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101.
BCL2 mutations do not confer adverse prognosis in follicular lymphoma patients treated with rituximab 下载免费PDF全文
Sarah Huet Edith Szafer‐Glusman Bruno Tesson Luc Xerri Wayne J. Fairbrother Kiran Mukhyala Chris Bolen Elizabeth Punnoose Laurie Tonon Catherine Chassagne‐Clément Pierre Feugier Alain Viari Fabrice Jardin Gilles Salles Pierre Sujobert 《American journal of hematology》2017,92(6):515-519
BCL2 mutations have been suggested to confer an adverse prognosis to follicular lymphoma (FL) patients, but their prognostic value has not been assessed in patients treated with a rituximab‐containing regimen. Here we evaluated the prognostic value of BCL2 mutations in a large prospective cohort of 252 patients with FL treated with immunochemotherapy in the PRIMA randomized trial. Using a DNA‐targeted sequencing approach, we detected amino acid altering mutations in 135 patients (54%) and showed that these mutations were probably mediated by the over‐activation of AICDA (activation‐induced cytidine deaminase) in the context of the t(14;18) translocation. The BCL2 variants identified in PRIMA patients affected the BH1, BH2, and BH3 functional motifs at a lower frequency than the N‐terminus and flexible loop domain, with mostly conservative aminoacid changes. With a median follow‐up of 6.7 years, we did not observe any impact of BCL2 mutations either on overall survival or progression‐free survival. 相似文献
102.
Walter J Paulus Carsten Tsch?pe John E Sanderson Cesare Rusconi Frank A Flachskampf Frank E Rademakers Paolo Marino Otto A Smiseth Gilles De Keulenaer Adelino F Leite-Moreira Attila Borbély István Edes Martin Louis Handoko Stephane Heymans Natalia Pezzali Burkert Pieske Kenneth Dickstein Alan G Fraser Dirk L Brutsaert 《European heart journal》2007,28(20):2539-2550
Diastolic heart failure (DHF) currently accounts for more than 50% of all heart failure patients. DHF is also referred to as heart failure with normal left ventricular (LV) ejection fraction (HFNEF) to indicate that HFNEF could be a precursor of heart failure with reduced LVEF. Because of improved cardiac imaging and because of widespread clinical use of plasma levels of natriuretic peptides, diagnostic criteria for HFNEF needed to be updated. The diagnosis of HFNEF requires the following conditions to be satisfied: (i) signs or symptoms of heart failure; (ii) normal or mildly abnormal systolic LV function; (iii) evidence of diastolic LV dysfunction. Normal or mildly abnormal systolic LV function implies both an LVEF > 50% and an LV end-diastolic volume index (LVEDVI) <97 mL/m(2). Diagnostic evidence of diastolic LV dysfunction can be obtained invasively (LV end-diastolic pressure >16 mmHg or mean pulmonary capillary wedge pressure >12 mmHg) or non-invasively by tissue Doppler (TD) (E/E' > 15). If TD yields an E/E' ratio suggestive of diastolic LV dysfunction (15 > E/E' > 8), additional non-invasive investigations are required for diagnostic evidence of diastolic LV dysfunction. These can consist of blood flow Doppler of mitral valve or pulmonary veins, echo measures of LV mass index or left atrial volume index, electrocardiographic evidence of atrial fibrillation, or plasma levels of natriuretic peptides. If plasma levels of natriuretic peptides are elevated, diagnostic evidence of diastolic LV dysfunction also requires additional non-invasive investigations such as TD, blood flow Doppler of mitral valve or pulmonary veins, echo measures of LV mass index or left atrial volume index, or electrocardiographic evidence of atrial fibrillation. A similar strategy with focus on a high negative predictive value of successive investigations is proposed for the exclusion of HFNEF in patients with breathlessness and no signs of congestion. The updated strategies for the diagnosis and exclusion of HFNEF are useful not only for individual patient management but also for patient recruitment in future clinical trials exploring therapies for HFNEF. 相似文献
103.
Alexandre Janin Valrie Chanavat Pierre‐Antoine Rollat‐Farnier Claire Bardel Karine Nguyen Philippe Chevalier Jean‐Christophe Eicher Laurence Faivre Juliette Piard Emma Albert Severine Nony Gilles Millat 《Human mutation》2020,41(2):465-475
Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy, historically believed to affect 1 of 500 people. MYBPC3 pathogenic variations are the most frequent cause of familial HCM and more than 90% of them introduce a premature termination codon. The current study aims to determine the prevalence of deep intronic MYBPC3 pathogenic variations that could lead to splice mutations. To improve molecular diagnosis, a next‐generation sequencing (NGS) workflow based on whole MYBPC3 sequencing of a cohort of 93 HCM patients, for whom no putatively causative point mutations were identified after NGS sequencing of a panel of 48 cardiomyopathy‐causing genes, was performed. Our approach led us to reconsider the molecular diagnosis of six patients of the cohort (6.5%). These HCM probands were carriers of either a new large MYBPC3 rearrangement or splice intronic variations (five cases). Four pathogenic intronic variations, including three novel ones, were detected. Among them, the prevalence of one of them (NM_000256.3:c.1927+ 600 C>T) was estimated at about 0.35% by the screening of 1,040 unrelated HCM individuals. This study suggests that deep MYBPC3 splice mutations account for a significant proportion of HCM cases (6.5% of this cohort). Consequently, NGS sequencing of MYBPC3 intronic sequences have to be performed systematically. 相似文献
104.
Practice patterns and clinical outcomes among non‐ST‐segment elevation acute coronary syndrome (NSTE‐ACS) patients presenting to primary and tertiary hospitals: Insights from the EARLY glycoprotein IIb/IIIa inhibition in NSTE‐ACS (EARLY‐ACS) trial 下载免费PDF全文
Olga Toleva MD Cynthia M. Westerhout PhD Manohara P.J. Senaratne MBBS PhD Christoph Bode MD Magnus Lindroos MD PhD Vitaly A. Sulimov MD PhD Gilles Montalescot MD L. Kristin Newby MD MHS Robert P. Giugliano MD SM Frans Van de Werf MD PhD Paul W. Armstrong MD 《Catheterization and cardiovascular interventions》2014,84(6):934-942
105.
Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study 下载免费PDF全文
Salles G Mounier N de Guibert S Morschhauser F Doyen C Rossi JF Haioun C Brice P Mahé B Bouabdallah R Audhuy B Ferme C Dartigeas C Feugier P Sebban C Xerri L Foussard C 《Blood》2008,112(13):4824-4831
The FL2000 study was undertaken to evaluate the combination of the anti-CD20 monoclonal antibody rituximab with chemotherapy plus interferon in the first-line treatment of follicular lymphoma patients with a high tumor burden. Patients were randomly assigned to receive either 12 courses of the chemotherapy regimen CHVP (cyclophosphamide, adriamycin, etoposide, and prednisolone) plus interferon-alpha2a (CHVP+I arm) over 18 months or 6 courses of the same chemotherapy regimen combined with 6 infusions of 375 mg/m(2) rituximab and interferon for the same time period (R-CHVP+I arm). After a median follow-up of 5 years, event-free survival estimates were, respectively, 37% (95% confidence interval [CI], 29%-44%) and 53% (95% CI, 45%-60%) in the CHVP+I and R-CHVP+I arm (P = .001). Five-year overall survival estimates were not statistically different in the CHVP+I (79%; 95% CI, 72%-84%) and R-CHVP+I (84%; 95% CI, 78%-84%) arms. In a multivariate regression analysis, event-free survival was significantly influenced by both the Follicular Lymphoma International Prognostic Index score (hazard ratio = 2.08; 95% CI, 1.6%-2.8%) and the treatment arm (hazard ratio = 0.59; 95% CI, 0.44%-0.78%). With a 5-year follow-up, the combination of rituximab with CHVP+I provides superior disease control in follicular lymphoma patients despite a shorter duration of chemotherapy. This study's clinical trial was registered at the National Institutes of Health website as no. NCT00136552. 相似文献
106.
107.
Association between hepatitis B co‐infection and elevated liver stiffness among HIV‐infected adults in Lusaka,Zambia 下载免费PDF全文
Michael J. Vinikoor Lloyd Mulenga Alice Siyunda Kalo Musukuma Roma Chilengi Carolyn Bolton Moore Benjamin H. Chi Mary‐Ann Davies Matthias Egger Gilles Wandeler International Epidemiologic Databases to Evaluate AIDS in Southern Africa 《Tropical medicine & international health : TM & IH》2016,21(11):1435-1441
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