Introduction. - The psychiatric care of incarcerated minors represents a major public health issue and a critical challenge for child and adolescent psychiatry. Adolescents placed in detention exhibit a considerably higher prevalence of mental disorders than their peers in the general population. The prison environment, marked by isolation, loss of freedom, and often pre-existing psychosocial difficulties, tends to exacerbate their mental health issues. Psychiatric care modalities within juvenile detention facilities remain under-studied in scientific literature. In France, minors may be detained either in Establishments for Incarcerated Minors (EPM) or in Juvenile Wards (QM) within adult prisons. Despite representing less than 1% of the total prison population, these young detainees constitute a particularly vulnerable group. This study aims to explore psychiatric care systems within juvenile penitentiary institutions and juvenile wards in France, evaluating their effectiveness, limitations, encountered challenges, and suggesting areas for improvement. Objectives. - The primary objective of this study is to identify psychiatric care modalities and methods, available resources, and challenges faced by healthcare professionals in this specific context. The secondary objective is to document the clinical diagnoses and the prescribed treatments among this population. Materials and methods. - A descriptive, observational, and multicenter study was conducted through a comprehensive questionnaire distributed to healthcare professionals working in EPMs and QMs across metropolitan France and overseas territories. The questionnaire included 37 items covering organizational characteristics, clinical practices, coordination mechanisms, and perceived needs. Data collection occurred between November 2024 and February 2025 through both digital and paper formats, followed by reminder calls to increase participation. Thirty out of fifty eligible facilities (a 60% response rate) completed the survey, providing a representative overview of national practices. Both quantitative and qualitative analyses were performed, including descriptive statistics and thematic analysis of openended responses. Results. - Findings revealed striking heterogeneity in psychiatric care practices across French juvenile detention facilities. Although 86% of responding institutions had a dedicated psychiatric team, the composition of these teams varied widely. Some facilities lacked essential professionals, such as child psychiatrists or addiction specialists, and some facilities did not have dedicated consultation spaces for mental healthcare. Psychiatric evaluation at entry was systematic in 83% of establishments, typically occurring within the first three days of detention. However, the professional conducting the assessment differed (psychiatrist, psychologist, or nurse), and the evaluation content depended on the facilities. Ongoing psychiatric follow-up was primarily based on individual consultations, generally occurring weekly or biweekly. Nearly 40% of the respondents did not propose a systematic reevaluation of the minors that were not followed. Group therapies and therapeutic workshops were offered in more than half of institutions, while family interviews were reported in only one out of four facilities, revealing a limited involvement of parents or guardians. Preventive or health-promotion programs were present in one-third of the sites. Regarding clinical profiles, behavioral disorders were the most frequently reported (81%), followed by anxiety and stress-related disorders (63%), substance-use disorders (44%), and mood disorders (31%). Most respondents estimated that more than 60% of minors used tobacco before incarceration, and over 40% consumed cannabis. Pharmacological treatment initiation during detention was relatively rare. When prescribed, anxiolytics and hypnotics were the most common, followed by antipsychotics and antidepressants. Access to hospitalization remained limited and complex. The majority of emergency transfers occurred to adult psychiatric wards or specialized prison hospital units (UHSA), while pediatric psychiatric wards were rarely mobilized. Several professionals cited barriers such as lack of available beds, administrative constraints linked to the detainee status, and limited collaboration with external hospital services. Coordination between the various actors (medical, social, and judicial) was described as insufficient. Families were rarely contacted, and communication with community healthcare providers or probation services was often weak. Only 60% of institutions reported organizing a continuity-of-care plan for release, and in more than half of cases, this preparation began less than two weeks before the expected release date. Both healthcare and judicial constraints were identified as major barriers to effective follow-up. Discussion. - This national survey highlights the disparities and shortcomings in psychiatric care for incarcerated minors in France. The variability in human resources and infrastructure creates unequal access to quality care depending on the region. Despite some positive elements (such as the presence of dedicated mental health teams and early psychiatric evaluations) the system remains fragmented. The limited frequency of re-evaluations and the absence of standardized screening tools may lead to under-detection of emerging disorders, including suicidal ideation or adjustment disorders. Moreover, the lack of structured family involvement and the weak collaboration with external services hinder the continuity of care. Professionals also reported systemic difficulties such as staff shortages, the absence of pediatric psychiatric expertise, and institutional constraints that limit time and space for care. Many underlined the risk of "over-psychiatrization" of behavioral problems that may have primarily social or educational origins, emphasizing the need for multidisciplinary approaches rather than purely medicalized responses. The study further underscores the near invisibility of female minors in detention. Their confinement-often within adult women's units-raises significant ethical and practical concerns regarding isolation and access to age-appropriate care. Based on the data collected, several avenues for improvement emerge. For human resources, recruit more child psychiatrists and addiction specialists, provide targeted training for all staff working with adolescents. For the facilities, ensure dedicated and confidential spaces for psychiatric consultations and therapeutic activities. For clinical practices, systematize initial and periodic psychiatric assessments, integrate validated screening tools for suicide and substance-use risk, and expand group and family therapies. For the coordination, enhance interinstitutional communication between psychiatric teams, the Youth Judicial Protection Service (PJJ), and community health providers to guarantee continuity of care while preserving the doctor-patient confidentiality. And for the aftercare, strengthen post-release support by establishing structured referral networks and pre-release planning, including post-detention psychiatric consultations. Conclusion. - This study offers a rare, nationwide perspective on the psychiatric management of incarcerated minors in France. It reveals persistent inequalities in access to care, a shortage of specialized staff, and insufficient coordination among institutions. Despite the commitment of healthcare professionals, psychiatric care for young detainees remains inconsistent and under-resourced. To achieve parity of care between detained and non-detained adolescents, we must invest in dedicated resources, standardized procedures, and long-term intersectoral cooperation. Improving mental healthcare within juvenile detention is not only a medical priority but also a societal and ethical imperative, essential for reducing recidivism and supporting the reintegration of these vulnerable young people. (c) 2025 Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
Nosocomial infections are common in patients receiving extracorporeal membrane oxygenation (ECMO), with ECMO cannula-site infections (ECMO-CSI) being the most frequent infections directly related to the ECMO run. These infections can significantly impact patient outcomes. Currently, no adult guidelines exist for the prevention, diagnosis, and/or treatment of peripheral ECMO-CSI, resulting in heterogeneity in both clinical practice and research findings. We conducted a Delphi study involving 39 international experts in ECMO management. The experts participated in four Delphi rounds to reach consensus on various aspects of ECMO-CSI complicating peripheral ECMO (central ECMO excluded), including definition, clinical suspicion, diagnostic methods, preventive measures, and treatment. Consensus was defined as ≥ 70
Platelets are anucleate blood cells traditionally recognized for their central role in hemostasis but are now appreciated as active sentinels of innate immunity. During bacterial infection, platelets sense pathogen-associated molecular patterns and immune complexes through toll-like receptors, FcγRIIA, complement receptors, and adhesive integrins. This recognition enables platelets to interact with leukocytes and endothelial cells and to release proinflammatory and procoagulant mediators. While these responses contribute to pathogen containment, they also promote thromboinflammation and microvascular thrombosis, a process collectively referred to as immunothrombosis. This review synthesizes knowledge on platelet interactions with gram-positive and gram-negative bacteria and delineates how these pathways converge on immunothrombosis in clinical settings such as infective endocarditis and sepsis. Gram-positive bacteria, including Staphylococcus aureus and Streptococcus spp, activate platelets through FcγRIIA signaling following IgG opsonization and through αIIbβ3 engagement via plasma protein bridges. In contrast, gram-negative bacteria such as Escherichia coli, Pseudomonas aeruginosa, and Neisseria meningitidis predominantly trigger inflammatory platelet activation through TLR4-dependent recognition of lipopolysaccharide. Activated platelets form aggregates with neutrophils and monocytes, promote neutrophil extracellular trap formation, and support tissue factor-dependent coagulation. Although localized immunothrombosis may be host-protective by restricting bacterial dissemination, dysregulated systemic platelet activation contributes to disseminated intravascular coagulation and organ failure. We discuss mechanistic and translational implications and argue for selective modulation of platelet immune signaling rather than global platelet inhibition. We outline priorities for biomarker-guided interventions, including circulating markers of platelet activation such as soluble P-selectin, soluble GPVI, and NETosis markers, aimed at preserving antimicrobial defense while limiting pathological thrombosis.
Background Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for advanced non-small cell lung cancer (NSCLC), yet primary resistance remains common, with only ~50% of patients responding to first-line chemo-immunotherapy and 20-30% to monotherapy. Existing biomarkers such as PD-L1 expression and Tumor Mutational Burden (TMB) demonstrate limited predictive accuracy, underscoring the need for more comprehensive, integrative approaches. Methods We conducted a prospective, multicenter study involving 439 patients with advanced NSCLC treated with anti-PD-(L)1 ICI across first-line combo with chemotherapy and later-line monotherapy settings. A total of 443 pre-treatment tumor and blood-derived biomarkers-including genomic alterations, immune cell phenotypes, proteic markers, and routine laboratory tests-were profiled. Extensive biostatistics adjusted for PD-L1 expression were conducted. A rigorously benchmarked machine learning (ML) pipeline including 36 feature selection methods embedded into an optimism-correction framework was applied to identify predictors of primary resistance (PrR). Results Single biomarkers showed limited predictive utility, with PD-L1 (AUC 0.62, positive predictive value (PPV) 49.6%), TMB (AUC 0.55, PPV 43.1%), and key gene mutations (e.g., STK11, KEAP1) failing to achieve significance after multiple testing correction. A gradient boosting ML model integrating 18 selected features yielded a corrected AUC of 0.69 and a Positive Predictive Value (PPV) of 60% for PrR, outperforming standard biomarkers. In first-line patients, the model achieved a PPV of 51% and Negative Predictive Value (NPV) of 79% (baseline PrR rate: 29.9%); in subsequent-line patients, PPV reached 64% (PrR rate: 55.1%). Importantly, the signature also stratified Progression-Free Survival (PFS): high-risk patients had a median PFS of 3.9 vs. 14.6 months in low-risk patients (HR 0.307, p < 0.0001). Features from routine blood tests-such as serum chloride, albumin, CRP, and monocyte-to-lymphocyte ratio (MLR)-accounted for half of the final model and demonstrated independent associations with both PrR and PFS (e.g., chloride: OR 0.616, AUC 0.626; HR 0.685, C-index 0.61). SHAP-based individual-level model explainability revealed heterogeneous and nonlinear biomarker contributions, including cases where high CRP, low albumin, or elevated MLR overrode favorable PD-L1 or Treg profiles. A biomarker dashboard including interactive visualizations is available at https://compo.inria.fr/pioneer-website/. Conclusions Multimodal machine learning integration of clinical, genomic, immune, and laboratory data enables improved prediction of ICI resistance in NSCLC beyond current biomarkers. This approach not only captures the multifaceted nature of tumour-host interactions but also highlights the underrecognized predictive value of accessible blood-based markers, offering a path toward individualized immunotherapy decision-making. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work benefited from a government grant handled by the French National Research Agency (ANR) as part of the France 2030 investment plan, under the reference ANR-17-RHUS-0007. This work was supported by a partnership of Aix-Marseille Universite (AMU), Assistance Publique Hopitaux de Marseille (APHM), Centre National de La Recherche Scientifique (CNRS), Institut National de la Sante et de la Recherche Medicale (INSERM), Centre Leon Berard (CLB), Institut Paoli Calmettes (IPC), Gustave Roussy (GR), AstraZeneca (AZ), Veracyte (VERA), Innate Pharma (IPH) & ImCheck Therapeutics (ICT), and initiated by Marseille Immunopole. The authors gratefully acknowledge the support of the APHM, which sponsored the PIONeeR clinical studies. Its role was to control the appropriateness of ethical and legal considerations for all centers and to perform the monitoring of the consents signed and the clinical data recorded and coded as part of the study. The authors are grateful to all the patients and their families, as well as all the investigators, for their participation in the study. This work benefited from support from ITMO Cancer AVIESAN and French Institut National du Cancer (grant #19CM148-00) and from the French National Research Agency (ANR), under the France 2030 program, reference ANR-22-PESN-0017. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was conducted in accordance with the Helsinki declaration, French laws and regulations and the International Conference on Harmonization (ICH) E6 Guideline for Good Clinical Practice. The study was approved by the French ethics committee (Comite de Protection des Personnes Ouest II Angers, no. 2018/08) and the French drug and device regulation agency (Agence Nationale de Securite du Medicament, no. 2018020500208). Informed consent was obtained from each participant before any study procedure. The study is registered at ClinicalTrials.gov ([NCT03493581][1]). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03493581&atom=%2Fmedrxiv%2Fearly%2F2026%2F01%2F11%2F2026.01.09.26343779.atom
BACKGROUND:The bacterial determinants of Group A Streptococcus (GAS) associated with either invasive (IGASI) or non-invasive (NIGASI) infections remain controversial. METHODS:From 2014 to 2018, French children hospitalized for an IGASI were enrolled in a prospective multicenter study aimed at identifying bacterial virulence factors and predisposing immunologic and genetic factors. During the same period, age- and date-matched control children with NIGASI were enrolled. Whole genome sequencing was performed for all GAS isolates. The 27 specific single nucleotide polymorphisms characterizing the M1UK lineage were searched among the emm-1 isolates. RESULTS:A total of 192 GAS isolates were sequenced: 94 from the IGASI group and 98 from the NIGASI group. The emm-1 genotype predominated in the IGASI group (36% vs. 11% in NIGASI group, P < .05) and was followed by emm-4, emm-12, and emm-3 (12%, 11%, and 10% respectively). In the NIGASI group, emm-89 predominated (21% vs 7% in the IGASI group, P<.05). Among the 45 emm-1 isolates, 12 (27%) carried the mutations characterizing clone M1UK in both groups (7 in IGASI group and 5 in NIGASI group). The superantigenic toxins SpeA and SpeJ, SIC protein, and FCT type 1 pilus predominated in the IGASI group but were linked to emm-1 strains. Insertions/deletions in the covS regulator gene were observed in 5 invasive isolates versus 1 non-invasive isolate. CONCLUSIONS:Genotype emm-1 GAS strains remained the main cause of invasive infections in French children, associated to specific GAS virulence factors, and should be monitored together with the rapid spread of the M1UK lineage.
