Search

Resume Objet L’objectif de cette etude etait d’evaluer la morbidite des arthrodeses lombaires par voie anterieure (ALIF) utilisant un implant intervertebral en tantale. Ce materiau metallique extremement poreux possede une osteointegration, une osteoinduction, une osteoconduction et une stabilite primaire superieure aux autres materiaux utilises plus habituellement (polyetherethercetone PEEK, titane). La morbidite perioperatoire, les resultats fonctionnels a court terme (2 ans) et l’impaction radiographique des implants ont egalement ete analyses. Methodes Cette etude retrospective monocentrique a porte sur 94 patients operes, entre 2014 et 2017, pour une discopathie degenerative (75 %), un spondylolisthesis degeneratif (3 %) ou un spondylolisthesis par lyse isthmique (22 %). Soixante-cinq patients (69 %) ont ete operes par ALIF isolee (« stand-alone »), 24 (26 %) avec association d’une osteosynthese anterieure et 5 (5 %) avec une osteosynthese posterieure associee. Une courbe de survie a ete etablie selon Kaplan–Meier avec, comme critere principal d’echec, la reprise chirurgicale. Les complications perioperatoires ont ete recensees. L’evaluation clinique au dernier recul utilisait une echelle visuelle analogique radiculaire (EVA-R), lombaire (EVA-L) et le score d’Oswestry Disability Index (ODI). Les impactions, evaluees sur les radiographies, ont ete reparties en 2 groupes en fonction de la severite afin d’etablir des facteurs de risques (FDR). Resultats L’objectif principal montre un taux de survie a 2 ans de 94 % (IC 95 % [0,88 ; 0,99]). Deux patients ont ete repris precocement pour une impaction et 4 patients tardivement pour une pseudarthrodese. Le taux de complications perioperatoire etait de 8,5 %, de cause essentiellement vasculaire. Au recul moyen de 33 mois (24–59), les resultats cliniques etaient significativement ameliores et le taux d’impaction etait de 36 % en postoperatoire immediat (POI) et de 47 % a un an. Conclusion L’ALIF utilisant un implant intervertebral en tantale est une technique fiable, reproductible et a faible morbidite. Elle s’accompagne, neanmoins, d’un taux important d’impactions immediates et secondaires, mais sans retentissement sur les resultats cliniques a court terme. Niveau de preuve IV.

Thymidylate synthase (TS) is a key enzyme in nucleotide biosynthesis. A study performed by our group on human monocyte-derived macrophages (MDMs) infected with HIV-1 showed that many enzymes related to the folate cycle pathway, such as TS, are upregulated in productively infected cells. Here, we suggest that TS is essential for an effective HIV-1 infection in MDMs. Indeed, a TS specific small interfering RNA (siRNA) as well as the TS specific inhibitor Raltitrexed (RTX) caused a reduction in productively infected cells. Quantitative PCR analysis showed that this treatment decreased the efficacy of the early steps of the viral cycle. The RTX inhibitory effect was counteracted by dNTP addition. These results suggest that TS is essential for the early stages of HIV-1 infection by providing optimal dNTP concentrations in MDMs. TS and its related pathway may thus be considered as a potential therapeutic target for HIV-1 treatment.

Percutaneous spine surgery is on the rise; the main drawback is iterative irradiation of the care team in theater. The aim of the present study was to compare intraoperative radiation dose in percutaneous posterior thoracolumbar internal fixation (PPTLIF) using impedancemetry-guided pedicle sighting by the PediGuard device (SpineGuard®) versus gold-standard free-hand sighting.A single-center, single-surgeon continuous prospective randomized study was conducted from September 2017 to April 2018. Dose-area product (DAP, in cGy.cmSixteen patients were included in either group after 2 had been excluded. The groups were comparable for age, gender, body-mass index (BMI), indication and number of instrumented levels. Mean DPA at end of sighting and end of procedure was respectively 147.4 cGy.cmIn the present study, the PediGuard device did not reduce intraoperative radiation dose. The correlation between radiation dose and BMI was confirmed.II; prospective randomized study.

Resume Introduction L’utilisation d’un implant intervertebral augmente la stabilite et ameliore les resultats des arthrodeses lombaires par voie posterieure (APL). L’objectif de cette etude etait d’evaluer les resultats cliniques et radiologiques des APL avec implant intervertebral en tantale et sans greffe osseuse intersomatique associee. Materiel et methodes Il s’agit d’une etude retrospective, monocentrique de 52 cas d’APL sur un niveau (discopathie degenerative : 42 ; spondylolisthesis par lyse isthmique : 10) utilisant 2 cages intervertebrales en tantale, sans greffe osseuse intersomatique. Le recul minimum etait de 2 ans. L’evaluation clinique portait sur une echelle visuelle analogique (EVA), les scores d’Oswestry Disability Index (ODI) et de Roland Morris (RM). Des radiographiques statiques et dynamiques ont permis l’evaluation de l’osteointegration du tantale et de la mobilite intersegmentaire. Resultats Quarante-neuf patients ont pu etre inclus avec un recul moyen de 55 mois (25–74). Les resultats des scores EVA, ODI et RM etaient significativement ameliores au dernier recul (4 points, 30 points et 28 points respectivement). Aucune faillite mecanique du materiel n’etait observee en radiographie statique et tous les patients avaient moins de 5° de mobilite sur les radiographies dynamiques au dernier recul. Discussion Les APL avec implant intervertebral en tantale et sans greffe osseuse intersomatique permettent d’obtenir des resultats cliniques et radiologiques satisfaisants a moyen terme. Les resultats de cette serie illustrent la fiabilite en termes de stabilite primaire et d’osteointegration d’un implant en tantale. Niveau de preuve IV.

Several host factors influence HIV-1 infection and replication. The p53-mediated antiviral role in monocyte-derived macrophages (MDMs) was previously highlighted. Indeed, an increase in p53 level results in a stronger restriction against HIV-1 early replication steps through SAMHD1 activity. In this study, we investigated the potential role of some p53 isoforms in HIV-1 infection. Transfection of isoform-specific small interfering RNA (siRNA) induced distinctive effects on the virus life cycle. For example, in contrast to an siRNA targeting all isoforms, a knockdown of Δ133p53 transcripts reduced virus replication in MDMs that was correlated with a decrease in phosphorylated inactive SAMHD1. Combination of Δ133p53 knockdown and nutlin-3, a pharmacological inhibitor of MDM2 that stabilizes p53, further reduced susceptibility of MDMs to HIV-1 infection, thus suggesting an inhibitory role of Δ133p53 toward p53 antiviral activity. In contrast, p53β knockdown in MDMs increased the viral production independently of SAMHD1. Moreover, experiments with a Nef-deficient virus showed that this viral protein plays a protective role against the antiviral environment mediated by p53. Finally, HIV-1 infection affected the expression pattern of p53 isoforms by increasing p53β and p53γ mRNA levels while stabilizing the protein level of p53α and some isoforms from the p53β subclass. The balance between the various p53 isoforms is therefore an important factor in the overall susceptibility of macrophages to HIV-1 infection, fine-tuning the p53 response against HIV-1. This study brings a new understanding of the complex role of p53 in virus replication processes in myeloid cells. IMPORTANCE As of today, HIV-1 infection is still considered a global pandemic without a functional cure, partly because of the presence of stable viral reservoirs. Macrophages constitute one of these cell reservoirs, contributing to the viral persistence. Studies investigating the host factors involved in cell susceptibility to HIV-1 infection might lead to a better understanding of reservoir formation and will eventually allow the development of an efficient cure. Our team previously showed the antiviral role of p53 in macrophages, which acts by compromising the early steps of HIV-1 replication. In this study, we demonstrate the involvement of p53 isoforms, which regulate p53 activity and define the cellular environment influencing viral replication. In addition, the results concerning the potential role of p53 in antiviral innate immunity could be transposed to other fields of virology and suggest that knowledge in oncology can be applied to HIV-1 research.

Purpose The objective of this study was to assess the morbidity of Anterior Lumbar Interbody Fusion (ALIF) using an intervertebral tantalum implant. Tantulum is an extremely porous metallic material which possesses properties of osseointegration, osteoinduction and osteoconduction while offering superior primary stability, compared to other materials more commonly used (polyether ether ketone or PEEK, titanium). Perioperative morbidity, short-term functional outcomes (2 years) and radiographic impaction of implants were also analysed. Methods This retrospective monocentric study involved 94 patients operated on between 2014 and 2017 for degenerative disc disease (75%), degenerative spondylolisthesis (3%) or isthmic lytic spondylolisthesis (22%). Sixty-five patients (69%) had isolated (“stand-alone”) ALIF procedures, 24 (26%) with associated anterior osteosynthesis and 5 (5%) with associated posterior osteosynthesis. A Kaplan-Meier survival curve was established with surgical revision listed as the main criterion for failure. Perioperative complications were identified. The clinical evaluation at the last follow-up used a Visual Analogue Scale for radicular pain (VAS-R), for lumbar pain (VAS-L) and the Oswestry Disability Index (ODI) score. The impactions, assessed on x-rays, were divided into 2 groups according to severity in order to establish risk factors (RF). Results The primary objective showed a 2-year survival rate of 94% (95% CI [0.88; 0.99]). Two patients had early surgical revision for impaction and 4 patients had late surgical revision for pseudarthrosis. The rate of perioperative complications was 8.5%, mostly due to vascular causes. At the average follow-up of 33 months (24–59), the clinical results were significantly improved and the impaction rate was 36% in the immediate postoperative period (IPO) and 47% at one year. Conclusion ALIF using an intervertebral tantalum implant is a reliable, reproducible and low morbidity technique. However, it is accompanied by a significant rate of immediate and secondary impaction but without any resounding influence on short-term clinical outcomes. Level of evidence IV.

Introduction Intervertebral implants increase stability and improve results in lumbar interbody fusion (LIF). The aim of the present study was to assess clinical and radiological results of posterior lumbar interbody fusion (PLIF) using a tantalum intervertebral implant without associated interbody bone graft. Materiel and methods A single-center retrospective study included 52 cases of single-level PLIF, using 2 tantalum intervertebral cages, without interbody bone graft: 42 for degenerative disc disease, 10 for isthmic spondylolisthesis. Minimum follow-up was 2 years. Clinical assessment used a visual analog (pain) scale (VAS), the Oswestry Disability Index (ODI) and the Roland Morris (RM) scale. Tantalum osseointegration and intersegment mobility were assessed on static and dynamic X-ray. Results Forty-nine patients were included, with a mean 55 months’ follow-up (range, 25–74 months). VAS, ODI and RM scores showed significant improvement at last-follow-up, at 4, 30 and 28 points respectively. There was no mechanical failure on static X-ray; all patients had less than 5° mobility on dynamic X-ray at last follow-up. Discussion PLIF with tantalum intervertebral implant without interbody bone graft provided satisfactory clinical and radiological results at medium-term follow-up. The present findings showed reliable primary stability and osseointegration of the tantalum implant. Level of evidence IV.

The molecular basis for HIV-1 susceptibility in primary human monocyte-derived macrophages (MDMs) was previously evaluated by comparing the transcriptome of infected and bystander populations. Careful analysis of the data suggested that the ubiquitin ligase MDM2 acted as a positive regulator of HIV-1 replication in MDMs. In this study, MDM2 silencing through transcript-specific small interfering RNAs in MDMs induced a reduction in HIV-1 reverse transcription and integration along with an increase in the expression of p53-induced genes, including CDKN1A. Experiments with Nutlin-3, a pharmacological inhibitor of MDM2 p53-binding activity, showed a similar effect on HIV-1 infection, suggesting that the observed restriction in HIV-1 production results from the release/activation of p53 and not the absence of MDM2 per se. Knockdown and inhibition of MDM2 also both correlate with a decrease in the Thr592-phosphorylated inactive form of SAMHD1. The expression level of MDM2 and the p53 activation status are therefore important factors in the overall susceptibility of macrophages to HIV-1 infection, bringing a new understanding of signaling events controlling the process of virus replication in this cell type. IMPORTANCE Macrophages, with their long life span in vivo and their resistance to HIV-1-mediated cytopathic effect, might serve as viral reservoirs, contributing to virus persistence in an infected individual. Identification of host factors that increase the overall susceptibility of macrophages to HIV-1 might provide new therapeutic targets for the efficient control of viral replication in these cells and limit the formation of reservoirs in exposed individuals. In this study, we demonstrate the importance of p53 regulation by MDM2, which creates a cellular environment more favorable to the early steps of HIV-1 replication. Moreover, we show that p53 stabilization reduces virus infection in human macrophages, highlighting the important role of p53 in antiviral immunity.

Background Mammalian cells harbour RNA quality control and degradative machineries such as nonsense-mediated mRNA decay that target cellular mRNAs for clearance from the cell to avoid aberrant gene expression. The role of the host mRNA decay pathways in macrophages in the context of human immunodeficiency virus type 1 (HIV-1) infection is yet to be elucidated. Macrophages are directly infected by HIV-1, mediate the dissemination of the virus and contribute to the chronic activation of the inflammatory response observed in infected individuals. Therefore, we characterized the effects of four host mRNA decay proteins, i.e., UPF1, UPF2, SMG6 and Staufen1, on viral replication in HIV-1-infected primary monocyte-derived macrophages (MDMs). Results Steady-state expression levels of these host mRNA decay proteins were significantly downregulated in HIV-1-infected MDMs. Moreover, UPF2 and SMG6 inhibited HIV-1 gene expression in macrophages to a similar level achieved by SAMHD1, by directly influencing viral genomic RNA levels. Staufen1, a host protein also involved in UPF1-dependent mRNA decay and that acts at several HIV-1 replication steps, enhanced HIV-1 gene expression in MDMs. Conclusions These results provide new evidence for roles of host mRNA decay proteins in regulating HIV-1 replication in infected macrophages and can serve as potential targets for broad-spectrum antiviral therapeutics. Electronic supplementary material The online version of this article (10.1186/s12977-019-0465-2) contains supplementary material, which is available to authorized users.

HIV-1 infection is characterized by persistent viral replication, chronic immune activation, and CD4+ T cell depletion. Moreover, several immune dysfunctions are observed in cells that are not targeted by the virus, such as B cells. Some B cell abnormalities include hypergammaglobulinemia, nonspecific B cell activation, class switching, increased cell turnover, breakage of tolerance, and a loss of the capacity to generate and maintain memory. Several cytokines and growth factors that are increased in the serum of HIV-1–infected individuals have been suggested to directly or indirectly trigger B cell activation, and one of these is BAFF. In this study, we investigate the ability of fully competent (R5-tropic) HIV-1 to induce BAFF production by monocyte-derived macrophages (MDMs). We demonstrate here that HIV-1 drives BAFF production in MDMs in a type-I IFN– and TLR-independent manner. Moreover, we determine that HIV-1 Nef accessory protein is dispensable in BAFF upregulation as a nef-deleted HIV-1 strain is still able to increase BAFF at levels similar to the wild type strain. Finally, we show that the macrophage phenotype status affects HIV-1 replication and BAFF induction, as both were abrogated in MDMs displaying a M1 phenotype. This study provides new useful information about the increased levels of BAFF observed during HIV-1 infection and highlights the importance of macrophages as a source of BAFF, a phenomenon that might contribute to B cell dysfunctions at inflammatory tissue sites in infected individuals.