Clinical trials

The development of in vivo biomarkers sensitive to myelin disruption represents a major clinical need to be able to monitor the demyelination processes as well as the effect of remyelinating therapies in multiple sclerosis. The investigators recently proposed a technique, derived from the conventional magnetisation transfer (MT): inhomogeneous Magnetisation Transfer (ihMT). In preliminary studies, this simple-to-implement and robust technique has shown great sensitivity for evaluating the demyelination processes. The goal of the project is to evaluate the ability of ihMT to measure and describe the spontaneous demyelination and remyelination processes involved in active lesions in a population of patients with MS at the the disease onset.

Asthma affects the lower respiratory tract (bronchi), whereas chronic rhinosinusitis with nasal polyposis (CRSwNP) involves the upper airways. Despite this anatomical distinction, the upper and lower airways form a continuous respiratory tract and share common pathophysiological mechanisms. Consequently, asthma and CRSwNP frequently coexist, and several therapeutic strategies are effective for both conditions. Given these overlaps, we hypothesize that a multidisciplinary consultation involving both a pulmonologist and an ENT specialist could be more effective than separate consultations for patient care. We also believe that this innovative organization that would benefit the healthcare system. To test this hypothesis, we are conducting a study whose primary objective is to assess whether joint consultations lead to a reduction in oral corticosteroid need over the year following the initial consultation, by enabling more personalized treatment strategies. Secondary outcomes will include the frequency of asthma exacerbations, frequency of ENT-related events, respiratory symptoms, quality of life, and healthcare ressources utilization. We will compare outcomes between two patient groups: one receiving joint consultation from both specialists, and the other managed through standard, separate consultations as per current clinical practice.

Familial lymphohistiocytosis (FHL) is a group of rare genetic diseases (around fifteen cases per year in France). The defect in T lymphocyte cytotoxicity resulting from this disease is responsible for hemophagocytic lymphohistiocytosis (HLH). Promptly treatment of HLH is essential for prognosis. These diseases are fatal without a bone marrow transplant, with an overall 5-year survival rate of no more than 80% for FHL. The genetic or acquired nature of HLH is not easy to determine. An infectious trigger can be confounding when it occurs in an FHL. But above all, functional biological tests demonstrating a T lymphocyte cytotoxicity defects are difficult to interpret. Genetic diagnosis is therefore essential for confirming the primary nature of HLH, and for initiating targeted treatments (first stage: putting HLH into remission with chemotherapy or immunotherapy; second stage: bone marrow transplant). Genetic diagnosis of FHL is therefore a matter of emergency, and is currently based on targeted gene panel exploration (fragmentation sequencing) requiring 6 to 8 weeks. Recently, the development of third-generation sequencing (TGS) has revolutionized genomic medicine, enabling unitary sequencing in real time. As a result of this innovation, certain private molecular diagnostic specialties can now access this new emergency genomic medicine. Aim: the main aim of this study is to demonstrate the feasibility of a national circuit for ultra-rapid genetic diagnosis of pediatric HLH revealing familial lymphohistiocytosis. The secondary objective is to evaluate the impact of this early genetic diagnosis on the delay to remission of HLH and the delay to transplantation. Methods: This prospective, multicenter study measures the time required for genetic diagnosis of FHL in pediatric HLH, using innovative TGS sequencing technology. Perspectives: Fast genomic diagnosis of FHL will considerably shorten the time to confirm the diagnosis, to obtain HLH remission and, finally, to reach transplantation faster.

Preterm birth is a major cause of mortality and long-term disability. Bacterial vaginosis (BV) is a frequent form of dysbiosis that is often asymptomatic and increases the risk of preterm birth. BV is usually diagnosed using conventional tools such as the Nugent score. Molecular diagnosis of BV has now been shown to be more reproducible and to provide a more accurate characterization of dysbiosis. The main objective of this study is to evaluate the effectiveness of a self screen and treat strategy for vaginal flora dysbiosis, based on molecular point of care (POC) multiplex technology before 18 weeks' gestation, in reducing the rate of preterm birth among pregnant women at high risk, compared with usual care. The hypothesis is that a Screen-and-Treat strategy using molecular biology among women with previous preterm or/and an history of late abortion could be effective in reducing preterm births by 40%.

Patient-Reported Outcomes (PROs) are patient-centered measures used to assess health status, track changes over time, and evaluate the impact of treatment on the patient's perceived health. The SACHA study is a French prospective observational study developed by the Société Française de lutte contre les Cancers de l'Enfant et de l'adolescent (SFCE). It prospectively collects real-world safety and activity data on novel therapies given to patients aged 25 or younger with pediatric malignancies (solid tumors or hematologic malignancies) or related conditions, outside of a clinical trial. The Symptom Screening in Pediatrics Tool (SSPedi) is a validated questionnaire for measuring patient-reported symptoms in pediatric oncology. It includes 15 questions covering common symptoms in pediatric cancer patients and one open-ended question allowing patients to report any other bothersome symptoms. Patients complete the questionnaire through an online application. The PRO-SACHA study aims to describe the symptoms reported by participants receiving novel therapies in pediatric oncology and to examine the concordance between participant-reported symptoms and symptomatic adverse events (AEs) reported by investigators. This prospective observational study evaluates patient-reported symptoms in patients aged 2 to 18 years enrolled in the SACHA study. Participation is voluntary, based on an opt-out consent model (French category 3 interventional research involving the human person). Planned enrollment: 72 participants over 18 months, with each participant followed for 7 months (a 6-month follow-up period, with a 7th-month window for questionnaire completion). Participants are enrolled in PRO-SACHA at the same time as their enrollment in SACHA (two separate studies with separate enrollment). SSPedi responses (a self-report questionnaire capturing symptoms experienced by patients) are collected electronically through an online application. The extracted, anonymized data are then correlated with adverse events reported by investigators. The concordance between participant-reported symptoms and adverse events recorded in SACHA (CTCAE grading) will be analyzed.

This phase IV, multicenter, open-label randomized controlled trial will evaluate whether a JAK inhibitor discontinuation strategy is superior to standard maintenance therapy in adult patients with ulcerative colitis who are in sustained deep remission. A total of 224 patients treated with tofacitinib, upadacitinib, or filgotinib will be randomized to either treatment withdrawal or continuation of maintenance therapy and followed for 104 weeks. The primary objective is to compare safety, efficacy, and patient satisfaction at Week 52, while secondary objectives include assessment of remission maintenance, quality of life, treatment exposure, endoscopic outcomes, and relapse rates

Why is this study being conducted? For people with drug-resistant focal epilepsy, surgery, to remove the part of the brain where seizures start, is currently the most effective treatment. In many people, especially those with temporal lobe epilepsy, surgery can stop seizures completely and improve quality of life. However, doctors usually predict the chances of surgical success using brain scans and other neurological tests, while the possible influence of psychological and social factors remains less well understood. Mental health is an important part of overall health. People living with epilepsy are more likely than the general population to experience anxiety, depression, and post-traumatic stress disorder (PTSD). PTSD can develop after experiencing traumatic events and may affect emotional well-being, daily activities, relationships, and physical health. Some studies suggest that PTSD may affect brain networks involved in epilepsy. This raises an important question: could PTSD influence the success of epilepsy surgery? We hypothesize that PTSD and other psychological or social factors may affect surgical outcomes and recovery after surgery. At present, there is limited evidence available to answer this question. What is the aim of the study? The main objective of this study is to determine whether PTSD affects the success of epilepsy surgery two years after the operation. The study also aims to: * Describe the medical, psychological, and social characteristics of people undergoing epilepsy surgery and estimate how common traumatic experiences and PTSD are in this population; * Assess changes in PTSD symptoms, anxiety, depression, quality of life, social vulnerability, and patient satisfaction before and after surgery; * Identify biological, psychological, and social factors associated with successful surgical outcomes. Rather than focusing only on seizure control, this study aims to improve understanding of the factors that contribute to recovery, quality of life, and long-term well-being after epilepsy surgery. The findings may help healthcare professionals provide more personalized support before and after surgery. Who can take part? Between September 2026 and September 2028, the study will recruit 42 adults with drug-resistant focal epilepsy who are being evaluated for resective epilepsy surgery at Timone University Hospital in Marseille, France. What does participation involve? Participants will join the study approximately three months before surgery and will be followed for two years after the operation. During routine pre-operative and post-operative follow-up visits, participants will complete validated self-report questionnaires about: * Traumatic experiences and PTSD symptoms; * Anxiety and depression; * Quality of life; * Social vulnerability; * Satisfaction with surgery. Participants whose questionnaire results suggest possible PTSD will be offered a routine psychiatric assessment to confirm the diagnosis. Based on these assessments, participants will be classified into one of two groups: people with PTSD and people without PTSD. The study will also use clinical information routinely collected as part of epilepsy care, including brain imaging, electroencephalography (EEG), and neuropsychological assessments. What are the expected benefits of this research? This study may improve understanding of how psychological and social factors influence epilepsy surgery outcomes. The results may help healthcare professionals better identify patients who could benefit from additional support before and after surgery. In the future, the findings could contribute to the development of more personalized care pathways, including advanced practice nursing follow-up, improved mental health screening, and targeted support to enhance seizure outcomes, quality of life, emotional well-being, and patient satisfaction after epilepsy surgery

In France, 60,000 patients are receiving renal replacement therapy via dialysis in 2022, 90% of whom are on hemodialysis. This technique is based on the principle of exchange across a membrane between the patient's blood and the dialysate. The goal is to purify the patient's blood as effectively as possible by removing all solutes that have accumulated due to kidney failure. The dialysate is produced from municipal water, which is treated through several processes (reverse osmosis, filtration) to produce ultrapure water. Water consumption at the La Conception Hospital center in Marseille, which conducts 37,000 sessions per year (64 hemodialysis stations), is estimated at 120 m³ of water per day, which is discharged into the sewer system after use. In France, this would correspond to an estimated total consumption of nearly one million m³ of drinking water per year. In the context of climate change, which will lead to a reduction in water resources, it is important to rethink all aspects of water consumption. The investigator's reflection is part of a growing awareness of the environmental impact of dialysis within a working group of the Francophone Society of Nephrology, Dialysis, and Transplantation: "Green Dialysis." The quality of clearance depends on blood flow and dialysate flow rate (Qd). The Qd was set at 500 mL/min based on earlier studies that showed this flow rate corresponded to maximum clearance of urea and the main toxic solutes. These studies were conducted at a time when dialysis membranes were less efficient. Today, the investigators use membranes with higher exchange efficiency. Despite this, the investigators have not reevaluated the appropriateness of a Qd of 500 mL/min. The quality criterion in dialysis is a balanced urea Kt/V measurement \>1.2 for a 4-hour session (target set at 1.4 with certain "single-pool" dialysis machine measurement techniques). At the ivnestigator's center, the average urea Kt/V is 1.55 in "single-pool" mode. Reducing the Qd could be done without risk to patients, even if it leads to a decrease in urea Kt/V. A Colombian study with 5 years of follow-up demonstrates patient safety with a Qd of 400 mL/min (vs. 500 mL/min), with no difference in mortality or dialysis efficacy. The study population was not representative of chronic dialysis patients; 10% regained renal function, and the final analysis included only 25 of the 71 patients enrolled.

Drug-resistant focal epilepsy is a severe neurological disease that affects one-third of patients with epilepsy. Surgery is the only potentially curative treatment. Intracerebral exploration by stereo electroencephalography (SEEG) is an important step in the surgical pathway. It aims to establish the precise mapping of the epileptogenic network (EZN), including all the brain regions that generate seizures. At the end of SEEG, SEEG-guided radiofrequency thermocoagulation (SEEG RFTC) represents a therapeutic option that may be efficient as a palliative treatment in patients ineligible for resective surgery, or may lead, in some cases, to a definitive effect, avoiding open surgery. The safety and effectiveness of this approach have been established. However, the odds of remaining seizure-free after one year vary greatly between studies, ranging from 4% to 71%. This disparity in therapeutic responses could be linked to the absence of objective criteria for the selection of targets, but also to the existence of mechanisms of action outside of the direct lesional effect. A decrease in SEEG markers of epileptogenicity may predict thermocoagulation efficiency. However, no data are available regarding changes in alteration of the blood-brain barrier (BBB) connectivity, inflammation, or associated molecular changes and their relationship to prognosis. This study aims to elucidate the mechanisms underlying the clinical effect of SEEG RFTC by studying the changes in electrophysiological (SEEG), structural (ultra-high field MRI), and biological (blood biomarkers of neuro-glio-vascular damage and inflammation, molecular adaptations) markers. They will be correlated with clinical outcome in a prospective cohort of patients with drug-resistant focal epilepsy. As advantages for clinical care, this study will allow selection of RFTC targets based on scientifically validated criteria, and elaboration of predictive scores for therapeutic response in each patient. The primary objective is to study the predictive factors of response to SEEG RFTC, by correlating changes in BBB permeability with clinical response 3 months after RFTC, in a prospective cohort of patients with drug-resistant focal epilepsy.

The ADICROHN-3 study is a prospective, multicenter, open-label cohort study. Its design is supported by the following elements: * The results of the ADICROHN pilot study (EudraCT No. 2013-002602-31) and our 3-year study, which demonstrate an excellent safety profile with a promising efficacy signal. * Data from the literature confirming that cryopreservation of FVS does not compromise the clonogenic and differentiation potential of mesenchymal progenitors, nor its regenerative effect. * The ongoing ADICROHN-2 study (PHRC N 2019; EudraCT No. 2019-001948-21) confirming the feasibility of patient recruitment, mastery of the therapeutic approach, and the absence of adverse events related to the experimental treatment. * The opportunity for a second FVS injection for patients initially treated but who did not respond to the treatment. * The opportunity for a first FVS injection in patients in the placebo arm, thereby providing access to an innovative therapy available to patients included in this trial who are untreated and remain refractory to standard care. To avoid compromising the results of the ongoing ADICROHN-2 study, enrolled patients will remain blinded to the treatment arm to which they belonged in the ADICROHN-2 study.

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and debilitating side effect of many cancer treatments. It affects 28 to 48% of patients receiving chemotherapy. Symptoms include tingling, numbness, burning sensations, and pain mainly in the hands and feet. While CIPN often improves after chemotherapy ends, in some patients the pain persists and becomes chronic, severely impairing quality of life, sleep, and daily functioning. Currently, no treatment has been shown to prevent CIPN. For patients with chronic pain, duloxetine is the only recommended drug, but its efficacy is limited. When standard medications fail, patients have very few options. Spinal cord stimulation (SCS) is a well-established neurosurgical technique used to treat various forms of chronic neuropathic pain, including pain after surgery, trauma, or diabetes. In this procedure, thin electrodes are placed in the epidural space near the spinal cord and connected to a small implantable pulse generator. The electrical impulses delivered by the device modulate pain signals in the nervous system. Preliminary case reports suggest that SCS may be effective in patients with CIPN, but no randomized controlled trial has yet established its value in this specific indication. The CHEMOSTIM study aims to fill this gap. CHEMOSTIM is a multicenter, prospective, randomized crossover trial. All enrolled patients will undergo SCS implantation. Participants will then be randomized to receive either active stimulation first followed by sham stimulation, or sham stimulation first followed by active stimulation. In the sham phase, the device is implanted but switched off following a simulated programming session, so patients cannot tell which phase they are in. The primary outcome is the proportion of patients achieving more than 50% pain reduction on a Visual Analog Scale (VAS) during the active stimulation phase compared to the sham stimulation phase, assessed at 4 months. Secondary outcomes include changes in quality of life, anxiety and depression, sleep quality, medication use, individualized goal attainment, neurological examination, and nerve conduction studies. The study will also evaluate post-stimulation effects and complications. Eligible patients are adults with chronic CIPN evolving for at least one year, with pain greater than 5/10 in the lower limbs, who have failed at least two lines of pharmacological treatment (antidepressants, anticonvulsants, topical agents, etc.) and whose indication for SCS has been validated by a multidisciplinary team following SFETD/SFNM guidelines.

Sleep disturbances are reported by more than 50% of patients with Anorexia Nervosa (AN) and are associated with increased AN severity, psychiatric comorbidities, and poorer quality of life. To date, no pharmacological treatment has been approved or recommended for sleep disorders in children and adolescents with AN. Many drugs are currently prescribed off-label for their sedative side effects, without proven safety or efficacy in this population. Pediatric prolonged-release melatonin (PedPRM, Slenyto®) is the only melatonin formulation approved by the European Medicines Agency (EMA) for chronic insomnia in children aged 2 to 18 years with neurodevelopmental disorders. Its excellent safety profile, absence of tolerance, and long-acting formulation make it a prime candidate for treating sleep disturbances in children and adolescents with AN. MELSom-ANOREXIA is a multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase IIIb trial. Its primary objective is to assess the efficacy of PedPRM compared to placebo in improving Total Sleep Time (TST) in children and adolescents aged 6 to 18 years with AN and impaired sleep. Participants are randomized into two groups: the experimental group receives PedPRM (2 mg or 5 mg depending on response at Day 22) and the control group receives a matching placebo, both administered 0.5 to 1 hour before habitual bedtime for 13 weeks. Sleep is assessed by Sleep Diary and actigraphy. Secondary outcomes include other sleep parameters, AN severity (BMI, EDI-2, EDE-Q), associated symptoms (anxiety, depression, physical activity, executive function, emotionality), and quality of life. Melatonin secretion profiles and specific subgroups (ASD traits, early-onset AN) are also explored. The study includes a 2-week run-in period (D-14 to D0) for baseline sleep assessment, followed by 13 weeks of treatment, with visits at D0, D22, and D93. A total of 120 participants will be enrolled across 7 French pediatric psychiatry centers over 24 months.

This study aims to answer a key question in the field of rare genetic diseases by determining the prevalence of deleterious variants at RNA level in undiagnosed patients with intellectual disability and/or neonatal hypotonia. This study will put an end to diagnostic erraticism in a number of patients. Finally, the results of this study will make it possible to compare the two types of tissue used for RNAseq, with a view to facilitating the implementation of this analysis method in the diagnostic setting.

Need to improve understanding of oral dysbiosis in the elderly and/or immunocompromised individuals (involvement of nanogenes in these dysbiosis) Comparison of dysbiosis identification between results from dental plaque samples and saliva samples (the saliva sample is non-operator-dependent due to its ease of collection). Comparison of the reliability of results obtained with this type of saliva sample versus results obtained with dental plaque samples, which are considered the reference sample type (Antézack 2023). Primary objective To estimate the prevalence of dysbiosis in individuals with oral frailty versus individuals without oral frailty. In this project: * Dysbiosis will be defined by the presence of Archaea (Bringuier 2013). For the primary objective, prevalence will be estimated based on dental plaque samples. * The population with oral frailty will be defined as individuals over 60 years of age or those with immunosuppression. Hypothesis: The expected proportion of dysbiosis in the population with oral health vulnerability is 40%, whereas the expected proportion of dysbiosis in the population without oral health vulnerability is 20% (Li CL 2009). Secondary objectives Estimate the prevalence of dysbiosis in the two populations based on a saliva sample \- Compare the results from the sample

Women seeking asylum (WSA) are overexposed to sexual violence (SV) in their countries of origin, along migration routes, and within host countries. This overexposure does not cease upon arrival in host countries; on the contrary, the first months following arrival are characterised by heightened vulnerability, with an increased incidence of sexual violence, particularly among women with a prior history of victimisation. Sexual violence has major consequences on physical health, mental health, quality of life, and healthcare utilisation, and generates substantial individual and societal costs. International organisations, including the United Nations High Commissioner for Refugees, have identified the prevention of sexual violence and the improvement of care for survivors as public health priorities. Previous work suggests that addressing sexual violence within primary care, when embedded in a comprehensive, culturally informed, and coordinated approach integrating medical, psychological, social, and medico-legal dimensions, may contribute to preventing the occurrence or recurrence of sexual violence in host countries. However, no comparative study has yet evaluated the effectiveness of such a coordinated model of care on the prevention of sexual violence among women seeking asylum, nor assessed its efficiency or transferability. The primary objective of this study is to evaluate the effectiveness of a coordinated, transcultural, multidisciplinary outpatient care model on the prevention of sexual violence occurring in host European countries among women seeking asylum.

Many antineoplastic drugs are considered "hazardous to handle" for healthcare professionals, notably because of their carcinogenic, mutagenic and/or reprotoxic effects. Occupational exposure occurs mainly through the cutaneous route, either by direct contact with the drug and/or indirectly through contact with treated patients and their excreta, or through contact with contaminated surfaces or textiles. To date, physiotherapists have been little studied in terms of occupational exposure, even though they frequently perform care practices (massage, lymphatic drainage, limb mobilisation, respiratory physiotherapy) involving direct, prolonged and sustained skin contact with patients treated with antineoplastic drugs; these compounds may be eliminated in the sweat of the treated patient for several days after administration. In this context, the present study aims to assess the occupational exposure of physiotherapists to antineoplastic drugs in healthcare settings. The primary objective is to estimate the prevalence of internal contamination of physiotherapists by antineoplastic drugs after performing one of the care practices (massage, lymphatic drainage, limb mobilisation, respiratory physiotherapy) selected for the study, in patients receiving intravenous treatment with antineoplastic drugs. The secondary objectives are to describe for each antineoplastic drug studied the prevalence, the frequency of internal contamination of physiotherapists, and urinary concentration levels, to characterise the circumstances of exposure and the personal protective equipment worn, to describe the prevalence and the frequency of external cutaneous contamination on the hands and forearms of physiotherapists after performing an exposing care practice, to quantify this external cutaneous contamination, to identify the factors associated with internal and external contamination, and to co-develop preventive measures in collaboration with physiotherapists and stakeholders and to assess their acceptability. This study is a non-interventional (RIPH3), cross-sectional and multicenter study conducted at AP-HM (Public Assistance for Marseille hospitals) and Bordeaux University Hospital (CHU de Bordeaux). Twenty physiotherapists will be included in this study. Internal contamination will be assessed over 100 observation visits and external contamination over 70 observation visits (all participants combined). Observation visit include at least one " an exposing care practice" (massage, lymphatic drainage, limb mobilisation, respiratory physiotherapy) performed on a patient who received an intravenous antineoplastic drug from a predefined list, within a time window of 4 to 72 hours after the start of injection. \- Internal contamination assessment (urine samples collection) For each observation visit, two urine samples of the physiotherapist participant will be collected: one sample within the 3 hours preceding the start of the work shift, and a second sample 6 to 10 hours after the end of the shift (or the next morning after waking up). Data on exposure, activity and preventive practices (personal protective equipments worn) will be collected using an administered questionnaire (CRF). Information on the antineoplastic drugs administered to the patient receiving care by the physiotherapist will also be collected. \- Cutaneous external contamination assessment (dermal wipe sampling) For each observation visit, the physiotherapist will apply a standardized hands and forearms washing protocol, observed by the clinical research technician. Then, cutaneous swab samples will be taken immediately after the washing. The physiotherapist will then perform an exposing care practice, limiting contact with the environment (e.g., door handles/surfaces), and new samples will be taken immediately after the exposing care practice, without prior decontamination of hands and forearms. A total of eight cutaneous swab samples (four before and four after an exposing care practice) will be collected per observation visit, according to a protocol validated by the reference laboratory. The assessment of cutaneous external contamination of physiotherapists will be evaluated during visits separate from those used to study internal contamination. The expected outcomes of this study are: an individual assessment of exposure and potential internal contamination and/or external dermal contamination, for each physiotherapist; traceability of exposure in occupational health medical records, for each physiotherapist; improved knowledge on the proportion of contaminated physiotherapists (prevalence and frequency) and knowledge on urinary and cutaneous concentration levels of antineoplastic drugs in physiotherapists; increased awareness among physiotherapists regarding these exposures; implementation of co-developed preventive actions aiming to reduce exposures to the lowest possible level; and improved professional practices and working conditions.

Immune Checkpoint Inhibitors (ICI) have revolutionized cancer therapy, providing unprecedented responses in a wide range of malignancies. However, they induced various immune-related adverse events (iRAE) that can be life-threatening. About 20% of patients treated with an ICI monotherapy, and up to 60% of patients treated with a combination of ICIs, experienced a severe iRAE. Most side effects are reversible if managed early, but can affect survival and quality of life, leading to treatment interruptions or hospitalization. Some of these irAEs, particularly those affecting hormonal functions, may be irreversible and persist even after treatment discontinuation. The development of predictive biomarkers of such toxicities is an unmet medical need. The variety of mechanisms involved in iRAE, and the lack of effective animal models, could probably explain why the topic remains largely unexplored. To date, some biomarkers predictive of the occurrence of iRAE, irrespective of the type of organ affected, have been identified by state-of-the-art techniques on small cohorts prior to treatment initiation, but none is individually robust enough to be used in daily practice. We hypothesize that a signature derived from the integrative analysis of various biological parameters (immunomonitoring, auto-immunity features, viral monitoring, microbiota monitoring, fragmentome analysis, pharmacokinetics, radiomics and genetics), available in routine hospital practice, could answer this question, and thus enable the development of specific prevention strategies The objectives are : Primary objective: Identify a baseline predictive signature for severe iRAE, irrespective of the type of organ affected. Secondary objectives: * Identify a predictive signature for severe iRAE including baseline and T1 data, irrespective of the type of organ affected. * Identify a baseline predictive signature for organ-specific severe iRAE. * Identify a predictive signature for organ-specific severe iRAE including baseline and T1 data. * Identify a baseline predictive signature for severe iRAE, irrespective of the type of organ affected, for patient receiving an anti-PD(L)1 in monotherapy. * Identify a baseline predictive signature for severe iRAE, irrespective of the type of organ affected, for patient receiving an anti-PD(L)1 in combination. * Identify a baseline predictive signature for severe iRAE, irrespective of the type of organ affected, for each specific immunotherapy received. * Compare the predictive signatures between responders and non-responders according to RECIST 1.1 in order not to overlook the influence of clinical response on the variability observed. * Describe the results obtained for each biological parameter between severe irAEs and non-severe irAEs patients. * Describe patient-reported outcomes and quality of life parameters.

Anorexia nervosa (AN) is a psychiatric disorder belonging to the eating disorders (EDs). It is internationally recognized as a priority for improving health care. Among the markers of severity of undernutrition is hepatic cytolysis. Around 30-50% of patients with AN present with hepatic cytolysis, of variable intensity, and usually associated with severe undernutrition. In a previous study, we demonstrated the presence of autoantibodies against HIF1alpha (Hypoxic inducible Factor 1 alpha) in 22% of cases in a sample of patients with AN. HIF1alpha (HIF1a) is a major transcription factor involved in the regulation of satiety and hunger. These autoantibodies were positive in 80% of AN patients with hepatic cytolysis. Taken together, these data led us to hypothesize an anti-HIF1a autoimmune mechanism in AN, potentially involved in the patients' hepatic cytolysis. This pioneering study, demonstrating the existence of anti-HIF1a autoantibodies, was carried out on a population of 18 patients with AN. To extend investigator's hypothesis, these results need to be confirmed on a larger number of patients, thus increasing the number of patients with AN and hepatic cytolysis. To determine the relevance of these autoantibodies in AN, "healthy" subjects and patients without AN but with hepatic cytolysis should be tested in parallel. Finally, the in vitro pathogenic potential of autoantibodies can be confirmed on a larger scale and studied in greater detail. The main aim of our study is to evaluate the association between the presence of anti-HIF1a autoantibodies (AAHIF) and that of hepatic cytolysis in patients with anorexia nervosa and undernutrition. This study is a prospective, cross-sectional, descriptive, multicenter, 2-arm study. 250 patients will be included. Experimental group (n=100) * Patients with anorexia nervosa and undernutrition with hepatic cytolysis (CH) (n=70) * Patients with anorexia nervosa and undernutrition without hepatic cytolysis (n=30) Comparator control groups (n=150) * Control patients under 18 years of age, treated at the CHU de la Timone for scheduled non-inflammatory surgery (orthopedic, ENT, etc.) (n=50): Minor patients * Patients (children and adults) with hepatic cytolysis without anorexia nervosa (n=50): Patients without AN with CH * Samples from French blood donation establishment: control group consisting of biological blood samples from healthy individuals from the Etablissement Français du Sang (n=50)

Dental caries is a major public health probleme the result of hard tissue demineralization and oral microbiota changes. Methanogenic archaea, mainly Methanobrevibacter oralis, are associated with various oral problems, including pathologies periodontal. Previous research has not really studied the Archaea in carious lesions, hence the importance of our study. Our study aims to explore their potential role in the the development of caries by analysing their prevalence and their quantification in relation to the carious risk individual. The aim is to improve understanding of the Cavity microbiology to advance management of this pathology in terms of prevention or of treatment. Our team is particularly competent in the field of Archaea, especially in the cultivation of Archaea methanogens since we have a dedicated platform. We also discovered the first human Nanoarchaea, opening up a whole new possible search field.

Complications after lung transplantation are almost ubiquitous, among which postoperative acute renal failure may represent more than 50% of lung transplant patients and require extrarenal purification in 5 to 13% of cases. Multiple factors are associated with postoperative acute renal failure. These factors can be classified into preoperative, intraoperative, and postoperative factors. While some postoperative complications are explained by donor and recipient factors, the literature suggests that certain intraoperative events represent modifiable or avoidable risk factors that could be targeted by therapeutic interventions to reduce the risk of postoperative acute renal failure. Some of these factors (intraoperative hemodynamic instability, significant bleeding or hypoxemia) can generate renal hypoxic aggression, alone or in combination. However, to date, there is no validated tool available at the patient's bedside during surgery to detect renal hypoxia or guide interventions to restore renal perfusion during surgery. Yet, as recent recommendations suggest, intraoperative renal protection is an important axis for improving the outcome of lung transplant patients, to the extent that the recommendations of Marczin et al. recommend the establishment of a renal prevention protocol for each patient. Without a tool to guide this plan intraoperatively, anesthesia teams can't establish a renal prevention protocol. This research aims to establish whether renal NIRS is a reliable tool for monitoring intraoperative renal hypoxic aggression predictive of postoperative renal failure. Near-infrared spectroscopy (NIRS) is an optical technology that allows non-invasive measurement of tissue oxygen saturation. This technique is commonly used for intraoperative monitoring of cerebral perfusion in adults and children. Some studies have shown that regional renal oxygen saturation (renal rSO2) measured by NIRS during aortic-coronary bypass surgery under extracorporeal circulation (ECC) is correlated with renal venous oxygen saturation measured by catheterization. It is also associated with the risk of postoperative acute renal failure in patients undergoing cardiac surgery under ECC. However, there are no equivalent data in lung transplant patients, who frequently present with postoperative acute renal failure. In the available literature, no clear threshold of renal desaturation has been established. Because it is assumed that the depth of renal desaturation can be particularly deleterious, in addition to desaturation time, the investigator have chosen to retain in this project the integral of time and magnitude spent under a renal desaturation threshold, aggregated into a renal hypoxia index, during the intraoperative period. The primary objective of this research is to demonstrate the usefulness of measuring the intraoperative renal hypoxia index in predicting the risk of early postoperative acute renal failure

Haemophilia is a rare genetic disorder which, in its severe form and in the absence of treatment, can be life-threatening. Since the 1960s and the introduction of coagulation factor concentrates, the life expectancy of people with haemophilia has increased rapidly. Today, for most affected individuals, the disease is experienced as a chronic condition. The transition process enabling adolescents and young adults (AYA) with a chronic disease to move into adult life can be complex, as they must face all the changes experienced by AYA in general, combined with issues related to their chronic condition and its management. A successful transition involves a transfer of responsibility from parents to AYA regarding the management of their health condition, as well as the acquisition by AYA of knowledge, skills and autonomy. A difficult transition may lead to decreased adherence to follow-up or treatment, deterioration of overall health status and/or quality of life, or difficulties in entering adult life. In this context, the national cross-sectional study TRANSHEMO was initiated in 2017. Its objective was to compare adherence to healthcare management between two groups of AYA with severe haemophilia (adolescents \[for whom the transition is ongoing\] versus young adults \[for whom the transition may have been completed\]), and to identify the determinants of this adherence. The results showed that young adults had a lower adherence rate than adolescents (82.2% vs. 61.2%, p\<0.001). Among the determinants studied, being a young adult, having repeated at least one school year, and presenting psychological and emotional difficulties were factors that had a negative effect on adherence to healthcare management. However, the cross-sectional nature of the study represents a limitation that restricts causal inference. Complementing this project with a longitudinal study would address this limitation. The results obtained from this new study (TRANSHEMO 2) may contribute to the literature by providing insights into both the determinants of sustained adherence to healthcare management among adolescents with severe haemophilia who become young adults, and the associations between these determinants. The longitudinal design of the project will allow the establishment of a higher level of causal inference between the maintenance of adherence during the transition to adult life and its determinants, which represents a major epidemiological strength. Moreover, results addressing the issue of transition in the context of chronic diseases and derived from longitudinal studies remain scarce, making the findings of this project particularly original. Finally, haemophilia, a relatively frequent condition among rare diseases, could represent an interesting model for understanding the impact of transition in this type of pathology. Study hypothesis The extent of the reduction in adherence to healthcare during the transition process, and/or the determinants of the maintenance of adherence identified in the longitudinal TRANSHEMO 2 project, may differ from those highlighted in the original cross-sectional TRANSHEMO project. Specific aims Main objective: To compare the rate of adherence to healthcare among adolescents who participated in the TRANSHEMO project, using data collected during the original TRANSHEMO study when they were adolescents (before transition) and data to be collected as part of the TRANSHEMO 2 study when they have become young adults (after transition). Secondary objective: To identify the determinants of the maintenance of this adherence and the associations between these determinants, within the framework of a longitudinal study.

In a pilot study, water vapor therapy (RezumTM, Boston Scientific Corporation, Marlborough, MA) was proposed as a minimally invasive procedure for benign prostatic hyperplasia, but often requiring oral ± intravenous sedation or a transrectal prostatic block. Therefore, pain management during Rezum therapy remains a challenge and may lead to the use of pain control protocols and general anesthesia, limiting in some ways the concept of a minimally invasive ambulatory surgical approach. The Schelin® catheter (ProstaLund AB, Lund, Sweden), approved by the European Medicines Agency, is a device for injecting analgesic drugs directly into the prostate via the trans-urethral route, providing more effective local anesthesia and avoiding the need for transrectal route or general anesthesia. This catheter is therefore of crucial importance in offering to our patients an ultra-minimally invasive treatment, associated with a reduction in room occupancy time, outpatient surgery time, a procedure performed independently of the anesthesia team, and for the patient, an accelerated post-operative recovery. Our hypothesis is that the REZUM procedure under local anesthesia could be associated with a \>20% reduction in operating room occupancy time compared to procedures performed under general anesthesia.

Sepsis is a multifactorial syndrome characterized by a dynamic course and a clinical outcome dependent on several factors, and responsible for one in five deaths worldwide. The aim of this trial is to identify new prognostic markers for the progression of sepsis to septic shock, by comparing epigenetic markers between patients who have or have not developed severe forms of sepsis. The main objective of this preliminary study is to identify prognostic markers for the progression of sepsis to septic shock, i.e. to compare targeted markers between subjects with sepsis who progress to septic shock versus subjects with sepsis who do not progress to septic shock.

Deciding the optimal timing for extubation in patients who are mechanically ventilated can be challenging, and traditional weaning predictor tools are not accurate. Recent studies suggest that isolated sonographic assessment of the respiratory and cardiac function (ie diastolic function and filling pressure), in mechanically ventilated patients may assist in identifying patients at risk of weaning failure. Recently, the association of conventional echocardiography and lung ultrasound showed promising results for the prediction of post extubation distress. Speckle Tracking is an emerging tool in intensive care medicine that has never been investiguated for the prediction of weaning failure. It could early detects diastolic dysfunction and and elevated filling pressure. Of more, speckle tracking is known to be less operator dependant. The main objective of our study is to evaluate the diagnosis accuracy of speckle tracking echocardiography performed during a weaning trial to predict weaning failure. The secondary objectives are to assess the diagnosis accuracy of combined heart and lung ultrasound to predict weaning failure.

High-dose methotrexate (MTX) is the main componement of first line treatment in primary central nervous system lymphoma. Renal toxicity is the main dose limiting toxicity because of major MTX elimination by the kidneys. MTX crystallizes in renal tubules, leading to a renal failure (RF) and further delaying its elimination. When RF occurs, MTX accumulates, prolonging the duration of treatment exposure. MTX prolonging exposure can cause life-threatening complications and delay further treatments in the patient. Preventive measures have been developped, such as alkaline fluid hyperhydration and folic acid administration, to try to reduce the risk of these adverse events. In suspected severe RF in link to MTX is suspected, glucarpidase can be administared. However, this is an expensive treatment and not all patients recover normal renal function despite its use. MTX is an essential treatment for the management of PCNSL which is currently a curable disease especially in patients who are able to receive a consolidation treatment as thiotepa-based intensive consolidation followed by autologous stem cell transplantation (IC-ASCT). IC-ASCT requires a normal renal function, which could be impaired by severe RF secondary to MTX. The purpose of the study is to investigate how early dosing MTX could be used to simulate late concentrations. Early monitoring of MTX elimination could be implemented to identify patients at risk of delayed elimination and thus introduce rapid mesures as early administration of glucarpidase.