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41.
Yvan?BeaussantEmail author Florence?Mathieu-Nicot Lionel?Pazart Christophe?Tournigand Serge?Daneault Elodie?Cretin Aurélie?Godard-Marceau Aline?Chassagne Hélène?Trimaille Carole?Bouleuc Patrice?Cuynet Eric?Deconinck Régis?Aubry 《BMC palliative care》2015,14(1):61
Background
Little is known about what is at stake at a subjective level for the oncologists and the advanced cancer patients when they face the question whether to continue, limit or stop specific therapies. We studied (1) the frequency of such questioning, and (2) subjective determinants of the decision-making process from the physicians’ and the patients’ perspectives.Methods
(1) All hospitalized patients were screened during 1 week in oncology and/or hematology units of five institutions. We included those with advanced cancer for whom a questioning about the pursuit, the limitation or the withholding of specific therapies (QST) was raised. (2) Qualitative design was based on in-depth interviews.Results
In conventional units, 12.8 % of cancer patients (26 out of 202) were concerned by a QST during the study period. Interviews were conducted with all physicians and 21 advanced cancer patients. The timing of this questioning occurred most frequently as physicians estimated life expectancy between 15 days and 3 months. Faced with the most frequent dilemma (uncertain risk-benefit balance), physicians showed different ways of involving patients. The first two were called the “no choice” models: 1) trying to resolve the dilemma via a technical answer or a “wait-and-see” posture, instead of involving the patients in the questioning and the thinking; and 2), giving a “last minute” choice to the patients, leaving to them the responsibility of the decision. In a third model, they engaged early in shared reflections and dialogue about uncertainties and limits with patients, proxies and care teams. These schematic trends influenced patients’ attitudes towards uncertainty and limits, as they were influenced by these ones. Individual and systemic barriers to a shared questioning were pointed out by physicians and patients.Conclusions
This study indicate to what extent these difficult decisions are related to physicians’ and patients’ respective and mutually influenced abilities to deal with and share about uncertainties and limits, throughout the disease trajectory. These insights may help physicians, patients and policy makers to enrich their understanding of underestimated and sensitive key issues of the decision-making process.42.
Laurent Dortet Mirela Flonta Yves-Marie Boudehen Elodie Creton Sandrine Bernabeu Ana?s Vogel Thierry Naas 《Antimicrobial agents and chemotherapy》2015,59(11):7100-7103
Fifteen carbapenemase-producing Enterobacteriaceae isolates and 12 carbapenemase-producing Pseudomonas aeruginosa isolates were recovered from patients hospitalized between August 2011 and March 2013 at the Hospital of Infectious Disease, Cluj-Napoca, Romania. One KPC-, nine NDM-1-, four OXA-48-, and one VIM-4-producing Enterobacteriaceae isolates along with 11 VIM-2-producing and one IMP-13-producing P. aeruginosa isolates were recovered from clinical samples. All carbapenemase genes were located on self-conjugative plasmids and were associated with other resistance determinants, including extended-spectrum β-lactamases and RmtC methylases. 相似文献
43.
Séverine Bézie Elodie Picarda Jason Ossart Laurent Tesson Claire Usal Karine Renaudin Ignacio Anegon Carole Guillonneau 《The Journal of clinical investigation》2015,125(10):3952-3964
Cytokines and metabolic pathway–controlling enzymes regulate immune responses and have potential as powerful tools to mediate immune tolerance. Blockade of the interaction between CD40 and CD40L induces long-term cardiac allograft survival in rats through a CD8+CD45RClo Treg potentiation. Here, we have shown that the cytokine IL-34, the immunoregulatory properties of which have not been previously studied in transplantation or T cell biology, is expressed by rodent CD8+CD45RClo Tregs and human FOXP3+CD45RCloCD8+ and CD4+ Tregs. IL-34 was involved in the suppressive function of both CD8+ and CD4+ Tregs and markedly inhibited alloreactive immune responses. Additionally, in a rat cardiac allograft model, IL-34 potently induced transplant tolerance that was associated with a total inhibition of alloantibody production. Treatment of rats with IL-34 promoted allograft tolerance that was mediated by induction of CD8+ and CD4+ Tregs. Moreover, these Tregs were capable of serial tolerance induction through modulation of macrophages that migrate early to the graft. Finally, we demonstrated that human macrophages cultured in the presence of IL-34 greatly expanded CD8+ and CD4+ FOXP3+ Tregs, with a superior suppressive potential of antidonor immune responses compared with non–IL-34–expanded Tregs. In conclusion, we reveal that IL-34 serves as a suppressive Treg–specific cytokine and as a tolerogenic cytokine that efficiently inhibits alloreactive immune responses and mediates transplant tolerance. 相似文献
44.
Elodie Fallet Michel Rayar Amandine Landrieux Christophe Camus Pauline Houssel-Debry Caroline Jezequel Ludivine Legros Thomas Uguen Martine Ropert-Bouchet Karim Boudjema Dominique Guyader Edouard Bardou-Jacquet 《World journal of gastroenterology : WJG》2020,26(16):1938-1949
BACKGROUND Liver transplantation(LT) is the best treatment for patients with liver cancer or end stage cirrhosis, but it is still associated with a significant mortality. Therefore identifying factors associated with mortality could help improve patient management. The impact of iron metabolism, which could be a relevant therapeutic target, yield discrepant results in this setting. Previous studies suggest that increased serum ferritin is associated with higher mortality.Surprisingly iron deficiency which is a well described risk factor in critically ill patients has not been considered.AIM To assess the impact of pre-transplant iron metabolism parameters on posttransplant survival.METHODS From 2001 to 2011, 553 patients who underwent LT with iron metabolism parameters available at LT evaluation were included. Data were prospectively recorded at the time of evaluation and at the time of LT regarding donor and recipient. Serum ferritin(SF) and transferrin saturation(TS) were studied as continuous and categorical variable. Cox regression analysis was used to determine mortality risks factors. Follow-up data were obtained from the local and national database regarding causes of death.RESULTS At the end of a 95-mo median follow-up, 196 patients were dead, 38 of them because of infections. In multivariate analysis, overall mortality was significantly associated with TS 75% [HR: 1.73(1.14; 2.63)], SF 100 μg/L [HR: 1.62(1.12;2.35)], hepatocellular carcinoma [HR: 1.58(1.15; 2.26)], estimated glomerular filtration rate(CKD EPI Cystatin C) [HR: 0.99(0.98; 0.99)], and packed red blood cell transfusion [HR: 1.05(1.03; 1.08)]. Kaplan Meier curves show that patients with low SF( 100 μg/L) or high SF( 400 μg/L) have lower survival rates at 36 mo than patients with normal SF(P = 0.008 and P = 0.016 respectively). Patients with TS higher than 75% had higher mortality at 12 mo(91.4% ± 1.4% vs 84.6% ±3.1%, P = 0.039). TS 75% was significantly associated with infection related death [HR: 3.06(1.13; 8.23)].CONCLUSION Our results show that iron metabolism imbalance(either deficiency or overload)is associated with post-transplant overall and infectious mortality. Impact of iron supplementation or depletion should be assessed in prospective study. 相似文献
45.
Elodie Elkaim Christophe Picard Claire Galambrun Vincent Barlogis Anderson Loundou Catherine Curtillet Claire Oudin Isabelle Thuret Hervé Chambost Gérard Michel 《British journal of haematology》2014,166(4):557-565
This study aimed to describe kinetics of complete donor chimerism occurrence (cDC, >99·9% donor) after unrelated cord blood transplantation (UCBT), to identify its predictive factors and its impact on post‐transplant outcome. Ninety‐four children who received single UCBT after a myeloablative conditioning regimen had blood chimerism evaluation at predefined post‐transplant dates, using a real‐time polymerase chain reaction method with 0·1% sensitivity. Cumulative incidence of cDC at 1 year post‐transplantation was 61·8%. Three predictive factors were identified in multivariate analysis: history of malignant disease (P = 0·03), older age (above 2·16 years, the first quartile of age, P = 0·0055) and higher level of cord/recipient human leucocyte antigen mismatch (4/6 vs. 5‐6/6, P < 0·001) increased the probability of post‐transplant cDC. Although graft cell dose had a strong impact on haematological recovery, it did not apparently influence cDC occurrence. Early cDC (i.e. more than 99·9% donor chimerism on days 15–30 post‐transplant) appeared useful to predict engraftment (P = 0·003) as well as acute and chronic graft‐versus‐host disease (GvHD). Severe acute or chronic GvHD never occurred in patients with DC ≤99·9%, suggesting than even minimal residual host haematopoiesis is associated with a very low risk of GvHD after UCBT. 相似文献
46.
Martine Vaxillaire Loïc Yengo Stéphane Lobbens Ghislain Rocheleau Elodie Eury Olivier Lantieri Michel Marre Beverley Balkau Amélie Bonnefond Philippe Froguel 《Diabetologia》2014,57(8):1601-1610
Aims/hypothesis
Genome-wide association studies have firmly established 65 independent European-derived loci associated with type 2 diabetes and 36 loci contributing to variations in fasting plasma glucose (FPG). Using individual data from the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) prospective study, we evaluated the contribution of three genetic risk scores (GRS) to variations in metabolic traits, and to the incidence and prevalence of impaired fasting glycaemia (IFG) and type 2 diabetes.Methods
Three GRS (GRS-1, 65 type 2 diabetes-associated single nucleotide polymorphisms [SNPs]; GRS-2, GRS-1 combined with 24 FPG-raising SNPs; and GRS-3, FPG-raising SNPs alone) were analysed in 4,075 DESIR study participants. GRS-mediated effects on longitudinal variations in quantitative traits were assessed in 3,927 nondiabetic individuals using multivariate linear mixed models, and on the incidence and prevalence of hyperglycaemia at 9 years using Cox and logistic regression models. The contribution of each GRS to risk prediction was evaluated using the C-statistic and net reclassification improvement (NRI) analysis.Results
The two most inclusive GRS were significantly associated with increased FPG (β?=?0.0011 mmol/l per year per risk allele, p GRS-1 ?=?8.2?×?10?5 and p GRS-2 ?=?6.0?×?10?6), increased incidence of IFG and type 2 diabetes (per allele: HR GRS-1 1.03, p?=?4.3?×?10?9 and HR GRS-2 1.04, p?=?1.0?×?10?16), and the 9 year prevalence (OR GRS-1 1.13 [95% CI 1.10, 1.17], p?=?1.9?×?10?14 for type 2 diabetes only; OR GRS-2 1.07 [95% CI 1.05, 1.08], p?=?7.8?×?10?25, for IFG and type 2 diabetes). No significant interaction was found between GRS-1 or GRS-2 and potential confounding factors. Each GRS yielded a modest, but significant, improvement in overall reclassification rates (NRI GRS-1 17.3%, p?=?6.6?×?10?7; NRI GRS-2 17.6%, p?=?4.2?×?10?7; NRI GRS-3 13.1%, p?=?1.7?×?10?4).Conclusions/interpretation
Polygenic scores based on combined genetic information from type 2 diabetes risk and FPG variation contribute to discriminating middle-aged individuals at risk of developing type 2 diabetes in a general population. 相似文献47.
Agnès B. Jousset Sandrine Bernabeu Remy A. Bonnin Elodie Creton Garance Cotellon Aimie Sauvadet Thierry Naas Laurent Dortet 《International journal of antimicrobial agents》2019,53(3):302-309
Plasmid-mediated colistin resistance is increasingly described worldwide in Enterobacteriaceae from animal and human isolates. Diffusion of these resistance traits among carbapenem-resistant enterobacterial isolates is of particular concern as colistin has become the last resort antibiotic for treating human infections with these organisms. Therefore, being able to monitor the presence of these transferable colistin resistance genes (mcr-1 to mcr-5-variants) is crucial. This paper describes the development of a multiplex polymerase chain reaction (PCR) protocol for detection of all currently known transferable colistin resistance genes in Enterobacteriaceae. Five primer pairs were designed to amplify mcr-1, mcr-2, mcr-3, mcr-4 and mcr-5 gene products in a multiplex PCR. This assay was validated retrospectively on colonies of 50 Escherichia coli, 44 Klebsiella pneumoniae and 12 Salmonella enterica isolates of animal and human origin, all well characterized, and validated prospectively on 450 carbapenem-resistant enterobacterial isolates received by the French National Reference Centre. In addition, 82 Aeromonas spp. and 10 Shewanella spp. known to be the progenitors of mcr-3 and mcr-4 alleles, respectively, were screened. Mcr-multiplex PCR assay displayed 100% specificity, sensitivity, negative predictive value and positive predictive value. The assay was able to detect all variants of the different mcr alleles, and was able to detect chromosomally encoded mcr-4-like variants present in two Shewanella bicestrii JAB-1 and Shewanella woodyi S539. In conclusion, a rapid and robust multiplex PCR assay able to detect all known mcr gene families described in Enterobacteriaceae was developed and validated. This type of test is critical for the epidemiological surveillance of plasmid-encoded resistance, especially in carbapenem-resistant bacteria. 相似文献
48.
49.
Thachil E Hugot JP Arbeille B Paris R Grodet A Peuchmaur M Codogno P Barreau F Ogier-Denis E Berrebi D Viala J 《Gastroenterology》2012,142(5):1097-1099.e4
Autophagy-related 16 like-1 (ATG16L-1), immunity-related GTPase-M (IRGM), and nucleotide-binding oligomerization domain-containing 2 (NOD2) regulate autophagy, and variants in these genes have been associated with predisposition to Crohn's disease (CD). However, little is known about the role of autophagy in CD. Intestinal biopsies from untreated pediatric patients with CD, celiac disease, or ulcerative colitis were analyzed by immunohistochemistry and electron microscopy. We observed that autophagy was specifically activated in Paneth cells from patients with CD, independently of mucosal inflammation or disease-associated variants of ATG16L1 or IRGM. In these cells, activation of autophagy was associated with a significant decrease in number of secretory granules and features of crinophagy. These observations might account for the disorganization of secretory granules previously reported in Paneth cells from patients with CD. 相似文献
50.
Chandler EM Seo BR Califano JP Andresen Eguiluz RC Lee JS Yoon CJ Tims DT Wang JX Cheng L Mohanan S Buckley MR Cohen I Nikitin AY Williams RM Gourdon D Reinhart-King CA Fischbach C 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(25):9786-9791
Multipotent adipose-derived stem cells (ASCs) are increasingly used for regenerative purposes such as soft tissue reconstruction following mastectomy; however, the ability of tumors to commandeer ASC functions to advance tumor progression is not well understood. Through the integration of physical sciences and oncology approaches we investigated the capability of tumor-derived chemical and mechanical cues to enhance ASC-mediated contributions to tumor stroma formation. Our results indicate that soluble factors from breast cancer cells inhibit adipogenic differentiation while increasing proliferation, proangiogenic factor secretion, and myofibroblastic differentiation of ASCs. This altered ASC phenotype led to varied extracellular matrix (ECM) deposition and contraction thereby enhancing tissue stiffness, a characteristic feature of breast tumors. Increased stiffness, in turn, facilitated changes in ASC behavior similar to those observed with tumor-derived chemical cues. Orthotopic mouse studies further confirmed the pathological relevance of ASCs in tumor progression and stiffness in vivo. In summary, altered ASC behavior can promote tumorigenesis and, thus, their implementation for regenerative therapy should be carefully considered in patients previously treated for cancer. 相似文献