Impact de l'hyperoxie après reperfusion du greffon en transplantation hépatique orthotopique chez l'adulte

Objective: The objective of our study was to evaluate the impact of hyperoxia after graft reperfusion during orthotopic liver transplantation in adults.Background: Hyperoxia is common in peri-operative liver transplantation without being supported by any recommendation. Recent studies, however, have shown the potential deleterious effect of hyperoxia in similar models of ischemia-reperfusion.Methods: We conducted a pilot, retrospective and monocentric study. All adult liver transplant patients from July 26, 2013 to December 26, 2017 were considered for inclusion. Patients were classified into two groups: a hyperoxic group (PaO2> 200mmhg) and a normoxic group (PaO2 200 mmhg after revascularization of the graft during liver transplantation. This could be the consequence of the aggravation of ischemia-reperfusion-induced lesions. A multicenter prospective study should be performed to confirm these results.Objectif : L’objectif de notre étude était d’évaluer l’impact de l’hyperoxie après revascularisation du greffon en transplantation hépatique orthotopique chez l’adulte.Contexte : L’hyperoxie est fréquente en per-opératoire de transplantation hépatique sans qu’elle ne soit soutenue par aucune recommandation. Des études récentes ont pourtant montré le potentiel effet délétère de l’hyperoxie dans des modèles similaires d’ischémie-reperfusion.Matériel et Méthodes : Nous avons mené une étude pilote, observationnelle, rétrospective et monocentrique. Tous les patients adultes transplantés hépatiques du 26 juillet 2013 au 26 décembre 2017 ont été considérés pour l’inclusion. Les patients ont été classés en deux groupes : un groupe hyperoxique (PaO2>200mmhg) et un groupe normoxique (PaO2 200 mmhg après revascularisation du greffon en transplantation hépatique. Cela pourrait être la conséquence de l’aggravation des lésions induites par l’ischémie-reperfusion. Une étude prospective multicentrique devra être réalisée pour confirmer ces résultats

Analysis of the Diversity of Xylophilus ampelinus Strains Held in CIRM-CFBP Reveals a Strongly Homogenous Species

Xylophilus ampelinus is the causal agent of blight and canker on grapevine. Only a few data are available on this species implying that the occurrence of this pathogen may be underestimated, and its actual ecological niche may not be understood. Moreover, its genetic diversity is not well known. To improve our knowledge of this species, an analysis of the complete genome sequences available in NCBI was performed. It appeared that several sequences are misidentified. The complete genome sequence of the type strain was obtained and primers designed in order to sequence gyrB and rpoD genes for the strains held in CIRM-CFBP. The genetic barcoding data were obtained for 93 strains, isolated over 35 years and from several geographical origins. The species revealed to be strongly homogenous, displaying nearly identical sequences for all strains. However, the oldest strains of this collection were isolated in 2001 therefore, a new isolation campaign and epidemiological surveys are necessary, along with the obtention of new complete genome sequences for this species

Relationships between Plasma Pyrophosphate, Vascular Calcification and Clinical Severity in Patients Affected by Pseudoxanthoma Elasticum

International audiencePseudoxanthoma elasticum (PXE; OMIM 264800) is an autosomal recessive metabolic disorder characterized by progressive calcification in the skin, the Bruch’s membrane, and the vasculature. Calcification in PXE results from a low level of circulating pyrophosphate (PPi) caused by ABCC6 deficiency. In this study, we used a cohort of 107 PXE patients to determine the pathophysiological relationship between plasma PPi, coronary calcification (CAC), lower limbs arterial calcification (LLAC), and disease severity. Overall, our data showed a deficit in plasma PPi in PXE patients compared to controls. Remarkably, affected females showed higher PPi levels than males, but a lower LLAC. There was a strong correlation between age and PPi in PXE patients (r = 0.423, p < 0.0001) but not in controls (r = 0.059, p = 0.828). A weak correlation was found between PPi and CAC (r = 0.266, p < 0.02); however, there was no statistically significant connection with LLAC (r = 0.068, p = 0.518) or a severity score (r = 0.077, p = 0.429). Surprisingly, we found no significant correlation between plasma alkaline phosphatase activity and PPi (r = 0.113, p = 0.252) or between a 10-year cardiovascular risk score and all other variables. Multivariate analysis confirmed that LLAC and CAC were strongly dependent on age, but not on PPi. Our data showed that arterial calcification is only weakly linked to circulating PPi levels and that time (i.e., age) appears to be the major determinant of disease severity and calcification in PXE. These data are important to better understand the natural history of this disease but also for the follow-up and management of patients, and the design of future clinical trials. Our results also show that PPi is not a good biomarker for the evaluation of disease severity and progression

The ABCC6 Transporter: A New Player in Biomineralization

Pseudoxanthoma elasticum (PXE) is an inherited metabolic disease with autosomal recessive inheritance caused by mutations in the ABCC6 gene. Since the first description of the disease in 1896, alleging a disease involving the elastic fibers, the concept evolved with the further discoveries of the pivotal role of ectopic mineralization that is preponderant in the elastin-rich tissues of the skin, eyes and blood vessel walls. After discovery of the causative gene of the disease in 2000, the function of the ABCC6 protein remains elusive. More than 300 mutations have been now reported and the concept of a dermal disease has progressively evolved toward a metabolic disorder resulting from the remote effects caused by lack of a circulating anti-mineralization factor. Very recently, evidence has accumulated that this anti-mineralizing factor is inorganic pyrophosphate (PPi). This leads to decreased PPi/Pi (inorganic phosphate) ratio that results from the lack of extracellular ATP release by hepatocytes and probably renal cells harboring the mutant ABCC6 protein. However, the mechanism by which ABCC6 dysfunction causes diminished ATP release remains an enigma. Studies of other ABC transporters, such as ABCC7 or ABCC1 could help our understanding of what ABCC6 exact function is. Data and a hypothesis on the possible roles of ABCC6 in acquired metabolic diseases are also discussed

Référentiel de Formation en Sécurité et Sûreté Biologiques

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Therapeutic Challenges in Patients with Gynecologic Carcinosarcomas: Analysis of a Multicenter National Cohort Study from the French Prospective TMRG Network

International audienceBackground: Gynecological carcinosarcomas are rare and aggressive diseases, with a poor prognosis. The rarity of these tumors explains the lack of robust and specific data available in the literature. The objective of this study was to investigate the impact of initial adjuvant treatment and recurrent therapeutic strategies. Patients and methods: A multicentric cohort study within the French national prospective Rare Malignant Gynecological Tumors (TMRG) network was conducted. Data from all included carcinosarcomas diagnosed between 2011 and 2018 were retrospectively collected. Results: 425 cases of uterine and ovarian carcinosarcomas (n = 313 and n = 112, respectively) were collected and analyzed from 12 participating centers. At diagnosis, 140 patients (48%) had a FIGO stage III–IV uterine carcinosarcoma (UCS) and 88 patients (83%) had an advanced ovarian carcinosarcoma (OCS) (FIGO stage ≥ III). Two hundred sixty-seven patients (63%) received adjuvant chemotherapy, most preferably carboplatin-paclitaxel regimen (n = 227, 86%). After a median follow-up of 47.4 months, the median progression-free survival (mPFS) was 15.1 months (95% CI 12.3–20.6) and 14.8 months (95% CI 13.1–17.1) for OCS and UCS, respectively. The median overall survival for OCS and UCS was 37.1 months (95% CI 22.2–49.2) and 30.6 months (95% CI 24.1–40.9), respectively. With adjuvant chemotherapy followed by radiotherapy, mPFS was 41.0 months (95% CI 17.0–NR) and 18.9 months (95% CI 14.0–45.6) for UCS stages I–II and stages III–IV, respectively. In the early stage UCS subgroup (i.e., stage IA, n = 86, 30%), mPFS for patients treated with adjuvant chemotherapy (n = 24) was not reached (95% CI 22.2–NR), while mPFS for untreated patients (n = 62) was 19.9 months (95% IC 13.9–72.9) (HR 0.44 (0.20–0.95) p = 0.03). At the first relapse, median PFS for all patients was 4.2 months (95% CI 3.5–5.3). In the first relapse, mPFS was 6.7 months (95% CI 5.1–8.5) and 2.2 months (95% CI 1.9–2.9) with a combination of chemotherapy or monotherapy, respectively (p < 0.001). Conclusions: Interestingly, this vast prospective cohort of gynecological carcinosarcoma patients from the French national Rare Malignant Gynecological Tumors network (i) highlights the positive impact of adjuvant CT on survival in all localized stages (including FIGO IA uterine carcinosarcomas), (ii) confirms the importance of platinum-based combination as an option for relapse setting, and (iii) reports median PFS for various therapeutic strategies in the relapse setting

An experimental design to test the effect of wheat variety mixtures on biodiversity and ecosystem services

The present document details how the Wheatamix consortium, inspired by ecological experiments exploring relationships between plant biodiversity and ecosystem functioning (e.g. the Jena experiment), selected bread wheat (Triticum aestivum L.) lines, phenotyped them across a range of functional traits and used this information to set up an experimental design able to unravel the effects of variety number and of the functional diversity and identity within variety mixtures for evaluating the impact of intraspecific crop diversity on a range of ecosystem services.Website: https://www6.inra.fr/wheatamix The present document details how the Wheatamix consortium, inspired by ecological experiments exploring relationships between plant biodiversity and ecosystem functioning (e.g. the Jena experiment Weisser et al. 2017), selected bread wheat (Triticum aestivum L.) lines, phenotyped them across a range of functional traits and used this information to set up an experimental design able to unravel the effects of variety number and of the functional diversity and identity within variety mixtures for evaluating the impact of intraspecific crop diversity on a range of ecosystem services. Wheat line selection The Wheatamix project investigates the potential benefits of variety mixtures in the Paris basin wheat supply chain, and therefore focuses on varieties and lines adapted to the local climate. A consensus list of 57 wheat lines (Table 1) was thus settled on these grounds and to meet the expectations of agronomists, geneticists, phytopathologists and ecophysiologists of the group. This list is composed of i) 32 elite bread wheat varieties registered in the French catalogue, selected for their high yields under conventional farming, ii) 5 modern varieties bred for organic farming (OF), iii) 10 landraces resulting from farmers' mass-selection, cultivated in France in the early 1900es, and iv) 11 lines from an INRA-MAGIC multiparental and highly recombinant population (Thepot et al., 2015), adapted to Northern France. Due to the heterogeneity of information available for each variety and line, various criteria were used for this selection. The 32 elite bread wheat varieties were chosen on the basis of their wide use in the Paris Basin, and to ensure representativeness of the diversity for earliness, disease resistance or bread-making quality, using the available information in the variet

Prospective comparison of prognostic scores for prediction of outcome after out-of-hospital cardiac arrest: results of the AfterROSC1 multicentric study

International audienceBackground Out-of-hospital cardiac arrest (OHCA) is a heterogeneous entity with multiple origins and prognoses. An early, reliable assessment of the prognosis is useful to adapt therapeutic strategy, tailor intensity of care, and inform relatives. We aimed primarily to undertake a prospective multicentric study to evaluate predictive performance of the Cardiac Arrest Prognosis (CAHP) Score as compare to historical dataset systematically collected after OHCA (Utstein style criteria). Our secondary aim was to evaluate other dedicated scores for predicting outcome after OHCA and to compare them to Utstein style criteria. Methods We prospectively collected data from 24 French and Belgium Intensive Care Units (ICUs) between August 2020 and June 2022. All cases of non-traumatic OHCA (cardiac and non-cardiac causes) patients with stable return of spontaneous circulation (ROSC) and comatose at ICU admission (defined by Glasgow coma score ≤ 8) on ICU admission were included. The primary outcome was the modified Rankin scale (mRS) at day 90 after cardiac arrest, assessed by phone interviews. A wide range of developed scores (CAHP, OHCA, CREST, C-Graph, TTM, CAST, NULL-PLEASE, and MIRACLE2) were included, and their accuracies in predicting poor outcome at 90 days after OHCA (defined as mRS ≥ 4) were determined using the area under the receiving operating characteristic curve (AUROC) and the calibration belt. Results During the study period, 907 patients were screened, and 658 were included in the study. Patients were predominantly male (72%), with a mean age of 61 ± 15, most having collapsed from a supposed cardiac cause (64%). The mortality rate at day 90 was 63% and unfavorable neurological outcomes were observed in 66%. The performance (AUROC) of Utstein criteria for poor outcome prediction was moderate at 0.79 [0.76–0.83], whereas AUROCs from other scores varied from 0.79 [0.75–0.83] to 0.88 [0.86–0.91]. For each score, the proportion of patients for whom individual values could not be calculated varied from 1.4% to 17.4%. Conclusions In patients admitted to ICUs after a successfully resuscitated OHCA, most of the scores available for the evaluation of the subsequent prognosis are more efficient than the usual Utstein criteria but calibration is unacceptable for some of them. Our results show that some scores (CAHP, sCAHP, mCAHP, OHCA, rCAST) have superior performance, and that their ease and speed of determination should encourage their use. Trial registration https://clinicaltrials.gov/ct2/show/NCT0416789