Prevention of post-mastectomy neuropathic pain with memantine: study protocol for a randomized controlled trial

International audienceBackground: N-methyl-D-aspartate receptor antagonists are potential therapies for neuropathic pain, and memantine has a good tolerance profile. A preclinical study recently reported that presurgery memantine may prevent neuropathic pain development and cognition dysfunction. Considering the high prevalence of breast cancer and of post-mastectomy neuropathic pain, a clinical trial is carried out to evaluate if memantine may prevent neuropathic pain development and maintain cognitive function and quality of life in cancer patients. Methods/Design: A randomized clinical trial (NCT01536314) includes 40 women with breast cancer undergoing mastectomy at the Oncology Hospital, Clermont-Ferrand, France. Memantine (5 to 20 mg/day; n = 20) or placebo (n = 20) is administered for 4 weeks starting 2 weeks before surgery. Intensity of pain, cognitive function, quality of life and of sleep, anxiety and depression are evaluated with questionnaires. The primary endpoint is pain intensity on a 0 to 10) numerical scale at 3 months post-mastectomy. Data analysis is performed using mixed models and the tests are two-sided, with a type I error set at α = 0.05. Discussion: The hypothesis of this translational approach is to confirm in patients the beneficial prophylactic effect of memantine observed in animals. Such a protective action of memantine against neuropathic pain and cognitive dysfunction would greatly improve the quality of life of cancer patients. Trial registration: ClinicalTrials.gov: NCT01536314 on 16 February 201

janvier-février 2015

Rendre hommage et dire non, ensemble ! Face à la barbarie et au fanatisme, l’équipe de l’OCIM rend hommage à l’ensemble des victimes des actes terroristes perpétrés les 7 et 9 janvier dernier et affirme son soutien aux journalistes, auteurs et dessinateurs de presse. Pour la défense de la liberté de la presse, de la liberté d’expression et plus généralement de la démocratie, un double mot d’ordre : résistance et solidarité. À cet égard, le rôle des acteurs culturels et singulièrement celui des musées et du monde de la culture scientifique et technique est important et aujourd‘hui, le discours sur la biodiversité culturelle et plus largement le questionnement éclairé sur la place de l’Homme dans le monde, délivrés par le musée des Confluences de Lyon, récemment ouvert, prennent tout leurs sens. Deux des contributions de ce numéro de La Lettre de l’OCIM – consacrées d’une part à l’expérience d’art-thérapie menée au musée de Dreux et d’autre part à la médiation scientifique et culturelle conçue par le muséum de Clermont-Ferrand pour les enfants hospitalisés – apportent des éléments de réponses à plusieurs interrogations : comment les animations culturelles au musée ou/et à l’hôpital peuvent-elles venir en complément des soins prodigués aux malades ? Face à la technicisation des traitements, comment ces animations permettent-elles de retisser du lien entre patients et soignants et contribuer à rompre l’isolement des malades ? Des enquêtes sur les conservations départementales des musées et sur la visite des musées en famille complètent le sommaire. En 2015, l’OCIM a trente ans et, parmi les événements organisés à l’occasion de cet anniversaire partagé,chaque numéro de La Lettre de l’OCIM proposera un nouvel éclairage sur une problématique développée dans un article publié au cours de ces années : pour ce premier numéro, Laure Cadot réexamine la question des restes humains dans les musées. Meilleurs vœux 2015 à toutes et à tous Serge Lochot, rédacteur en chef de la Lettre de l'OCIM

Predicting Pain Trajectories in the One Year Following Breast Cancer Diagnosis—An Observational Study

International audienceThe impact of psychosocial vulnerability on pain in the year following breast cancer diagnosis has been little studied. To identify a score of psychosocial vulnerability (cognitive, emotional, quality of life and precariousness parameters) as a predictor of a pain trajectory, we conducted an observational prospective study and included women with newly diagnosed breast cancer. One year follow-up with 3 visits (day of breast cancer diagnosis; 6 and 12 months) aimed to identify distinct pain-time trajectories. Baseline psychosocial vulnerability was characterized by z-score transformation, a higher score representing a more vulnerable patient. A total of 89 patients were included (59.3 ± 10.7 years). Two trajectories of pain were identified-"Transient Pain trajectory" (TP) (39/89 patients) and "Persistent Pain trajectory" (PP) (50/89). A significant difference of pain over time between trajectories (PP vs. TP at 6 months: 2.23 ± 0.23 vs. 0.27 ± 0.09, p < 0.001) was observed. Psychosocial vulnerability showed a large effect size (d, -0.82; 95% CI, -1.25 to -0.38; p < 0.001) and a higher score in "Persistent pain trajectory" (PP vs. TP: 0.12 ± 0.36 vs. -0.14 ± 0.26, p < 0.001). A predictive vulnerability marker of pain development is proposed and could be used at cancer diagnosis to orientate the care pathway of patients experiencing breast cancer

MRI investigation of internal defects in potato tubers with particular attention to rust spots induced by water stress

International audiencePotato quality is a major concern for both producers and customers. However, potato tubers are affected by various forms of internal damage with no external symptoms, leading to substantial economic losses. MRI was used as a non-invasive and quantitative method to evaluate internal defects in potato tubers and their evolution during storage. Rust spots, induced by water stress, were considered in particular. To this end, potato plants were cultivated both in the field and in pots and their water uptake was controlled. Following harvest and throughout the storage period, 3D images of tubers were recorded on a 1.5 T MRI scanner using a fast spin echo sequence. In parallel, the multi-exponential transverse relaxation times (T2) of the tubers were mapped in order to provide information on changes in water status and distribution at the subcellular level in rust spots and in healthy perimedullary regions. The occurrence of rust spots correlated with water conditions in greenhouse where water intake was carefully controlled. The number and individual volume of rust spots did not change during storage period, but they significantly increased with tuber size. Bi-exponential transverse relaxation revealed differences between healthy and damaged tissue

MRI method to evaluate effects of water stress on potato tubers during growing

International audienceDrought is a major problem affecting agricultural practices as a result of global warming. Potato is considered as a drought sensitive crop, which results in loss of yield and tuber quality. Further, water shortage may induce physiological disorders such as glassy tubers and internal rust spots. Potato response to drought is complex: it depends on cultivar, climatic and soil conditions and water stress timing within the growing period. Characterization of plant adaptive responses is a major issue in the field of phenotyping. There is therefore a demand for the emergence of analytical techniques that are non-invasive, allowing better performance of this phenotyping.In the current work, MRI was used to evaluate the effects of water stress on potato tubers by in situ monitoring of tubers growth kinetics during an eight-week period. In this respect, potato plants were cultivated in pots under controlled and stressed conditions. In the latter case, irrigation was monitored in a way to simulate cultivation of potatoes during drought seasons. The stress experienced by plant was evaluated through the monitoring of soil water potential and soil humidity. 3D morphological images of the underground part of the potato plant in pots were recorded on a 1.5 T MRI scanner (Avanto, Siemens) using a fast spin echo sequence (Fig. 1). The objectives were i) to evaluate the effect of water stress on the individual growth kinetics of tubers and ii) to detect the stage at which rust spots appear and monitor their evolution until harvest.The approaches developed in the present study were shown to be effective to characterize tuber development and quality, providing a quantitative analysis of morphological features of tubers. The results were discussed from the perspective of applying this methodology for phenotyping of plant under water shortage

Un moulin en bois de la première moitié du Ier siècle à Art-sur-Meurthe, L'Embanie (Départment Meurthe-et-Moselle, France)

International audienceSur la commune d’Art-sur-Meurthe les soubassements d’un moulin en bois, des canaux matérialisés par des piquets clayonnés et quelques éléments provenant du mécanisme (alluchon) et de la roue à aube (pales) ont été mis au jour dans un paléochenal situé le long de la Meurthe. Le moulin est installé dans un milieu largement ouvert dédié aux pâtures et à l’agriculture. Les matériaux ligneux qui ont permis sa construction et les aménagements connexes, proviennent de la plaine alluviale, mais également de la forêt présente à proximité sur les versants de la vallée. Le mobilier et la stratigraphie indiquent que ce moulin a fonctionné durant la première moitié du Ier s. av. notre ère

Characterization of the Water Shortage Effects on Potato Tuber Tissues during Growth Using MRI Relaxometry and Biochemical Parameters

International audienceThe potato is one of the most cultivated crops worldwide, providing an important source of food. The quality of potato tubers relates to their size and dry matter composition and to the absence of physiological defects. It depends on the spatial and temporal coordination of growth and metabolic processes in the major tuber tissues: the cortex, flesh and pith. In the present study, variations in the biochemical traits of each of these tissues were investigated during tuber growth under optimal and water-deficit conditions. MRI relaxometry was used as a non-invasive and quantitative method to access information on cellular water status. The presence of slight but significant variations in organic compound contents quantified in the cortex and flesh revealed a tissue-dependent metabolic pattern. The T2 and relative I0 of the bi-exponential relaxation signal allowed a distinction to be made between the pith and the cortex, whereas the flesh could be differentiated from these tissues only through its relative I0. T2 values did not vary significantly during tuber development, in accordance with the typical growth pattern of tubers, but were shown to be sensitive to water stress. The interpretation of the multi-exponential transverse relaxation times is discussed and could be further developed via microscopic analysis

Genome Editing Tools for Potato Improvement

The tetraploid and highly heterozygous potato serves as a staple food for billions of people worldwide. Genetic features of the potato make classical breeding strategies challenging because elite cultivars are vegetatively propagated to avoid the loss of optimal agronomic traits through allele segregation during sexual reproduction. Therefore, genome editing is a promising tool for both functional genomics and crop breeding through the efficient introduction of favorable alleles. In the past few years, the plant science community has successfully and extensively applied the powerful, precise, and versatile clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system to modify genes of interest and confer new traits in crops, including potato. Until recently, CRISPR was most commonly used to generate knockout mutants, but new CRISPR technologies have emerged that can induce precise modifications in genomic loci of interest. In this chapter, we summarize the current knowledge of genome editing with a special focus on applications in potato. We describe the current CRISPR toolbox that can be applied to potato research and cultivar development, allowing the introduction of a large range of edits in almost any locus of interest. The current advances and challenges specific to potato molecular breeding are also discussed, including strategies to generate transgene-free edited plants. Finally, we review the traits that have been targeted so far and those of interest for future improvement, including pathogen resistance traits that could help meet current environmental challenges, according to international regulatory frameworks

Memantine before Mastectomy Prevents Post-Surgery Pain: A Randomized, Blinded Clinical Trial in Surgical Patients

<div><p>Background</p><p>Neuropathic pain following surgical treatment for breast cancer with or without chemotherapy is a clinical burden and patients frequently report cognitive, emotional and quality of life impairment. A preclinical study recently showed that memantine administered before surgery may prevent neuropathic pain development and cognitive dysfunction. With a translational approach, a clinical trial has been carried out to evaluate whether memantine administered before and after mastectomy could prevent the development of neuropathic pain, the impairment of cognition and quality of life.</p><p>Method</p><p>A randomized, pilot clinical trial included 40 women undergoing mastectomy in the Oncology Department, University Hospital, Clermont-Ferrand, France. Memantine (5 to 20 mg/day; n = 20) or placebo (n = 20) was administered for four weeks starting two weeks before surgery. The primary endpoint was pain intensity measured on a (0–10) numerical rating scale at three months post-mastectomy.</p><p>Results</p><p>Data analyses were performed using mixed models and the tests were two-sided, with a type I error set at α = 0.05. Compared with placebo, patients receiving memantine showed at three months a significant difference in post-mastectomy pain intensity, less rescue analgesia and a better emotional state. An improvement of pain symptoms induced by cancer chemotherapy was also reported.</p><p>Conclusions</p><p>This study shows for the first time the beneficial effect of memantine to prevent post-mastectomy pain development and to diminish chemotherapy-induced pain symptoms. The lesser analgesic consumption and better well-being of patients for at least six months after treatment suggests that memantine could be an interesting therapeutic option to diminish the burden of breast cancer therapy.</p><p>Trial Registration</p><p>Clinicaltrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01536314" target="_blank">NCT01536314</a></p></div

Effect of memantine on pain in patients who had chemotherapy.

<p>(A) ΔNRS score is the pain intensity difference between Month 3 or Month 6 and baseline. It is significant in the subgroup of chemotherapy which received memantine (n = 11) compared with placebo (n = 10) at Month 3 (p = 0.01) and at Month 6 (p = 0.01). (B) Neuropathic pain (ΔDN4 score) is the neuropathic pain score difference between Month 3 or Month 6 and baseline. Neuropathic pain score in four questions was significantly diminished in the memantine group at Month 3 (***p = 0.001) and at Month 6 (p = 0.009). (C) Number of patients n (%) who replied positively to question 2 (Q2) of DN4 (dysesthesias and paresthesias). In the memantine group, a decrease of 55% of dysesthesias and paresthesias was reported at Month 3 compared with the day of inclusion (Baseline) (p = 0.01).</p