CHARACTERIZATION OF LOWER AIRWAY CELL ACTIVATION PROFILES IN LUNG TRANSPLANTATION

Introduction Le renouvellement homéostatique de la matrice extracellulaire conditionne la structure et la fonction du poumon sain. Le succès à long terme des transplantations pulmonaires reste limité par la dysfonction chronique du greffon pulmonaire (Chronic lung allograft dysfunction - CLAD). Cette entité aux multiples phénotypes est caractérisée par un remodelage tissulaire pathologique dans les voies respiratoires, menant à une dégradation de la fonction pulmonaire. Objectif Evaluer le lien entre le microbiote pulmonaire et les cellules immunitaires de l'hôte, ainsi que son implication vis-à-vis du remodelage tissulaire des voies respiratoires, chez le patient transplanté. Méthodes De l'ADN du microbiote et de l'ARN des cellules hôtes ont été isolés de 189 lavages bronchoalvéolaires obtenus chez 116 patients transplantés du poumon. Une analyse par PCR quantitative a permis de mesurer l'expression de 11 gènes en lien avec le remodelage tissulaire, codant pour des composants de la matrice ou des facteurs impliqués dans la synthèse ou la dégradation de celle-ci (remodelage tissulaire respectivement anabolique ou catabolique). La composition du microbiote a été caractérisée à la fois par le séquençage de l'ARN ribosomique 16S et la mise en culture du lavage broncho-alvéolaire. Résultats Nous avons identifié quatre profils d'expression génique, parmi lesquels le remodelage catabolique, avec une expression importante de métallopetidase-7, -9 et -12, s'opposait au remodelage anabolique caractérisé par une expression élevée de thrombospondine et du facteur de croissance dérivé des plaquettes PDGFD. Alors que le remodelage catabolique s'est révélé être associé à un microbiote dominé par des bactéries pro-inflammatoires (.Staphylococcus, Pseudomonas et Corynebacterium), le remodelage anabolique était lié à des bactéries typiques du poumon sain (Prevotella, Streptococcus and Veillonella). Ces observations ont été complétées par des expériences d'activation de macrophages et fibroblastes in vitro, qui ont permis de montrer l'effet direct de ces bactéries sur le niveau d'accumulation de matrice extracellulaire. Conclusion La relation hôte-microbes détermine potentiellement l'activité de remodelage tissulaire dans le poumon transplanté, soulevant de nouvelles opportunités thérapeutiques pour améliorer le succès à long terme de la transplantation pulmonaire

The long-term effect of complex regional pain syndrome type 1 on disability and quality of life after foot injury

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The long-term effect of complex regional pain syndrome type 1 on disability and quality of life after foot injury

Purpose: To study the long-term evolution of patients with lower-limb Complex Regional Pain Syndrome (CRPS), focusing on functional and proprioceptive aspects and quality of life. Methods: In 20 patients suffering from chronic distal lower-limb CRPS diagnosed using Budapest criteria, we assessed joint position sense and strength of the knee muscles at the CRPS and unaffected leg, functional exercise capacity, pain, CRPS severity score, quality of life and kinesiophobia. Similar assessments were performed in 20 age-matched controls. Results: The joint position performance (at 45 degrees ) was significantly lower for the CRPS leg as compared to controls. The knee extensor strength of the CRPS leg was significantly reduced as compared to the unaffected leg (-27%) and controls (-42%). CRPS patients showed significantly reduced performance at the 6 min-walk test as compared to their age group predicted value and controls. Patients suffering from CRPS for 3.8 years in average still exhibit high pain, severity and kinesiophobia scores. Conclusions: Long-term deficits in strength and proprioceptive impairments are observed at the knee joint of the CRPS leg. This persistent functional disability has significant repercussions on the quality of life. We highlight the importance of including strength and proprioceptive exercises in the therapeutic approaches for CPRS patients. IMPLICATIONS FOR REHABILITATION The long-term evolution of patients suffering from lower-limb Complex Regional Pain Syndrome is associated with persistent disability, pain and impacts the quality of life. Strength, proprioceptive, functional and subjective assessments are necessary to better identify deficits. Rehabilitation should focus on the overall deficit of the affected and contralateral limb

3D augmented reality mirror visual feedback applied to the treatment of persistent neuropathic pain in the upper extremity.

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3D augmented reality mirror visual feedback applied to the treatment of persistent neuropathic pain in the upper extremity

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3D augmented reality mirror visual feedback therapy applied to the treatment of persistent, unilateral upper extremity neuropathic pain: a preliminary study.

Objective: We assessed whether or not pain relief could be achieved with a new system that combines 3D augmented reality system (3DARS) and the principles of mirror visual feedback. Methods: Twenty-two patients between 18 and 75 years of age who suffered of chronic neuropathic pain. Each patient performed five 3DARS sessions treatment of 20 mins spread over a period of one week. The following pain parameters were assessed: (1) visual analogic scale after each treatment session (2) McGill pain scale and DN4 questionnaire were completed before the first session and 24 h after the last session. Results: The mean improvement of VAS per session was 29% (p < 0.001). There was an immediate session effect demonstrating a systematic improvement in pain between the beginning and the end of each session. We noted that this pain reduction was partially preserved until the next session. If we compare the pain level at baseline and 24 h after the last session, there was a significant decrease (p < 0.001) of pain of 37%. There was a significant decrease (p < 0.001) on the McGill Pain Questionnaire and DN4 questionnaire (p < 0.01). Conclusion: Our results indicate that 3DARS induced a significant pain decrease for patients who presented chronic neuropathic pain in a unilateral upper extremity. While further research is necessary before definitive conclusions can be drawn, clinicians could implement the approach as a preparatory adjunct for providing temporary pain relief aimed at enhancing chronic pain patients’ tolerance of manual therapy and exercise intervention. Level of Evidence: 4.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Airway microbiota signals anabolic and catabolic remodeling in the transplanted lung.

Homeostatic turnover of the extracellular matrix conditions the structure and function of the healthy lung. In lung transplantation, long-term management remains limited by chronic lung allograft dysfunction, an umbrella term used for a heterogeneous entity ultimately associated with pathological airway and/or parenchyma remodeling. This study assessed whether the local cross-talk between the pulmonary microbiota and host cells is a key determinant in the control of lower airway remodeling posttransplantation. Microbiota DNA and host total RNA were isolated from 189 bronchoalveolar lavages obtained from 116 patients post lung transplantation. Expression of a set of 11 genes encoding either matrix components or factors involved in matrix synthesis or degradation (anabolic and catabolic remodeling, respectively) was quantified by real-time quantitative PCR. Microbiota composition was characterized using 16S ribosomal RNA gene sequencing and culture. We identified 4 host gene expression profiles, among which catabolic remodeling, associated with high expression of metallopeptidase-7, -9, and -12, diverged from anabolic remodeling linked to maximal thrombospondin and platelet-derived growth factor D expression. While catabolic remodeling aligned with a microbiota dominated by proinflammatory bacteria (eg, Staphylococcus, Pseudomonas, and Corynebacterium), anabolic remodeling was linked to typical members of the healthy steady state (eg, Prevotella, Streptococcus, and Veillonella). Mechanistic assays provided direct evidence that these bacteria can impact host macrophage-fibroblast activation and matrix deposition. Host-microbes interplay potentially determines remodeling activities in the transplanted lung, highlighting new therapeutic opportunities to ultimately improve long-term lung transplant outcome

L’expérimentation animale reste indispensable (OPINION)

Trop fréquemment, l’expérimentation animale est présentée comme une pratique archaïque. Elle a bien changé. Et 100 % des patients traités le sont grâce aux concepts et techniques développés grâce à elle