| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Hjorth-Hansen, H., et al.
(författare)
-
Safety and efficacy of the combination of pegylated interferon-alpha 2b and dasatinib in newly diagnosed chronic-phase chronic myeloid leukemia patients
- 2016
-
Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 30:9, s. 1853-1860
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 5. |
- Kontro, M, et al.
(författare)
-
HOX gene expression predicts response to BCL-2 inhibition in acute myeloid leukemia
- 2017
-
Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 31:2, s. 301-309
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 6. |
|
|
| 7. |
- Yamamoto, Shinji, et al.
(författare)
-
Liver transplantation for familial amyloidotic polyneuropathy (FAP) : a single-center experience over 16 years
- 2007
-
Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 7:11, s. 2597-2604
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 8. |
|
|
| 9. |
- Bartels, Stefan, et al.
(författare)
-
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
-
Ingår i: Journal of Bone and Joint Surgery. - 0021-9355. ; 104:15, s. 1341-1351
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Gjerde, Cecilie, et al.
(författare)
-
Cell therapy induced regeneration of severely atrophied mandibular bone in a clinical trial
- 2018
-
Ingår i: Stem Cell Research & Therapy. - : BMC. - 1757-6512. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Autologous grafting, despite some disadvantages, is still considered the gold standard for reconstruction of maxillofacial bone defects. The aim of this study was to evaluate bone regeneration using bone marrow-derived mesenchymal stromal cells (MSCs) in a clinical trial, a less invasive approach than autologous bone grafting. This comprehensive clinical trial included subjects with severe mandibular ridge resorption. Methods: The study included 11 subjects aged 52-79 years with severe mandibular ridge resorption. Bone marrow cells were aspirated from the posterior iliac crest and plastic adherent cells were expanded in culture medium containing human platelet lysate. The MSCs and biphasic calcium phosphate granules as scaffolds were inserted subperiosteally onto the resorbed alveolar ridge. After 4-6 months of healing, new bone formation was assessed clinically and radiographically, as were safety and feasibility. Bone at the implant site was biopsied for micro computed topography and histological analyses and dental implants were placed in the newly regenerated bone. Functional outcomes and patient satisfaction were assessed after 12 months. Results: The bone marrow cells, expanded in vitro and inserted into the defect together with biphasic calcium phosphate granules, induced significant new bone formation. The regenerated bone volume was adequate for dental implant installation. Healing was uneventful, without adverse events. The patients were satisfied with the esthetic and functional outcomes. No side effects were observed. Conclusions: The results of this comprehensive clinical trial in human subjects confirm that MSCs can successfully induce significant formation of new bone, with no untoward sequelae. Hence, this novel augmentation procedure warrants further investigation and may form the basis of a valid treatment protocol, challenging the current gold standard.
|
|
| 15. |
|
|
| 16. |
- Gronhaug, K. M. L., et al.
(författare)
-
Subsequent ipsi- and contralateral femoral fractures after intramedullary nailing of a trochanteric or subtrochanteric fracture: a cohort study on 2012 patients
- 2022
-
Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background The literature is inconclusive as to whether an intramedullary nail changes the distribution of a subsequent ipsi- or contralateral fracture of the femur. We have compared the incidence, localisation, and fracture pattern of subsequent femoral fractures after intramedullary nailing of trochanteric or subtrochanteric fractures in patients without previous implants in either femur at the time of surgery. Methods Retrospective analysis was performed of a two-centre cohort of 2012 patients treated with a short or long intramedullary nail for the management of trochanteric or subtrochanteric fracture between January 2005 and December 2018. Subsequent presentations with ipsi- and contralateral femoral fractures were documented. Only patients with no previous femoral surgery performed, other than the index nailing were followed. Odds ratios (ORs) for subsequent femoral fracture were calculated using robust variance estimates in logistic regression. Results The mean age of the cohort was 82.4 years and 72.1% were female. The total number of patients presenting with subsequent femoral fractures was 299 (14.9%). The number of patients presenting with subsequent ipsilateral and contralateral femoral fractures was 51 (2.5%) and 248 (12.3%) respectively (OR 5.0; CI 3.7-6.9). Twenty-six (8.7%) of all subsequent femoral fractures occured in the ipsilateral shaft, 14 (4.7%) in the ipsilateral metaphyseal area, one (0.33%) in the contralateral shaft, and three (1.0%) in the contralateral metaphysis (OR 10; CI 3.6-29). Conclusion An intramedullary nail significantly changes the fracture pattern in the event of a second low-energy trauma, reducing the risk of subsequent proximal ipsilateral femoral fractures and increasing the risk of subsequent ipsilateral femoral fractures in the shaft and distal metaphyseal area compared with the native contralateral femur.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Hochhaus, Andreas, et al.
(författare)
-
Bosutinib for pretreated patients with chronic phase chronic myeloid leukemia : primary results of the phase 4 BYOND study
- 2020
-
Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 34:8, s. 2125-2137
-
Tidskriftsartikel (refereegranskat)abstract
- Bosutinib is approved for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML) and for Ph+ CP, accelerated (AP), or blast (BP) phase CML after prior treatment with tyrosine kinase inhibitors (TKIs). In the ongoing phase 4 BYOND study (NCT02228382), 163 CML patients resistant/intolerant to prior TKIs (n = 156 Ph+ CP CML, n = 4 Ph+ AP CML, n = 3 Ph-negative/BCR-ABL1+ CML) received bosutinib 500 mg once daily (starting dose). As of ≥1 year after last enrolled patient (median treatment duration 23.7 months), 56.4% of Ph+ CP CML patients remained on bosutinib. Primary endpoint of cumulative confirmed major cytogenetic response (MCyR) rate by 1 year was 75.8% in Ph+ CP CML patients after one or two prior TKIs and 62.2% after three prior TKIs. Cumulative complete cytogenetic response (CCyR) and major molecular response (MMR) rates by 1 year were 80.6% and 70.5%, respectively, in Ph+ CP CML patients overall. No patient progressed to AP/BP on treatment. Across all patients, the most common treatment-emergent adverse events were diarrhea (87.7%), nausea (39.9%), and vomiting (32.5%). The majority of patients had confirmed MCyR by 1 year and MMR by 1 year, further supporting bosutinib use for Ph+ CP CML patients resistant/intolerant to prior TKIs.
|
|
| 21. |
|
|
| 22. |
- Johansen, Antony, et al.
(författare)
-
Using national hip fracture registries and audit databases to develop an international perspective
- 2017
-
Ingår i: Injury. - : Elsevier. - 0020-1383 .- 1879-0267. ; 48:10, s. 2174-2179
-
Tidskriftsartikel (refereegranskat)abstract
- Hip fracture is the commonest reason for older people to need emergency anaesthesia and surgery, and leads to prolonged dependence for many of those who survive. People with this injury are usually identified very early in their hospital care, so hip fracture is an ideal marker condition with which to audit the care offered to older people by health services around the world. We have reviewed the reports of eight national audit programmes, to examine the approach used in each, and highlight differences in case mix, management and outcomes in different countries. The national audits provide a consistent picture of typical patients - an average age of 80 years, with less than a third being men, and a third of all patients having cognitive impairment - but there was surprising variation in the type of fracture, of operation and of anaesthesia and hospital length of stay in different countries. These national audits provide a unique opportunity to compare how health care systems of different countries are responding to the same clinical challenge. This review will encourage the development and reporting of a standardised dataset to support international collaboration in healthcare audit. (C) 2017 Elsevier Ltd. All rights reserved.
|
|
| 23. |
- Kansoul, H A, et al.
(författare)
-
Parameters obtained by hepatobiliary scintigraphy have significant correlation with biochemical factors early after liver transplantation
- 2007
-
Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 48:6, s. 597-604
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Early postoperative hepatobiliary scintigraphy after liver transplantation is performed worldwide, but data on its significance for graft function are currently limited. Purpose: To examine the correlation between the result of early postoperative hepatobiliary scintigraphy and pre- and postoperative biochemical parameters in liver transplantation (LTx) patients. Material and Methods: Six parameters of hepatobiliary scintigraphy using 99mTc mebrofenin were statistically analyzed in 108 LTx patients: 1) half-life of the activity of elimination of mebrofenin from the blood; 2) total clearance of mebrofenin from the blood due to all possible routes; 3) half-life of the activity due to liver uptake; 4) clearance of mebrofenin from the blood due to liver uptake; 5) time to maximal uptake in the liver; and 6) the hepatic extraction fraction (HEF) and biochemical data. Analysis between patients with preoperative normal liver function, familial amyloid polyneuropathy (FAP), and end-stage liver disease (non-FAP) was also performed. Results: Univariate and multivariate analysis revealed that total bilirubin postoperative day 3 correlated with all three scintigraphic parameters, and peak aspartate aminotransferase and alanine aminotransferase correlated with HEF. The analysis between patients with FAP and non-FAP revealed no significant difference of scintigraphic data between the two groups. Conclusion: A significant correlation between early postoperative scintigraphic results and biochemical parameters was demonstrated.
|
|
| 24. |
|
|
| 25. |
- Leta, Tesfaye H., et al.
(författare)
-
Periprosthetic Joint Infection After Total Knee Arthroplasty With or Without Antibiotic Bone Cement
- 2024
-
Ingår i: JAMA Network Open. - 2574-3805. ; 7:5, s. 2412898-2412898
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: Despite increased use of antibiotic-loaded bone cement (ALBC) in joint arthroplasty over recent decades, current evidence for prophylactic use of ALBC to reduce risk of periprosthetic joint infection (PJI) is insufficient. Objective: To compare the rate of revision attributed to PJI following primary total knee arthroplasty (TKA) using ALBC vs plain bone cement. Design, Setting, and Participants: This international cohort study used data from 14 national or regional joint arthroplasty registries in Australia, Denmark, Finland, Germany, Italy, New Zealand, Norway, Romania, Sweden, Switzerland, the Netherlands, the UK, and the US. The study included primary TKAs for osteoarthritis registered from January 1, 2010, to December 31, 2020, and followed-up until December 31, 2021. Data analysis was performed from April to September 2023. Exposure: Primary TKA with ALBC vs plain bone cement. Main Outcomes and Measures: The primary outcome was risk of 1-year revision for PJI. Using a distributed data network analysis method, data were harmonized, and a cumulative revision rate was calculated (1 - Kaplan-Meier), and Cox regression analyses were performed within the 10 registries using both cement types. A meta-analysis was then performed to combine all aggregated data and evaluate the risk of 1-year revision for PJI and all causes. Results: Among 2 168 924 TKAs included, 93% were performed with ALBC. Most TKAs were performed in female patients (59.5%) and patients aged 65 to 74 years (39.9%), fully cemented (92.2%), and in the 2015 to 2020 period (62.5%). All participating registries reported a cumulative 1-year revision rate for PJI of less than 1% following primary TKA with ALBC (range, 0.21%-0.80%) and with plain bone cement (range, 0.23%-0.70%). The meta-analyses based on adjusted Cox regression for 1 917 190 TKAs showed no statistically significant difference at 1 year in risk of revision for PJI (hazard rate ratio, 1.16; 95% CI, 0.89-1.52) or for all causes (hazard rate ratio, 1.12; 95% CI, 0.89-1.40) among TKAs performed with ALBC vs plain bone cement. Conclusions and Relevance: In this study, the risk of revision for PJI was similar between ALBC and plain bone cement following primary TKA. Any additional costs of ALBC and its relative value in reducing revision risk should be considered in the context of the overall health care delivery system.
|
|
