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Segmentation automatisée de structures cérébrales profondes à partir d'IRMs à Inversion-Récupération
No full textInternational audienceLa segmentation automatique des structures cérébrales est un sujet majeur en recherche médicale. Les petites structures du cerveau profond ont reçu peu d'attention, notamment en raison de l'absence de contourage manuel par des experts. Dans cette étude, nous avons évalué la segmentation automatique par un réseau nnU-Net entrainé grâce à un nouveau jeu de données cliniques contenant des images IRM WAIR (White Matter Attenuated Inversion-Recovery) représentant cinq structures segmentées manuellement chez 53 patients atteints d'une maladie de Parkinson sévère. Des images T1 et DTI ont également été utilisées. Nous avons évalué l'impact de la réorientation des vecteurs de diffusion DTI par rapport à la ligne ACPC. Les sous-ensembles d'entrainement et de test comprenaient respectivement 38 et 15 patients. Comme critères d'évaluation, nous avons utilisé le coefficient de similarité de Dice (DSC), la distance de Hausdorff à 95% (95HD) ainsi que la similarité volumétrique (VS). Des modèles à effets aléatoires ont été utilisés afin de comparer statistiquement les performances. Les résultats montrent notamment que WAIR est nettement plus performant que T1 pour DSC (0,739 ± 0,073), 95HD (1,739 ± 0,398) et VS (0,892 ± 0,044). Les valeurs DSC pour la segmentation automatisée de MB, RN, SN, STN et MT-fa ont plus ou moins diminué selon la complexité de la segmentation manuelle. Par ailleurs, la réorientation des vecteurs DTI a amélioré la segmentation automatisée
Eicosanoids and Oxylipin Signature in Hereditary Hemochromatosis Patients Are Similar to Dysmetabolic Iron Overload Syndrome Patients but Are Impacted by Dietary Iron Absorption
No full textInternational audienceIntroduction: Oxylipins are mediators of oxidative stress. To characterize the underlying inflammatory processes and phenotype effect of iron metabolism disorders, we investigated the oxylipin profile in hereditary hemochromatosis (HH) and dysmetabolic iron overload syndrome (DIOS) patients. Methods: An LC-MS/MS-based method was performed to quantify plasma oxylipins in 20 HH and 20 DIOS patients in fasting conditions and 3 h after an iron-rich meal in HH patients. Results: Principal component analysis showed no separation between HH and DIOS, suggesting that the clinical phenotype has no direct impact on oxylipin metabolism. 20-HETE was higher in DIOS and correlated with hypertension (p = 0.03). Different oxylipin signatures were observed in HH before and after the iron-rich meal. Discriminant oxylipins include epoxy fatty acids derived from docosahexaenoic acid and arachidonic acid as well as 13-HODE and 9-HODE. Mediation analysis found no major contribution of dietary iron absorption for 16/22 oxylipins significantly affected by the meal. Discussion: The oxylipin profiles of HH and DIOS seemed similar except for 20-HETE, possibly reflecting different hypertension prevalence between the two groups. Oxylipins were significantly affected by the iron-rich meal, but the specific contribution of iron was not clear. Although iron may contribute to oxidative stress and inflammation in HH and DIOS, this does not seem to directly affect oxylipin metabolism
Single-drug versus combination antimicrobial therapy in critically ill patients with hospital-acquired pneumonia and ventilator-associated pneumonia due to Gram-negative pathogens: a multicenter retrospective cohort study
No full textInternational audienceKey messages: In this study including 391 critically ill patients with nosocomial pneumonia due to Gram-negative pathogens, combination therapy was not associated with a reduced hazard of death at Day 28 or a greater likelihood of clinical cure at Day 14. No over-risk of AKI was observed in patients receiving combination therapy. Background: The benefits and harms of combination antimicrobial therapy remain controversial in critically ill patients with hospital-acquired pneumonia (HAP), ventilated HAP (vHAP) or ventilator-associated pneumonia (VAP) involving Gram-negative bacteria. Methods: We included all patients in the prospective multicenter OutcomeRea database with a first HAP, vHAP or VAP due to a single Gram-negative bacterium and treated with initial adequate single-drug or combination therapy. The primary endpoint was Day-28 all-cause mortality. Secondary endpoints were clinical cure rate at Day 14 and a composite outcome of death or treatment-emergent acute kidney injury (AKI) at Day 7. The average effects of combination therapy on the study endpoints were investigated through inverse probability of treatment-weighted regression and multivariable regression models. Subgroups analyses were performed according to the resistance phenotype of the causative pathogens (multidrug-resistant or not), the pivotal (carbapenems or others) and companion (aminoglycosides/polymyxins or others) drug classes, the duration of combination therapy (Results: Among the 391 included patients, 151 (38.6%) received single-drug therapy and 240 (61.4%) received combination therapy. VAP (overall, 67.3%), vHAP (16.4%) and HAP (16.4%) were equally distributed in the two groups. All-cause mortality rates at Day 28 (overall, 31.2%), clinical cure rate at Day 14 (43.7%) and the rate of death or AKI at Day 7 (41.2%) did not significantly differ between the groups. In inverse probability of treatment-weighted analyses, combination therapy was not independently associated with the likelihood of all-cause death at Day 28 (adjusted odd ratio [aOR], 1.14; 95% confidence interval [CI] 0.73–1.77; P = 0.56), clinical cure at Day 14 (aOR, 0.79; 95% CI 0.53–1.20; P = 0.27) or death or AKI at Day 7 (aOR, 1.07; 95% CI 0.71–1.63; P = 0.73). Multivariable regression models and subgroup analyses provided similar results. Conclusions: Initial combination therapy exerts no independent impact on Day-28 mortality, clinical cure rate at Day 14, and the hazard of death or AKI at Day 7 in critically ill patients with mono-bacterial HAP, vHAP or VAP due to Gram-negative bacteria
Cryptococcus neoformans Infections Differ Among Human Immunodeficiency Virus (HIV)–Seropositive and HIV-Seronegative Individuals: Results From a Nationwide Surveillance Program in France
No full textInternational audienceAmong 1107 cryptococcosis cases from the French surveillance network (2005–2020), the proportion of HIV-seronegative individuals has recently surpassed that of HIV-seropositive individuals. We observed marked differences in patient characteristics, disease presentations, cryptococcal antigen results, infecting species, and mortality according to HIV serostatus
Risque de poussée après vaccination contre le COVID-19 chez les patients atteints de sclérose en plaques en France utilisant un design « self-controlled case series »
No full textInternational audienceIntroductionLes patients avec sclérose en plaques (SEP) ont eu un accès prioritaire à la vaccination contre le SARS-CoV-2. De nombreux cas de poussées subséquents à la vaccination ont été reportés dans la littérature, décourageant les patients à recevoir la dose de rappel, dans cette population parfois déjà réticente. L'objectif de cette étude était d’évaluer le risque de poussée suivant la vaccination contre le COVID-19 dans la population de patients avec SEP en France.MéthodesL’étude a été réalisée en utilisant les données du Système national des données de santé (SNDS). Les patients avec SEP ont été identifiés sur la base d'une affection de longue durée (ALD) pour SEP via un code CIM-10 ou traitement spécifique et suivis jusqu'en mars 2022. Les poussées nécessitant des corticoïdes à hautes doses ont été identifiées en utilisant un algorithme précédemment publié. Un design de type « self-controlled case series » (SCCS) a été utilisé pour évaluer le risque de poussée dans les 45 jours suivant la vaccination (analyse de sensibilité avec 90 jours). Le risque a été évalué pour la première, deuxième et troisième (rappel) dose et exprimé sous la forme d'un ratio du taux d'incidence (IRR), en prenant en compte les potentiels biais liés à des critères variants dans le temps tels que la saisonnalité et les traitements de fond de la SEP.RésultatsAu total, 124.545 patients avec SEP ont été identifiés au 1er janvier 2021, dont 82,3 % (n=102 524) ont reçu au moins une dose de vaccin contre le COVID-19 au 31 décembre 2021, pour un total de 259 880 doses. Aucune majoration du risque de poussée n'a été constatée pour les 1e, 2e et 3e doses, pour un effet combiné donnant un IRR=0,97 [0,91–1,03], p=0,30. Cette absence de risque était aussi valable pour les sous-groupes (âge <50ans, ancienneté de la SEP <10 ans, patients utilisant des traitements de fond de la maladie). Une légère augmentation du risque de poussée a été remarquée après la dose de rappel pour les patients fortement inflammatoires (au moins deux poussées sur les deux années précédentes), principalement portée par les patients non traités, là où les traités n'avaient pas d'augmentation significative du risque.ConclusionDans cette étude d'envergure nationale sur plus de 100 000 patients avec SEP, nous n'avons pas trouvé d'augmentation du risque de poussée nécessitant l'utilisation de corticothérapie, suivant une vaccination contre le COVID-19. La vaccination contre le COVID-19 peut donc être recommandée chez les patients vivant avec une SEP les plus à risque d'infection sévère, avec une prudence toutefois pour les patients avec une forte activité inflammatoire et qui devraient être traités
DOP05 Bowel damage and its correlation with the disability index in patients with recently diagnosed Crohn´s Disease
No full textMeeting abstract du "19th Congress of ECCO", Stockholm, Suède, 21-24 février, 2024International audienceBackground Crohn’s disease (CD) progression can lead to bowel damage (BD) and disability. However, the longitudinal characterization of BD and disability in early CD patients remains limited. Methods The Crohn´s Disease Cohort (CROCO) is a multicentre, European cohort study of newly diagnosed CD patients (<12 months following diagnosis) intended to prospectively characterize BD progression and disability. At one year following inclusion (Y1), BD progression was evaluated using the Lémann Index (LI). Magnetic resonance enterography was completed by all patients, with additional endoscopy and/or pelvic MRI based on disease location. Absence of BD was defined as a LI=0, and any presence of bowel damage was indicated by LI>0. Disability was assessed using the validated IBD-disability index (IBD-DI) encompassing various domains. We report the LI at Y1 and its association with significant disease features and with the IBD-DI. Results Among the 261 included patients, 135 have completed the Y1 visit, with 100 having their LI calculated [57% male, median age at diagnosis of 36 years old (IQR 26-48)]. Most patients (90%) had ileal or ileocolonic involvement, 68% had inflammatory phenotype, and 11% had perianal disease. At inclusion, 7% of patients had undergone surgery (5 intestinal and 2 perianal), and 53% had initiated biological therapy within the first year of disease, primarily anti-TNF in mono or combination therapy. Of those with stricturing (B2) or penetrating (B3) behaviour, 77% and 79%, respectively, were on anti-TNF therapy. Overall, 61% of the patients exhibited some degree of BD (LI>0), yet the median LI at Y1 was low [0.6 (IQR 0-2)]. Univariate analysis revealed an association between the presence of any bowel damage at Y1 and disease behaviour at inclusion (B2 OR 3.33, 95%CI 0.84-13.18 and B3 OR 8.5, 95%CI 1.82, 39.66; p<0.01). Additionally, there was a significant association with anti-TNF therapy (OR 2.88, 95%CI 1.24-6.66, p=0.012). In a multivariate logistic model, only older age at diagnosis appeared protective against any BD (Table 1). Among those evaluated for the LI, 84 completed the IBD-DI at Y1. The median IBD-DI was 17.3 (IQR 10.7-32.6) and 30% experienced moderate-to-severe disability (IBD-DI>35). No association was observed between LI and IBD-DI at Y1 (OR 1.09, 95%CI 0.39-3.04, p=0.86) and there were no differences in the median LI across disability categories (p=0.67) (Figure 1). Conclusion In a cohort of newly diagnosed CD patients, one-third exhibited no bowel damage as per the LI evaluation. For those presenting any degree of damage, the global LI remained low. No association was found with disability assessed by the IBD-DI. These data add to the growing concept that early disease represents a window of opportunity
Impact of heterozygous ALK1 mutations on the transcriptomic response to BMP9 and BMP10 in endothelial cells from hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension donors
No full textInternational audienceAbstract Heterozygous activin receptor-like kinase 1 ( ALK1 ) mutations are associated with two vascular diseases: hereditary hemorrhagic telangiectasia (HHT) and more rarely pulmonary arterial hypertension (PAH). Here, we aimed to understand the impact of ALK1 mutations on BMP9 and BMP10 transcriptomic responses in endothelial cells. Endothelial colony-forming cells (ECFCs) and microvascular endothelial cells (HMVECs) carrying loss of function ALK1 mutations were isolated from newborn HHT and adult PAH donors, respectively. RNA-sequencing was performed on each type of cells compared to controls following an 18 h stimulation with BMP9 or BMP10. In control ECFCs, BMP9 and BMP10 stimulations induced similar transcriptomic responses with around 800 differentially expressed genes (DEGs). ALK1 -mutated ECFCs unexpectedly revealed highly similar transcriptomic profiles to controls, both at the baseline and upon stimulation, and normal activation of Smad1/5 that could not be explained by a compensation in cell-surface ALK1 level. Conversely, PAH HMVECs revealed strong transcriptional dysregulations compared to controls with > 1200 DEGs at the baseline. Consequently, because our study involved two variables, ALK1 genotype and BMP stimulation, we performed two-factor differential expression analysis and identified 44 BMP9-dysregulated genes in mutated HMVECs, but none in ECFCs. Yet, the impaired regulation of at least one hit, namely lunatic fringe ( LFNG ), was validated by RT-qPCR in three different ALK1 -mutated endothelial models. In conclusion, ALK1 heterozygosity only modified the BMP9/BMP10 regulation of few genes, including LFNG involved in NOTCH signaling. Future studies will uncover whether dysregulations in such hits are enough to promote HHT/PAH pathogenesis, making them potential therapeutic targets, or if second hits are necessary
Multiple molecular diagnoses in the field of intellectual disability and congenital anomalies: 3.5% of all positive cases
No full textInternational audiencePurpose : Wide access to clinical exome/genome sequencing (ES/GS) enables the identification of multiple molecular diagnoses (MMDs), being a long-standing but underestimated concept, defined by two or more causal loci implicated in the phenotype of an individual with a rare disease. Only few series report MMDs rates (1.8% to 7.1%). This study highlights the increasing role of MMDs in a large cohort of individuals addressed for congenital anomalies/intellectual disability (CA/ID). Methods : From 2014 to 2021, our diagnostic laboratory rendered 880/2658 positive ES diagnoses for CA/ID aetiology. Exhaustive search on MMDs from ES data was performed prospectively (January 2019 to December 2021) and retrospectively (March 2014 to December 2018). Results : MMDs were identified in 31/880 individuals (3.5%), responsible for distinct (9/31) or overlapping (22/31) phenotypes, and potential MMDs in 39/880 additional individuals (4.4%). Conclusion : MMDs are frequent in CA/ID and remain a strong challenge. Reanalysis of positive ES data appears essential when phenotypes are partially explained by the initial diagnosis or atypically enriched overtime. Up-to-date clinical data, clinical expertise from the referring physician, strong interactions between clinicians and biologists, and increasing gene discoveries and improved ES bioinformatics tools appear all the more fundamental to enhance chances of identifying MMDs. It is essential to provide appropriate patient care and genetic counselling
Trends in fatal poisoning among medical users of analgesics in France from 2013 to 2022: an analysis of the DTA register
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Neuropathic Component Characteristics in Chronic Secondary Musculoskeletal Pain After Postmenopausal Osteoporotic Fractures: A Pilot Cross‐Sectional Study
No full textInternational audienceBackground: Te neuropathic characteristics of pain occurring after an osteoporosis (OP)-related fracture are often underrecognized. Te aim of this pilot study is to identify, in patients sufering from pain localized on the site of a previous osteoporotic fracture, the presence of neuropathic characteristics, their medical management, and their impact on quality of life. Methods: Tis pilot cross-sectional study on consecutive patients in University Hospital, Rheumatology Department, Clermont-Ferrand, France, was approved by the Ethics Committee (IRB number 2023-CF34). Pain was evaluated with the Numeric Pain Rating Scale (NPRS), Neuropathic Component of Chronic pain (NCCP) was screened with the DN4 questionnaire, and sleep was assessed with the Pittsburg questionnaire. Depression, anxiety, quality of life, and concomitant treatment were also evaluated. Results were expressed using efect sizes (ESs) and 95% confdence intervals. Results: Fifty new patients with a history of at least one fully documented fragility vertebral fracture (VF) or nonvertebral fracture (NVF) due to osteoporosis, in the last 2 years minus the previous 6 months, were included. Findings show that 21% patients with VF and 28% patients with NVF reported NCCP (DN ≥ 4). NCCP patients had more intense pain (NPRS � 5.1 ± 2.9 vs. 2.9 ± 2.7, ES � 0.82 [0.18; 1.44], p � 0.019) and impaired sleep compared to patients without NCCP (ES � 0.71 [0.08; 1.33], p � 0.043). A remarkable point was that patients had no specifc oral or topical treatment for NCCP and were only taking on demand paracetamol and nonsteroidal anti-infammatory drugs. Conclusions: Future research should focus on the neuropathic characteristics of pain patients with OP, in order to better manage OP-related pain.</div