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- d'Amore, Francesco, et al.
(författare)
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Phase II trial of zanolimumab (HuMax-CD4) in relapsed or refractory non-cutaneous peripheral T cell lymphoma
- 2010
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 150:5, s. 565-573
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Tidskriftsartikel (refereegranskat)abstract
- The efficacy and safety of zanolimumab (HuMax-CD4) in patients with relapsed or refractory peripheral T Cell lymphoma (PTCL) was evaluated. Twenty-one adult patients with relapsed or refractory CD4+ PTCL of non-cutaneous type (angioimmunoblastic T cell lymphoma (AITL) n = 9, PTCL-not otherwise specified (NOS) n = 7, anaplastic large cell lymphoma (ALCL) n = 4 and enteropathy type T cell lymphoma n = 1) were treated in a single-arm multi-centre study, with weekly intravenous infusions of zanolimumab 980 mg for 12 weeks. Median age was 69 years (range 26-85). Seventeen of the patients had advanced stage disease (Ann Arbor stages III-IV). Objective tumour responses were obtained in 24% of the patients with two complete responses unconfirmed (CRu) and three partial responses (PR). One of the CRus lasted more than 252 d. Responses were obtained in different PTCL entities: AITL (n = 3), ALCL (n = 1) and PTCL-NOS (n = 1). In general, the trial drug was well tolerated with no major toxicity. Zanolimumab at a dose of 980 mg weekly demonstrated clinical activity and an acceptable safety profile in this poor-prognosis patient population, suggesting that the potential benefit combining zanolimumab with standard chemotherapy in the treatment of PTCL should be investigated.
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| 2. |
- Mahajan, Anubha, et al.
(författare)
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Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
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Tidskriftsartikel (refereegranskat)abstract
- We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
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| 3. |
- Persson, Jonas, et al.
(författare)
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Efficacy and safety of clopidogrel after PCI with stenting in patients on oral anticoagulants with acute coronary syndrome
- 2011
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Ingår i: EUROINTERVENTION. - : EUROPA EDITION, 5, RUE SAINT-PANTALEON, BP 61508, TOULOUSE CEDEX 6, 31015, FRANCE. - 1774-024X. ; 6:9, s. 1046-1052
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To evaluate crude cardiovascular risk in patients with acute coronary syndrome (ACS) who are on oral anticoagulants (OAC) after percutaneous coronary intervention with stents (PCI-S) and also to evaluate if the patients on OAC after PCI-S benefit from clopidogrel. less thanbrgreater than less thanbrgreater thanMethods and results: Data from RIKS-HIA and SCAAR on patients admitted to coronary care units 1997 to 2005, undergoing PCI-S (n=27,972), were evaluated. OAC were prescribed to 4.2% (n=1,183) of the patients and they had higher crude 1-year mortality than the non-OAC group, (3.6% [n=421 vs. 1.5% [n= 413], p=0.008), but after adjusting for pre-treatment patient characteristics there were no significant difference in 1-year mortality (adjusted risk ratio [adj. RR] 0.82 [95% CI 0.58-1.16]). Of patients on OAC, 56% (n=659) were also on clopidogrel at discharge. Incidence of death or myocardial infarction (MI) within one year did not differ between the clopidogrel and non-clopidogrel group, adj. RR 0.93 (95% Cl 0.65-1.34). Triple therapy (OAC, clopidogrel plus aspirin) was associated with four times higher risk of any bleeding than OAC plus aspirin, adj. RR 4.27 (95% Cl 1.2-15.1) but a lower incidence of death or MI than OAC plus clopidogrel adj. RR 0.63 (95% Cl 0.40-0.99) less thanbrgreater than less thanbrgreater thanConclusions: Patients discharged on OAC after PCI-S in ACS have higher crude 1-year mortality than patients not on OAC, largely explained by age and comorbidities. Adding clopidogrel is not associated with lower incidence of death or MI at one year. Triple therapy is associated with higher risk of any bleeding than OAC plus aspirin but lower risk of death or MI than OAC plus clopidogrel.
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