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International audience; The anti-Müllerian hormone (AMH) is a heterodimeric glycoprotein belonging to the TGFb superfamily implicated in human embryonic development. This hormone was first described as allowing regression of the epithelial embryonic Müllerian structures in males, which would otherwise differentiate into the uterus and fallopian tubes. It activates a signaling pathway mediated by two transmembrane receptors. Binding of AMH to its receptor induces morphological changes leading to the degeneration of Müllerian ducts. Recently, new data has shown the role played by this hormone on structures other than the genital tract. If testicular AMH expression decreases in humans over the course of a lifetime, synthesis may persist in other tissues in adulthood. The mechanisms underlying its production have been unveiled. The aim of this review is to describe the different pathways in which AMH has been identified and plays a pivotal role.

There exists a need for prognostic tools for the early identification of COVID-19 patients requiring intensive care unit (ICU) admission and mortality. Here we investigated the association between a clinical (initial prehospital shock index (SI)) and biological (initial prehospital lactatemia) tool and the ICU admission and 30-day mortality among COVID-19 patients cared for in the prehospital setting.We retrospectively analysed COVID-19 patients initially cared for by a Paris Fire Brigade advanced (ALS) or basic life support (BLS) team in the prehospital setting between 2020, March 08th and 2020, May 30th. We assessed the association between prehospital SI and prehospital lactatemia and ICU admission and mortality using logistic regression model analysis after propensity score matching with Inverse Probability Treatment Weighting (IPTW) method. Covariates included in the IPTW propensity analysis were: age, sex, body mass index (BMI), initial respiratory rate (iRR), initial pulse oximetry without (SpO2i) and with oxygen supplementation (SpO2i.O2), initial Glasgow coma scale (GCSi) value, initial prehospital SI and initial prehospital lactatemia.We analysed 410 consecutive COVID-19 patients [254 males (62%); mean age, 64 ± 18 years]. Fifty-seven patients (14%) deceased on the scene, of whom 41 (72%) were male and were significantly older (71 ± 12 years vs. 64 ± 19 years; P 〈10Neither prehospital initial SI nor lactatemia were associated with ICU admission and 30-day mortality among COVID-19 patients initially cared for by a Paris Fire Brigade BLS or ALS team. Further prospective studies are needed to confirm these preliminary results.

Objective To determine whether the adenomyosis phenotype affects the proton nuclear magnetic resonance (1H-NMR)-based serum metabolic profile of patients. Design Cohort study. Setting University hospital-based research center. Patients Seventy-seven patients who underwent laparoscopy for a benign gynecologic condition. Interventions Pelvic magnetic resonance imaging and collection of a venous peripheral blood sample were performed during the preoperative workup. The women were allocated to the adenomyosis group (n = 32), or the control group (n = 45). The adenomyosis group was further subdivided into two groups: diffuse adenomyosis of the inner myometrium (n = 14) and focal adenomyosis of the outer myometrium (n = 18). Other adenomyosis phenotypes were excluded. Main Outcome Measures Metabolomic profiling based on 1H-NMR spectroscopy in combination with statistical approaches. Results The serum metabolic profiles of the patients with adenomyosis indicated lower concentrations of 3-hydroxybutyrate, glutamate, and serine compared with controls. Conversely, the concentrations of proline, choline, citrate, 2-hydroxybutyrate, and creatinine were higher in the adenomyosis group. The focal adenomyosis of the outer myometrium and the diffuse adenomyosis phenotypes also each exhibited a specific metabolic profile. Conclusion Serum metabolic changes were detected in women with features of adenomyosis compared with their disease-free counterparts, and a number of specific metabolic pathways appear to be engaged according to the adenomyosis phenotype. The metabolites with altered levels are particularly involved in immune activation as well as cell proliferation and cell migration. Nevertheless, this study did find evidence of a correlation between metabolite levels and symptoms thought to be related to adenomyosis. Further studies are required to determine the clinical significance of these differences in metabolic profiles.

Resume La sclerose en plaques (SEP) est une maladie chronique inflammatoire d’origine auto-immune, qui se caracterise par une demyelinisation progressive des neurones, conduisant a des desordres neurologiques : perturbations motrices, sensitives, cognitives, visuelles ou encore sphincteriennes. La SEP atteint plus les femmes que les hommes, est plus frequente dans les pays developpes et represente la premiere cause de handicap non traumatique du sujet jeune. Le diagnostic de la maladie repose sur un faisceau d’arguments cliniques, d’imagerie mais egalement biologiques. Plusieurs marqueurs dosables parallelement dans le serum et le liquide cerebro-spinal (LCS) ont ete etudies pour mettre en evidence l’atteinte auto-immune du systeme nerveux central (SNC). Le mieux defini est actuellement la recherche de bandes oligoclonales (BOC) d’immuno- globulines G (IgG) dans le LCS qui reflete l’activation lympho-cytaire B chronique cerebrale. La revision en 2017 des criteres diagnostiques de Mac Donald a d’ailleurs reintegre la presence de BOC comme element diagnostic. Ces dernieres annees ont vu l’emergence de nouveaux biomarqueurs quantitatifs tels que le dosage des chaines legeres libres d’Ig pour le diagnostic ou des chaines legeres de neurofilaments pour le pronostic et la reponse au traitement.

Resume Introduction Les Sapeurs-Pompiers de Paris sont soumis en intervention a l’avertisseur sonore des vehicules de secours d’urgence. L’impact sur l’audition de cette exposition chronique a des sons d’intensite elevee n’est, a ce jour, pas connue. L’hypothese de depart etait que l’avertisseur sonore des vehicules de secours d’urgence emettant a une frequence proche de 500 a 800 Hz entrainait chez les conducteurs une baisse d’audition predominante a gauche, cote de la fenetre. La sirene etant placee sur le toit de la cabine de pilotage, nous avons suppose une plus forte exposition sonore de leur oreille gauche, cote fenetre, frequemment ouverte. L’objectif de cette etude retrospective etait de decrire les effets de l’exposition chronique a des avertisseurs sonores sur l’audition et de preciser si cette exposition etait lateralisee chez les conducteurs des vehicules de secours d’urgence de la Brigade de Sapeurs-Pompiers de Paris (BSPP). Methodologie Entre septembre et novembre 2017, tous les conducteurs de vehicules de secours d’urgence de la BSPP ayant beneficie de leur visite d’aptitude reguliere, ont participe sur la base du volontariat a une enquete sous forme de questionnaire. Les donnees collectees etaient : le sexe, l’âge, les antecedents ORL, les conduites a risque auditif, l’anciennete d’exercice a la BSPP. Les valeurs des audiogrammes a l’incorporation, a 5 ans, a 10 ans, a 15 ans et en fin de contrat ont ete colligees. Une analyse uni puis multivariee avec regression logistique a ete effectuee. Le p etait considere comme significatif lorsque inferieur a 0,05. Resultats Soixante-dix conducteurs dont 69 hommes (99 %) ont ete inclus. L’âge moyen etait de 32 ± 3 ans. L’anciennete mediane d’exercice a la BSPP etait de 12 [9–14] ans dont 9 [6–10] ans en tant que conducteur. Avec un seuil de 25 dB considere comme significatif pour la perte auditive, 18 (26 %) conducteurs presentaient un deficit auditif. Aucune difference significative entre l’oreille gauche et l’oreille droite n’a ete retrouvee. Conclusion Un quart des conducteurs de vehicules de secours d’urgence de la BSPP presentaient un deficit auditif significatif. L’exposition professionnelle chronique a l’avertisseur sonore des vehicules de secours d’urgence ne semblait pas etre a l’origine de ce deficit et n’etait pas associee a une lateralisation de cette derniere.

Resume La douleur est un symptome frequent, un axe majeur de la prise en charge des patients et une priorite pour les pouvoirs publics. C’est un defi majeur en cas d’afflux massif de victimes en termes technique, organisationnel et pharmacologique. Nous avons etudie les modalites d’antalgie hors palier 1 dans les situations de multivictimes au sein de la Brigade de sapeurs-pompiers de Paris pour l’annee 2018 et, sur 162 interventions impliquant cinq victimes ou plus, 33 ont donne lieu a un transport par une ambulance de reanimation. Une majorite de ces patients (18 sur 25) n’ont pas eu recours a des traitements relevant du palier 3. Malgre toutes ses limites, cette etude laisse penser que la douleur pourrait etre insuffisamment prise en compte en cas de multivictimes. Pourtant, il existe des moyens therapeutiques disponibles : des moyens non medicamenteux, des therapeutiques classiques comme la morphine ou l’anesthesie locoregionale. Le Tactical Combat Casulaty Care recommande depuis quelques annees d’autres medicaments comme le sufentanyl ou la ketamine. Mais les limites de ces techniques sont vite atteintes, compte tenu des contraintes specifiques aux afflux massifs. Des perspectives cherchent a s’amender de la voie intraveineuse et reposent sur la voie transmuqueuse ou intranasale, voire par inhalation. Malgre une prise en charge bien codifiee et connue, la douleur reste encore sous-evaluee et sous-traitee, surtout en cas d’afflux massif. Concernant l’analgesie en medecine de catastrophe, l’enjeu des prochaines annees sera le developpement de dispositifs permettant une administration plus facile, ne necessitant pas d’abord veineux, et en toute securite.

Research question What is the correlation between serum metabolic profile and endometriosis phenotype? Design A pilot study nestled in a prospective cohort study at a university hospital, including 46 patients with painful endometriosis who underwent surgery and 21 controls who did not have macroscopic endometriotic lesions. Endometriosis was strictly classified into two groups of 23 patients each: endometrioma (OMA) and deep infiltrating endometriosis (DIE). Serum samples were collected before surgery for metabolomic profiling based on proton-nuclear magnetic resonance spectroscopy in combination with statistical approaches. Comparative identification of the metabolites in the serum from endometriosis patients and from controls was carried out, including an analysis according to endometriosis phenotype. Results The serum metabolic profiles of the endometriosis patients revealed significantly lower concentrations of several amino acids compared with the controls, whereas the concentrations of free fatty acids and ketone bodies were significantly higher. The OMA and the DIE phenotypes each had a specific metabolic profile, with higher concentrations of two ketone bodies in the OMA group, and higher concentrations of free fatty acids and lipids in the DIE group. Conclusion Proton-nuclear magnetic resonance-based metabolomics of serum samples were found to have ample potential for identifying metabolic changes associated with endometriosis phenotypes. This information may improve our understanding of the pathogenesis of endometriosis.

Résumé L’état d’urgence sanitaire est levé en France le 10 juillet 2020. A cette date, la Brigade de sapeurs-pompiers de Paris (BSPP) a déjà réalisé 11 737 interventions en lien direct avec l’épidémie. Au paroxysme de cette crise sanitaire, la Brigade a répondu à plus de 2 600 appels quotidiens et réalisé presque 600 interventions COVID-19 par jour, sans ne jamais avoir à dégrader la qualité de sa réponse contre les incendies. Cet article rapporte l’expérience de la BSPP et les enseignements issus de la crise COVID-19. Il décrit la cinétique de sa montée en puissance progressive ainsi que les actions diverses menées au profit de la population défendue ainsi que de ses propres personnels.

Resume Objectif Comparaison des interventions pharmaceutiques (IP) realisees par un pharmacien integre dans l’equipe medicale de medecine interne (analyse de niveau 3) par rapport a une analyse centralisee en pharmacie a usage interieur (PUI). Materiel et methode Une comparaison prospective est realisee durant 17 jours. Les prescriptions ont ete analysees simultanement par deux internes en pharmacie. Les parametres evalues ont inclus le nombre, la nature, la classe pharmacologique, l’impact clinique estime des IP et l’acceptation par le prescripteur. Resultats Les 180 prescriptions analysees ont fait l’objet de 121 IP. L’analyse de niveau 3 a produit 51 % d’IP supplementaires. La nature et le type d’IP etaient repartis de facon globalement homogene (p Discussion L’analyse integree au sein du service permet la production de certaines IP specifiques et ameliore la pertinence de l’analyse, notamment pour les IP a fort impact clinique. L’acces a une information plus complete du pharmacien present dans l’unite de soins explique cet etat de fait. Conclusion La connaissance des specificites de l’analyse au sein d’un service de soins est un atout pour le pharmacien clinicien conduisant a une meilleure efficacite.

Introduction: The terrorist threat leads to challenge nations to train numerous non-trauma care providers, with different backgrounds, in damage control (DC) strategies. The purpose of this work was to propose a specific DC training program. Methods: A Task Force of 16 civilian and military physicians met for a 24-hour session, to propose the construction of a DC training program for non-specialised caregivers. Results: Existing DC training programs are heterogeneous, mainly theoretical and almost only for physicians. A program entitled Damage Control for Terrorist Attack Victims (DC-TAV) was then proposed. Identified training targets were care providers from prehospital and hospital staffs, with no trauma experience. The training objectives were the improvement of individual and collective skills for DC strategies for management of terrorist attacks casualties. The tools selected for training concerned e-learning on a dedicated digital teaching platform (including a core section of four modules with types and mechanisms of injury, basic DC techniques, triage, organisation of emergency medical response; and two complementary modules for doctors with DC resuscitation including remote transfusion and DC surgery), hands-on workshops with procedural simulation and full-scale simulation exercises, technical (tourniquets, haemostatic gauzes, needle thoracostomy, chest tube drainage, management of airway, coniotomy) and non-technical (leadership, communication, coordination and triage, decision-making, appropriate use of resources) skills. Finally, an evaluation of the DC-TAV program was planned. Conclusions: The DC-TAV program is an ambitious, civilian-military, nationwide and long-term program, based on a harmonised standard of care and including multidimensional training. Further studies are required to assess its efficacy.

PURPOSE/OBJECTIVE(S) Minibeam radiation therapy (MBRT) is a novel therapeutic approach that uses narrow beams (0.5 to 1 mm) to create a distinct spatial modulation of the dose, featuring alternating regions of high dose (peaks) and low dose (valleys). MBRT with both x-rays and protons was shown to provide a remarkable normal (skin and brain) tissue preservation in preclinical experiments, including sparing of cognitive, emotional, and motor processes. Equivalent or superior (glioma) tumor control compared to conventional radiation therapy was observed, and that even with highly heterogeneous dose distributions in small animal experiments. The underlying biological mechanisms under MBRT efficiency remain elusive. The aim of this work was to investigate the possible participation of the immune system in the anti-tumor response of MBRT. We also hypothesized the possible establishment of a long-term anti-tumor immunity. MATERIALS/METHODS We collected original in vivo radiopathological data in rats, thanks to the implementation of MBRT on a small animal radiation system. Firstly, we compared the response to MBRT of RG2-bearing nude (athymic) rats versus immunocompetent (Fischer) rats. The dose prescription was 30 Gy (average) in one fraction, with approximately one half of the tumor volume receiving (valley) doses of 6 Gy. Secondly, RG2-bearing rats having survived to the first part of the study were reinjected with the same tumor cell line and tumor development was monitored by MRI and bioluminescence imaging. RESULTS While a significant increase of lifespan was observed in the irradiated immunocompetent rats with respect to non-irradiated controls, the irradiated nude rats showed no response to the treatment, pointing out a determinant role of T-cells in MBRT efficiency. Quantification of immune cells is ongoing. Additionally, the irradiated and cured immunocompetent RG2-bearing rats were rechallenged with RG2 tumor cells (3 to 6 months after irradiation). While naive controls developed tumor normally, this was not the case for any of the previously irradiated animals. CONCLUSION These results suggest that T cells play a central role in tumor cell killing in MBRT. Moreover, MBRT seems to act as an anti-tumor vaccine. The remarkable reduction in neurotoxicity along with the potential activation of the immune system makes MBRT an ideal candidate to achieve an effective radio-immunotherapy in very infiltrative and immunosuppressive brain tumors, such as high-grade gliomas (GBM).

The immune system of snails is highly sensitive to pollutants, which can suppress its immune response. We investigated the effects of exposure to the glyphosate-based herbicide Roundup® Original on the snail Biomphalaria glabrata infected by the platyhelminth Echinostoma paraensei by evaluating changes in the snail's internal defense system. Four cohorts were studied: control group, infected snails, snails treated with Roundup®, and snails infected and treated with Roundup®. The hemocyte viability was assessed, morphological differentiation of cells was observed and flow cytometry was performed to determine the morphology, viability and the lectin expression profiles. The frequencies of dead hemocytes were lower in the infected group and higher in both pesticide treated groups. Three cell types were identified: blast-like cells, hyalinocytes and granulocytes. The highest number of all types of hemocytes, as well as the highest number of dead cells, were observed in the infected, pesticide-treated group. The association between infection and herbicide exposure greatly increased the frequency of dead hemocytes, suggesting that this condition impairs the internal defense system of B. glabrata making the snails more vulnerable to parasitic infections.