St Yorre, France

The Efficacy of Fecal Microbiota Transplatation on Axial Spondyloarthritis Patients Resistant to Conventional Treatment

Axial spondyloarthritis (SpA) is a chronic inflammatory disease primarily affecting the sacroiliac and spinal joints that usually begins in young adults and is a major cause of chronic pain and disability that profoundly alter the quality of life of patients. Besides non-steroidal anti-inflammatory drugs, the development of anti-tumor necrosis factor-α (TNFα) and anti-interleukin (IL-17) biotherapies and of JAK inhibitors, has improved the management of these patients. However only half of the patients respond to these treatments and many of them are only partially relieved. Remarkably, this disorder frequently combines with overt inflammatory bowel disease (IBD) -i.e. Crohn's disease (CD) or ulcerative colitis (UC)- and even more frequently with subclinical gut inflammation, leading to suspect a role of the gut microbiota as a possible trigger. Consistently, recent studies evidenced an alteration of gut microbiota composition -or dysbiosis- in the course of SpA that appeared all the more pronounced that disease was more active. It was notably shown a restriction of bacterial diversity and an expansion of species considered as potentially pro-inflammatory, including Ruminococcus gnavus. Given its potential involvement in the pathogenesis of SpA, gut microbiota could be considéred as a promising therapeutic target. Fecal microbiota transplantation (FMT) is a technic consisting in thorough replacement of dysbiotic microbiota by healthy dondor's microbiota that has recently been developped to correct dysbiosis. It has been validated for the treatment of intractable colitis due to Clostridium difficile and its efficacy has been reported in CD or UC. The current trial, aims to evaluate efficacy of FMT in drug-resistant axial SpA.

Research of the Consequences on the Digestive Tract Following the Proposed Treatments for a Urinary Infection in Children

Treatment of Cardiovascular Disease With Low Dose Rivaroxaban in Advanced Chronic Kidney Disease

Background and Rationale Chronic Kidney Disease (CKD) is a major international health burden. Despite the unacceptably high burden of cardiovascular disease (CVD) and associated mortality, trial-data on the management of CVD in people with advanced stages of CKD and dialysis-dependent kidney failure are sparse. Risk of bleeding in CKD and dialysis-dependent kidney failure is increased when compared to the general population. Anticoagulant agents, such as rivaroxaban, are a core intervention in the prevention of CVD in the general population. Nevertheless, to mitigate trial risks, 90% of the trials evaluating this form of intervention exclude these patient populations. The TRACK trial will evaluate the effect of low dose rivaroxaban in patients with CKD dialysis-dependent kidney failure. Other trials have demonstrated that rivaroxaban reduces the risk of major cardio-vascular outcomes in high risk patients, and the limited data showed that CKD status did not significantly affect this result. Hypothesis Compared to placebo, low dose rivaroxaban reduces the risk of major adverse cardiac event (MACE) in people with CKD stages 4 or 5 or dialysis-dependent kidney failure, and elevated cardiovascular (CV) risk (marked by a history of CAD or PAD, or non-haemorrhagic non-lacunar stroke OR diabetes mellitus OR age ≥65 years). Objectives The primary objective is to determine whether low dose rivaroxaban, compared to placebo, significantly reduces the risk of a composite outcome of; - CV death, - non-fatal myocardial infarction, - stroke, or - peripheral artery disease (PAD) events in people with CKD stages 4 or 5 or dialysis-dependent kidney failure, and an elevated CV risk (marked by a history of CAD or PAD, or non-haemorrhagic non-lacunar stroke OR diabetes mellitus OR age ≥65 years). A full list of secondary objectives are detailed in the protocol, and include identifying risk reduction in the treatment group, and whether this treatment is cost effective. Methodology The TRACK trial is an investigator-initiated, multicentre, prospective, randomised, quadruple-blind (participant, healthcare provider, data collector, outcomes assessor), placebo-controlled trial. The trial will test for the superiority of the trial intervention using a 1:1 allocation to parallel trial groups, on the basis of a pre-specified number of primary outcomes events. This is a global trial and will be conducted in renal units that provide comprehensive CKD care. Approximately 2,000 participants will be recruited.

Nitrous Oxide for Analgesia During Nasogastric Tube Placement in Young Children

In the context of mild to moderate dehydration in young children, enteral rehydration is the treatment of choice because it is more physiological than parenteral rehydration which has more serious side effects. Thus, nasogastric tube placement has become a more common procedure in the pediatric emergency care setting. Although, it is widely accepted that this procedure is invasive and painful, to date, no analgesic approach has been shown to be effective for children aged 3 months to 3 years. Currently, standard care is the placement of nasogastric tube without any analgesic intervention. Inhalation of nitrous oxide mixed with oxygen (50/50) has been shown to be effective to reduce pain and anxiety induced by invasive procedures in children, adolescents and adults. Its use is very safe and it is associated with only minor and transient side effects such as nausea, vomiting or dizziness in les than 10% of patients. Its use is very common in many countries such as France, United Kingdom, The Netherlands or Australia. The investigators hypothesized that its inhalation would reduce pain during nasogastric tube placement in young children. The purpose of this study is to evaluate the analgesic efficacy of 50%/50% nitrous/oxide mixture in reducing pain induced by nasogastric tube insertion in children aged 3 months to 3 years in the pediatric emergency department. A randomized controlled trial will be performed in two pediatric emergency departments to assess the efficacy of 50/50 nitrous oxide/oxygen during nasogastric tube insertion. The control group will receive standard care. Primary outcome: Pain assessed with the FLACC scale during tube insertion The investigators believe that this randomized study comparing nitrous oxide inhalation against current practice (no analgesic means) will highlight the intensity of pain caused by nasogastric tube placement and will assess the effectiveness of nitrous oxide inhalation to reduce pain and anxiety induced by the procedure

The Role of Intestinal Microbiota Dysbiosis in the Development of Spondyloarthritis

As secondary objectives, the study aims: - to research the abundance of bacterial strain of R. gnavus in mucosal sampling by biopsy; - to study the interaction between R. gnavus bacterium and mucus from histological sampling; - to correlate the expression of genes of intestinal mucus with the variations of identified microbiota of mucus biopsy; - to study the interaction between bacteria and intestinal epithelial cells during culture; - to demonstrate perturbations of the immune responses by dysbiosis.

Efficacy of Dalbavancin in Osteoarticular Infections Associated With Hip and Knee Replacements

Impact of Hemodialysis on Cutaneo-muscular Electrical Impedance

The study will be realized in dialysis facility of Ambroise Paré hospital, APHP. The duration of enrollment of subjects will be 3 months, each enrolled patient will has 2 or 3 week's follow-up.

Zimmer® Natural Nail® (ZNN) Bactiguard Tibia Post-Market Clinical Follow-up Study

This is a multicenter, prospective, Post-market Clinical Follow-up (PMCF) Study with retrospective controls. The study will enroll patients that will be implanted with the Zimmer Natural Nail Bactiguard Tibia device and retrospective controls implanted with standard titanium-alloy tibia nails. 500 tibias will be recruited at maximum 15 sites and allocated on a 1:1 ratio into an: - investigational group (prospective/consecutive series of 250 tibias treated with ZNN Bactiguard tibia) - a control group (retrospective series of 250 tibias treated with uncoated titanium-alloy tibia nail - data collection will be retrospective, these subjects will not have to undergo any study-related procedure). The primary endpoint is the Fracture Related Infection (FRI) rate in the study population 12 months after fracture fixation. The secondary endpoint is the confirmation of safety, performance and clinical benefits of ZNN Bactiguard implant and related instrumentation through the following measure systems: - Radiologic (RUST) & clinical (FIX-IT) fracture healing 12 months after fracture fixation (performance). - Patients' outcomes assessed by the Oxford Knee Score 12 months after fracture fixation (clinical benefits). - EQ5D-5L (patients' quality of life). - Incidence and frequency of adverse events (safety). Data will be collected at 2 weeks, 3 months, 6 months and 1 year after fracture fixation.

Safety and Efficacy of Itacitinib in Adults with Systemic Sclerosis

Systemic sclerosis (SSc) is a rare systemic autoimmune connective tissue-disease characterized by fibrosis, inflammation, and vasculopathy. SSc is responsible for skin fibrosis that can either be limited or diffuse. The latter phenotype of the disease is commonly associated with visceral involvement and therefore similar to graft versus host disease (GvHD) reaction. It can be life threatening in case of pulmonary or cardiovascular involvement. Nonetheless SSc remains a severe disease responsible for important disability and a poor quality of life. There is a growing body of evidence that supports the implication of the JAK-STAT tyrosine kinases pathway in the activation of fibroblasts of patients with SSc. A genetic polymorphism of STAT4 was found to be associated with the diffuse form of the disease and inhibition of STAT4 gene is associated with a decrease in TGF-ß and IL-6 cytokines activation, which are two major cytokines implicated in SSc pathogenesis. Recently, Pedroza et al. confirmed the implication of STAT3 in skin fibrosis mechanisms. Indeed, the authors showed an enhanced activation of STAT3 and demonstrated in vivo that the inhibition of STAT3 phosphorylation prevented skin fibrosis in a murine model of SSc. These data were confirmed by a work of Zhang et al. who showed that the inhibition of JAK1 was also needed to prevent skin and lung fibrosis. Altogether these works confirmed the implication of the JAK pathway in fibrosis mechanism. Itacitinib is a Janus kinase inhibitor that specifically targets JAK1 and decreases STAT3 phosphorylation. Itacitinib was shown to efficiently treat patients with myelofibrosis, rheumatoid arthritis, and chronic plaque psoriasis. Very interestingly, itacitinib efficacy has also been reported in patients with acute GvHD. Altogether these data and studies reinforced the investigator's working hypothesis. The efficacy and safety of this proposal must be tested.