandatory.
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- Bartels, Stefan, et al.
(author)
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Total Hip Arthroplasty Leads to Better Results After Low-Energy Displaced Femoral Neck Fracture in Patients Aged 55 to 70 Years : A Randomized Controlled Multicenter Trial Comparing Internal Fixation and Total Hip Arthroplasty
- 2022
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In: Journal of Bone and Joint Surgery. - 0021-9355. ; 104:15, s. 1341-1351
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Journal article (peer-reviewed)abstract
- Background:The optimal treatment of displaced femoral neck fractures in patients 55 to 70 years old remains controversial. The aim of the present study was to assess the effect of closed reduction and internal fixation with cannulated screws (IF) compared with total hip arthroplasty (THA) on hip pain and function, with use of data for outcome measures, complications, and reoperations.Methods:This multicenter randomized controlled trial included all patients 55 to 70 years old who presented with a low-energy displaced femoral neck fracture between December 2013 and December 2018. Patients were randomly allocated to undergo either IF or THA. The primary outcome was the Harris Hip Score (HHS) at 12 months postoperatively. Secondary outcomes were the HHS at 4 and 24 months postoperatively, Oxford Hip Score (OHS), Hip Disability and Osteoarthritis Outcome Score (HOOS), health-related quality of life (EQ-5D-3L [EuroQol 5 Dimensions 3 Levels] index score and EQ-VAS [visual analogue scale]), VAS for pain, and VAS for patient satisfaction at 4, 12, and 24 months postoperatively. Complications and reoperations were continuously monitored. The primary analyses were performed according to the intention-to-treat principle.Results:A total of 102 patients with a mean (± standard deviation) age of 63.7 ± 4.2 years were allocated to IF (n = 51) or THA (n = 51). The mean difference in the primary outcome, the HHS at 12 months postoperatively (5.3; 95% confidence interval, 0.9 to 9.7; p = 0.017), was below the predefined minimal clinically important difference of 10 points. However, patients who underwent THA had a significantly higher HHS at 4 and 12 months, better OHS at 4 and 12 months, and better HOOS at 4, 12, and 24 months postoperatively. Patients who underwent THA also reported better health-related quality of life at 4 months postoperatively and reported greater satisfaction and less pain at 4 and 12 months postoperatively. A total of 26 patients in the IF group (51%; 95% confidence interval, 37% to 65%) and 2 patients in the THA group (4%; 95% confidence interval, 0.5% to 13%) underwent a major reoperation.Conclusions:In this randomized controlled trial, we showed that patients between 55 and 70 years old who underwent THA for a low-energy displaced femoral neck fracture experienced better outcomes than those who underwent closed reduction and internal fixation.Level of Evidence:Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
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