Mont De Marsan

Myeloproliferative Neoplasms (MPN) are hematological malignancies associated with an increased risk of thrombosis. Although different cell types have been involved in these complications (platelets, red blood cells, leucocytes and endothelial cells), there do not exist any reliable biomarker to predict the thrombotic risk in MPN patients. While some studies suggested that the JAK2V617F allele burden measured in leukocytes was associated with the risk of thrombosis, other studies did not confirm these results. Besides, a recent work demonstrated that in some patients, the JAK2V617F allele burden measured in platelets and red blood cells was higher than the one determined in leukocytes. Moreover, some patients present JAK2V617F mutated endothelial cells, known as pro-thrombotic in in vitro and animal models. The CLOJAK project will search for an association between the thrombotic risk in MPN and the proportion of cells carrying the JAK2V617F mutation in erythroid cells and platelets or its presence in endothelial cells. The objective is to determine a clonality profile (i.e. the profile of repartition of the JAK2V617F allele burden in the different hematopoietic and endothelial lineages) associated with the occurrence of thrombosis in MPN patients. One hundred and twenty PV and ET patients will be studied at diagnosis. Their platelets, red blood cells, granulocytes and endothelial cells will be isolated. The JAK2V617F allele burden will be measured in these cells thanks to a digital PCR technic. An association between the clonality profile and the existence of a thrombosis at diagnosis, the MPN phenotype (PV or ET), the IPSET-thrombosis score and the type of thrombosis (venous, arterial, splanchnic) will be searched.

Tyrosine kinase inhibitors (TKI) have revolutionized the management and prognosis of chronic myeloid leukemia (CML). Daily treatment with TKI, which is necessary due to lack of cure, is frequently associated with moderate, chronic and sometimes severe adverse effects. The ability to permanently stop treatment with TKI has thus become a major goal in CML to prevent the occurrence of adverse events, improve quality of life and reduce the general cost of the treatment; we talk about Treatment Free Remission (TFR). It now remains to be demonstrated in a comparative prospective study that a strategy of de-escalation of the TKI treatment dose before treatment discontinuation optimizes TFR results. At the same time, it is possible to reduce adverse reactions and improve the quality of life of patients. In this context, the investigator propose to conduct a randomized clinical trial including CML patients, allowing to compare the results of TFR at 24 months between a sudden stop of treatment after a maintenance phase of dosage for 12 months and a de-escalation arm of dose (dosage reduced by 50%) for 12 months before stopping. A secondary immunological translational objective of this project will be to compare the quantitative and qualitative evolution of innate CD8 T cells between the 2 arms (abrupt cessation of ITK treatment versus progressive withdrawal) and look for a predictive innate CD8 T cells blood signature at the time of stopping treatment of a successful TFR in both arms.

Chair positioning is one of a series of early mobilization techniques. At present, this technique, which involves moving a patient out of the resuscitation bed, can be performed passively or actively. It does not constitute a rehabilitative act as such, but it is considered in common paradigms as a technique to improve "the patient's breathing and strength". However, recommendations issued in 2013 by the Society of intensive care physiotherapy and the society "Société de réanimation de langue française (SRLF)", reveal that this chair position cannot be recommended with a high grade. The aim of the investigators is therefore to break down this early mobilization process in intensive care, to find out whether the armchair is an indispensable tool for improving functional and muscular processes. The research hypothesis is therefore as follows: "Early armchairing of the resuscitation patient, improves functional recovery compared to a conservative positioning strategy (sitting in bed)."

This study is designed as a multicenter, randomized, parallel groups, open-label, phase 3 study in subjects with untreated newly diagnoses Multiple Myeloma eligible for ASCT. 824 patients will be enrolled in this study from approximately 70 study sites. The 2 parts in the Treatment Phase are described below. Part 1: Induction/ASCT/Consolidation Phase (1:1 Randomization) After the screening period, patients will be randomly allocated (1:1) to either: * Arm A (standard of care arm): standard induction therapy with 4 cycles of D-VRd, followed by HDCT (Melphalan) + ASCT, D-VRd consolidation therapy * Arm B (experimental arm): standard induction therapy with 4 cycles of D-VRd, followed by elranatamab and lenalidomide consolidation therapy. Part 2: Maintenance Phase (1:1 Re-randomization) Patients will be re-randomized (1:1) and will enter the Maintenance Phase upon completion of consolidation therapy. * Arm C (standard of care arm): lenalidomide * Arm D (experimental arm): elranatamab

The objective of this all-comers registry is to explore the safety, efficacy, and cost-efficiency of the LUMINOR© DEB in de-novo and restenotic-FP lesions. For de-novo and restenotic lesions, especially for calcified and/or long lesions/occlusions, the use of debulking devices to improve recalibration and drug penetration will be evaluated in a specific sub-group.

The objective of the study is to describe the therapeutic management of patients more than or equal to 18 years old eligible for systemic therapy or treated by systemic therapy for atopic dermatitis (AD). This study will be proposed to a sample of French dermatologists experienced in the management of AD, practicing in hospital centers and/or office-based dermatologists. The study will be conducted in real conditions of practice, systemic treatment decisions will be taken at the sole initiative of the participating physician irrespective of the patient enrollment decision. Each patient will be followed-up in routine care setting for 1 year.

This is a randomized, parallel group, double-blind Phase 2 study with a 52-week blinded extension evaluating the safety and efficacy of 3 dose levels of frexalimab in comparison with placebo in participants with newly diagnosed T1D on insulin treatment. Study details include: Screening period: at least 3 weeks and up to 5 weeks Double-blind treatment period (104 weeks): * Main treatment period: 52 weeks * Blinded extension: 52 weeks Optional Open Label Extension: 104 weeks Safety follow-up: up to 26 weeks The treatment duration will be up to 104 weeks, the total study duration will be up to 135 weeks.

Ventilator-associated pneumonia is the leading nosocomial infection in the intensive care units, and is associated with prolonged mechanical ventilation and overuse of antibiotics. Initiating antibiotic therapy immediately after bacteriological sampling (immediate strategy) may expose uninfected patients to unnecessary treatment, while waiting for bacteriological confirmation (conservative strategy) may delay ventilator-associated pneumonia in infected patients. The decision to start antibiotic therapy for ventilator-associated pneumonia takes three points into account: diagnostic probability, the risks to the patient if Antibiotic Therapy is delayed, and the risk of selection of resistant bacteria. Diagnostic probability is limited, given the subjective and non-specific nature of the diagnostic criteria, and only 30-50% of suspected cases are confirmed bacteriologically (whereas samples are only taken when the pre-test probability is sufficient). The risks associated with delayed antibiotic therapy are unknown, as few observational studies have directly assessed the impact of the timing of Antibiotic Therapy initiation on outcome (frequent confusion between delayed and inappropriate Antibiotic Therapy). Iregui et al. found that delaying Antibiotic Therapy by more than 24 hours was associated with higher mortality. However, more recent before-and-after studies have shown that the conservative strategy was associated with lower mortality, more frequently appropriate initial Antibiotic Therapy and shorter duration of Antibiotic Therapy. Similarly, in a recent before-and-after study by our team, initiating antibiotic therapy only upon microbiological confirmation of ventilator-associated pneumonia without septic shock or severe acute respiratory distress syndrome was not associated with an increase in ventilation time, length of stay or excess mortality at D28; but was associated with antibiotic therapy that was more often appropriate (DELAVAP, MARTIN et al, Annals of Intensive Care, 2024). Finally, the recent multicenter TARPP pilot study in surgical intensive care suggests that antibiotic therapy initiated on the basis of microbiological data in patients with suspected ventilator-associated pneumonia not requiring vasopressor support is not associated with a poorer outcome than immediate antibiotic therapy without documentation (the only randomized study on this subject). Antibiotic Therapy for suspected ventilator-associated pneumonia that is not subsequently confirmed is an unnecessary use of antibiotics and carries a risk of selection of resistant bacteria, with adverse effects on public health. It has been reported that a conservative Antibiotic Therapy prescription strategy for intensive care units -acquired infections reduces Antibiotic Therapy use and the incidence of acquired β-lactamase-producing Enterobacteriaceae infections. Overall, in patients with suspected ventilator-associated pneumonia but no signs of clinical severity, given the uncertainty about attributable mortality and concerns about bacterial resistance, the evaluation of the conservative Antibiotic Therapy strategy is reasonable. Some French intensive care units already delay Antibiotic Therapy until confirmation of ventilator-associated pneumonia, except in patients with severe hypoxemia or the need for vasopressor support.

Kidney cancer represents 2 to 3% of solid cancers in adults. Worldwide, an estimated 431,288 people a year are diagnosed with kidney cancer. Each year, in France, 13,500 patients undergo total or partial nephrectomy. The development of minimally invasive surgical techniques and the structuring of innovative care pathways for the management of renal tumors in Enhanced Rehabilitation After Surgery (RAAC) and even on an outpatient basis have led to a significant reduction in the length of stays. The physiognomy of the course of care for patients operated on for a renal tumor is completely modified and generates for the patient a feeling of deterioration in the quality of care and disruption of medical follow-up. The objective is to deploy a model for coordinating the perioperative care pathway of patients who have undergone nephrectomy for renal tumor in several French centers in order to assess the impact for patients, caregivers and the health system. This coordination would lead to the formalization of a nurse coordinator job profile adapted to the specificities of oncological surgery and the tools necessary for its implementation. The UroConnect device has a "patient" interface for presenting self-questionnaires and access to a library of educational content and a "caregiver" interface to rationalize and optimize the nurse's activity of perioperative coordination in his task.

In this study, platelet activation is targeted as it could play a key role in the pathogenesis of SSc. It has been shown in several publications that platelets are activated in SSc with a correlation between the level of activation and disease activity. Secondary to this activation, soluble and membrane effectors were increased, and induced vascular damages and fibrosis. The results obtained in the laboratory (CNRS UMR-5164) directly involved platelets in this mechanism by inducing the thymic stromal lymphopoietin (TSLP) production by endothelial cells and by showing the pro-fibrotic effect of TSLP. In vivo data in SSc murine model recently obtained, confirmed the preventive role on fibrosis of clopidogrel. The early control of this platelet activation could prevent the course of events leading to SSc. The therapeutic strategy assessed in this study will be the oral administration of clopidogrel (75 mg per day) during two years to subjects presenting an association of specific dysimmunity and Raynaud phenomenon (RP). The administration of clopidogrel will be double-blinded versus placebo. Subjects will be included and treated during a 2-year period and will be followed for a period of 36 months after treatment, i.e. a total of 60 months. The follow-up will be every six months mainly comprising clinical examination, patient reported outcomes and blood sampling.