Faitanar, Spain

Long-Term Evaluation of TAILORED Vs Anatomical Ablation Strategy for Persistent Atrial Fibrillation

The TAILORED-AF study demonstrated at one year's follow-up that a tailored ablation strategy guided by Volta Medical AI-software targeting areas of spatio-temporal dispersed electrograms in combination with pulmonary vein isolation (PVI) ablation is more effective to an anatomical ablation strategy targeting PVI alone (current standard of care) for the treatment of persistent atrial fibrillation (AF). VX1 legacy device renamed Volta AF-Xplorer was used in the TAILORED-AF study in the treatment arm. No additional treatments are specifically required in the scope of this ancillary TAILORED-LT study which aims to follow the patients previously treated in the initial TAILORED-AF study over the long-term. However, in the event of repeat procedures during the TAILORED-LT study, the choice of the ablation technique will be left to the investigator's discretion, regardless of the patient's randomization arm in the TAILORED-AF study. The annual follow-up will be performed as in routine clinical practice post AF ablation procedures: visits at 24 months, 36 months, 48 months and 60 months post TAILORED-AF Study index procedure. It is possible that some of these annual visits cannot be completed prospectively due to time already having elapsed between the end of the subject participation in the TAILORED-AF study and the date of enrollment in the extension TAILORED-LT study. In this case, available data (among those expected by the study protocol) will be collected retrospectively. The additional procedures related to this clinical investigation are limited to annual 24-hour Holters and to the administration of Quality Of Life questionnaires (SF-36 and AFEQT) to the patients during follow-up visits.

A Study to Assess the Efficacy and Safety of Induction Therapy With RO7790121 in Participants With Moderately to Severely Active Crohn's Disease

Contribution of Point of Care Ultrasound by the Emergency Physician to Rule Out the Small Bowel Obstruction: a Diagnostic, Multicenter Study

Small Bowel Obstruction (SBO) is a frequent pathology, leading to admissions to emergency departments (ED). Diagnosis is currently based on an abdominal CT scan (CT). However, CT is associated with drawbacks such as radiation exposure, increased cost and ED length-of-stay. A recent meta-analysis including 1178 patients showed that Point of care ultrasound (POCUS) had a good diagnostic accuracy (sensitivity 83% [95%CI 71.7%-90.4%]), specificity 93% [95%CI 55.3% -99.3%]). Another meta-analysis with 433 patients, found rather similar results: sensitivity 83% [95% CI 89.0% to 94.7%], specificity 96,6% [95% CI 88.4% to 99.1%]). Since CT is almost warranted to guide the treatment strategy, which could include surgery, medical treatment or both, CHU of Nantes emergency unit explored a different approach focusing on POCUS rule-out ability. This study also introduced the notion of SBO Gestalt probability which is a global clinical evaluation by the physician. Gestalt probability has mainly been explored in patients with suspected pulmonary embolism and was found as effective as clinical prediction rules. It is used in the routine clinical evaluation of patient with suspicion of pulmonary embolism. When applied to patients with SBO suspicion, the physician chooses between low, moderate or high risk of SBO. Based on CT results, prevalence of SBO based on Gestalt probability were 21%, 45% and 87% in the low, moderate and high risks, respectively. Our team studied POCUS with the following items that were searched in the whole abdomen divided into nine zones: dilated incompressible fluid-filled intestinal loop (>25 mm) with back-and-forth fluid movement. When at least one of these signs was present in one zone, the SBO was highly suspected. As it was an observational study, a CT was performed in all patients and was the gold standard. This approach was associated with a POCUS sensitivity in the whole population of 99% [95% CI: 93-99.8] [2]. POCUS would thus have a role in patients with low and moderate SBO risks because the prevalence of SBO was major in the high risk Gestalt probability category of patients, and thus CT is the only imaging needed in these latter. Furthermore, in patients with low or moderate probability, the sensitivity was 100% [95% CI: 88-100] In previous studies, the sensitivity was not able to exclude SBO with sufficient security since the lower 95% confidence interval margin was near 90%. By (i) focusing on patients with a low or moderate clinical Gestalt probability and (ii) increasing the number of patients, CHU of Nantes emergency unit intends to demonstrate that POCUS should be able to safely exclude SBO in this population. In case of positive results, the diagnostic strategy in case of SBO suspicion could be modified in: firstly, assess the clinical Gestalt probability; secondly perform a POCUS in patients with low or moderate Gestalt probability and thirdly, prescribe a CT only for patients with high clinical probability or presence of POCUS signs of SBO. This would avoid unnecessary CT and thus lower patient's. exposure, costs, ED length-of-stay and radiologist workload. A study performed in the USA simulated a POCUS first approach in patients with suspected SBO and found that it could save ED length of stay, radiation and money. In France in 2017, about ¾ of ED were equipped with ultrasound machines and half of the emergency physicians were trained in POCUS. Furthermore, SBO detection is easily performed: in our study, the operator self-assessed ultrasound experience was beginner or intermediate for 59% of patients. In case of positive results, this technique would be largely deployed. Inclusion criteria will be patients with low or moderate Gestalt clinical probability of SBO. A POCUS will be performed followed by a CT (gold standard). This CT will be realized and interpreted blindly from the POCUS results. The main objective will be the ability of POCUS to rule-out SBO in patients with low or moderate Gestalt clinical probability

Antimicrobial Therapy for Difficult-to-treat Pseudomonas Aeruginosa

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).

Epidemiological Study of a Prospective Cohort of Patients Aged 60 and Over Managed for Acute Myeloid Leukemia (AML) and Receiving Intensive Induction Therapy

A Phase Ⅲ Study of Rilvegostomig in Combination With Fluoropyrimidine and Trastuzumab Deruxtecan as the First-line Treatment for HER2-positive Gastric Cancer

The purpose of this study is to assess the efficacy and safety of rilvegostomig in combination with fluoropyrimidine and T-DXd (Arm A) compared to trastuzumab, chemotherapy, and pembrolizumab (Arm B) in HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma participants whose tumors express PD L1 CPS ≥ 1. Rilvegostomig in combination with trastuzumab and chemotherapy will be evaluated in a separate arm (Arm C) to assess the contribution of each component in the experimental arm. This study will be conducted at up to 200-250 sites globally in approximately 25 countries.

A Phase III Renal Outcomes and Cardiovascular Mortality Study to Investigate the Efficacy and Safety of Baxdrostat in Combination With Dapagliflozin in Participants With Chronic Kidney Disease and High Blood Pressure

The purpose of this study is to investigate the efficacy, safety, and tolerability of baxdrostat in combination with dapagliflozin, compared with placebo and dapagliflozin, in reducing the risk of the composite of > 50% decline in eGFR, kidney failure, or CV death, in individuals with CKD and HTN. This study consists of a 4-week dapagliflozin Run-in Period for participants untreated with SGLT2i at screening, and a double-blinded period where participants will receive either baxdrostat/dapagliflozin or placebo/dapagliflozin. Site visits will take place at 2-, 4-, 8-, 16-, 34, and 52-weeks following randomisation. Thereafter visits will occur approximately every 4 months. The study closure procedures will be initiated when the predetermined number of primary endpoint events is predicted to have occurred ie, the PACD. All randomised participants including any participants who have prematurely discontinued study intervention will be scheduled for a SCV within a few weeks of the PACD. This period can be extended by the Sponsor. In case of premature discontinuation of blinded study intervention, participants will continue in the study and receive dapagliflozin 10 mg, unless the participant meets dapagliflozin specific discontinuation criteria. If study intervention is temporarily or permanently discontinued, the participant should remain in the study, and it is important that the scheduled study visits (including the PTDV for participants with permanent discontinuation of study intervention) and data collection continue according to the study protocol until the SCV.

Predictive Diagnosis of Ulcero-Necrotizing EnteroColitis in Premature Babies Using an Artificial Intelligence Approach Based on Early Analysis of the Fecal Microbiota

Systematic collection of stool (excluding meconium) from premature infants up to 21 days of age. Systematic analysis of the first two stools at the MEDiS laboratory: analysis of fecal microbiota by direct metagenomic sequencing (RiboTaxa), coupled with artificial intelligence (deep neural network previously trained on literature data). The test gives us a dichotomous response (yes/no) for each stool. In the event of discordant analysis between the 2 stools (approximately 35% of cases in our preliminary study), a 3ème stool will be analyzed in order to classify the child as being at risk of NEC or not. The person performing these analyses will not be informed of the child's clinical evolution. The diagnosis of NEC will be made by the clinician in charge of the child, according to the Bell classification. Follow-up until return home or transfer to a peripheral center. A telephone call will be made to parents at 3 months of age, to ensure that no NECN has occurred after transfer to a peripheral center.

Validation of KELIM as a Predictive/Prognostic Factor for Maintenance Treatment With iPARP in First-Line Ovarian Cancer

Preservation of Women's Fertility: Evaluation of Innovative Methods for Ovarian Tissue Cryopreservation

The aim of this project is to determine whether the type of cryogenic tube (with screw caps or thermosoldered) influences the quality and functionality of ovarian tissue after cryopreservation. First, a characterization of the thermodynamic properties of the freezing medium using a differential scanning calorimeter (Diamond DSC, PerkinElmer) will be carried out to optimize freezing and thawing protocols. This analysis will define important parameters such as crystallization temperature (Tc), end-of-melting temperature (Tm), and transition temperatures (Tg'1). Once freezing and thawing protocols are optimized, we will use human ovarian cortex surrounding benign cysts, a model previously validated by our laboratory, to determine whether the type of cryotube influences the quality of human ovarian tissue. These ovarian cortical samples usually destroyed in clinics share similar characteristics with normal ovarian cortex. Ovarian tissue will be cut into 1mm3 fragments and divided into three groups: fresh ovarian cortex (group1, control), ovarian cortex cryopreserved in thermosoldered cryogenic tubes (group 2) or in screw cap (group 3). We will assess ovarian tissue quality immediately after resection for group 1 or after thawing for group 2 and 3 by analyzing follicle density and morphology (HES staining) and proliferation/apoptosis balance (Immunohistochemistry (IHC) for KI67 and cleaved caspase 3). To assess the functionality of the ovarian tissue after thawing, ovarian cortex fragments will be in vitro cultured. We will analyze i) follicle density, type and morphology (HES staining), ii) the proliferation/apoptosis balance (IHC for KI67 and cleaved caspase 3), iii) the expression levels of major folliculogenesis regulators (IHC for GDF-9) and iv) the levels of folliculogenesis-associated hormones (AMH, estrogen) secreted in culture medium.