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101.
ASXL1 and CBL mutations are independently predictive of inferior survival in advanced systemic mastocytosis 下载免费PDF全文
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Calreticulin variant stratified driver mutational status and prognosis in essential thrombocythemia 下载免费PDF全文
Yoseph C. Elala Terra L. Lasho Naseema Gangat Christy Finke Daniela Barraco Mahnur Haider Ahmed K. Abou Hussein Curtis A. Hanson Rhett P. Ketterling Animesh Pardanani Ayalew Tefferi 《American journal of hematology》2016,91(5):503-506
About 85% of patients with essential thrombocythemia (ET) harbor one of three driver mutations: JAK2, calreticulin (CALR), and MPL; the remaining ( ~15%) are wild type for all three mutations and are referred to as being “triple negative.” Furthermore, CALR mutations in ET are structurally classified as type 1/type 1‐like or type 2/type 2‐like variants. The objective of the current study was to examine the impact of CALR mutation variant stratified driver mutational status on overall (OS), myelofibrosis‐free (MFFS), thrombosis‐free, and leukemia‐free survival (LFS) in ET; 495 patients (median age 58 years; 61% females) with ET were fully annotated for the their driver mutational status: 321 (65%) harbored JAK2, 109 (22%) CALR, and 12 (2%) MPL mutations and 11% were triple‐negative. Among the 109 CALR‐mutated cases, 52% were classified as type 1/type 1‐like and 48% as type 2/type 2‐like. In univariate analysis, triple‐negative patients displayed the best and MPL mutated the worst OS (P = 0.007); however, the difference in OS was no longer apparent on multivariable analysis that included age and sex as covariates (P = 0.5). LFS was also similar among the different mutational groups (P = 0.6) whereas MFFS was significantly shorter in MPL‐mutated patients on both univariate and multivariable analyses (age‐adjusted P = 0.02; HR 7.9, 95% CI 2.0–31.5). Also in multivariable analysis that included thrombosis history, age, and cardiovascular risk factors, the presence of JAK2 or MPL mutations was independently associated with higher risk of thrombosis (P = 0.02; HR 1.9, 95% CI 1.1–3.4). In conclusion, driver mutational status in ET does not appear to influence overall or LFS, even after CALR variant stratification. However, the presence of MPL mutations might be associated with a higher risk of fibrotic transformation and the presence of JAK2/MPL mutations with higher risk of thrombosis. Am. J. Hematol. 91:503–506, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
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Douglas A. MacDonald Joel Martin Kathir K. Muthusamy Jiann-Kae Luo Erica Pyles Ashique Rafique Tammy Huang Terra Potocky Yang Liu Jingtai Cao Françoise Bono Nathalie Delesque Pierre Savi John Francis Ali Amirkhosravi Todd Meyer Carmelo Romano Meredith Glinka George D. Yancopoulos Neil Stahl Stanley J. Wiegand Nicholas Papadopoulos 《Angiogenesis》2016,19(3):389-406
Anti-vascular endothelial growth factor (VEGF) therapies have improved clinical outcomes for patients with cancers and retinal vascular diseases. Three anti-VEGF agents, pegaptanib, ranibizumab, and aflibercept, are approved for ophthalmic indications, while bevacizumab is approved to treat colorectal, lung, and renal cancers, but is also used off-label to treat ocular vascular diseases. The efficacy of bevacizumab relative to ranibizumab in treating neovascular age-related macular degeneration has been assessed in several trials. However, questions persist regarding its safety, as bevacizumab can form large complexes with dimeric VEGF165, resulting in multimerization of the Fc domain and platelet activation. Here, we compare binding stoichiometry, Fcγ receptor affinity, platelet activation, and binding to epithelial and endothelial cells in vitro for bevacizumab and aflibercept, in the absence or presence of VEGF. In contrast to bevacizumab, aflibercept forms a homogenous 1:1 complex with each VEGF dimer. Unlike multimeric bevacizumab:VEGF complexes, the monomeric aflibercept:VEGF complex does not exhibit increased affinity for low-affinity Fcγ receptors, does not activate platelets, nor does it bind to the surface of epithelial or endothelial cells to a greater degree than unbound aflibercept or control Fc. The latter finding reflects the fact that aflibercept binds VEGF in a unique manner, distinct from antibodies not only blocking the amino acids necessary for VEGFR1/R2 binding but also occluding the heparin-binding site on VEGF165. 相似文献
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Robert Hemke Marion A. J. van Rossum Mira van Veenendaal Maaike P. Terra Eline E. Deurloo Milko C. de Jonge J. Merlijn van den Berg Koert M. Dolman Taco W. Kuijpers Mario Maas 《European radiology》2013,23(4):1075-1083
Objectives
To assess the reliability and responsiveness of a new Juvenile Arthritis MRI Scoring (JAMRIS) system for evaluating disease activity of the knee.Methods
Twenty-five juvenile idiopathic arthritis (JIA) patients with clinical knee involvement were studied using open-bore 1-T MRI. MRI features of synovial hypertrophy, bone marrow changes, cartilage lesions and bone erosions were independently scored by five readers using the JAMRIS system. In addition, the JAMRIS system was determined to be a follow-up parameter by two readers to evaluate the response to therapy in 15 consecutive JIA patients.Results
Inter-reader (ICCs 0.86–0.95) and intra-reader reliability (ICCs 0.92–1.00) for the scoring of JAMRIS features was good. Reliability of the actual scores and changes in scores over time was good for all items: ICCs 0.89–1.00, 0.87–1.00, respectively. Concerning therapy response, the mean synovial hypertrophy scores decreased significantly (mean 1.1 point; P?<?0.001, SRM?=??0.65). No change was observed with respect to bone marrow change, cartilage lesion and bone erosion scores.Conclusions
The JAMRIS proved to be a simple and highly reliable assessment score in the evaluation of JIA disease activity of the knee. The JAMRIS system may serve as an objective and accurate outcome measure in future research and clinical trials.Key Points
? MRI is increasingly used to diagnose and assess juvenile idiopathic arthritis. ? A simple and reliable scoring method would help monitor progress and research. ? The Juvenile Arthritis MRI Scoring (JAMRIS) system provides reliable objective measures. ? JAMRIS evaluates synovial hypertrophy, bone marrow changes, cartilage lesions and bone erosions. ? The JAMRIS system can detect therapeutic response and should help future research. 相似文献106.
Favoreto Michael Willian Vochikovski Laína Terra Renata Maria Oleniki Campos Veridiana Silva Santos Mariana Evangelista Meireles Sônia Saeger Reis Alessandra Loguercio Alessandro D. 《Clinical oral investigations》2022,26(3):2555-2564
Clinical Oral Investigations - To evaluate if the topical application of Otosporin® before in-office bleaching with a 35% hydrogen peroxide (HP) gel reduces the risk and intensity of tooth... 相似文献
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