Nouveautés dans la prise en charge des fractures vertébrales ostéoporotiques: place de la vertébroplastie et de la kyphoplastie [Trends in the treatment of spinal osteoporic fractures: vertebroplasty and kyphoplasty].

Vertebral osteoporotic fracture (VOF) is a major problem of public health. Surgical treatments such as vertebroplasty and kyphoplasty are interesting adjuvant treatments for the management of osteoporosis. A consensus proposed by the principal contributors of this management is important. Regarding the actual data, we propose a vertebroplasty or a kyphoplasty for all patients suffering of an acute VOF. If a previous kyphosis or an important local kyphosis exists, secondary to the acute VOF or others, we propose a kyphoplasty. If the VOF is older and the conservative treatment is inefficient, we propose a vertebroplasty. In all cases, a specific management and treatment of osteoporosis is proposed.

Thrombose veineuse superficielle: quelles nouveautés dans la prise en charge [Superficial vein thrombosis: what's new in the management?].

Lower limbs superficial venous thrombosis (SVT) is a relatively frequent disease. Its prevalence among patients consulting their treating physician is estimated to be 10.8% among women and 4.9% among men. Up to 25% of at risk patients with isolated SVT present with a concomitant DVT. Ultrasound imaging may play a role in the management of these patients allowing precise diagnosis, determination of thrombus extension and presence of associated DVT. From data recently appeared in the literature treatment of SVT with prophylactic doses of fondaparinux may be proposed to at risk patients with isolated SVT.

Surface modification of biomaterials for conjugation with human fetal osteoblasts.

Surface functionalization of hydroxyapatite (HA) and beta-tricalcium phosphate (TCP) bioceramics with chemical ligands containing a pyrrogallol moiety was developed to improve the adhesion of bone cell precursors to the biomaterials. Fast and biocompatible copper-free click reaction with azido-modified human fetal osteoblasts resulted in improved cell binding to both HA and TCP bioceramics, opening the way for using this methodology in the preparation of cell-engineered bone implants.

V3 net charge: additional tool in HIV-1 tropism prediction.

Genotype-based algorithms are valuable tools for the identification of patients eligible for CCR5 inhibitors administration in clinical practice. Among the available methods, geno2pheno[coreceptor] (G2P) is the most used online tool for tropism prediction. This study was conceived to assess if the combination of G2P prediction with V3 peptide net charge (NC) value could improve the accuracy of tropism prediction. A total of 172 V3 bulk sequences from 143 patients were analyzed by G2P and NC values. A phenotypic assay was performed by cloning the complete env gene and tropism determination was assessed on U87_CCR5(+)/CXCR4(+) cells. Sequences were stratified according to the agreement between NC values and G2P results. Of sequences predicted as X4 by G2P, 61% showed NC values higher than 5; similarly, 76% of sequences predicted as R5 by G2P had NC values below 4. Sequences with NC values between 4 and 5 were associated with different G2P predictions: 65% of samples were predicted as R5-tropic and 35% of sequences as X4-tropic. Sequences identified as X4 by NC value had at least one positive residue at positions known to be involved in tropism prediction and positive residues in position 32. These data supported the hypothesis that NC values between 4 and 5 could be associated with the presence of dual/mixed-tropic (DM) variants. The phenotypic assay performed on a subset of sequences confirmed the tropism prediction for concordant sequences and showed that NC values between 4 and 5 are associated with DM tropism. These results suggest that the combination of G2P and NC could increase the accuracy of tropism prediction. A more reliable identification of X4 variants would be useful for better selecting candidates for Maraviroc (MVC) administration, but also as a predictive marker in coreceptor switching, strongly associated with the phase of infection.

Place du pathologiste dans la prise en charge néoadjuvante des cancers du sein [Neoadjuvant treatment of breast cancer: implications for the pathologist].

These past few years, neoadjuvant strategy has taken an increasing place in the management of breast cancer patients. This strategy is mainly indicated to obtain a tumour bulk regression allowing a breast conserving surgery in patients that otherwise would have undergone mastectomy. Of note, development of new chemotherapy agents and targeted therapies has critically helped in the progress of neoadjuvant strategy as it is currently associated with better pathological response rates. In this context, the pathologist is at the crossroad of this multidisciplinary process. First, he provides on the initial core needle biopsy the tumour pathological characteristics that are critical for the choice of treatment strategy, i.e. histological type, histological grade, proliferative activity (mitotic count and Ki67/MIB1 index labeling), hormone receptor status (oestrogen receptor and progesterone receptor) and HER2 status. Secondly, the pathologist evaluates the pathological response and the status of surgical margins with regards to the residual tumour on the surgical specimen after neoadjuvant treatment. These parameters are important for the management of the patient, since it has been shown that complete pathological response is associated with improved disease free survival. Several grading systems are used to assess the pathological response in breast and axillary lymph nodes. The most frequently used in France are currently the systems described by Sataloff et al. and Chevallier et al. In this review, we detail the different steps involving the pathologist in neoadjuvant setting, with special regards to the quality process and future perspectives such as emerging predictive biomarkers.

Prise en charge du cholestérol pour prévenir le risque cardiovasculaire:recommandations américaines 2013.Prise de position du Groupe de travail Suisse Lipides et Athérosclérose (GSLA).

Les dernières recommandations américaines de l'American College of Cardiology et de l'American Heart Association proposent d'abaisser le seuil de prescription de statines pour la prévention cardiovasculaire primaire, et d'abandonner les cibles de LDL-cholestérol pour utiliser le plus souvent des statines de haute intensité. Le Groupe de travail Suisse Lipides et Athérosclérose (GSLA) pense que ces recommandations ne devraient pas être appliquées en Suisse, car elles augmenteraient très fortement le nombre de personnes à bas risque sous statines, chez qui le rapport bénéfice/risque au long cours est incertain, et pourraient diminuer l'importance du style de vie, première priorité dans la prévention cardiovasculaire primaire. En outre, l'abandon des cibles de LDL-cholestérol limite l'individualisation de la prise en charge quant au choix du type et du dosage de la statine, et pourrait diminuer l'adhérence thérapeutique. Pour ces raisons, le GSLA recommande de poursuivre avec les stratégies de prévention bien établies en Suisse et résumées dans les recommandations du GSLA 2012.

Conjugation of a Ru(II) Arene Complex to Neomycin or to Guanidinoneomycin Leads to Compounds with Differential Cytotoxicities and Accumulation between Cancer and Normal Cells

A straightforward methodology for the synthesis of conjugates between a cytotoxic organometallic ruthenium(II) complex and amino- and guanidinoglycosides, as potential RNA-targeted anticancer compounds, is described. Under microwave irradiation, the imidazole ligand incorporated on the aminoglycoside moiety (neamine or neomycin) was found to replace one triphenylphosphine ligand from the ruthenium precursor [(η6-p-cym)RuCl(PPh3)2]+, allowing the assembly of the target conjugates. The guanidinylated analogue was easily prepared from the neomycin-ruthenium conjugate by reaction with N,N′-di-Boc-N″-triflylguanidine, a powerful guanidinylating reagent that was compatible with the integrity of the metal complex. All conjugates were purified by semipreparative high-performance liquid chromatography (HPLC) and characterized by electrospray ionization (ESI) and matrix-assisted laser desorptionionization time-of-flight (MALDI-TOF) mass spectrometry (MS) and NMR spectroscopy. The cytotoxicity of the compounds was tested in MCF-7 (breast) and DU-145 (prostate) human cancer cells, as well as in the normal HEK293 (Human Embryonic Kidney) cell line, revealing a dependence on the nature of the glycoside moiety and the type of cell (cancer or healthy). Indeed, the neomycinruthenium conjugate (2) displayed moderate antiproliferative activity in both cancer cell lines (IC50 ≈ 80 μM), whereas the neamine conjugate (4) was inactive (IC50 ≈ 200 μM). However, the guanidinylated analogue of the neomycinruthenium conjugate (3) required much lower concentrations than the parent conjugate for equal effect (IC50 = 7.17 μM in DU-145 and IC50 = 11.33 μM in MCF-7). Although the same ranking in antiproliferative activity was found in the nontumorigenic cell line (3 2 > 4), IC50 values indicate that aminoglycoside-containing conjugates are about 2-fold more cytotoxic in normal cells (e.g., IC50 = 49.4 μM for 2) than in cancer cells, whereas an opposite tendency was found with the guanidinylated conjugate, since its cytotoxicity in the normal cell line (IC50 = 12.75 μM for 3) was similar or even lower than that found in MCF-7 and DU-145 cancer cell lines, respectively. Cell uptake studies performed by ICP-MS with conjugates 2 and 3 revealed that guanidinylation of the neomycin moiety had a positive effect on accumulation (about 3-fold higher in DU-145 and 4-fold higher in HEK293), which correlates well with the higher antiproliferative activity of 3. Interestingly, despite the slightly higher accumulation in the normal cell than in the cancer cell line (about 1.4-fold), guanidinoneomycinruthenium conjugate (3) was more cytotoxic to cancer cells (about 1.8-fold), whereas the opposite tendency applied for neomycinruthenium conjugate (2). Such differences in cytotoxic activity and cellular accumulation between cancer and normal cells open the way to the creation of more selective, less toxic anticancer metallodrugs by conjugating cytotoxic metal-based complexes such as ruthenium(II) arene derivatives to guanidinoglycosides.

Prise en charge des plaies, quoi de neuf? [Advances in wound care]

Wound care made great progress during last years related to several factors. The first is an awakening of the importance of wounds. The progress made in the comprehension of the physiopathology of wounds led to innovations in all stages of this complex process which is the wound healing. Autologus platelet concentrate producing growth factors are in use to stimulate the first phase of the healing. The second phase which is the phase of proliferation and secretion is currently better managed with new categories of bandages which are true local treatments. The nutrition became one of the pillars of wound treatments especially among old patients. The reconstructive surgery took great steps since the physiology and the vascular anatomy of the skin and soft tissues are better known. Finally the bio-engineering has entered the treatment of the wound there is more than 20 years ago and methods have improved and become more reliable

Evaluation de la prise en charge des femmes de plus de 30 ans avec un diagnostic de L-SIL du col de l'utérus en vigueur depuis 2009 au CHUV

Introduction : Les lésions malpighiennes intraépithéliales de bas grade (LSIL) sont un diagnostic rencontré fréquemment lors des frottis de dépistage du cancer du col utérin. Leur prise en charge reste controversée. Au CHUV, avant 2009, un test HPV était effectué chez toutes les femmes avec un diagnostic de L-SIL et seules les patientes avec un test HPV positif pour les hauts risques (HR) étaient adressées en colposcopie. Actuellement, suivant les guidelines européennes de 2006, l'attitude est de faire une colposcopie à toutes les patientes avec un diagnostic initial de L-SIL, sans faire préalablement un test HPV. Cette démarche semble efficiente chez les jeunes patientes, mais pas chez les plus de 30 ans chez qui la prévalence de tests HPV HR positifs est inférieure. Plus de 40% des femmes de plus de 30 ans seraient référées inutilement en colposcopie car elles ne seraient pas infectées par un HPV HR et n'auraient pas de risque d'évolution de leur L-SIL vers une lésion de haut grade. Buts : Comparer les deux différentes prises en charge des femmes de plus de 30 ans présentant un diagnostic de L-SIL, soit celle qui était en vigueur au CHUV avant 2009 et la prise en charge actuelle. Etudier le rôle et l'utilité du test HPV et de la colposcopie dans le suivi de ces femmes. Méthode : Il s'agit d'une étude rétrospective, monocentrique. Nous avons étudié le dossier de toutes les femmes de plus de 30 ans ayant eu une cytologie avec un diagnostic initial de L-SIL du col de l'utérus au CHUV entre le 01.01.09 et le 31.12.10, soit 61 patientes. Résultats : Parmi les 61 femmes inclues dans notre étude 60 ont eu un test HPV effectué lors du diagnostic de L-SIL, dont seuls 29 (48,33%) étaient positifs pour les hauts risques. Comparé aux femmes avec test HPV négatif pour HR, les femmes positives pour HPV HR ont eu un taux inférieur d'évolution spontanément résolutive de leur lésion et un taux supérieur de conisation ou vaporisation du col. Cinq des femmes inclues dans l'étude ont eu une évolution de leurs lésions vers une pathologie plus avancée, dont 4 vers un CIN2 et 1 vers un CIN3. Ces cinq cas étaient positifs pour HPV HR. Conclusion : Les nouvelles guidelines en vigueur au CHUV concernant la prise en charge des femmes avec diagnostic de L-SIL n'étaient pas encore appliquées en 2010, en effet le test HPV a été effectué chez presque la totalité de ces patientes. Ces nouvelles guidelines ne semblent pas être applicables aux femmes de plus de 30 ans, chez qui la prévalence du HPV HR est inférieure, et qui risquent alors de subir des examens complémentaires invasifs, sans qu'il y ait de réel bénéfice sur le pronostic de leur pathologie.

Orthogonal protection of peptides and peptoids for cyclization by the thiol-ene reaction and conjugation

Cyclic peptides and peptoids were prepared using the thiolene Michael-type reaction. The linear precursors were provided with additional functional groups allowing for subsequent conjugation: an orthogonally protected thiol, a protected maleimide, or an alkyne. The functional group for conjugation was placed either within the cycle or in an external position. The click reactions employed for conjugation with suitably derivatized nucleoside or oligonucleotides were either cycloadditions (Diels-Alder, Cu(I)-catalyzed azide-alkyne) or the same Michael-type reaction as for cyclization.