La Grand Croix, France

Exploration of the Transfer of Barium From Thermal Mud

The presence of barium in thermal clays was noted by the ARS (french administration) who interviewed the Directorate General of Health (DGS); the latter seized the National Academy of Medicine (June 2016) which reported in February 2017. In this report it was stated that there was no argument in favor of toxic phenomena related to the presence of barium but that it was appropriate, in particular, to evaluate a possible passage of barium in the skin in subjects who are treated with thermal mud - by observing, where appropriate, an increase in serum and urinary barium levels in the subjects concerned and - by measuring a possible depletion of barium in the sludge used. The DGS validated the various recommendations of the Academy and asked, in January 2018, the National Council of Thermal Establishments (CNETH) to implement the recommendations of the Academy. It will therefore be a prospective before-after interventional study, implementing 15 daily applications of 6 mud poultices made with a clay used as thermal clay and containing appreciable barium levels. A surveillance will be put in place with the event of suspected event, the volunteer can then be seen by a doctor.

Combination of Baricitinib and Anti-TNF in Rheumatoid Arthritis

Intensive combination therapies have revolutionised the management of solid neoplasms, hematologic malignancies, and acquired-immune-deficiency syndrome. These intensive strategies are based on the need to obtain rapid control of disease activity to afford the chance of stable full remission and avoid irreversible complications. The same goal applies to management of RA. Because current therapeutic strategies may fall short of these target goals and fail to improve quality of life in some patients, novel approaches are needed to improve outcomes. RA is a complex disease involving numerous cell types and inflammatory mediators of innate and adaptive immune systems. The investigators are aware that most of combination bDMARD strategies have been associated with little or no incremental benefit in efficacy compared to single-biologic therapy. However, our study will target mechanisms that differ from those in previous studies. Strategies that simultaneously target different pathways involved in the pathogenesis of RA may enhance treatment responses in patients with RA. Of note, baricitinib does not directly block signalling downstream of TNF, even if an indirect effect on TNF production is likely to occur. Targeting multiple inflammatory cytokines in combination may lead to more effective treatment and enhanced clinical responses in patients with RA compared to the current second-line strategies. The different mechanisms of action of baricitinib and anti-TNF, should ensure the efficacy of the combination. No concurrent trial evaluating similar strategies is registered at ClinicalTrial.gov.

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.

Role of Gut Microbiota in the Pathophysiology of Aseptic Abscesses

- Included patients will be adult patients meeting the diagnostic criteria for aseptic abscess syndrome described by André et al. - Controls will be adults without aseptic abscess syndrome living in the same environment as the patients, whether related to the patient or not. Patients and controls must be able to provide informed consent and be affiliated with the French Social Security system.

Identification of Physiological Data by a Wearable Monitor in Subjects Suffering From Major Depression Disorders

Covid-19 Pediatric Observatory

Regional Central Database Recording of Chronic Myeloid Leukemia

Given the complexity and evolution of recommendations and to harmonize these, it appears necessary to establish a central database for recording , monitoring patients with CML supported by the participating centers the region and evaluation of care practices in use . Indeed , the main purpose of this database is to provide diagnostic and therapeutic management of reported cases of chronic myeloid leukemia and to study the prognostic factors . The main objective is to improve significantly the percentage of patients treated adequately load in the region, in the initial stages of the disease and during its evolution.

Survey on Epidemiology of Hypoparathyroidism in France

Very few data has been published on the epidemiology of hypoparathyroidism worldwide. None exists specifically in France. Hypoparathyroidism could led to complications: e.g. symptomatic hypocalcemia, calcifications (brain, eye and other soft tissues), nephrolithiasis/nephrocalcinosis, renal insufficiency. Here,the investigators plan to collect data about both epidemiology, medication and complication of hypoparathyroidism in France.

Can Nephrocheck™ Predict the Reversibility of Early, Acute Kidney Injury During Septic Shock?

Patients with septic shock in the intensive care unit have an elevated risk of developing acute kidney injury (AKI). AKI is an independent factor for mortality. Interventions that limit the worsening of renal function might have an impact on the mortality rate in these patients. Given the absence of validated pharmacological treatments for limiting the progression of AKI or for accelerating recovery from AKI, early intervention and the restoration of the glomerular filtration rate (GFR) in this context of hemodynamic change during the initial phase of septic shock might improve the patients' prognosis. One major challenge is therefore how to determine whether or not the AKI is reversible. The best-studied biomarkers (NGAL and KIM 1) have little discriminant power in septic patients because of their poor specificity or unsuitable kinetics for very early diagnosis. The combination of urine assays for tissue inhibitor of metalloproteinase 2 (TIMP2) and insulin-like growth factor binding protein 7 (IGFBP7) has shown good diagnostic performance for the very early detection of the risk of developing AKI in the following 12 hrs. Urine levels of these two markers specifically reflect damage to kidney tubules. Moreover, the levels appear to be strongly correlated with the severity of tubule damage. Thus, one can reasonably hypothesize that measurement of these markers in the very early stages of septic shock might determine the presence and severity of kidney tubule damage. A threshold (yet to be defined) would help to differentiate between (i) transient, non-severe injury and (ii) injury that is already too severe to be reversible.

Risk of Morbidity, Mortality and Long-term Monitoring of Antiretroviral Treatment in People Living With HIV

The survival of people living with HIV (PLHIV) taking antiretroviral therapy (ART) is now close to what is reported in the general population in northern countries. However, PLHIV experience an increased risk of morbidities that the ANRS CO3 Aquitaine Cohort has largely contributed to describe in the last years. Among contributing factors to this excess of morbidity, immune suppression, immune activation, and exposition to cardiovascular and cancer risk factors as well as ageing represent possible intervention targets. Long-term follow-up is required to describe and understand the evolution of morbidities and complications as well as ART side effects. Moreover, the global evaluation of health in PLHIV, including psychiatric, neurologic and social determinants and not only biomedical determinants represents one of the public health challenges of the next decade in the field of HIV infection. The aim of the present study is to study the emerging morbidity occurring during the course of HIV infection in people treated with ART as well as to describe the tolerance and efficacy of new available ART regimens. The follow-up of patients will be performed according to national guidelines. Demographic, clinical, biological and therapeutic data will be captured at each patient's hospital contact according to a standardized questionnaire. All events occurring during the course of clinical management will be prospectively registered in the database according to the ICD 10th revision. A biobank will be collected from every consenting PLHIV at inclusion in the cohort and then every two years.