Sepsis-trained macrophages promote antitumoral tissue-resident T cells.

Sepsis induces immune alterations, which last for months after the resolution of illness. The effect of this immunological reprogramming on the risk of developing cancer is unclear. Here we use a national claims database to show that sepsis survivors had a lower cumulative incidence of cancers than matched nonsevere infection survivors. We identify a chemokine network released from sepsis-trained resident macrophages that triggers tissue residency of T cells via CCR2 and CXCR6 stimulations as the immune mechanism responsible for this decreased risk of de novo tumor development after sepsis cure. While nonseptic inflammation does not provoke this network, laminarin injection could therapeutically reproduce the protective sepsis effect. This chemokine network and CXCR6 tissue-resident T cell accumulation were detected in humans with sepsis and were associated with prolonged survival in humans with cancer. These findings identify a therapeutically relevant antitumor consequence of sepsis-induced trained immunity.

Lysine Methylation Regulators Moonlighting outside the Epigenome.

Landmark discoveries made nearly two decades ago identified known transcriptional regulators as histone lysine methyltransferases. Since then, the field of lysine methylation signaling has been dominated by studies of how this small chemical posttranslational modification regulates gene expression and other chromatin-based processes. However, recent advances in mass-spectrometry-based proteomics have revealed that histones are just a subset of the thousands of eukaryotic proteins marked by lysine methylation. As the writers, erasers, and readers of histone lysine methylation are emerging as a promising therapeutic target class for cancer and other diseases, a key challenge for the field is to define the full spectrum of activities for these proteins. Here we summarize recent discoveries implicating non-histone lysine methylation as a major regulator of diverse cellular processes. We further discuss recent technological innovations that are enabling the expanded study of lysine methylation signaling. Collectively, these findings are shaping our understanding of the fundamental mechanisms of non-histone protein regulation through this dynamic and multi-functional posttranslational modification.

Epigenome-wide meta-analysis of BMI in nine cohorts: Examining the utility of epigenetically predicted BMI.

This study sought to examine the association between DNA methylation and body mass index (BMI) and the potential of BMI-associated cytosine-phosphate-guanine (CpG) sites to provide information about metabolic health. We pooled summary statistics from six trans-ethnic epigenome-wide association studies (EWASs) of BMI representing nine cohorts (n = 17,034), replicated these findings in the Women's Health Initiative (WHI, n = 4,822), and developed an epigenetic prediction score of BMI. In the pooled EWASs, 1,265 CpG sites were associated with BMI (p < 1E-7) and 1,238 replicated in the WHI (FDR < 0.05). We performed several stratified analyses to examine whether these associations differed between individuals of European and African descent, as defined by self-reported race/ethnicity. We found that five CpG sites had a significant interaction with BMI by race/ethnicity. To examine the utility of the significant CpG sites in predicting BMI, we used elastic net regression to predict log-normalized BMI in the WHI (80% training/20% testing). This model found that 397 sites could explain 32% of the variance in BMI in the WHI test set. Individuals whose methylome-predicted BMI overestimated their BMI (high epigenetic BMI) had significantly higher glucose and triglycerides and lower HDL cholesterol and LDL cholesterol compared to accurately predicted BMI. Individuals whose methylome-predicted BMI underestimated their BMI (low epigenetic BMI) had significantly higher HDL cholesterol and lower glucose and triglycerides. This study confirmed 553 and identified 685 CpG sites associated with BMI. Participants with high epigenetic BMI had poorer metabolic health, suggesting that the overestimation may be driven in part by cardiometabolic derangements characteristic of metabolic syndrome.

E4F1 and ZNF148 are transcriptional activators of the -57A > C and wild-type TERT promoter.

Point mutations within the TERT promoter are the most recurrent somatic noncoding mutations identified across different cancer types, including glioblastoma, melanoma, hepatocellular carcinoma, and bladder cancer. They are most abundant at -146C > T and -124C > T, and rarer at -57A > C, with the latter originally described as a familial case, but subsequently shown also to occur somatically. All three mutations create de novo E26-specific (ETS) binding sites and result in activation of the TERT gene, allowing cancer cells to achieve replicative immortality. Here, we used a systematic proteomics screen to identify transcription factors preferentially binding to the -146C > T, -124C > T, and -57A > C mutations. Although we confirmed binding of multiple ETS factors to the mutant -146C > T and -124C > T sequences, we identified E4F1 as a -57A > C-specific binder and ZNF148 as a TERT wild-type (WT) promoter binder that showed reduced interaction with the -124C > T allele. Both proteins are activating transcription factors that bind specifically to the -57A > C and WT (at position 124) TERT promoter sequence in corresponding cell lines, and up-regulate TERT transcription and telomerase activity. Our work describes new regulators of TERT gene expression with possible roles in cancer.

Breast and bowel cancers diagnosed in people 'too young to have cancer': A blueprint for research using family and twin studies.

Young breast and bowel cancers (e.g., those diagnosed before age 40 or 50 years) have far greater morbidity and mortality in terms of years of life lost, and are increasing in incidence, but have been less studied. For breast and bowel cancers, the familial relative risks, and therefore the familial variances in age-specific log(incidence), are much greater at younger ages, but little of these familial variances has been explained. Studies of families and twins can address questions not easily answered by studies of unrelated individuals alone. We describe existing and emerging family and twin data that can provide special opportunities for discovery. We present designs and statistical analyses, including novel ideas such as the VALID (Variance in Age-specific Log Incidence Decomposition) model for causes of variation in risk, the DEPTH (DEPendency of association on the number of Top Hits) and other approaches to analyse genome-wide association study data, and the within-pair, ICE FALCON (Inference about Causation from Examining FAmiliaL CONfounding) and ICE CRISTAL (Inference about Causation from Examining Changes in Regression coefficients and Innovative STatistical AnaLysis) approaches to causation and familial confounding. Example applications to breast and colorectal cancer are presented. Motivated by the availability of the resources of the Breast and Colon Cancer Family Registries, we also present some ideas for future studies that could be applied to, and compared with, cancers diagnosed at older ages and address the challenges posed by young breast and bowel cancers.

Trans-ancestral fine-mapping of MHC reveals key amino acids associated with spontaneous clearance of hepatitis C in HLA-DQß1.

Spontaneous clearance of acute hepatitis C virus (HCV) infection is associated with single nucleotide polymorphisms (SNPs) on the MHC class II. We fine-mapped the MHC region in European (n = 1,600; 594 HCV clearance/1,006 HCV persistence) and African (n = 1,869; 340 HCV clearance/1,529 HCV persistence) ancestry individuals and evaluated HCV peptide binding affinity of classical alleles. In both populations, HLA-DQß1Leu26 (p valueMeta = 1.24 × 10-14) located in pocket 4 was negatively associated with HCV spontaneous clearance and HLA-DQß1Pro55 (p valueMeta = 8.23 × 10-11) located in the peptide binding region was positively associated, independently of HLA-DQß1Leu26. These two amino acids are not in linkage disequilibrium (r2 < 0.1) and explain the SNPs and classical allele associations represented by rs2647011, rs9274711, HLA-DQB1∗03:01, and HLA-DRB1∗01:01. Additionally, HCV persistence classical alleles tagged by HLA-DQß1Leu26 had fewer HCV binding epitopes and lower predicted binding affinities compared to clearance alleles (geometric mean of combined IC50 nM of persistence versus clearance; 2,321 nM versus 761.7 nM, p value = 1.35 × 10-38). In summary, MHC class II fine-mapping revealed key amino acids in HLA-DQß1 explaining allelic and SNP associations with HCV outcomes. This mechanistic advance in understanding of natural recovery and immunogenetics of HCV might set the stage for much needed enhancement and design of vaccine to promote spontaneous clearance of HCV infection.

Adequate versus deep response to ursodeoxycholic acid in primary biliary cholangitis: To what extent and under what conditions is normal alkaline phosphatase level associated with complication-free survival gain?

BACKGROUND AND AIMS: Normal alkaline phosphatase (ALP) levels in ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC) are associated with better long-term outcome. However, second-line therapies are currently recommended only when ALP levels remain above 1.5 times the upper limit of normal (×ULN) after 12-month UDCA. We assessed whether, in patients considered good responders to UDCA, normal ALP levels were associated with significant survival gains. APPROACH AND RESULTS: We performed a retrospective cohort study of 1047 patients with PBC who attained an adequate response to UDCA according to Paris-2 criteria. Time to liver-related complications, liver transplantation, or death was assessed using adjusted restricted mean survival time (RMST) analysis. The overall incidence rate of events was 17.0 (95% CI: 13.7-21.1) per 1000 out of 4763.2 patient-years. On the whole population, normal serum ALP values (but not normal gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST); or total bilirubin < 0.6 ×ULN) were associated with a significant absolute complication-free survival gain at 10 years (mean 7.6 months, 95% CI: 2.7 - 12.6 mo.; p = 0.003). In subgroup analysis, this association was significant in patients with a liver stiffness measurement ≥ 10 kPa and/or age ≤ 62 years, with a 10-year absolute complication-free survival gain of 52.8 months (95% CI: 45.7-59.9, p < 0.001) when these 2 conditions were met. CONCLUSIONS: PBC patients with an adequate response to UDCA and persistent ALP elevation between 1.1 and 1.5 ×ULN, particularly those with advanced fibrosis and/or who are sufficiently young, remain at risk of poor outcome. Further therapeutic efforts should be considered for these patients.

Methylation of DNA Ligase 1 by G9a/GLP Recruits UHRF1 to Replicating DNA and Regulates DNA Methylation.

DNA methylation is an essential epigenetic mark in mammals that has to be re-established after each round of DNA replication. The protein UHRF1 is essential for this process; it has been proposed that the protein targets newly replicated DNA by cooperatively binding hemi-methylated DNA and H3K9me2/3, but this model leaves a number of questions unanswered. Here, we present evidence for a direct recruitment of UHRF1 by the replication machinery via DNA ligase 1 (LIG1). A histone H3K9-like mimic within LIG1 is methylated by G9a and GLP and, compared with H3K9me2/3, more avidly binds UHRF1. Interaction with methylated LIG1 promotes the recruitment of UHRF1 to DNA replication sites and is required for DNA methylation maintenance. These results further elucidate the function of UHRF1, identify a non-histone target of G9a and GLP, and provide an example of a histone mimic that coordinates DNA replication and DNA methylation maintenance.

A genetic screen identifies BEND3 as a regulator of bivalent gene expression and global DNA methylation.

Epigenetic mechanisms are essential to establish and safeguard cellular identities in mammals. They dynamically regulate the expression of genes, transposable elements and higher-order chromatin structures. Consequently, these chromatin marks are indispensable for mammalian development and alterations often lead to disease, such as cancer. Bivalent promoters are especially important during differentiation and development. Here we used a genetic screen to identify new regulators of a bivalent repressed gene. We identify BEND3 as a regulator of hundreds of bivalent promoters, some of which it represses, and some of which it activates. We show that BEND3 is recruited to a CpG-containg consensus site that is present in multiple copies in many bivalent promoters. Besides having direct effect on the promoters it binds, the loss of BEND3 leads to genome-wide gains of DNA methylation, which are especially marked at regions normally protected by the TET enzymes. DNA hydroxymethylation is reduced in Bend3 mutant cells, possibly as consequence of altered gene expression leading to diminished alpha-ketoglutarate production, thus lowering TET activity. Our results clarify the direct and indirect roles of an important chromatin regulator, BEND3, and, more broadly, they shed light on the regulation of bivalent promoters.

Sustained Hypothetical Interventions on Midlife Alcohol Consumption in Relation to All-Cause and Cancer Mortality: The Australian Longitudinal Study on Women's Health.

No randomized controlled trial has evaluated the effect of long-term alcohol interventions on mortality. Results reported in existing observational studies may be subject to selection bias and time-varying confounding. Using data from the Australian Longitudinal Study on Women's Health 1946-1951 birth cohort, collected regularly from 1996-2016, we estimated all-cause and cancer mortality had women been assigned various alcohol interventions (in categories ranging from 0 to >30 g/day ethanol, or reduced to ≤20 g/day if higher) at baseline, and had they maintained these levels of consumption. The cumulative risks for all-cause and cancer mortality were 5.6% (10,118 women followed for 20 years) and 2.9% (18 years), respectively. For all-cause and cancer mortality, baseline ethanol up to 30 g/day showed lower risk and >30 g/day showed higher risk relative to abstention. Had women sustainedly followed the interventions, a similar relationship was observed for all-cause mortality. However, the negative association observed for intakes ≤30 g/day and positive association for intakes >30 g/day was not evident for cancer mortality. Our findings suggest that all-cause mortality could have been lower than observed if this cohort of women had consumed some alcohol (no more than 30 g/day) rather than no consumption, but cancer mortality might not.

Short peripheral blood leukocyte telomere length in rheumatoid arthritis-interstitial lung disease.

Shortened telomere lengths (TLs) can be caused by single nucleotide polymorphisms and loss-of-function mutations in telomere-related genes (TRG), as well as ageing and lifestyle factors such as smoking. Our objective was to determine if shortened TL is associated with interstitial lung disease (ILD) in individuals with rheumatoid arthritis (RA). This is the largest study to demonstrate and replicate that shortened peripheral blood leukocytes-TL is associated with ILD in patients with RA compared with RA without ILD in a multinational cohort, and short PBL-TL was associated with baseline disease severity in RA-ILD as measured by forced vital capacity percent predicted.

Luminescent Supramolecular Ionic Frameworks based on Organic Fluorescent Polycations and Polyanionic Phosphorescent Metal Clusters.

Emissive ionic supramolecular frameworks are designed by associating tetraphenylethylene-based tetra-cationic units and di-anionic molybdenum or tetra-anionic rhenium octahedral clusters. Obtained structures were characterized by single-crystal X-ray diffraction. The emission properties of the hybrids were investigated as dry powders or in various solvents by one photon and two photon absorption leading to a O2 concentration dependent luminescence color for the Mo based hybrid.

Scoping review of clinical decision support systems for multiple sclerosis management: Leveraging information technology and massive health data.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system, with numerous therapeutic options, but a lack of biomarkers to support a mechanistic approach to precision medicine. A computational approach to precision medicine could proceed from clinical decision support systems (CDSSs). They are digital tools aiming to empower physicians through the clinical applications of information technology and massive data. However, the process of their clinical development is still maturing; we aimed to review it in the field of MS. METHODS: For this scoping review, we screened systematically the PubMed database. We identified 24 articles reporting 14 CDSS projects and compared their technical and software development aspects. RESULTS: The projects position themselves in various contexts of usage with various algorithmic approaches: expert systems, CDSSs based on similar patients' data visualization, and model-based CDSSs implementing mathematical predictive models. So far, no project has completed its clinical development up to certification for clinical use with global release. Some CDSSs have been replaced at subsequent project iterations. The most advanced projects did not necessarily report every step of clinical development in a dedicated article (proof of concept, offline validation, refined prototype, live clinical evaluation, comparative prospective evaluation). They seek different software distribution options to integrate into health care: internal usage, "peer-to-peer," and marketing distribution. CONCLUSIONS: This review illustrates the potential of clinical applications of information technology and massive data to support MS management and helps clarify the roadmap for future projects as a multidisciplinary and multistep process.

Changing hemostatic management in post-partum hemorrhage.

Early and fast assessment of hemostasis during postpartum hemorrhage (PPH) is essential to allow early characterization of coagulopathy, estimate bleeding severity and improve outcome. During PPH, fibrinogen decrease occurs earlier than other coagulation factors deficiency and hypofibrinogenemia is an early marker of PPH severity of progression. With good evidence in the context of PPH, point-of-care viscoelastic (VET) hemostatic assays have been shown to provide rapid assessment of hemostatic disorders, low fibrinogen levels, and allow VET-guided fibrinogen replacement. Further studies are needed to define the thresholds for the other coagulation parameters.

Ex Vivo Comparison of the Elastic Properties of Vascular Substitutes Used for Pulmonary Artery Replacement.

INTRODUCTION: Study aims were to evaluate the elastic properties of vascular substitutes frequently used for pulmonary artery (PA) replacement, and then to compare their compliance and stiffness indexes to those of human PA. METHODS: A bench-test pulsatile flow experiment was developed to perfuse human cadaveric vascular substitutes (PA, thoracic aorta, human pericardial conduit), bovine pericardial conduit, and prosthetic vascular substitutes (polytetrafluorethylene and Dacron grafts) at a flow and low pulsed pressure mimicking pulmonary circulation. Intraluminal pressure was measured. An ultrasound system with an echo-tracking function was used to monitor vessel wall movements. The diameter, compliance, and stiffness index were calculated for each vascular substitute and compared to the human PA at mean pressures ranging from 10 to 50 mmHg. RESULTS: The compliance of the PA and the thoracic aorta were similar at mean physiological pressures of 10 mmHg and 20 mmHg. The PA was significantly less compliant than the aorta at mean pressures above 30 mmHg (P = 0.017). However, there was no difference in stiffness index between the two substitutes over the entire pressure range. Compared to the PA, human pericardial conduit was less compliant at 10 mmHg (P = 0.033) and stiffer at 10 mmHg (P = 0.00038) and 20 mmHg (P = 0.026). Bovine pericardial conduit and synthetic prostheses were significantly less compliant and stiffer than the PA for mean pressures of 10, 20, and 30 mmHg. There were no differences at 40 and 50 mmHg. CONCLUSIONS: Allogenic arterial grafts appear to be the most suitable vascular substitutes in terms of compliance and stiffness for PA replacement.

STABILISE (Stent-Assisted Balloon-Induced Intimal Disruption and Relamination in Aortic Dissection Repair) Is Associated With Good Anatomical Results on the Distal Thoracoabdominal Aorta at 2 Years.

PURPOSE: The aim of this comparative study was to evaluate the increased aortic diameter of the distal aorta after implementing the STABILISE technique in complicated type B aortic dissection (AD). DESIGN: This is a comparative monocentric retrospective study. MATERIALS AND METHODS: All patients who underwent an STABILISE procedure for complicated AD between 2018 and 2020 were included and compared with a historic cohort treated with thoracic endovascular aortic repair (TEVAR) alone. Aortic diameters were measured at 6 different levels on the thoracic and abdominal aorta. The primary end point was an increased aortic diameter at 1 and 2 years. The exclusion criterion was the absence of a computed tomography (CT) scan at 1 or 2 years. RESULTS: A total of 55 patients were included: 24 in the TEVAR group and 31 in the STABILISE group. At the level of the stent graft, there was a decrease in aortic diameters in both groups without significant differences. At the level of the distal aorta, there was an increase in aortic diameters in both groups without significant differences. There were significantly more patients in the TEVAR group with an unfavorable increase in aortic diameter >5 mm of the distal aorta at 2 years than in the STABILISE group: 8 (33%) vs 1 (3%) (p=0.01). For chronic ADs, a significantly greater increase in aortic diameters of the distal aorta was observed in the STABILISE group. CONCLUSIONS: The STABILISE technique is technically feasible and potentially leads to decreased longer re-intervention rates; indeed, more patients had an unfavorable increase in aortic diameter in the TEVAR group than in the STABILISE group at 2 years. The high rate of long-term distal aortic aneurysm progression and reintervention after TEVAR alone suggests that this option is not sufficient to definitively treat these complex patients. CLINICAL IMPACT: This article reported the results of stent assisted balloon induced intimal disruption and relamination (STABILISE) with a follow-up at 2 years. This is the first comparative study between STABILISE, which has emerged as a new technique inducing aortic remodeling and therefore better long-term outcome, and the standard technique TEVAR alone. STABILISE technique is associated with good results on the distal aorta at 2 years with a rate of patient with unfavorable aortic diameter evolution greater in TEVAR group compared to STABILISE group and could improve the long-term results on the distal aorta by inducing extensive aortic remodeling.

Fatal bowel perforation caused by ingestion of high-powered magnets in a 6-year-old boy.

Foreign body ingestion in children is a frequent cause for medical consultation. Although most foreign bodies are spontaneously eliminated from the gastrointestinal tract, life-threatening complications such as gastrointestinal obstruction or perforation can occur. We report the case of a 6-year-old boy who died 2 days after the onset of nausea and abdominal pain, with no foreign body ingestion witnessed or reported in the previous days. Autopsy showed a diffuse peritonitis and a perforation of the transverse colon caused by three high-powered magnets stacked together, and attached to the outer stomach wall via a fourth magnet located in the stomach. The cause of death was peritonitis due to bowel perforation by ingested magnets, which were shown to have come from a toy belonging to the child. Ingestion of multiple high-powered magnets carries a high risk of gastrointestinal complications and can exceptionally have a fatal outcome, especially as it often goes unreported and causes non-specific gastrointestinal symptoms that can delay diagnosis and management. This case highlights the need to raise public awareness of the potential risks of ingesting such magnets and to strengthen safety standards to protect children from this serious health hazard.

Design, cohort profile and comparison of the KTD-Innov study: a prospective multidimensional biomarker validation study in kidney allograft rejection.

There is an unmet need for robust and clinically validated biomarkers of kidney allograft rejection. Here we present the KTD-Innov study (ClinicalTrials.gov, NCT03582436), an unselected deeply phenotyped cohort of kidney transplant recipients with a holistic approach to validate the clinical utility of precision diagnostic biomarkers. In 2018-2019, we prospectively enrolled consecutive adult patients who received a kidney allograft at seven French centers and followed them for a year. We performed multimodal phenotyping at follow-up visits, by collecting clinical, biological, immunological, and histological parameters, and analyzing a panel of 147 blood, urinary and kidney tissue biomarkers. The primary outcome was allograft rejection, assessed at each visit according to the international Banff 2019 classification. We evaluated the representativeness of participants by comparing them with patients from French, European, and American transplant programs transplanted during the same period. A total of 733 kidney transplant recipients (64.1% male and 35.9% female) were included during the study. The median follow-up after transplantation was 12.3 months (interquartile range, 11.9-13.1 months). The cumulative incidence of rejection was 9.7% at one year post-transplant. We developed a distributed and secured data repository in compliance with the general data protection regulation. We established a multimodal biomarker biobank of 16,736 samples, including 9331 blood, 4425 urinary and 2980 kidney tissue samples, managed and secured in a collaborative network involving 7 clinical centers, 4 analytical platforms and 2 industrial partners. Patients' characteristics, immune profiles and treatments closely resembled those of 41,238 French, European and American kidney transplant recipients. The KTD-Innov study is a unique holistic and multidimensional biomarker validation cohort of kidney transplant recipients representative of the real-world transplant population. Future findings from this cohort are likely to be robust and generalizable.

Stomach size in anorexia nervosa: A new challenge?

BACKGROUND & AIMS: Changes in stomach size may impact eating behaviour. A recent study showed gastric dilatation in restrictive eating disorders using computed tomography scans. This study aimed to describe stomach size in the standing position in women with anorexia nervosa (AN). METHODS: Women treated for AN at our institution were retrospectively included if they had undergone upper gastrointestinal radiography (UGR) after the diagnosis of AN. Two control groups (CG1 and CG2) were included, both comprising female patients: CG1 patients were not obese and underwent UGR for digestive symptoms of other aetiologies, and CG2 comprised obese individuals who had UGR before bariatric surgery. A UGR-based Stomach Size Index (SSI), calculated as the ratio of the length of the stomach to the distance between the upper end of the stomach and the top of the iliac crests, was measured in all three groups. Gastromegaly was defined as SSI >1.00. RESULTS: 45 patients suffering from AN (28 with restrictive and 17 with binge/purge subtype), 10 CG1 and 20 CG2 subjects were included in this study. Stomach Size Index was significantly higher in AN (1.27 ± 0.24) than in CG1 (0.80 ± 0.11) and CG2 (0.68 ± 0.09); p < 0.001, but was not significantly different between patients with the restrictive and binge/purge subtypes. Gastromegaly was present in 82.2% of patients with AN and not present in the control groups. In patients with AN, gastromegaly was present in 12/15 patients without digestive symptoms (80.0%) and in 25/30 patients with digestive complaints (83.3%) at time of UGR (p = 0.99). In the AN group, no significant relationship was found between SSI and body mass index. CONCLUSION: Gastromegaly is frequent in AN and could influence AN recovery. This anatomical modification could partially explain the alterations of gastric motility previously reported in AN.

Prevalence of mental disorders in closed educational centers in France.

INTRODUCTION: Closed educational centres (CEC) receive young offenders who most often have a conduct disorder (CD). Mental disorders other than conduct disorder are a negative factor in the effect of educational actions. Moreover, adverse life experiences are frequent vulnerability factors in this population. This article aims to document the prevalence and links between psychiatric disorders, exposure to trauma, and the psycho-behavioural characteristics of adolescents placed in CEC. METHOD: We conducted a multicentre epidemiological study on a sample of 101 adolescents placed in nine closed educational centres in France. Psychiatric disorders were measured by the MINI-KID 2 and Conners Rating Scale questionnaires. Several questionnaires were used to collect sociodemographic data and the psychological profile of each adolescent. RESULTS: Among the adolescents, 90.2% had at least one mental disorder with a predominance of conduct disorder (80%). Comorbidity was also frequently found: among the subjects with conduct disorder, 37% had at least one other psychiatric disorder. Interestingly, the intensity of conduct disorder and the Adverse Childhood Experiences (ACE) score were significantly correlated. Furthermore, two subgroups were identified: adolescents with isolated conduct disorder (44.6%) and adolescents with other psychiatric disorders (45.7%) with or without conduct disorder. The latter subgroup showed higher vulnerability and poorer outcomes in terms of attachment patterns, feelings of abandonment, hostility and impulsivity. CONCLUSION: This study is the first French epidemiological study of mental disorders in juvenile offenders. It suggests that the detection of psychiatric disorders in young people in CEC is an important prerequisite for the implementation of targeted interventions according to different profiles. Furthermore, collaboration between the medical-psychological and judicial fields, in the form of an operational partnership, is necessary to guarantee better support for these young people.