Bethune

The aim is to describ rare primary hepatic cancers clinical, histological and radiological features, to obtain a biological tumor and blood collection, and to evaluate the efficacy of treatments received in clinical practice in order to determine optimal therapeutic sequences.

WAYFIND-R is a registry that aims to capture high-quality real-world data linking next-generation sequencing, treatments and outcomes from cancer patients diagnosed with a solid tumour. The WAYFIND-R has three main overarching objectives: 1. To provide a platform to support the design and conduct of clinical and epidemiological research; 2. To develop an evidence-generation platform to better understand health outcomes and cancer care processes; and 3. To characterize the treatments and clinical course of solid tumor cancers in patients who have undergone NGS testing.

Pancreatic cancer represents the fourth cause of death by cancer in Western countries. In over 90% of cases, it is due to an adenocarcinoma. The only curative treatment for pancreatic cancer remains the surgical exeresis. This one can only be suggested as a curative treatment in only 10 to 15% of cases. Besides, prevention or screening is difficult to set up due to the absence of clearly identified risk factors or groups and to the absence of useful markers for the diagnosis in clinical practice. The research efforts in this area must face a double challenge: saving time while improving the diagnosis period and strengthen the therapeutic equipment. It is important to identify and characterise the new molecular markers applicable for a better diagnosis and/or treatment (especially the response factors to chemotherapy). The present project aims to enrich with fresh tumor tissue and somatic genetic analysis the existing propective collection BACAP in order to support support future research projects on: * the development of new diagnostic tools, * understanding the development of tumors of the pancreas * the development of new therapeutic targets * understanding the response to chemotherapy…

Infections due to Pseudomonas aeruginosa isolates with acquired resistances to all first-line antipseudomonal beta-lactams and fluoroquinolones (difficult-to-treat isolates - DTR), pose serious therapeutical challenges, especially in critically ill and/or immunocompromised patients. Certain new beta-lactam/beta-lactamase inhibitor combinations (BL/BLI (beta lactamine/ beta lactamase inhibitor) - i.e., ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam, others) and cefiderocol have shown promising results for the treatment of infections due to DTR P. aeruginosa. However, multicenter data on their real-life utilization in this indication are still scarce. The ADDICT study is a prospective, multicenter cohort study including unselected patients with DTR P. aeruginosa infection requiring definite intravenous antimicrobial therapy. The primary objective of the study is to investigate the clinical efficacy of available options (new BL/BLI, cefiderocol or older agents such as aminoglycosides and colistin) in this population. Secondary objectives are to compare the clinical and microbiological efficacy of available options in infections due to DTR P. aeruginosa with in vitro susceptibility to more than one last-resort drug, to compare the incidence of non-ecological adverse events observed with these drugs, to assess the incidence of resistance emergence under therapy and to elucidate the molecular mechanisms of resistance emergence, to assess the benefits and risks of combination therapy in this indication, to compare the acquisition rates of multidrug-resistant bacteria other than DTR P. aeruginosa, and Clostridioides difficile infection, to compare Day-28 and in-hospital all-cause mortality rates. Patients will be recruited in 60 hospital centers contributing to four French networks of research in infectious diseases and critical care (CRICS-TRIGGERSEP, ReaRezo, OutcomeRéa, RENARCI - PROMISE metanetwork). Clinical variables will be collected through an electronic case-report form. DTR P. aeruginosa isolates will be sent to the National Reference Center of Antimicrobial Resistance in P. aeruginosa for centralized analyses (extended antimicrobial susceptibility testing, MLST, whole-genome sequencing of successive isolates if resistance emergence under therapy).

Asplenia can be congenital or acquired. Acquired asplenia can be due to diagnostic or therapeutic surgery, splenic artery embolization, or radiotherapy. Incidence of splenectomized patients was estimated between 10 and 15/100 000 persons in 2003. More recent data suggested a decrease in splenectomy due to increase of splenic artery embolization. From 212 to 2016, about 4000 splenectomy had still been performed. Three different risks are known for asplenic patients: infectious, neoplastic, and thromboembolic. Prevalence rate of infectious complications in splenectomized patients was 3.2% with a mortality rate of 1.4%. A US cohort study including 8149 splenectomized veterans have shown that the risk of cancer was increased, so did the risk of thromboembolic disease, on a 27-year period of follow-up. Pathophysiology of these risks are not well known. There are very few tools to assess splenic function: Howell-Jolly bodies in red blood cells, scintigraphy. These tools lack sensitivity and are not correlated with complications in asplenic patients. To better understand how splenic function and how immunity evolves during time in asplenic patients, a longitudinal follow-up could be useful. There may be some differences between splenectomized patients, those who benefited from splenic artery embolization, and those who received radiotherapy. Infectious risk may be different between these three groups. Implementing new tools assessing residual splenic function could improve management of these patients. A prospective follow-up aims at accurately estimate the incidence rate of infectious and non-infectious complications in this population.

There is a toxicity linked to the chronic use of nitrous oxide, leading to neurological disorders such as combined sclerosis of the spinal cord. One thus frequently observes patients presenting disorders of walking or paresthesias, of more or less resolving evolution being able to go until the need for using a wheelchair and more recently cases of thrombosis were reported Serum or urine N2O assays are rarely performed routinely, because they do not allow to ensure a real exposure due to the very short half-life of this gas in the body. Thus, other biological monitoring markers are mentioned in the literature, such as vitamin B12 or homocysteine. Unfortunately, there are still no recommendations for biological monitoring of nitrous oxide consumption. Moreover, underlying mechanisms leading to clinical outcomes remains misunderstood.

Sporadic Alzheimer's disease is a multifactorial illness arising a major medico-economic stakes for our aging societies. There is currently no curative treatment available. Coffee is a complex beverage with psychostimulant properties whose main effective element, caffeine, has a pleiotropic effect on the central nervous system. Caffeine pharmacological properties enable its use like an Alzheimer's disease symptomatic treatment. Its supposed benefits mustn't obscure anxiety and insomnia caffeine effect at large dose, which Alzheimer's patients might be more vulnerable. The main study objective is to evaluate placebo-controlled caffeine efficacy (30 treatments weeks) on cognitive decline in Alzheimer's disease dementia at beginning to moderate stage (MMSE 16-24).

Multicentre randomized non-inferiority trial comparing cotrimoxazole to standard antibiotic therapy for enterobacterial VAP. Selection of patients will be done by physicians in ICU. All clinically suspected VAP will be confirmed with a lung sample (preferably bronchoalveolar lavage or protected distal specimen, otherwise endotracheal aspiration). Patients with a microbiologically confirmed VAP due to an Enterobacteriaceae susceptible to cotrimoxazole and at least one antibiotic of the empiric antibiotic therapy (based on international recommendations) will be included. After written informed consent, they will be randomized (1:1), using a computer-generated randomization scheme of various-sized blocks, stratified by presence of septic shock at VAP diagnosis and by presence of COVID-19 pneumonia on ICU admission, through a centralized 24 hours internet service (CleanWEB™) to cotrimoxazole, or best standard of care (either a beta-lactam or a fluoroquinolone), after randomization for a total duration of 7 days (including empiric initial appropriate treatment). Posology and modalities of antibiotic administration will be optimized based on most recent recommendations for ICU patients. Because antibiotic therapy will be variable in the control group, single or double blind is not appropriate. Daily follow-up until death or ICU discharge or day 28 will be performed (vital status, antibiotic therapy, new infection, Clostridium-difficile infection). Clinical (arterial blood gas, temperature, haematology, tracheal secretions) and radiological cure (chest X-ray) will be assessed at Day 7. Systematic MDR bacteria screening will be performed weekly and at ICU discharge. Vital status will be assessed at day 90. Alive patients leaving ICU before 90 days will be contacted by phone (if discharge at home) or by interview at hospital (if transferred in a different ward). Assessment of the clinical and radiological cure by an independent committee (1 specialist in infectious disease and 1 intensivist), blinded of the randomization arm (PROBE methodology).

Among patients admitted after an out-of-hospital cardiac arrest (OHCA) in intensive care unit (ICU), almost two thirds of patients will develop in the first hours a post-cardiac arrest (CA) shock. This post-CA shock, combines cardiac and hemodynamic failure, generally resulting in multi-organ failure and early death in up to 35% of patients. Experimental data suggest that intravenous ascorbic acid (vitamin C) may attenuate inflammation and vascular injury related to sepsis or surgery. Preclinical and clinical studies also provide safety data of high dose intravenous vitamin C (\> 200mg/kg/day) with no significant adverse event reported and favorable impact on outcome. Experimental data also suggest beneficial effect of vitamin C in post-CA management with improvement of shock and multi-organ failure with potential benefit on neuroprotection and outcome. The study is a phase II multicenter prospective controlled open-label trial randomized in two parallel groups : * Expérimental group: Standard of care care for post-CA shock + Vitamin C (Vit-C) 200mg/kg/d IV (started as early as possible, no later than 1 h after randomization + thiamin (Vit B1) 200mg every 12 h during 3 days. * Control group: Standard of care care for post CA shock according international guidelines. Patient number to be enrolled : 234, Study duration :24 months and 28 days, Inclusion duration : 24 months, Patient participation : duration : 28 days

Recent studies show the impact of frailty in a middle-aged or even young population of patients admitted to critical care in terms of mortality (13), and the persistent risk of impairment of physical and mental capacities after resuscitation (14). To date, few studies have looked at clinical frailty as a risk factor for mortality in a middle-aged or young population, more specifically those suffering from septic shock, which is already known to be a major factor in morbidity and mortality (15,16), with repercussions on long-term quality of life. The aim of the study is to demonstrate that "frail" patients, defined as having a CFS score greater than or equal to 5, and "severely" frail patients, defined as having a CFS score between \[6-7\] as defined by Bagshaw et al (14), constitute an independent risk factor (RF) for mortality. In the same way, as an exploratory study, we will try to find out whether clinical frailty constitutes a risk factor for extending the length of hospital stay, the risk of short/medium-term readmission, as has already been demonstrated for patients admitted to intensive care from all causes (15), or for impaired quality of life. The objective is to have a better understanding of the implications and outcomes associated with pre-hospital frailty in young critically ill patients. This analysis will also help to clarify prognoses and contribute to better decision-making on the intensity and proportionality of care, as well as providing better information and helping to manage the expectations of patients and their families in terms of survival prognosis and subsequent quality of life.