Clinical trials

Septic syndromes are a major although largely under-recognized health care problem and represent the first cause of mortality in intensive care units (ICU). While it has long been known that sepsis deeply perturbs immune homeostasis by inducing a tremendous systemic inflammatory response, novel findings indicate that sepsis indeed initiates a more complex immune response that varies over time, with the concomitant occurrence of both pro- and anti-inflammatory mechanisms. As a resultant, after a short pro-inflammatory phase, septic patients enter a stage of protracted immunosuppression. This is illustrated in those patients by reactivation of dormant viruses (cytomegalovirus (CMV) or Herpes Simplex Virus (HSV)) or infections due to pathogens, including fungi, which are normally pathogenic solely in immunocompromised hosts. These alterations might be directly responsible for worsening outcome in patients who survived initial resuscitation as nearly all immune functions are deeply compromised. New promising therapeutic strategies are currently emerging from those recent findings such as adjunctive immunostimulation for the most immunosuppressed patients. The prerequisite for immunostimulation administration (Interferon gama (IFNg), Granulocyte Macrophage Colony Stimulating Factor (GM-CSF), interleukin 7 (IL-7)) however relies on clinicians' capacity to identify patients who could benefit the most from these immunoadjuvant therapies, as there is no clinical sign of immune dysfunctions. In this context, the main objectives of IMMUNOSEPSIS 4 study are: 1. to identify the best biomarkers for sepsis-induced immunosuppression 2. to evaluate ex vivo candidate treatments which could rejuvenate immune functions after septic shock

Septic syndromes are a major although largely under-recognized health care problem and represent the first cause of mortality in intensive care units (ICU). While it has long been known that sepsis deeply perturbs immune homeostasis by inducing a tremendous systemic inflammatory response, novel findings indicate that sepsis indeed initiates a more complex immune response that varies over time, with the concomitant occurrence of both pro- and anti-inflammatory mechanisms. As a resultant, after a short pro-inflammatory phase, septic patients enter a stage of protracted immunosuppression. This is illustrated in those patients by reactivation of dormant viruses (cytomegalovirus (CMV) or Herpes Simplex Virus (HSV)) or infections due to pathogens, including fungi, which are normally pathogenic solely in immunocompromised hosts. These alterations might be directly responsible for worsening outcome in patients who survived initial resuscitation as nearly all immune functions are deeply compromised. New promising therapeutic strategies are currently emerging from those recent findings such as adjunctive immunostimulation for the most immunosuppressed patients. Recent studies have described the induction of immunoregulatory cells (of myeloid and lymphoid origin) following septic shock and have revealed a similar induction kinetics across all subpopulations of regulatory cells. Nevertheless, these observations need to be confirmed and linked to the underlying mechanisms responsible for the induction of these cells (notably the activation of the inflammasome pathway), which remain largely unknown. IMMUNOSEPSIS 5 study will therefore, as part of a prospective observational study involving a large cohort of patients, demonstrate the concurrent induction of all regulatory cell subpopulations following sepsis and the activation of the hyper-inflammatory response, including the inflammasome pathway. The association between these parameters and patient outcomes will also be assessed (death and/or the occurrence of a secondary infection).

Advanced heart failure (AHF) represents the end stage of chronic heart failure with reduced ejection fraction and affects up to 10% of patients with heart failure. These patients have refractory disease despite optimal guideline-directed medical therapy, and their management is discussed within a multidisciplinary "Heart Team". Renal dysfunction is highly prevalent in this population. The coexistence of cardiac and renal dysfunction has been classified under the entity of cardiorenal syndrome. Impaired renal function is an independent predictor of adverse cardiovascular and renal outcomes, including death, heart failure decompensation, worsening renal function, and the need for renal replacement therapy. However, patients with AHF remain a particularly complex population, and the lack of longitudinal biological data and limited understanding of the dynamics of cardiorenal syndrome in relation to therapeutic interventions make prognosis assessment and individualized management challenging. In addition, little is known about renal tubular function in AHF, despite its central role in hydro-electrolytic balance regulation. Biomarkers of tubular injury such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) have shown prognostic value in therapeutic studies, but their relationship with cardiac function and outcomes in advanced heart failure remains insufficiently characterized. The primary objective of this study is to evaluate renal function parameters and their evolution over time through measurement of glomerular filtration rate (GFR) and assessment of tubular function in patients with advanced heart failure, and to investigate their association with major adverse cardiovascular events. This is a prospective, single-center RIPH2 cohort study including 100 patients aged 18 to 75 years managed for advanced heart failure at the Louis Pradel Cardiovascular Hospital (Hospices Civils de Lyon, France). Patients will be followed according to standard care at 6, 12, 18, and 24 months. More comprehensive nephrological and cardiological evaluations will be performed at baseline, 12 months, and 24 months. Biobanking and quality-of-life questionnaires will also be conducted during these visits. Blood and urine samples will be collected at baseline and 12 months for NGAL et KIM-1 analysis. In addition, a subgroup of 50 consenting patients without contraindications will undergo multiparametric non-contrast renal MRI combined with tissue sodium quantification using 23Na MRI of the leg.

In the LIVERSLEEP study, investigators provide an overview of sleep disorders among patients in a liver transplantation (LT) pathway and a description of the criteria that can influence their sleep. This is a prospective longitudinal monocentric pilot study, generating hypotheses whose main objective is to describe the evolution of sleep quality in LT patients between pre-LT evaluation (PLTE) and 6 months post-LT. The secondary objective(s) are, before LT, 2 months and 6 months after, (1) to describe the level of anxiety in our patients, (2) to estimate the proportion of patients with impaired sleep quality, and (3) to describe the characteristics of our patients' sleep. This study will cover all adult patients on the LT waiting list at the Croix Rousse Hospital transplant center for the duration of the study. The duration of the inclusion period is 18 months. For each patient, the participation period will be 1 year on average (pre-LT measurement with an average waiting time of 6 months for LT, then measurements at TH+2 months and at TH+ 6 months). The total duration of the study will be 30 months, with a theoretical start of inclusions in the third quarter of 2026. Patients likely to participate in the study will be identified by the transplant nurse coordinatoir (TNC) within the digestive surgery and LT department of the Croix-Rousse hospital in Lyon. These are all the patients seen in hepatology consultation for the announcement of a LT project. Verification of the selection or contraindication criteria will be carried out by the principal investigator. During the consultation with the hepatologist and the TNC to announce the indication for LT, the study will be presented by the physician and then detailed by the TNC (objectives, steps, submission of upcoming questionnaires). After collecting the patient's non-opposition, clinical data will be collected (weight, height, BMI, sex, age, indication, MELD score, and presence or absence of hepatic encephalopathy). Given the emotional burden of this consultation, no questionnaire will be submitted to the patient at this stage. During the PLTE, then 2 months and 6 months after LT, 5 questionnaires will need to be completed by the patient (evaluation of sleep quality, anxiety, chronotype, physical activity, and pain). The TNC also collects the presence of psychotropic treatments that can influence sleep. A sleep schedule will be sent to the patient with their appointment for the PLTE and to be completed before hospitalization. This diary will be retrieved during the PLTE by the TNC. The presence or absence of psychotropic treatment will also be recorded. Two and six months after the LT, during follow-up visits in ambulatory care, conventional hospitals, or consultations, the patient responds again to these five questionnaires on a tablet, and the TNC also collects the presence of psychotropic treatment. Finally, at a distance from the LT (2 months later), the TNC collects the duration of the patient's transplant wait (from the date of activation on the waiting list to the LT date), the number of examinations performed during the PLTE, and post-LT complications (return to the operating room, stent-like endovascular treatment, drain adhered to the skin), the duration of the PLTE (date of the first PLTE examination on the date of activation on the waiting list) and the immediate post-LT hospitalization period (in days). A comparative analysis will be conducted between patients whose sleep quality is altered and those for whom it is maintained, with some factors of interest related to the patient's clinic and care pathway. The results will serve as a basis for the implementation of a relevant intervention aimed at treating and reducing sleep disorders in our patients.

The urological management of neurological patients is crucial to ensure patient survival and improve their quality of life. The natural progression of disease in central neurological bladders typically involves a major decrease in both bladder capacity and contractile function, often necessitating cystectomy. One alternative to urinary reconstruction is continent catheterizable urinary diversion (e.g., Miami pouch, Mitrofanoff, Monti, etc.). A common complication of these diversions is the formation of intravesical stones, which require surgical management. When the urethra allows access to the urinary diversion, the gold standard is transurethral lithotripsy using a cystoscope; however, when this is not feasible, several techniques exist, albeit without clear recommendations. In the literature, the most frequently discussed techniques include bladder dilation, percutaneous bladder lithotripsy using nephrolithotripsy (NLPC) equipment, and trans-stomal lithotripsy using a flexible fibroscope. Although bladder dilation has shown higher complication rates in case series compared to other techniques, there is very little comparative data between the percutaneous and trans-stomal methods in the literature. Case series indicate a higher risk of fistula formation with the percutaneous technique for urinary diversions performed in the gastrointestinal tract as compared to native bladder diversions, and a risk of stenosis or loss of continence with the trans-stomal technique. At the Hospices Civils de Lyon (HCL), the Urology Department of the Lyon Sud Hospital has expertise in neuro-urology with a large cohort of patients presenting continent catheterizable urinary diversions, and the Urology Department of Edouard Herriot Hopspital has expertise in NLPC, particularly with the use of mini-NLPC (smaller nephroscope diameter). The synergy between these two departments has enabled the creation of a large cohort, with frequent use of the percutaneous route for bladder lithotripsy and, since 2020, the trans-stomal route using mini-NLPC equipment. Therefore, given the limited data available in the literature, this retrospective comparative study would provide stronger evidence to improve the management of these patients.

Obstructive sleep apnea (OSA) is characterized by repetitive partial and/or total closure of the upper airway during sleep, inducing oxygen desaturation and sleep disturbance. Its prevalence in the pediatric population is 1-5%. In children, OSA can have negative consequences on the cardiovascular system and on the neurocognitive development. It is essential to diagnose OSA and to treat it efficiently. The OSA-18 questionnaire assesses the symptômes of OSA in children and its repercussions. It is composed of 18 items scored on a Likert scale by caregivers. This system allows a more sensitive scoring than binary answers available in other questionnaires like the Pediatric Sleep Questionnaire. The OSA-18 questionnaire would thus be an interesting tool to use for evaluating treatment efficacy in interventional studies and in clinical practice. This questionnaire is not yet available in French. The main objective of this study is thus to evaluate the validity of a French version compared to the gold standard method to evaluate OSA: polysomnography.

Metastatic breast cancer remains an incurable disease for most patients. While surgical treatment of the primary breast tumor is commonly performed in localized breast cancer, its role in metastatic breast cancer remains controversial due to the lack of demonstrated survival benefit and the potential interruption of systemic anticancer therapies. Cryoablation is a minimally invasive outpatient procedure that destroys tumor tissue through controlled freezing. In localized breast cancer, cryoablation has shown promising results regarding local tumor control, safety, and patient quality of life. However, evidence regarding its use in metastatic breast cancer remains limited.The primary objective of this prospective single-center cohort study is to evaluate local tumor control 12 months after cryoablation of the primary breast tumor in patients with metastatic breast cancer.

Memory consolidation transforms unstable memory traces into lasting representations, a process enhanced by both sleep and rehearsal during learning. Rehearsal is thought to accelerate consolidation by inducing memory reactivations that resemble those occurring during sleep. However, the respective mechanisms of sleep- and rehearsal-induced consolidation-and their potential interactions-remain poorly understood, especially in patients with temporal lobe epilepsy, where rehearsal might help compensate for memory deficits linked to hippocampal dysfunction, and where sleep may exacerbate epileptic activity. The CORESOM-EPI study aims to compare the effects of rehearsal and sleep on memory consolidation in patients undergoing video-EEG monitoring. Participants will learn "object-place" associations under two conditions (single versus repeated encoding), with memory tested immediately and again after a 12-hour delay. This delay will either include a full day awake or a night of sleep, allowing direct comparison of sleep- and rehearsal-related consolidation effects. Each participant will perform the task twice, with "wake" and "sleep" condition, in a balanced order. As a preliminary phase of the CRIMES study (ANR-DFG 2024), CORESOM-EPI will help assess how sleep and rehearsal influence memory consolidation in epilepsy. It will also serve to adapt the behavioral task for clinical use, paving the way for a future intracranial EEG investigations that will explore the neural networks involved and their modulation by epileptic activity.

Circulating biomarkers play a central role in translational research and precision medicine, particularly for the diagnosis, prognostic, monitoring of inflammatory or infectious diseases and patient stratification. Advances in analytical technologies enable standardised, sensitive and multiplexed assays, but their application remains limited by the lack of reliable reference values derived from well-characterised healthy populations. Indeed, the available data are often heterogeneous and difficult to transfer between platforms. In this context, the establishment of institutional reference cohorts appears essential for the correct interpretation of immunological parameters-which could be strongly influenced by demographic and clinical factors-and for defining relevant cut-off values when identifying new biomarkers of interest. This issue is particularly critical in the field of viral respiratory infections, where current diagnostic approaches still have several limitations. Circulating biomarkers play a central role in translational research and precision medicine, particularly for the diagnosis, prognostic, monitoring of inflammatory or infectious diseases and patient stratification. Advances in analytical technologies enable standardised, sensitive and multiplexed assays, but their application remains limited by the lack of reliable reference values derived from well-characterised healthy populations. Indeed, the available data are often heterogeneous and difficult to transfer between platforms. In this context, the establishment of institutional reference cohorts appears essential for the correct interpretation of immunological parameters-which could be strongly influenced by demographic and clinical factors-and for defining relevant cut-off values when identifying new biomarkers of interest. This issue is particularly critical in the field of viral respiratory infections, where current diagnostic approaches still have several limitations. Diagnosis is usually based on PCR tests targeting the DNA or RNA of pathogens, requiring a virus-specific test. In practice, only a few viruses (SARS-CoV-2, RSV, influenza) are tested for as a first-line investigation, whilst many other agents may be involved. As a comprehensive approach is difficult to achieve, viral infections often remain under-reported. Furthermore, the detection of a virus by PCR may indicate either an active infection or residual traces of a past infection. Although viral load can aid interpretation, it does not always allow for a definitive conclusion, making it difficult to distinguish between ongoing viral replication and the persistence of genetic material. It is therefore necessary to have additional markers associated with active infection. In this context, analysing the host response represents a promising alternative. Viruses induce, in particular, the production of type I interferons (IFN-I), the measurement of which could point the diagnosis towards a viral origin and reflect ongoing infectious activity. However, the interpretation of these biomarkers requires robust reference standards, taking into account their variability across individuals and contexts. Several studies illustrate the value of such approaches, such as the REFIPA study (NCT07239830), conducted in subjects over 80 years of age, which aims to characterise the immune response, particularly IFN-I, in the context of immunosenescence. This type of study highlights the need for well-phenotyped healthy ? control populations according to age groups and clinical contexts. Finally, beyond the creation of reference databases, the development of biobanks appears essential. This would enable the establishment of harmonised and directly usable reference values, thereby facilitating translational, basic and pre-clinical research projects, as well as the identification and validation of new biomarkers.

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a spectrum of liver disorders ranging from simple steatosis-a relatively benign and non-progressive condition-to metabolic dysfunction-associated steatohepatitis (MASH), characterized by hepatocellular inflammation. MASLD is now the leading cause of chronic liver disease worldwide, affecting approximately one in three adults, particularly those with obesity or type 2 diabetes. Recent studies have highlighted a strong interconnection between the gut microbiota, the liver, metabolism, and the immune system, collectively referred to as the gut-liver axis. Alterations in the gut microbiota are observed at all stages of MASLD, and several microbial metabolites-such as trimethylamine, bile acids, short-chain fatty acids, and ethanol-have been implicated in disease progression. Emerging evidence points to a role for gut-derived metabolites of tryptophan (Trp) and phenylalanine (Phe), including phenylacetic acid (PAA), 3-(4-hydroxyphenyl)-lactate (HPL), and phenyllactate (PL). These compounds have been associated with the severity of MASLD, particularly with hepatic steatosis and fibrosis. Elevated plasma levels of aromatic amino acids (AAAs), such as L-phenylalanine and L-tyrosine, are also correlated with increased hepatic fat content. A newly identified Phe-derived metabolite, N-acetyl-phenylalanine (NAPA), together with PAA, HPL, and PL, has been shown to correlate with hepatic steatosis. These metabolites can induce steatosis both in vitro and in vivo, acting through the disruption of endoplasmic reticulum-mitochondria interactions. They therefore represent potential new therapeutic targets. These four metabolites of interest (NAPA, PAA, HPL, PL) can be produced both by gut bacteria and through endogenous human metabolism. Positive correlations between plasma NAPA concentrations and specific bacterial species have been observed, although the responsible taxa remain to be identified. HYPOTHESIS We hypothesize that the gut microbiota of MASLD patients produces aromatic amino acid-derived metabolites, contributing to the elevated plasma concentrations observed in these patients Two complementary strategies will be used : Human Microbiota Culture and Fecal Microbiota Transplantation

The Microrchidia CW-type zinc finger 2 (MORC2) gene encodes a protein expressed in all tissues and enriched in the brain. It is involved in Charcot-Marie-Tooth disease, with mire than 30 families presenting MORC2 mutations. Recently, MORC2 mutation have been shown to be responsible for more complex phenotypes like DIFGAN: developmental delay, impaired growth, dysmorphic facies and axonal neuropathy. Different mutations are responsible from a diverse spectrum of phenotype, from CMT to DIFGAN. MORC2 is involved, through its ATPase activity, in DNA repair, chromatin remodeling and epigenetic silencing via the Human silencing hub (HUSH) complex. Our hypothesis is that the hypo- or hyper-activation of the HUSH complex by different MORC2 mutations could be responsible for different phenotypes in patients. The aim of this study is to perform a genotype-phenotype correlation study in patients presenting MORC2 mutations.

Obstructive Sleep Apnea (OSA) is characterised by repetitive collapse of the upper airway during sleep, inducing breathing disturbances that can result in oxygen desaturation and frequent arousals. In children, OSA can have long-term consequences on the development and on the cardiovascular system. Down Syndrome (DS) is a genetic disorder associated with intellectual disability and many comorbidities. The prevalence of OSA is particularly high in patients with DS, from infancy. In a recent study, OSA was diagnosed in 97% infants and early diagnosis and intervention from the age of 6 months was associated with better neurocognitive outcome at 3 years old. Therefore, there is a need to develop new strategies to prevent OSA early in infancy. OSA can be linked to some orofacial abnormalities presented by patients with DS. Indeed, orofacial functions and structures ca play a crucial role in OSA. For example, nose breathing allows the tongue to act as a stimulator of the transverse maxillary growth during childhood, allowing the upper airway to develop properly. The primary objective of the present study is to evaluate the effects of a pacifier used by infants with Down Syndrome (from the age of 1 months) on the severity of OSA at the age of 6 months, by comparing a group of infants with the pacifier vs a group of infants without the pacifier. The main hypothesis is that infants who used the pacifier from 1 month- to 6 month-old will have lower OSA severity (estimated by the obstructive apnea hypopnea index on polysomnography (PSG)).

Pain, when it becomes chronic, can be a threat to patients and it is very common to observe a fear of pain and a fear of movement (kinesiophobia). Avoidance of movement due to fear of pain can lead to a deterioration of body image. Non-medicinal therapies are essential to correct this fear and movement avoidance behavior, to decrease "catastrophic" judgments and thus anxiety. The use of art-therapy in the accompaniment of patients with pain has shown, in particular, decreases in the intensity of pain, the level of anxiety, an improvement in stress, mood and overall psychological state. However, according to the current literature, it appears that 1) this technique is rarely used in children or adolescents, for whom non-medicinal therapies are fundamental, and 2) in the case of chronic pain, the form of art used is very rarely related to the body (most often painting, drawing, music...). In this project, investigators propose to set up and test the potential benefit of art-therapy sessions related to the body, namely dance-therapy, in adolescents and young adults suffering from chronic pain.

Liver transplantation (LT) is the only curative treatment option for patients with severe liver disease. Since 2007, the implementation of the MELD score in liver transplant allocation guidelines has led to a change in the profile of transplant recipients, notably with an increase in the proportion of patients receiving transplants for severe liver failure. Thus, in 2023, nearly 40% of liver transplant recipients whose primary indication for LT was cirrhosis had a MELD score greater than 35 (ABM Scientific Report 2023). These patients with severe pre-transplant liver failure often present with associated organ failure (Acute-on-Chronic Liver Failure, ACLF). Infections are the leading cause of death at 1 year post-transplant for patients transplanted with ACLF and are a major concern for all patients, representing one of the leading causes of death at 3 months post-transplant. Another common complication following LT is acute cellular rejection. Although frequent, this complication is reversible with treatment and results in graft loss in fewer than 5% of cases. The expression of the HLA-DR marker by monocytes (mHLA-DR) is correlated with immunoparesis and the risk of secondary infection and mortality in patients admitted to critical care. In a prospective, single-center pilot study of 99 liver transplant recipients, the Hepatology and Gastroenterology service at the Croix Rousse Hospital, Hospices Civils de Lyon, demonstrated that the kinetics of mHLA-DR levels measured immediately after transplantation could predict the risk of early significant infection (\< 1 month) after transplantation and 1-year post-transplant mortality. The early post-transplant kinetics of mHLA-DR expression recovery appeared to be a more relevant predictor of the risk of early post-transplant infection than a single-point-in-time value. The profile of immune recovery kinetics, as well as a pre-LT MELD score \> 30, were associated in multivariate analysis with the risk of developing an infection at 1 month post-LT and with 1-year post-LT survival. PREDITH study team hypothesize that the implementation of mHLA-DR testing immediately post-LT would enable the development of a predictive score for early post-LT infection combining clinical and biological risk factors for post-LT infection and immune monitoring.

Epilepsy is one of the most common neurological disorders, with one of the highest morbidity rates of all diseases. Despite the development of new anticonvulsant drugs, around a third of patients suffer from drug-resistant epilepsy (RPE). The onset of RPE can be lengthy, prolonging the period during which affected patients live with seizures that have a negative impact on their quality of life. Epilepsy surgery can be a curative treatment, and can enable anticonvulsant medication to be discontinued, optimizing quality of life and cognitive development. In addition, as it has been shown that the prolonged duration of epilepsy prior to surgery has an impact on the occurrence of postoperative seizures, early surgery is increasingly being considered. Focal cortical dysplasia (FCD) is the leading cause of focal lesional epilepsy and is generally drug-resistant. Good postoperative seizure results after surgical resection are strongly linked to complete resection of the dysplastic tissue. Consequently, accurate localization and precise delineation of FCD lesions are crucial during surgery. Currently, the extent of surgical resection is based primarily on preoperative examination, as the macroscopic appearance of dysplastic tissue does not differ from normal cortex. The various intraoperative techniques available to improve the quality of excision (neuronavigation, ultrasound, intraoperative MRI and intraoperative guidance by fluorescence microscopy) all have their limitations. In this context, new intraoperative tools are needed to help the neurosurgeon delineate lesions during surgery. Intraoperative fluorescence spectroscopy is used for surgical guidance of gliomas and other brain pathologies, and has demonstrated its ability to characterize pathological tissues. DCFs exhibit metabolic differences that can also be detected by 5-amino-levulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence intraoperatively. Indeed, in some patients who underwent surgery after a diagnosis of glioma, fluorescence was observed even though histological analysis classified the excised tissue as DCF. What's more, glioma and DCF share a common feature: the mitochondria of affected cells are deficient in complex IV. Cytochrome c oxidase (CCO) is largely involved in mitochondrial complex IV, and NAD is a central metabolite involved in redox reactions within cells. Both metabolites (CCO and NAD) can be visualized intraoperatively by optical and fluorescence spectroscopy. FLUOFOCODYS is a prospective, non-comparative, single-center, human drug pilot clinical trial. 5 patients will be included.

The human skull is a complex structure that protects the underlying tissues, including the brain. Certain rare conditions and diseases, such as craniosynostosis-which affects 1 in 2,000 to 2,500 children-impair these functions and lead to increased intracranial pressure, posing a neurological risk. The most common form of craniosynostosis is scaphocephaly (50%), which manifests as premature closure of the sagittal suture, halting growth at that site and causing an abnormal skull shape and altered local biomechanical properties. The parietal bone is a flat, regular bone that embryologically originates from the neurocranium. Its characteristics vary according to age, sex, and morphotype. Studies on the multimodal characterization of the properties of growing cortical bone focus on the characterization of growing fibulae and femurs. A comparison was made with adult bone, allowing for the establishment of specific pediatric characteristics. The mechanical, morphological, architectural, and tissue properties of the skull vary considerably between adults and children. They are uniquely adapted to the rapid growth and development of the brain. The analysis of the mechanical, architectural, and tissue properties of the parietal bone in infants involves evaluating its ability to resist applied forces and stresses, analyze its shape, composition, and the quality of the bone tissue itself, including aspects such as mineralization, collagen fiber structure, and bone mineral density. A study conducted on samples obtained from parietal resections in infants operated on for scaphocephaly evaluated the microstructural and mechanical characteristics of this region of the skull vault, allowing for the determination of mechanical and morphological characteristics. However, the samples were located near the stenosis, with the sampling site determined macroscopically by the surgeon. The characteristics of the parietal bone in infants with scaphocephaly were also evaluated and show properties correlated with the degree of ossification regardless of age. However, the available data have a significant limitation: existing characterizations are based on pathological samples taken near the stenotic area, or on models of growing long bones that do not reflect the specific characteristics of the cranial vault. To date, there is no certainty regarding the mechanical, architectural, and tissue properties of the parietal bone considered healthy regardless of craniosynostosis in infants, taking into account the developmental constraints specific to the first months of life. These properties are, however, strongly influenced by the compressive forces experienced during birth and then by the gradual changes in gravitational and postural forces associated with motor development (head control, sitting, crawling, and walking on all fours). These data could help improve our understanding of normal cranial physiology and its variations in the presence of pathology. The primary objective is to describe the mechanical, architectural, tissue, and histological properties of the parietal bone in infants with craniosynostosis. To evaluate ex vivo, both near and far from the stenosis, the mechanical, architectural, tissue, and histological properties of the parietal bone and sutures in infants aged 3 to 12 months with craniosynostosis.

Covert actions are cognitive processes that involves the motor system. They include motor imagery, movement preparation, action observation or action language. They imply mental simulations, based on activations of neural networks, involved in specific operations such as perceiving or acting. These mental phenomena have intrigued and still intrigue philosophers, psychologists, and neuroscientists, as they are complex and introspective processes, which play a major role in human cognition. To decipher similarities and differences between these types of covert actions, the investigators will focus on persons living with aphantasia, which is a neurocognitive specificity present in a small proportion of the population (5 to 8%). Aphantasia is characterized by the alteration or the absence of explicit mental representations. This population offers an ideal testbed to disentangle the involvement of cognitive and motor processes in different forms of covert actions. By means of magnetoencephalography, this study aims to identify and compare brain patterns and their temporal dynamics in alpha and beta bands during covert actions in two groups of healthy volunteers: aphantasics and non-aphantasics (i.e., having a non-altered imagery capacity). If covert actions indeed share brain networks, the investigators expect aphantasics to present reduced neural and behavioral activation during the explicit (i.e., motor imagery) and implicit (movement preparation, action language and action observation) forms of covert actions.

Type I interferon (IFN-I) production is triggered by the detection of viral molecules, such as strands of viral RNA or DNA, by receptors known as PRRs (Pattern Recognition Receptors) present on many cell types. These interferons are secreted in minimal concentrations but can activate neighboring cells to secrete over 700 proteins with antiviral properties (inhibition of viral replication, destabilization of viral membranes, etc.). Thus, the IFN-I response serves as the immune system's first line of defense during a viral infection. Very early in the COVID-19 pandemic, several research teams, including ours, identified a defect in the type I interferon response in about one in five subjects with severe COVID-19. In-depth studies have shown that 5 to 20% of these patients with severe COVID-19 disease have genetic mutations affecting genes involved in the activation cascade of the IFN-I pathway or produce autoantibodies that neutralize IFN-I, significantly impairing the effectiveness of their IFN-I response. However, to date, not all causes of IFN-I response alteration are clearly identified, and 80% of patients suffering from severe COVID-19 do not appear to have evident genetic predispositions or anti-IFN-I autoantibodies, with the techniques currently available. This suggests the presence of other risk factors or causes that could potentially lead to alterations in the IFN-I response. The gut microbiota is recognized for its influence on host health and immunity. SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus 2) infection has been associated with altered gut microbiota and correlated with inflammatory and immune responses. However, the association between dysbiosis and IFN-I response has yet to be studied in humans. Therefore, to improve the management of individuals affected by viral respiratory infections, it seems essential to explore alterations in the IFN-I response to identify individuals potentially at risk of developing severe forms. It is known that a failure in the IFN-I response in the early stages of a viral infection leads to uncontrolled viral replication, which may result in a severe form of the disease. Since this IFN-I response is essential for controlling all viral infections, regardless of the virus involved, the investigators hypothesize that this IFN-I deficiency could be responsible for severe infections from various respiratory viruses that may lead to severe forms, even though a direct association between IFN-I deficiency and higher mortality risk has only been reported for a few viruses, such as SARS-CoV-2 and influenza. Furthermore, the investigators consider the possibility of other underlying causes of IFN-I deficiencies, distinct from the already observed anti-IFN-I autoantibodies and genetic mutations. To achieve this, the investigators hypothesize that the use of functional immune tests could reveal these other alterations. By identifying these alterations in individuals, the investigators hope to more accurately predict their propensity to develop severe forms of viral infections. Patients who experienced : * mild forms of COVID-19 during the first wave, without any prior vaccination, selected from the pre-existing COVID-Ser cohort (ClinicalTrial no. NCT04341142) * severe forms of COVID-19 during the first wave, without any prior vaccination, selected from the pre-existing NOSO-COR IMMUNO cohort (ClinicalTrial no. NCT04637867) and the RNIPH study (Research Not Involving Human Persons) named MIR-COVID (compliance with MR004 n°20\_097\_v2) could be recruited. Biological samples will be collected specifically for the study, outside of a healthcare procedure. No biological sample in biocollections coming from COVID-ser and NOSO-COR IMMUNO studies and the RNIPH study (Research Not Involving Human Persons) named MIR-COVID will be used for this new protocol.

Sepsis is a disruption of homeostasis in the human body in response to bloodstream infection and is associated with a high risk of mortality. Worldwide, sepsis is affecting approximately 30 million people and resulting in six million deaths. Blood culture is a specific blood sample used to identifying microbial agent (bacterium or yeast) and determine the sensitivity of these microorganisms to antibiotics and antifungals. Any delay in identifying the microorganism and/or determining the AST (antibiotic susceptibility testing) has a direct impact on the administration of appropriate antibiotic treatment and, consequently, on mortality of the patient. The faster the diagnosis, the faster the antibiotic treatment will be adapted, the higher the survival rate/probability of patients, and the lower the ecological impact. In routine, clinical microbiology laboratories currently use 2 automatized techniques: MALDI-TOF MS® for microorganisms identification and VITEK2® method for AST determination. Based on a proteomic approach, the IDBIORIV method is a rapid method (90 minutes) in comparison of current methods (24/48 hours) able to identifying a large panel of 113 pathogens and determine the antibiotic resistance profile of 49 species for 4 classes of antibiotics (Beta-lactams, Aminosides, Glycopeptides, Colistin). The main objective of this study is to evaluate the performance of the IDBIORIV method in pathogen identification and antibiotic susceptibility testing in comparison with current methods of analysis of positive blood cultures used at the microbiology laboratory of the Hospices Civils de Lyon, in a real clinical situation, over a 2-year period.

This exploratory study will focus on the development of the analyses of blood biomarkers to better understand the circulating biomarkers associated with cancer diagnosis, treatment efficacy and progressive disease

The selection of kidneys from living donors is based on strict glomerular filtration rate (GFR) values, in the setting of the increasing proportion of older donors. The 2017 KDIGO recommendations consider that approving kidney donation for a donor with a GFR between 60 and 89 mL/min/1.73 m² should be individually discussed, possibly using a calculator. A GFR \< 60 mL/min/1.73 m² should contraindicate donation without considering the donor's age. GFR physiologically decreases with age, so older donors frequently have a GFR below 90 ml/min/1.73 m². However, the proportion of older donors continues to rise. Kidney grafts from older living donors maintain better renal function than those from deceased donors, aiming to counteract the organ shortage. Kidneys possess functional reserves, allowing an increase in GFR during stimulations and adaptation to reduced functional nephron count (as after nephrectomy). Assessing this adaptive capacity clinically is challenging. It might be dependent on vascularization and/or absence of fibrosis, but these parameters are poorly understood due to a lack of current in vivo exploration methods. The development of functional renal MRI enables the evaluation of these parameters, allowing measurements on separate, regional, non-invasive, quantitative kidney segments coupled with morphological studies. BOLD-MRI can measure regional oxygen content, thus accessing more precise medullary data. The DWI sequence can estimate renal microstructure and study interstitial fibrosis. Therefore, evaluating renal performance (by measuring GFR, renal perfusion, fibrosis, inflammation, and oxygen content) in donors, and studying the evolution of these parameters in recipients and donors, could optimize donor selection. Hence, the aim of our study is to 1) investigate the evolution of renal functional parameters in the transplanted kidney up to 1 year post-transplant, and 2) study the evolution of these same parameters in the contralateral kidney of the donor.

This single-center, randomized, single-blind, 2-period crossover interventional study will evaluate whether exposure to a pleasant food odor 10 minutes before a 75 g oral glucose tolerance test (OGTT) modifies glucose homeostasis in adults with different metabolic phenotypes. Participants will undergo two experimental conditions in random order: food odor stimulation and control condition without odor, separated by a 4-week washout. The main objective is to quantify the within-subject effect of food odor stimulation on the incremental area under the glucose curve (iAUC) from 0 to 120 minutes during OGTT and to assess whether this effect differs according to metabolic status. Two predefined groups will be enrolled: adults without overweight and without insulin resistance, and adults with class I obesity and low-to-moderate insulin resistance. Secondary objectives include characterization of cephalic phase insulin release (CPIR), C-peptide and GLP-1 responses, glycemic kinetics, associations between CPIR and metabolic responses, and participant acceptability of the test environment and olfactory stimulation. A plasma biobank will be constituted from part of the collected samples for future research.

Links between sleep and food intake are manyfold. In healthy individuals, sleep deprivation promotes obesity by stimulating food intake of high glycemic index (GI) foods. Conversely, high GI foods induce sleepiness. Obesity is observed in 30-50% of patients with Narcolepsy type 1 (NT1). Its determinism may involve transient changes in basal metabolism at the early stage of the disease, eating disorders, disrupted nighttime sleep and sleepiness. In contrast, patients suffering from idiopathic hypersomnia (IH), whose nocturnal sleep is generally long and of good quality, rarely present with obesity. By studying the relationships between diet, body composition and sleep patterns in these two populations and in healthy controls, the NARCOFOOD study aims to provide a better understanding of the determinants of obesity in narcolepsy and, more generally, of the effects of food intake on sleepiness. Patients will be recruited at the Lyon and Clermont-Ferrand sleep centers and Controls at the Lyon Neuroscience Research Center or through communications to the general public. Data from clinical evaluation (including body mass index and body composition), and questionnaires (sleep quality, insomnia, sleepiness, anxiety and depression, impulsivity, eating behaviors) will be collected. During 4 days, at home, the following parameters will be explored : 1) eating behaviors (meals' photos) and sugar consumption (FreeStylePro sensor measuring interstitial glucose) 2) sleep/wake rhythm (diary and actigraphy) 3) nocturnal sleep parameters (Somfit device) 4) sleepiness (Karolinska sleepiness scale and EEG markers of sleepiness with the Somfit device) before and after meals. The hypothesis is that increased sleepiness would favor food intake of high GI foods, which would worsen sleepiness in all 3 groups, with a more pronounced effect in NT1. Compared to IH patients and controls, NT1 patients may present more snacking of high GI foods, especially at night if sleep is disrupted, and this would be correlated with body composition. The findings will help to better understand the mechanisms of obesity in narcolepsy and may lay the ground for the development of new therapeutic strategies in disorders of hypersomnolence, targeting dietary behaviors.

Autoinflammatory diseases are part of a heterogeneous group of diseases that manifest themselves through an inflammatory reaction in their initial phase (innate immunity) that is activated inappropriately: either because the reaction is too strong or because it is unjustified (for example, in the absence of infection). In many cases, and in their initial description, autoinflammatory diseases have a genetic origin (and are therefore hereditary or familial) and preferentially affect children or young adults. However, a significant number of other diseases have expanded this nosological field due to the preponderance of autoinflammation in explaining the symptoms. Sometimes, autoinflammatory disease can also remain "unclassified." In general, autoinflammatory diseases manifest as recurrent attacks combining fever, skin rashes, and joint pain. Certain signs are more specific to certain diseases, such as hives, abdominal pain, mouth ulcers, or swollen lymph nodes in the neck. It is mainly the recurrence of attacks and their unprovoked nature that attract the attention of the patient and the doctor. These attacks are systematically associated with an increase in inflammatory markers in the blood. Currently, most autoinflammatory diseases are diagnosed based on a combination of clinical and biological evidence, following a thorough investigation by specialists in these diseases. Biological markers that can confirm the disease are rare. However, for some of them, confirmation can be obtained through genetic analysis. In certain cases, extensive genetic analysis may be offered. Autoinflammatory diseases are managed by specialists (internists, rheumatologists, etc.) in close collaboration with primary care physicians and other healthcare professionals (nurses, physical therapists, social workers, etc.). Treatment is sometimes based on exceptional drugs that can only be prescribed and dispensed in hospitals. This multicenter, national study, which targets children and adults with rare autoinflammatory diseases, aims to identify: * the "key" parameters for a faster diagnosis, * the determining factors and their associated characteristics, and * the treatments used and their effectiveness.

The incidence of hip fractures in France is 50,000 cases per year among women and 16,000 among men, with a 1-year mortality rate of 20-24%. After a fracture, 10-30% of patients become functionally dependent. The increasing aging of the population and the rise in dependency are likely to worsen the situation of older patients in hospital settings. Several tools are available to assess functional independence, including the New Mobility Score (NMS), which evaluates mobility through three domains: mobility indoors, mobility outdoors, and shopping activities. The NMS has shown good performance in predicting patient mortality and functional recovery, and its use is recommended in clinical practice. However, the French version of the NMS has not yet been validated. The French validation of the NMS is important to facilitate its implementation in clinical practice and research, particularly because of its simplicity and the need for rapid assessment tools for healthcare professionals. A French version of the NMS has been translated, and the MOB-SCORE study aims to assess its reliability and validity among healthcare professionals caring for patients with hip fractures.